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ISBN-13: 978-0-7216-0422-0
ISBN-10: 0-7216-0422-6
▼
Contributors
Nancy L. Anderson, DVM, PhD, ABUPC (Avian) Jamie R. Bellah, DVM, Diplomate ACVS
Director of Wildlife Services, Lindsay Wildlife Staff Surgeon, Affiliated Veterinary Specialists, Orange
Museum, Walnut Creek, California Park, Florida
Pet Rodents Surgery of Intertriginous Dermatoses
Basic Husbandry and Medicine of Pet Reptiles
Larry Berkwitt, DVM, Diplomate ACVIM
Francisco J. Alvarez, DVM Chief of Staff, Internal Medicine, Veterinary Referral
Chief Resident, Clinical Oncology Service, Veterinary and Emergency Center, Norwalk, Connecticut
Medical Teaching Hospital, Department of Veterinary Diagnostic Methods in Respiratory Disease
Clinical Services, The Ohio State University,
Columbus, Ohio Sonya V. Bettenay, BVSC (Hons), FACVSc
Respiratory Neoplasia (Dermatology), Diplomate ECVD
Dermatopathology, Laboklin, Munich, Germany
Laura J. Armbrust, DVM, Diplomate ACVR Skin Cytology and Biopsy
Assistant Professor, Radiology, Clinical Sciences,
Kansas State University College of Veterinary David S. Biller, DVM, Diplomate ACVR
Medicine, Manhattan, Kansas Professor and Head of Radiology, Department of
Radiographic and Ultrasonographic Techniques Clinical Sciences, College of Veterinary Medicine,
Kansas State University, Manhattan, Kansas
Dennis N. Aron, DVM, Diplomate ACVS Radiographic and Ultrasonographic Techniques
Professor, Small Animal Surgery, Department of Small
Animal Medicine, College of Veterinary Medicine, Stephen J. Birchard, DVM, MS, Diplomate ACVS
University of Georgia, Athens, Georgia Associate Professor, Small Animal Surgery,
Luxation, Subluxation, and Shearing Injuries of the Department of Veterinary Clinical Sciences, The Ohio
Tarsal Joint State University, Columbus, Ohio
Diseases of the Thyroid Gland
Shane W. Bateman, DVM, DVSc, Selected Skin Graft and Reconstructive Techniques
Diplomate ACVECC Surgery of the Liver and Biliary Tract
Associate Professor-Clinical, Head of Emergency Diseases and Surgery of the Exocrine Pancreas
and Critical Care, Department of Veterinary Peritonitis
Clinical Sciences, The Ohio State University, Pleural Effusion
Columbus, Ohio Principles of Thoracic Surgery
Emergency and Critical Care Techniques and Nutrition
Fluid Therapy for Dogs and Cats Dale E. Bjorling, DVM, MS Diplomate ACVS
Professor and Chair, Surgical Sciences, Affiliate
Karin Muth Beale, DVM, Diplomate ACVD Professor, Division of Urology, Department of Surgery,
Staff Dermatologist, Gulf Coast Veterinary Specialists, School of Veterinary Medicine, University of
Houston, Texas Wisconsin, Madison, Wisconsin
Dermatology Consultant, ANTECH Diagnostics, Surgery of the Kidney and Ureter
Irvine, California Surgery of the Urethra
Dermatophytosis Thoracic Trauma
vii
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viii Contributors
John D. Bonagura, DVM, MS, Diplomate ACVIM Marjory B. Brooks, DVM, Diplomate ACVIM
(Internal Medicine, Cardiology) Associate Director, Comparative Coagulation
Professor, Cardiology and Internal Medicine, Laboratory, Animal Health Diagnostic Center,
Department of Veterinary Clinical Sciences, The Ohio Population Medicine and Diagnostic Science, College
State University, Columbus, Ohio of Veterinary Medicine, Cornell University
Cardiovascular Radiography Ithaca, New York
Cardiovascular Drugs Coagulation Diseases
Heart Failure in Dogs
Syncope Steven C. Budsberg, DVM, MS, Diplomate ACVS
Valvular Heart Disease Professor, Department of Small Animal Medicine and
Cardiomyopathy Surgery, University of Georgia, Athens, Georgia
Pericardial Diseases Orthopedic Disorders of the Distal Extremities
Vascular Diseases
Congenital Heart Disease C. Anthony Buffington, DVM, PhD, Diplomate
Respiratory Infections ACVN
Professor, Department of Veterinary Clinical Sciences,
Jennifer Bonczynski, DVM, Diplomate ACVS College of Veterinary Medicine, The Ohio State Uni-
Staff Surgeon, Department of Surgery, The Animal versity, Columbus, Ohio
Medical Center, New York, New York Emergency and Critical Care Techniques and Nutrition
Pancreatic Beta Cell Neoplasia
Clay A. Calvert, DVM, Diplomate ACVIM
Harry W. Boothe, DVM, MS Professor, Department of Small Animal Medicine and
Professor, Small Animal Surgery, Department of Surgery, College of Veterinary Medicine, University of
Clinical Sciences, College of Veterinary Medicine, Georgia, Athens, Georgia
Auburn University, Auburn, Alabama Heartworm Disease
Surgery for Otitis Media and Otitis Interna
Surgery of the Prostate Gland Marcia A. Carothers, DVM, Diplomate ACVIM
Surgery of the Testes and Scrotum (Internal Medicine)
Surgery of the Penis and Prepuce Staff Veterinarian, Akron Veterinary Referral and
Emergency Center, Akron, Ohio
Randy J. Boudrieau, DVM, Diplomate ACVS Respiratory Neoplasia
Professor, Surgery, Clinical Sciences, Tufts University
School of Veterinary Medicine, North Grafton, Sue Chen, DVM
Massachusetts Gulf Coast Veterinary Specialists, Houston, Texas
Section Head, Small Animal Surgery, Henry & Lois Avian Reproductive Tract Disorders
Foster Hospital for Small Animals, North Grafton, Rabbits
Massachusetts
Delayed Union, Nonunion, and Malunion Dennis J. Chew, DVM, Diplomate ACVIM
Professor, Department of Veterinary Clinical Sciences,
Heather L. Bowles, DVM, Diplomate ABVP College of Veterinary Medicine, The Ohio State
Fallston Veterinary Clinic, Fallston, Maryland University, Columbus, Ohio
Avian Reproductive Tract Disorders Fluid Therapy for Dogs and Cats
Diseases of the Parathyroid Gland and Calcium Metabolism
Ronald M. Bright, DVM, MS, Diplomate ACVS Diseases of the Urinary Bladder
Affiliate Professor, Department of Clinical Sciences,
College of Veterinary Medicine, Colorado State Lynette K. Cole, DVM, MS, Diplomate ACVD
University Assistant Professor, Dermatology, College of Veterinary
Staff Surgeon, Surgical Referral Services, Fort Collins, Medicine, Veterinary Teaching Hospital, The Ohio
Colorado State University, Columbus, Ohio
Staff Surgeon, Veterinary Consultation Services, Inc., Diseases of the Pinna
Knoxville, Tennessee Otitis Media and Otitis Interna
Surgery of the Esophagus
Diseases of the Stomach Carmen M. H. Colitz, DVM, PhD, Diplomate ACVO
Surgery of the Stomach Assistant Professor, Ophthalmology, Department of
Surgery of the Intestines Veterinary Clinical Sciences, The Ohio State
Anorectal Surgery University, Columbus, Ohio
Diseases of the Lacrimal System
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Contributors ix
Sarah Colombini Osborn, DVM, MS, William R. Fenner, DVM, Diplomate ACVIM
Diplomate ACVD (Neurology)
Co-Owner, Dermatology, Gulf Coast Veterinary Emeritus Faculty, College of Veterinary Medicine, The
Dermatology & Allergy, Houston, Texas Ohio State University, Columbus, Ohio
Consultant, Dermatopathology/Dermatology, Antech Diagnostic Approach to Neurologic Disease
Diagnostics, Phoenix, Arizona
Canine and Feline Demodicosis Roger B. Fingland, DVM, MS, MBA,
Diplomate ACVS
Paul A. Cuddon, DVM, Diplomate ACVIM Associate Dean, Clinical Programs, Professor and
(Neurology) Director, Veterinary Medical Teaching Hospital,
Neurological Center for Animals, Lakewood, Colorado College of Veterinary Medicine, Kansas State
Disorders of the Spinal Cord University, Manhattan, Kansas
Surgery of the Urinary Bladder
Támara M. Costa-Gómez, DVM Surgery of the Ovaries and Uterus
Arboretum View Animal Hospital, Downers Grove, Surgery of the Vagina and Vulva
Illinois Obstructive Upper Airway Disorders
Surgery of the Kidney and Ureter
Surgery of the Urethra Richard B. Ford, DVM, MS, Diplomate ACVIM,
Diplomate (Hon) ACVPM
Kechia M. Davis, DVM Professor, Medicine, Department of Clinical Sciences,
Resident, Small Animal Surgery, Department of College of Veterinary Medicine, North Carolina State
Clinical Sciences, Veterinary Teaching Hospital, North University, Raleigh, North Carolina
Carolina State University, Raleigh, North Carolina Vaccination Guidelines for the Dog and Cat
Mammary Gland Neoplasia
S. Dru Forrester, DVM, MS, Diplomate ACVIM
Charles E. DeCamp, DVM, MS, (Small Animal Internal Medicine)
Diplomate ACVS Professor, College of Veterinary Medicine,
Professor, Michigan State University, East Lansing, Western University of Health Sciences, Pomona,
Michigan California
Open Fractures Diseases of the Kidney and Ureter
R. Tass Dueland, DVM, MS, Diplomate ACVS Linda A. Frank, MS, DVM, Diplomate ACVD
Professor, Orthopedic Surgery, Affiliate Professor, Professor, Dermatology, Small Animal Clinical
Division of Orthopedic Surgery, Medical School, Sciences, College of Veterinary Medicine, University
University of Wisconsin-Madison, Madison, Wisconsin of Tennessee, Knoxville, Tennessee
Orthopedic Disorders of the Stifle Sex Hormone and Endocrine Look-alike Dermatoses
Joan Dziezyc, DVM, Diplomate ACVO Rance M. Gamblin, DVM, Diplomate ACVIM
Associate Professor, Department of Small Animal (Oncology)
Medicine and Surgery, College of Veterinary Medicine Staff Oncologist, Akron Veterinary Internal Medicine
Staff Ophthalmologist, Veterinary Medical Teaching Oncology Practice, Metropolitan Veterinary Hospital,
Hospital, Texas A&M University, College Station, Akron, Ohio
Texas Principles of Oncology
Diseases of the Retina, Choroid, and Optic Nerve
Jennifer Gieg, DVM
Erick L. Egger, DVM, Diplomate ACVS Resident, Internal Medicine, Department of
Special Appointment, Small Animal Orthopedics, Veterinary Clinical Sciences, The Ohio State
Veterinary Clinical Sciences, Colorado State University, Columbus, Ohio
University, Fort Collins, Colorado Diseases of the Urinary Bladder
Fractures of the Tibia and Fibula
Stephen D. Gilson, DVM, Diplomate ACVS
Christine Ellis, DVM Sõnorã Veterinary Specialists, Scottsdale, Arizona
Exotic Animal Veterinary Service, Fort Collins, Principles of Oncology
Colorado
Ferrets
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x Contributors
Mary B. Glaze, DVM, MS, Diplomate ACVO Robert L. Hamlin, DVM, PhD, Diplomate ACVIM
Professor, Veterinary Ophthalmology, Louisiana State (Cardiology)
University, Veterinary Clinical Sciences Professor, Veterinary Biosciences and Biomedical
Veterinary Ophthalmologist, Veterinary Teaching Engineering, The Ohio State University, Columbus,
Hospital and Clinic, Louisiana State University, Baton Ohio
Rouge, Louisiana Auscultation and Physical Diagnosis
Diseases of the Orbit
Don J. Harris, DVM
Joanne C. Graham, DVM, MS, Diplomate ACVIM Owner and Director, Avian and Exotic Animal
(Oncology) Medical Center, Miami, Florida
Assistant Professor and Staff Oncologist, Iowa State Avian Infectious Diseases
University, Ames, Iowa
Soft Tissue Sarcomas and Mast Cell Tumors Callum W. Hay, BVMS, Diplomate ACVS
President, Veterinary Surgical Services, Inc., Tampa,
David Grant, DVM, MS, Diplomate ACVIM Florida
(Small Animal Internal Medicine) Osteomyelitis
Clinical Instructor, Department of Small Animal Osteoarthritis
Clinical Sciences, Virginia-Maryland Regional College Immune-Mediated Arthritis
of Veterinary Medicine, Blacksburg, Virginia
Diseases of the Kidney and Ureter Cheryl S. Hedlund, DVM, MS, Diplomate ACVS
Professor, Surgery, Veterinary Clinical Sciences, School
Thomas K. Graves, DVM, PhD, Diplomate ACVIM of Veterinary Medicine, Louisiana State University,
Assistant Professor, Small Animal Medicine, Veterinary Baton Rouge, Louisiana
Clinical Medicine, University of Illinois, Urbana, Surgery of the Nasal Cavity and Sinuses
Illinois
Diseases of the Testes and Scrotum Karen Helton-Rhodes, DVM, Diplomate ACVD
Diseases of the Penis and Prepuce Veterinary Referral Centre, Little Falls, New Jersey
Diseases of the Ovaries and Uterus Immune-Mediated Dermatoses
Contributors xi
Lynelle R. Johnson, DVM, PhD, Diplomate ACVIM William C. Kisseberth, DVM, PhD, Diplomate
(Small Animal Internal Medicine) ACVIM
Assistant Professor, VM: Medicine & Epidemiology, Assistant Professor, Department of Veterinary Clinical
University of California, Davis, California Sciences, The Ohio State University, Columbus, Ohio
Bronchopulmonary Disease Diseases of the Spleen
Susan E. Johnson, DVM, MS, Diplomate ACVIM David W. Knapp, DVM, Diplomate ACVS
(Internal Medicine) Staff Surgeon, Angell Animal Medical Center, Boston,
Associate Professor, Veterinary Clinical Sciences, The Boston, Massachusetts
Ohio State University, Columbus, Ohio Management of the Open Wound
Diseases of the Esophagus and Disorders of Swallowing
Diseases of the Stomach Shianne L. Koplitz, DVM, PhD Diplomate ACVIM
Diseases of the Intestines (Cardiology)
Diseases of the Liver and Biliary Tract Cardiology Resident, Department of Veterinary
Diseases and Surgery of the Exocrine Pancreas Clinical Sciences, The Ohio State University,
Columbus, Ohio
Matthew S. Johnston, VMD, DABVP (Avian) Syncope
Assistant Professor, Zoological Medicine, Clinical
Sciences, Colorado State University, Fort Collins, Michael P. Kowaleski, DVM, Diplomate ACVS
Colorado Assistant Professor, Small Animal Orthopedic Surgery,
Avian Respiratory System Disorders Department of Veterinary Clinical Sciences, The Ohio
State University, Columbus, Ohio
Denise Jones, DVM, BS Fractures and Dislocations of the Carpus
Partner and Staff Veterinarian, Findlay Animal Osteochondrosis
Hospital, Findlay, Ohio
History and Physical Examination Gail A. Kunkle, DVM, Diplomate ACVD
Professor, SACS-CVM, University of Florida,
Nancy D. Kay, DVM, Diplomate ACVIM Gainesville, Florida
Staff Internist, Animal Care Center of Sonoma Necrotizing Skin Diseases
County, Rohnert Park, California
Diseases of the Prostate Gland Kenneth W. Kwochka, DVM, Diplomate ACVD
Vice President for Research and Development, DVM
Bruce W. Keene, DVM, MSc, Diplomate ACVIM Pharmaceuticals, Miami, Florida
(Cardiology) Keratinization Defects
Professor, Cardiology, Department of Clinical
Sciences, North Carolina State University, Raleigh, Mary Anna Labato, DVM, Diplomate ACVIM
North Carolina (Small Animal)
Heart Failure in Dogs Clinical Associate Professor, Department of Clinical
Sciences, Cummings School of Veterinary Medicine at
Thomas J. Kern, DVM, Diplomate ACVO Tufts University
Associate Professor, Ophthalmology, Department of Staff Veterinarian, Small Animal Medicine, Foster
Clinical Sciences, College of Veterinary Medicine Hospital for Small Animals, North Grafton,
Cornell University, Ithaca, New York Massachusetts
Diseases of the Cornea and Sclera Disorders of Micturition
Peter P. Kintzer, DVM, Diplomate ACVIM Linda B. Lehmkuhl, DVM, MS, Diplomate ACVIM
Staff Internist, Boston Rood Animal Hospital, (Cardiology)
Springfield, Massachusetts Staff Cardiologist, Cardiology, Med Vet, Medical
Diseases of the Adrenal Gland Center for Pets, Worthington, Ohio
Cardiomyopathy
Susan E. Kirschner, DVM, Diplomate ACVO
Ophthalmologist, The Animal Eye Doctor, Beaverton, Patricia J. Luttgen, DVM, MS, Diplomate ACVIM
Oregon (Neurology)
Diseases of the Eyelid Staff Neurologist, Neurological Center for Animals,
Denver, Colorado
Disorders of the Spinal Cord
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xii Contributors
Paul A. Manley, DVM, MSc, Diplomate ACVS Darryl L. Millis, DVM, MS, Diplomate ACVS
Professor, Chief of Small Animal Services, Surgical Professor, Orthopedic Surgery, Small Animal Clinical
Sciences, School of Veterinary Medicine, University of Sciences, University of Tennessee, Knoxville,
Wisconsin, Madison, Wisconsin Tennessee
Osteoarthritis Postoperative Physical Rehabilitation
Immune-Mediated Arthritis
Milan Milovancev, DVM
Philip A. March, DVM, MS, Diplomate ACVIM Resident, Small Animal Surgery, University of
(Neurology) Wisconsin, Madison, Wisconsin
Associate Professor, Department of Veterinary Clinical Neoplasia of Thoracic and Pelvic Limbs
Sciences, The Ohio State University, Columbus, Ohio
Diagnostic Approach to Neurologic Disease Cecil P. Moore, DVM, MS, Diplomate ACVO
Diseases of the Brain and Cranial Nerves Professor and Chairman, Department of Veterinary
Medicine and Surgery, University of Missouri,
Sandra Manfra Marretta, DVM, Diplomate ACVS, Columbia, Missouri
Charter Dipolomate AVDC Diseases of the Conjunctiva
Professor and Head, Small Animal Surgery and
Dentistry, Veterinary Clinical Medicine, College of Daniel O. Morris, DVM, Diplomate, ACVD
Veterinary Medicine, University of Illinois, Urbana, Assistant Professor and Chief, Dermatology and
Illinois Allergy, Clinical Studies-Philadelphia, University of
Dentistry and Diseases of the Oropharnyx Pennsylvania, Philadelphia, Pennsylvania
Malassezia Dermatitis
Hilary K. Matthews, DVM, PhD, Diplomate ACVIM
Section Head, Internal Medicine, Capital Veterinary Ralf S. Mueller, DMV, DMVH, Diplomate ACVD,
and Referral Center, Columbus, Ohio FACVs
Diseases of the Urethra Chief, Dermatology Service, Medizinische Tierklinik,
Universität München, Munich, Germany
Margaret C. McEntee, DVM, Diplomate Disorders of the Claw
ACVIM (Medical Oncology), Diplomate ACVR
(Radiation Oncology) William W. Muir III, DVM, PhD, Diplomate ACVA,
Assistant Clinical Professor, University of California, Diplomate ACVECC
Davis, School of Veterinary Medicine, Davis, California Professor, Department of Veterinary Clinical Sciences,
Diseases of the Spleen College of Veterinary Medicine, The Ohio State
University Columbus, Ohio
Mary A. McLoughlin, DVM, MS, Diplomate ACVS Cardiopulmonary Cerebral Resuscitation
Assisstant Professor Department of Veterinary Clinical
Sciences, The Ohio State University, Columbus, Ohio Alan C. Mundell, DVM
Diseases of the Urinary Bladder Animal Dermatology Service, Seattle, Washington
Diseases of the Vagina and Vulva Mycobacteriosis
Michael S. Miller MS, VMD, Diplomate, ABVP Rhett Nichols, DVM, ACVIM
Co-owner and Cardiology Consultant, Veterinary Endocrinology and Internal Medicine Consult, Antech
Specialty Center of Delaware, Wilmington, Delaware, Diagnostics, Lake Success, New York
Director, Cardiology-Ultrasound Referral Service, Diseases of the Hypothalamus and Pituitary
Thornton, Pennsylvania
Electrocardiography James O. Noxon, DVM, Diplomate ACVIM
Disorders of the Cardiac Rhythm (Internal Medicine)
Professor, Department of Veterinary Clinical Sciences,
Nicholas J. Millichamp, BSC, BVM, PhD, Iowa State University, Ames, Iowa
DVOpthal, Diplomate ACVO, Diplomate MRCS Adjunct Professor, Department of Companion
Associate Professor, Small Animal Medicine and Animals, Atlantic Veterinary College, University of
Surgery, College of Veterinary Medicine, Staff Prince Edward Island, Charlottetown, Prince Edward
Opthalmologist, Veterinary Teaching Hospital, Texas Island, Canada
A&M University, College Station, Texas Otitis Externa
Diseases of the Retina, Choroid, and Optic Nerve
W0422-PR.qxd 11/15/05 6:07 PM Page xiii
Contributors xiii
Marvin L. Olmstead, DVM, MS, Diplomate ACVS Michael Podell, DVM, MSc, Diplomate ACVIM
Emeritus Professor, Small Animal Orthopedics, (Neurology)
Department of Veterinary Clinical Sciences, The Ohio Adjunct Professor, Veterinary Clinical Medicine,
State University, Columbus, Ohio University of Illinois, Champaign-Urbana, Illinois
Oregon Veterinary Associates, Springfield, Oregon Medical Director and Staff Neurologist, Animal
Disorders of the Coxofemoral Joint Emergency and Critical Care Center, Northbrook,
Illinois
Rodney L. Page, DVM, MS, Diplomate ACVIM Adjunct Professor, Veterinary Biosciences, The Ohio
(Internal Medicine, Oncology) State University, Columbus, Ohio
Professor, Oncology, North Carolina State University, Seizures
Raleigh, North Carolina
Principles of Oncology James C. Prueter, DVM, Diplomate ACVIM
Hospital Director, The Veterinary Referral Clinic,
Matthew Palmisano, DVM, MS, Diplomate ACVS Cleveland, Ohio
Veterinary Referral and Emergency Center, Norwalk, Diagnostic Methods in Respiratory Disease
Connecticut
Neoplasia of the Maxilla and Mandible Katherine E. Quesenberry, DVM, Diplomate ABVP
Fractures and Dislocations of the Spine (Avian Practice)
Orthopedic Disorders of the Stifle Avian and Exotic Pet Service, The Animal Medicine
Surgery of the Skeletal Muscle and Tendon Center, New York, New York
Neoplasia of Thoracic and Pelvic Limbs Avian Neurologic Disorders
Pediatric Fractures Rabbits
David L. Panciera, DVM, MS, Diplomate ACVIM John F. Randolph, DVM, Diplomate ACVIM
(Small Animal Internal Medicine) Professor of Medicine, Cornell University Hospital for
Professor, Department of Small Animal Clinical Animals, Department of Clinical Sciences, College of
Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Cornell University, Ithaca, New
Veterinary Medicine, Viginia Tech, Blacksburg, Virginia York
Diseases of the Thyroid Gland Diseases of the Hypothalamus and Pituitary
Robert B. Parker, DVM, Diplomate ACVS Rose E. Raskin, DVM, PhD, Diplomate ACVP
Chairman, Department of Surgery, Animal Medical Professor, Veterinary Clinical Pathology, Department
Center, New York, New York of Veterinary Pathobiology, School of Veterinary
Fractures of the Humerus Medicine, Purdue University, West Lafayette, Indiana
Erythrocytes, Leukocytes, and Platelets
Janet L. Peterson, DVM, Diplomate ACVIM
(Oncology) Nyssa J. Reine, DVM Diplomate ACVIM
Staff Veterinarian, Mission MedVet, Mission, Kansas Department of Medicine, The Animal Medical Center,
Tumors of the Skin and Subcutaneous Tissues New York, New York
Pancreatic Beta Cell Neoplasia
Mark E. Peterson, DVM, Diplomate ACVIM
Head, Division of Endocrinology, Department of Laura G. Ridge, DVM, Diplomate ACVIM
Medicine, The Animal Medical Center, New York, New Internal Medicine Resident, Department of Small
York Animal Medicine and Surgery, University of Georgia,
Diseases of the Thyroid Gland Athens, Georgia
Diseases of the Adrenal Gland Heartworm Disease
Diseases of the Hypothalamus and Pituitary
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xiv Contributors
Mark C. Rochat, DVM, Diplomate ACVS Eric R. Schertel, DVM, PhD, Diplomate ACVS
Associate Professor and Chief, Small Animal COO, Surgery, MedVet, Worthington, Ohio
Surgery, Department of Veterinary Clinical Sciences, Surgical Correction of Patent Ductus Arteriosus
College of Veterinary Medicine, Oklahoma State Shock
University, Stillwater, Oklahoma Principles of Thoracic Surgery
Fractures of the Pelvis
Amputation of the Digit Karsten E. Schober, DVM, PhD, Diplomate
ECVIM-CA
Wayne S. Rosenkrantz, DVM, Diplomate ACVD Clinical Assistant Professor, Veterinary Teaching
Partner, Animal Oncology Clinic, Tustin and San Hospital, The Ohio State University, Columbus, Ohio
Diego, California Cardiovascular Drugs
Miliary Dermatitis and Eosinophilic Granuloma Complex
Linda G. Shell, DVM, Diplomate ACVIM
Edmund J. Rosser, Jr., DVM, Diplomate ACVD (Neurology)
Professor, Dermatology, Small Animal Clinical Editor and Consultant, Veterinary Information
Sciences, Michigan State University, College of Network, Davis, California
Veterinary Medicine, East Lansing, Michigan Neurology and Internal Medicine Consultant,
Pyoderma Veterinary Neurology Education and Consulting, Pilot,
Virginia
James K. Roush, DVM, MS, Diplomate ACVS Peripheral Nerve Disorders
Professor and Section Head, Small Animal Surgery,
Veterinary Clinical Sciences, Kansas State University, G. Diane Shelton, DVM, PhD, Diplomate ACVIM
Manhattan, Kansas (Internal Medicine)
Fractures of the Shoulder Professor, Director, Comparative Neuromuscular
Miscellaneous Diseases of Bone Laboratory, Department of Pathology, University of
California, San Diego, La Jolla, California
John E. Rush, DVM, MS, Diplomate ACVIM Disorders of the Muscle and Neuromuscular Junction
(Cardiology), Diplomate ACVECC
Professor and Associate Department Chair, Robert G. Sherding, DVM, Diplomate ACVIM
Department of Clinical Sciences, Cummings School of Professor, Small Animal Internal Medicine,
Veterinary Medicine at Tufts University, North Department of Veterinary Clinical Sciences, The Ohio
Grafton, Massachusetts State University, Columbus, Ohio
Valvular Heart Disease Feline Leukemia Virus
Feline Immunodeficiency Virus
Valerie F. Samii, DVM, Diplomate ACVR Feline Infectious Peritonitis (Feline Coronavirus)
Associate Professor, Department of Veterinary Feline Infectious Respiratory Disease
Clinical Sciences, The Ohio State University, Canine Infectious Tracheobronchitis (Kennel Cough)
Columbus, Ohio Canine Distemper
Cardiovascular Radiolography Intestinal Viruses
Diagnostic Imaging in Respiratory Disease Rabies and Pseudorabies
Miscellaneous Viral Diseases
Randall H. Scagliotti, DVM Rickettsiosis, Ehrlichiosis, Anaplasmosis, and Neorickettsiosis
Associate Clinical Professor, Department of Surgical Borreliosis (Lyme Disease)
and Radiological Sciences, University of California, Systemic Bacterial Infectious Diseases
Davis, California Systemic Mycoses
Neuro-opthalmology Toxoplasmosis and Other Systemic Protozoal Infections
Diseases of the Esophagus and Disorders of Swallowing
Vicki J. Scheidt, DVM, Diplomate ACVD Diseases of the Stomach
Hanover Veterinary Clinic, Hanover, New Hampshire Diseases of the Intestines
Feline Symmetrical Alopecia Diseases of the Liver and Biliary Tract
Diseases and Surgery of the Exocrine Pancreas
Patricia A. Schenck, DVM, PhD Constipation and Anorectal Diseases
Assistant Professor, Diagnostic Center for Population Respiratory Infections
and Animal Health, Endocrine Diagnostic Section, Pleural Effusion
Michigan State University, Lansing, Michigan
Diseases of the Parathyroid Gland and Calcium Metabolism
W0422-PR.qxd 11/15/05 6:07 PM Page xv
Contributors xv
Peter Shires, BVSc, MS, Diplomate ACVS Michael Stone, DVM, Diplomate ACVIM (Small
Professor, Small Animal Surgery, Director, Veterinary Animal Internal Medicine)
Educational Technologies, Virginia-Maryland Regional Assistant Clinical Professor, Department of Clinical
College of Veterinary Medicine, Virginia Polytechnic Studies, Cummings School of Veterinary Medicine at
Institute and State University, Blacksburg, Virginia Tufts University, North Grafton, Massachusetts
Fractures of the Femur Ultrasonographer, Veterinary Internal Medicine
Mobile Specialists, North Woodstock, Connecticut
Gretchen K. Sicard, DVM Systemic Immune-Mediated Diseases
Assistant Professor, Small Animal Surgery, College of
Veterinary Medicine, Kansas State University, Steven F. Swaim, DVM, MS
Manhattan, Kansas Professor, Small Animal Surgery, College of Veterinary
Surgery of the Urinary Bladder Medicine, Auburn University, Auburn, Alabama
Surgery of the Ovaries and Uterus Management of the Traumatic Wound by Primary Closure
Surgery of the Vagina and Vulva
Robert A. Taylor, BS, DVM, MS, Diplomate ACVS
Daniel D. Smeak, DVM, Diplomate ACVS Clinical Affiliate, Veterinary Teaching Hospital,
Professor, Small Animal General Surgery, Head, Colorado State University, Fort Collins, Colorado
Small Animal Surgery, Department of Veterinary Chief Surgeon, Alameda East Veterinary Hospital,
Clinical Sciences, The Ohio State University, Denver, Colorado
Columbus, Ohio Scapulohumeral Luxation
Selected Skin Graft and Reconstructive Techniques
Surgery of the External Ear Canal and Pinna Larry P. Tilley, DVM, Diplomate ACVIM
(Internal Medicine)
Francis W. K. Smith Jr., DVM, Diplomate ACVIM VetMed Consultants, Inc., Santa Fe, New Mexico
(Cardiology, Small Animal Internal Medicine) Electrocardiography
Clinical Assistant Professor, Clinical Sciences, Tufts Disorders of Cardiac Rhythm
University School of Veterinary Medicine, North
Grafton, Massachusetts James Tomlinson, DVM, MVSc, Diplomate, ACVS
Vice-President, VetMed Consultants, Inc., Santa Fe, Professor, Orthopedic Surgery, Veterinary Medicine
New Mexico and Surgery, College of Veterinary Medicine,
Electrocardiography University of Missouri, Columbia, Missouri
Disorders of the Cardiac Rhythm Fractures and Growth Deformities of the Radius and Ulna,
Luxation of the Elbow
Mark M. Smith, VMD, Diplomate ACVS,
Diplomate AVDC David M. Vail, DVM, Diplomate ACVIM
Center for Veterinary Dentistry and Oral Surgery, (Oncology)
Gaithersburg, Maryland Professor, Oncology, Animal Cancer Center,
Fractures of the Skull Department of Clinical Sciences, Colorado State
Neoplasia of the Axial Skeleton University, Fort Collins, Colorado
Lymphoid Neoplasia
Rebecca L. Stepien, DVM, MS, Diplomate ACVIM
Clinical Associate Professor, Cardiology, Clinical Raymund F. Wack, DVM, Diplomate ACZM
Cardiologist, Department of Medical Sciences, Assistant Clinical Professor, Medicine and
University of Wisconsin School of Veterinary Epidemiology, College of Veterinary Medicine,
Medicine, Madison, Wisconsin University of California, Davis, California
Vascular Diseases Basic Husbandry and Medicine of Pet Reptiles
Elizabeth A. Stone, DVM, Diplomate ACVS Stephen D. White, DVM, Diplomate ACVD
Dean and Professor, Surgery, Ontario Veterinary Professor, Medicine and Epidemiology, School of
College/University of Guelph, Guelph, Ontario, Veterinary Medicine, University of Califonia
Canada Davis, California
Mammary Gland Neoplasia Food Hypersensitivity
Preface
▼
The world of small animal veterinary medicine contin- nosis of skin disorders; an overview of current imaging
ues to grow in scope and complexity. Practicing veteri- techniques such as digital radiography, computed axial
narians and veterinary students are continuously tomography, and magnetic resonance imaging; tech-
bombarded with new information on the diagnosis and nique for laser declaw; indications for laparoscopic
treatment of diseases affecting pet animals. Busy veteri- and thorascopic surgery; and a brief discussion of
narians have precious little time to keep up with current arthroscopic procedures for certain joint disorders.
developments in the profession. We recognize that chal- Additionally, all chapters, even if rewritten by the same
lenge, and thus we attempt to provide a comprehensive author, have been thoroughly and meticulously revised
book that covers the commonly encountered disorders and updated, and several new illustrations have been
seen in small animal practice. added. The Appendix of Drug Dosage Guidelines has
Although difficult to include all the pertinent mate- also been updated and many new drugs included.
rial in a one-volume text, the semi-outline format used We are very grateful to all those who have con-
in the Manual allows our authors to be concise, yet thor- tributed to the third edition of the Manual. The section
ough. As in the first two editions, we continue to make editors and chapter authors have done an excellent job
information user friendly by including many key points, organizing and presenting information in their areas of
condensing information into tables and bulleted lists, expertise. They have correlated their own clinical expe-
and illustrating procedures and surgical techniques rience with information available in the literature and
with many simple line drawings. However, it is impossi- have provided useful and practical information. We also
ble to provide an exhaustive discussion of all small wish to thank the faculty, residents, and students at The
animal diseases in one book. Pathophysiology of Ohio State University College of Veterinary Medicine
disease, rare conditions, and infrequently used diag- for their support and advice on the preparation of this
nostic and treatment methods are not included. edition.
Readers are directed to many well-written veterinary The Manual is the result of a tremendous amount of
textbooks or journals that cover various subjects in organizing, copyediting, proofreading, and attending to
greater detail than what we have space for in the details. We are indebted to the staff at Elsevier for all
Manual. But the Manual seems to have found a niche. their hard work, particularly Ms. Jolynn Gower, Manag-
From what countless practitioners and students have ing Editor. Thanks also to Ms. Joy Moore, Senior Project
told us, it is a text that is not kept on a bookshelf gath- Manager. We also thank Ms. Sarah Self, Production
ering dust, but is open on a counter, desk, or exam table Editor and the staff at Graphic World Publishing
where it is almost constantly being used to update or Services. Finally, we appreciate the work of our very
review important clinical information. This is exactly talented medical illustrator, Ms. Felecia Paras.
how we hoped the book would be used. As we have indicated in both of the previous editions
Although we have stayed true to the book’s original of the Manual, we are striving for continued improve-
style, we have added some new authors, section editors, ment of our work. We welcome any comments or criti-
and chapters. New chapters include Pain Management, cisms that will help make future editions an even more
Vaccination Guidelines, Disorders of the Claw, Post- valuable part of the small animal clinicians’ library.
operative Physical Rehabilitation, and Syncope. Exam-
ples of other new areas covered in the third edition are: Stephen J. Birchard, DVM, MS
new emerging infectious diseases; skin cytology for diag- Robert G. Sherding, DVM
xvii
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▼
Section
1 Patient Management
Stephen J. Birchard
▼ Chapter
Veterinarians are faced with many diagnostic challenges or neutered. The patient’s breed will sometimes
on a daily basis. By far the most important diagnostic become a key factor when formulating differential
tool that veterinarians possess is their ability to obtain diagnoses. Congenital or hereditary disorders should
a complete history and perform a thorough physical be considered. For example, familial renal disease
examination. This information, when accurately inter- should be a primary differential for a young Shih Tzu
preted, lays the foundation for a logical diagnostic and presenting with polydipsia and polyuria. In other
therapeutic plan. A systematic and thorough history cases the disease process may not be congenital or
and physical examination prevents unnecessary diag- hereditary, but it may be more prevalent in certain
nostic testing and needless cost to the owner. breeds than others. For example, a small-breed dog
that presents with lameness that is localized to the
hip is more likely to have avascular necrosis of
GENERAL HISTORY the femoral head (Legg-Perthes disease) than hip
dysplasia.
Obtain both objective and subjective information when • Verify that previously recorded data are correct
collecting the history. and up-to-date. For example, the patient may have
been neutered since its last visit or the physical
• Objective data consist of the signalment, environ- examination may indicate that the recorded age is
ment, diet, and medical history. For a patient’s first
questionable.
visit, determine the length of ownership and the
place of origin.
• Subjective data include a description of the primary Environment
complaint and a historical overview of the patient’s
general health. The owner often may not realize how
• Gather environmental information as a routine part
of the patient’s history. In many circumstances, where
a seemingly unimportant observation may be related the pet is kept provides a vital clue in diagnosis.
to the primary problem. Tailor specific questions to
the individual case.
• Determine whether the pet is free roaming or con-
fined to a yard or house. If the patient is confined to
a yard, ask the owner if the yard is fenced, if the pet
Signalment is chained, and if an escape has been possible in the
• The signalment consists of the patient’s age, species, recent past. The free-roaming or recently escaped
breed, and gender. Note whether the patient is intact pet may have had access to toxins or have been
1
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subject to trauma, which is less likely for an indoor testing will be invalid since the FIV test is an antibody
pet. For example, in a dyspneic patient, diaphrag- test.
matic hernia ranks higher on the differential diag- • For a canine patient, record heartworm test dates and
nosis list for a free-roaming pet than for a strictly results. If the patient is receiving heartworm preven-
indoor pet. tive therapy, note the type, frequency, and dose (see
• Determine the geographic origin of the pet and any Chapter 152).
record of recent travels. This becomes paramount if
the patient has been exposed to diseases endemic to Prior Medical History: Previous Illnesses
certain regions but not prevalent in the current envi- and Surgeries
ronment, such as systemic mycoses and vector-borne
diseases. • Often the patient’s prior or ongoing health problems
• Determine the pet’s water source. This may be play a role in its presenting ailment; therefore, review
important if the pet has access to contaminated the information previously recorded in the medical
outdoor water, toilet-bowl water treated with deodor- record and discuss previous problems managed by
ants or cleansers, or if the pet has limited access to other veterinarians.
water. • Record the dates of the previous illness or surgery,
• Question the owner if there has been any potential followed by a brief description of the problem, how
exposure to toxins such as antifreeze, pesticides, it was managed, and the response to treatment.
or insecticides if the patient’s clinical presentation • Discern the relevance of prior illnesses before obtain-
is indicative of intoxication. Exposure to houseplants ing extensive details; otherwise, the history may
or outdoor vegetation may also provide a clue. For become unnecessarily lengthy and confusing.
a vomiting or anorexic patient, questions should • Specifically question the owner as to any medications
include access to potential ingested foreign bodies. the patient is currently or has recently been given.
Over-the-counter products as well as prescription
Dietary History medications should be noted.
• Determine the progression of the clinical signs. Once • Ask about ocular redness, swelling, and asymmetry.
again, this may help not only in formulating a list • Ask if the owner has noticed a color change in the pet’s
of differentials but also in developing a treatment eye. This change can occur with anterior uveitis and
plan. For example, a patient presenting with a history iriditis, in which hyphema may be present or the iridial
of seizures is managed more aggressively when the color may be altered. A localized pigment change in
seizures are increasing in frequency and length than the iris may occur with an iris cyst or melanoma.
when they have been the same for months or years. • Ask the owner if their pet seems to be experiencing
• Question the owner as to any intervening signs that any loss of vision. If there is an apparent problem,
might provide a clue to the most likely differential does it seem to be affected by daylight or darkness?
diagnosis. For example, a cat with chronic diarrhea Also ask if decreased vision appears to be a unilateral
and intermittent episodes of fever is considered a or bilateral problem. See also Section 10.
more likely candidate for infectious disease than for
dietary intolerance. Head, Neck, Ears, Nose, and Oral Cavity
• Attempt to further define and localize the problem.
• Record any history of swelling or asymmetry of the
For example, characterize diarrhea as originating in head and neck region.
the small or large bowel before proceeding to a diag-
nostic or therapeutic plan. Ask questions regarding
• Inquire about head shaking, ear scratching, and otic
discharge or odor that may indicate the possibility of
frequency, appearance (color and consistency), and otitis or a foreign body in the ear. Determine if any
presence or absence of straining to help localize this loss of hearing has been evident.
problem. Specific questions oriented by body systems
follow in the next section.
• Ask if any nasal discharge has been present. Note the
character of any nasal discharge (serous, mucoid,
• Determine treatments and response. For example, a mucopurulent, or hemorrhagic) and whether it has
dog presenting with pruritus unresponsive to previ- been unilateral or bilateral. Note any history of sneez-
ous treatment with corticosteroids is a more likely ing, nose rubbing, nasal asymmetry, or stridor.
candidate for food allergy dermatitis than for atopy.
Record what medication was given, the dose, the
• Request information relating to the oral cavity, such
as odor, difficulty eating or drinking, abnormal
duration of treatment, and the level of response swellings involving the gingiva or tongue, and
observed. changes in gingival pigmentation. Ask if there has
been any change in the patient’s ability to vocalize.
The patient’s voice can be affected either by a mass
HISTORY ORIENTED BY BODY SYSTEMS in the laryngeal region or by laryngeal paralysis.
• Characterize coughing as productive or nonproduc- • Ask how the patient’s appetite has been and how it
tive, moist or dry, and harsh or honking. Some compares with its normal appetite.
owners may confuse a productive cough with vomit- • Has any vomiting been noted (onset, frequency,
ing; therefore, ask whether abdominal heaving progression)?
occurs prior to the production of fluid or foam or • Has the owner actually observed the pet vomiting?
whether coughing and gagging are more typical. In a multi-pet household, verify that it is the pre-
Yellow or green fluid is indicative of vomitus. The senting patient that is actually vomiting.
circumstances surrounding the cough are often • Does the pet exhibit any retching or abdominal
relevant. For example, cough associated with tracheal heaving when “vomiting”?
collapse is often elicited with excitement or pulling • How frequently is the pet vomiting?
on the patient’s collar. Coughing secondary to con- • What is the relationship of vomiting to eating, if
gestive heart failure may be exacerbated with the pet any?
in a sternal position. Is the pet routinely exposed to • What is produced when the pet vomits? Describe
cigarette smoke? This can play a role in chronic the vomitus—digested or undigested food, fluid,
bronchitis or feline asthma. foam, and color. Green or yellow fluid is typical of
• Determine if dyspnea has been observed. It may be bile.
difficult for an owner to differentiate between heavy • Has the owner witnessed the patient defecating, and
panting and true dyspnea. Ask if the pet is breathing are there any abnormalities?
the same during the exam as it was at home. Also • How long since the last observed bowel move-
inquire if the pet seems reluctant to exercise or lie ment?
down, as would be expected with most dyspneic • Has any diarrhea been observed (onset, progres-
animals. Open-mouth breathing for a cat is always sion)?
considered abnormal except when it is excessively • Has the stool been persistently loose?
stressed. See also Chapter 142. • How frequently does the animal defecate?
• What volume of stool is typically produced? Small
amounts of stool produced frequently are indica-
Digestive System tive of large bowel disease, and larger amounts of
Most problems related to the digestive system are clini- stool produced less frequently are more typical of
cally manifested as anorexia, regurgitation, vomiting, small bowel disease.
diarrhea, constipation, weight loss, or a combination of • What is the color and consistency of the stool
these. Determine which clinical sign is being exhibited, (formed but soft, cow patty–like, watery)?
because the owner may incorrectly interpret what is • What is the consistency of the last stool produced?
observed. For example, owners often assume that their • Is there any blood or mucus present? (These are
pet is constipated if it is observed straining to defecate, indicative of large bowel disorders.)
when diarrhea may be the actual cause. Ask specific • Does the animal strain while defecating? Straining
questions to differentiate between vomiting and regur- is typical of diseases localized to the colon,
gitating. Regurgitation is characterized as a passive rectum, or anus.
ejection of ingested material from the esophagus. It typ- • Does the owner witness all eliminations (i.e., is the
ically occurs soon after a meal is eaten. The regurgitated pet walked on a leash, does it have access to a
material is usually undigested and tubular in form. Vom- fenced yard. or does it roam free)? Consider that
iting frequently involves an abdominal heave movement owners may not be fully aware of what their pet is
or retching. Time of vomiting in relation to eating eliminating.
should be noted and is variable depending on the
underlying disorder. Vomitus is not tubular in form See also Section 6.
and may consist of froth, fluid, yellow-green bile, food,
or ingested foreign material. Include the following
specific information in approaching a digestive system Urinary System
problem: Often, the owner complaint may be that the pet is
urinating excessively. The following questions help dis-
• Review dietary history, as previously described. Speci- tinguish whether excessive urination is due to polyuria
fically ask about treats or access to garbage. or pollakiuria:
• Record environmental history, as previously
described. • Has there been any change in the quantity of water
• Has there been any exposure to toxins, drugs, or that the pet consumes?
plants? • Are there other pets in the household that have
• Are there any toys or other foreign objects that the access to the same water source?
pet may have ingested? • Is the pet urinating inside the house (i.e., having
• Note vaccination status. “accidents”)?
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• Are these urinations observed? (The owner should previous history of pregnancy? If so, were there
verify that this is the pet having the accidents versus any complications (e.g., dystocia, abortions, masti-
another pet in the household.) tis, metritis, etc.)?
• Does the owner know if the accidents occur while • If there is a history of successful pregnancy, how
the animal is awake or asleep? If the owner has not many puppies were whelped?
observed the act, there may be other clues to • Has the patient been tested for brucellosis? When?
pursue. Where has the owner found the accidents Was the mate previously tested?
(where the pet sleeps, next to a door, etc.)? A
patient that is experiencing urinary incontinence Males
may be dribbling urine while resting in its sleeping
area. Dogs that are well house-trained may urinate
• Verify if the patient is intact or neutered.
close to an outside door if they are unable to hold
• Has the patient exhibited any evidence of difficulty
urinating or defecating?
their urine until allowed access to the outside yard.
Another clue to urinary incontinence is the pres-
• Has any preputial or penile discharge been noted?
(Describe the amount, consistency, color, and odor.)
ence of urine on the pet’s perineal region or rear
legs.
• The following questions apply to intact males:
• Has the patient been used for breeding? If so, when
• Does the animal seem to be consciously aware of was he last bred? Was there any difficulty in breed-
the act, or does the animal dribble urine without ing?
seeming to be aware? • Were any litters sired? If so, how many puppies
• Has there been any change in frequency of urina- were in each litter?
tion? If the patient is urinating frequent small • Has the patient been tested for brucellosis? When?
amounts (pollakiuria), then differentials should Was the mate previously tested?
include lower urinary tract disorders such as cystitis,
urolithiasis, and neoplasia. See also Section 7.
• Does the animal appear to strain while urinating?
(This is typical of lower urinary tract disease.) Swelling or Masses
• What quantity of urine is produced? Larger quanti-
ties of urine are indicative of polyuria, which occurs Ask if any abnormal masses or swellings have been
with a large number of underlying metabolic disor- observed that have not been previously mentioned.
ders (renal disease, liver disease, diabetes, mellitus, Note the location, how long the mass or swelling has
diabetes insipidus, hyperadrenocorticism, hypercal- been present, and any change in appearance, character,
cemia, etc.). or size. If the patient has not been examined in your
• Has the owner noticed any blood in the urine? If so, practice before, ask if the mass has been previously
is it before, during, or after urination? Bleeding only sampled by either a fine needle aspirate or a surgical
at the beginning of urination is more likely to be biopsy. Obtain a fine needle aspirate from masses that
from the urethra. Hematuria present throughout the have not been previously investigated.
urination is most typical of bleeding of renal origin.
Blood seen at the end of urination usually originates ▼ Key Point Perform diagnostics on masses that are
from the urinary bladder. Remember to consider the changing rapidly since there is a higher incidence
genital system as a potential source for the blood, as of malignancy associated with these.
with prostatic disease or vaginal masses.
See also Section 7.
Skin
An accurate and detailed history is essential for suc-
cessful management of dermatologic problems.
Genital System Remember that some systemic disease processes may
Females manifest themselves in cutaneous changes, such as
hyperadrenocorticism or systemic lupus erythematosus
• Verify if the patient is intact or spayed. (SLE). Some clinicians prefer to have the owner fill out
• Note any vulvar discharge and describe the amount, a standardized dermatologic history form prior to
consistency, color, and odor. This type of discharge specific questioning. Include the following questions
may be valid for spayed pets as well as intact ones. on such a form, or directly ask the owner:
• If the patient is intact, ask the following questions:
• When did the owner last observe a heat cycle for • Has any hair loss been observed? Did hair loss involve
the patient? Was it a normal cycle? How long did it the undercoat or the main coat?
last? • Is there evidence of pruritus (scratching, biting, or
• Have the heat cycles been at regular intervals? licking)?
• Has the pet been intentionally bred or is there any • Where does the pet seem to be most pruritic? Many
possibility of an accidental breeding? Is there any atopic and food-allergic patients may rub their faces
W0422-Ch001.qxd 11/10/05 4:39 PM Page 6
and lick their feet excessively. Flea-allergic patients Small-breed individuals have a higher tendency
predominantly chew the dorsal tail-base region. toward medial patellar luxation and avascular necro-
• If the pet is pruritic, how severe is it? Have the sis of the femoral head.
owner grade the degree of pruritus on a scale of 1 • When lameness has been observed, discern if the
to 10, with 10 being the most severe. This helps sub- patient has been bearing weight on the affected leg.
sequent evaluation of treatment response. Determine if lameness has been previously observed
• Is the skin problem continuous or seasonal? If in this limb or other limbs. For example, panosteitis
seasonal, then determine when the pet is most is often considered a shifting leg lameness. Ask if
severely affected. there are any other signs of illness in addition to the
• Has the owner noticed fleas? What flea products lameness. The lameness may be a manifestation of
have been used? Has the pet been on monthly systemic disease such as SLE or Lyme disease. Has the
preventive treatment? If so, which product? owner noticed any swelling or masses associated with
• What type of bedding does the pet use? the affected limb?
• Is there any exposure to feathers? • Is the lameness intermittent, progressive, or static? Is
• What type of carpet is in the house (wool, synthetic, the lameness worse before or after exercise? Arthritic
cotton)? patients often “warm out” of their lameness.
• What is the diet? What treats are given? • Question owner in regard to routine daily activity
• Are there any indoor plants? such as running, jumping, hunting, jumping on
• Is the pruritus worse indoors or outdoors? and off furniture, etc. Has the pet engaged in any
• Is there any exposure to tobacco smoke? activities out of the ordinary lately? These patients are
• Has the pet ever had any drug reactions? (describe) more at risk for traumatic injuries such as a cranial
• Describe odors, pigment changes, or texture changes cruciate ligament tear or a ruptured intervertebral
of the skin or hair coat. disc.
• Does the pet have any dandruff? If so, what areas are • Ascertain any possibility of trauma that could have
involved? resulted in a fracture. In some cases, the owner may
• How often is the patient groomed (clipped, brushed, have witnessed the traumatic incident. In others, the
combed)? patient may have been unsupervised during the time
• How often is the patient bathed? When was the pet in question. Specifically ask if the patient was con-
last bathed, and what products were used? fined to the house or a fenced area. If the animal was
• Are there other pets in the household? Has the pet free roaming and unobserved, determine how long it
been exposed to other animals outside of the house- was unsupervised to help assess the possibility of a
hold? Did any of these animals exhibit signs of skin traumatic incident.
disease? • Determine if the owner has observed loss of muscle
• Do any members of the household have skin mass, asymmetry of the limbs, or swollen joints.
problems? • Ask if the patient has demonstrated any difficulty
• Do any of the pet’s close relatives have a history of rising, climbing stairs, or descending stairs. These
skin problems? problems are frequently noted in patients with hip
• Has there been any previous treatment? When was dysplasia, intervertebral disc disease, or neurologic
the pet last treated? What was the name of the drug, diseases such as degenerative myelopathy.
the dose, the route of administration, and the fre- • In regions endemic for Lyme disease, ask if any ticks
quency of treatment? What level of response was have been observed on the pet. Check vaccination
noted? status regarding Lyme disease. In nonendemic areas,
obtain a travel history.
See also Section 5.
See also Section 8.
Musculoskeletal System
• History relating to the musculoskeletal system gener- Nervous System
ally focuses on lameness or discomfort. Many questions related to the nervous system may have
• Remember to correlate the age and breed of the indi- been previously asked while taking the history of the
vidual to the lameness observed. There are numer- other body systems. Once again, consider the age and
ous examples in which the signalment may provide breed to help provide clues to the differential diag-
a clue to the underlying disorder. Many muscu- noses. Small-breed dogs are more commonly seen with
loskeletal disorders occur predominantly in young, portosystemic shunts and may present with neurologic
large-breed dogs. These include but are not limited signs. Hypoglycemia and congenital diseases are prime
to osteochondritis dissecans, ununited anconeal differentials for seizuring puppies. Epilepsy typically has
process, panosteitis, and hypertrophic osteodystro- an onset in young adults. For seizures with an onset
phy. Middle-aged to older large-breed patients are during middle age or geriatric years, consider metabolic
more at risk for neoplasia such as osteosarcoma. disease or neoplasia. Diseases of the central nervous
W0422-Ch001.qxd 11/10/05 4:39 PM Page 7
system (CNS) may be reflected by abnormalities in cat. The most commonly used systems utilize either a
other systems (e.g., blindness, hearing loss, or urinary 5- or 9-point scale. I prefer the 5-point scale, where
incontinence). With a presenting complaint of rear score 1 correlates to an emaciated body condition
limb “weakness,” differentiate between disorders of the and score 5 indicates a grossly obese state. Score 3 is
musculoskeletal system and those of the nervous system considered an ideal weight for the patient. Those
with the history and physical examination. Consider the body conditions that fall between two scores are
following points in regard to the nervous system: assigned a half score. For example, a patient that is
just over its ideal weight would be scored as 3.5. Refer
• Verify vaccination history for distemper and rabies. to Tables 1-1 and 1-2 for details of body condition
• Focus on obtaining a good environmental history, scoring in dogs and cats, respectively. Record the
such exposure to toxins or plants. Is there any possi-
patient’s body condition score (BCS) in the patient’s
bility of a traumatic accident resulting in head trauma
record each visit.
or spinal injury?
• Ask if any behavioral changes, such as aggression or • If the collection of the history and the physical exam
result in a vague, poorly defined illness, consider
dementia, have been observed. If these signs are
hospitalizing the patient for observation. Sometimes
present, are they intermittent or persistent?
owners may find it difficult to accurately describe the
• Is there any evidence of pain when the patient is
pet’s behavior or clinical signs. Also, some patient’s
touched or picked up? Does the pet cry or yelp when
may mask their depression or pain when they initially
it moves? These signs can occur in a patient with
arrive in a new environment. A nervous patient
intervertebral disc protrusion.
should be reevaluated once it has adjusted to the
• Record any history of seizures, including their dura-
hospital surroundings. Occasionally, animals become
tion and the time interval between them. Obtain a
more agitated the longer they are away from their
description of the seizure.
owner. Finally, many disease processes become more
• If behavioral changes or seizures have been observed,
evident with time, so the physical should be repeated
ask if there is any relationship between when the pet
on any undiagnosed or hospitalized patient.
eats and when these signs occur. Neurologic signs
may be exacerbated postprandially in patients with a
portosystemic shunt.
• Ask if there has been any evidence of weakness in the
patient. If present, is the weakness generalized or
localized (i.e., to one side of the body, in the forelegs,
or to the rear)? Determine if any abnormalities in Table 1-1. BODY CONDITION SCORING FOR
posture or ambulation have been observed, such as DOGS
the pet’s tendency to fall to one side, to circle to one
side, to knuckle over, or to drag its toes. Be sure to Score Body Condition Parameters Evaluated
note the acuteness of onset and the progression of 1 Emaciated Skeletal in appearance with
the neurological signs. no obvious body fat and
minimal muscle mass. Boney
See also Section 9. prominences visible.
2 Thin Ribs slightly visible and easily
palpable. Prominent waist
and abdominal tuck from
side and dorsal views.
3 Ideal Ribs not visible but palpable
PHYSICAL EXAMINATION: with only a slight fat covering.
GENERAL OBSERVATION Abdominal tuck present from
side view, and waist present
from dorsal view. Smooth
• To begin the physical examination, watch the patient contour over tail base.
as it enters the room. 4 Overweight Difficult to palpate ribs because
• Continue the visual evaluation of the patient while of moderate fat layer. Loss of
the history is collected. Observe the general body abdominal tuck from side
condition and any abnormalities in behavior, atti- view, and wide waist from
dorsal view. Thickening over
tude, posture, ambulation, and respiratory pattern. tail base.
During this time, the patient may be placed on the 5 Obese Excessive fat cover over entire
examination table or allowed to roam the examina- body. Ribs extremely difficult
tion room. to palpate. No waist present
from dorsal view. Fat skin
• During the general observation of the patient, evalu- folds droop from caudal
ate its body condition. Several body condition scoring abdomen on side view. Thick
systems have been developed to aid in assessing the fat roll at tail base.
amount of body fat present in the individual dog or
W0422-Ch001.qxd 11/10/05 4:39 PM Page 8
Oral Cavity ▼ Key Point In the feline patient that presents for
• Perform a thorough oral examination if the patient’s vomiting, examine the sublingual area for evi-
demeanor allows (Fig. 1-1). If this examination is dence of a linear foreign body.
indicated but the patient is uncooperative or aggres-
sive, sedation (see Chapters 2 and 64) may be neces- • Use one of the following two methods:
sary. Sedation also allows the clinician to perform a • Open the patient’s mouth and, with the middle
more thorough oral exam in any patient presenting finger of the hand depressing the mandible, apply
with clinical signs suggestive of oral cavity disease pressure between the mandibular rami from the
(i.e., ptyalism, halitosis, bleeding, or oral pain). ventral aspect. In this manner, the tongue is ele-
• Always carefully evaluate the mucous membranes for vated so that the sublingual surface can be seen
color, moisture, and capillary refill time to assess the (see Fig. 1-1, top).
hydration status. Hyperemia, congestion, cyanosis, • Occasionally, a linear foreign body can be over-
jaundice, pallor, or petechiae can provide vital diag- looked with the first method. The sublingual tissue
nostic clues to the underlying disorder. can overlap a thin string that has been drawn taut
• Note gingival masses, ulcerations, inflammation, or so that it is not seen. In this case, the second
pigmentary changes. method is to grasp the tongue with a gauze sponge
• Examine the teeth for calculus or exudate at the gin- and pull the tongue out and laterally so that the
gival margin. Digital pressure applied to the gingiva string can be seen more completely (see Fig. 1-1,
may aid in expressing exudate when a tooth root bottom). Sedation may be required for this in some
abscess is suspected. Note any fractured teeth, and patients.
look for evidence of pulp exposure. Slab fractures of • Examine the hard palate in the neonate for clefts.
the upper fourth premolar may be difficult to iden- Evaluate the soft palate (if possible) for defects or
tify. Be suspicious of a fracture if a significant amount masses.
of calculus has accumulated on the surface of this • Examine the pharyngeal region for asymmetry,
tooth compared to the surrounding teeth and the masses, or foreign bodies or for evidence of inflam-
contralateral carnassial tooth. mation or trauma. Examine the tonsils for enlarge-
• Examine the tongue for evidence of trauma or masses ment or masses. Depress the caudal aspect of the
when unexplained oral hemorrhage has been tongue to see the caudal pharynx. Once again,
observed. sedation may be necessary for a thorough exam.
• In the cat, if pharyngeal polyps are a differential
diagnosis based on the history, examine the soft
palate for evidence of bulging. For a more complete
exam, sedate the patient to look under the soft
palate.
See also Chapter 64.
Nose
• Examine the nose for asymmetry or swelling. If a mass
or swelling is present, palpate it carefully to deter-
mine whether it is firm or fluctuant. Evaluate brachy-
cephalic breeds for stenotic nares.
• Note evidence of nasal discharge. Examine the nares
closely to determine if the discharge is unilateral or
bilateral. Characterize it as serous, mucoid, mucopu-
rulent, or hemorrhagic. It may be beneficial to gently
swab the external nares to detect a subtle discharge.
• If either nasal swelling or discharge is present, evalu-
ate the patency of each nostril. Several techniques
can be utilized to aid in this evaluation. Occluding
one nostril at a time and listening for stertorous
breathing may help identify a partially obstructed pas-
sageway. Another technique is wiping the examina-
tion table with an alcohol swab and positioning
the patient’s nose close to the table to observe
condensation of the patient’s breath on the surface.
Figure 1-1. Oral examination of the feline mouth and tongue. An alternative method is placing a wisp of cotton in
W0422-Ch001.qxd 11/10/05 4:39 PM Page 11
front of each nostril and observing movement from • Examine both the horizontal and vertical canals for
air flow stenosis, masses, foreign bodies, discharges, and
parasites (ear mites and ticks). Assess the tympanic
See also Chapter 160.
membrane for rupture or evidence of otitis media
(erythema or protrusion).
Ears
See also Chapters 58 to 60.
• Inspect both the external and inner surfaces of the
pinna for skin lesions, hair loss, erythema, or
swelling.
Neck
• Examine the external ear canals for erythema, dis- • Palpate the paratracheal area from the larynx to the
charge, and odor before an otoscopic examination. thoracic inlet.
Palpate the ear canal cartilages for calcification, • In middle-aged to older cats, this palpation is espe-
masses, pain, or other abnormalities. cially important because of the high incidence of
• An otoscopic exam is invaluable in assessing an ear- hyperthyroidism caused by thyroid adenomas. The
related problem. normal thyroid is not palpable.
• Otoscopic technique requires practice to be success- • Stand behind the cat with it standing or sitting,
ful. Sedation of the pet may be required if the patient extend the neck, and point the nose upward. Place
is painful or aggressive. your thumb and forefinger on each side of the
• Lift the pinna and gently place the otoscopic cone in trachea. Starting at the larynx, slide them down the
the vertical canal from a dorsal approach and direct length of the trachea using gentle pressure. The
it ventrally (Fig. 1-2). As the otoscope is guided typical thyroid nodule will “pop” as your thumb and
deeper into the vertical canal, pull the pinna and oto- forefinger slip over the caudal pole (Fig. 1-3A).
scope horizontally to bring the horizontal ear canal • Alternatively, palpate each side individually. Turn
and tympanic membrane into view. the patient’s head slightly to one side and place
your forefinger between the trachea and the adja-
cent muscles on the opposite side (Fig. 1-3B). Once
again, start at the larynx and slide your finger down
to the thoracic inlet. Turn the patient’s head to the
opposite side and repeat the procedure on the
second side. Repeated palpation may be necessary
to detect subtle nodules.
• In dogs, palpation may detect a thyroid tumor.
• Palpate the trachea for collapse, soft cartilage, or • The superficial cervical or prescapular lymph nodes
flattening. can usually be palpated just in front of the cranial
• Attempt to elicit a cough by gently encircling the border of the scapula. Grasp them by palpating
trachea with one hand and applying pressure on the beneath the scapular border. They may be more diffi-
tracheal muscle dorsally. If a cough is produced by cult to palpate in the obese or heavily muscled patient.
this method, it suggests tracheal collapse or tracheo- • The axillary lymph nodes are not always palpable
bronchitis. Conduct this part of the examination after because of their disc-like shape and the surrounding
the thorax has been auscultated because it may musculature.
induce paroxysms of coughing. • The superficial inguinal lymph nodes are located at
• Evaluate the jugular veins for distention. A jugular the junction of the abdominal wall and the medial
pulse extending more than one third of the way up thigh and may be difficult to palpate in the obese
the neck is indicative of right-sided heart disease. It patient.
may be necessary to moisten this area with alcohol or • The popliteal lymph nodes are usually palpable
to clip the hair to aid in visualization of the jugular caudal to the stifle joint. The surrounding subcuta-
vein. neous fat may make these nodes seem larger than
their actual size, especially in cats.
Lymph Nodes and Subcutaneous Masses • Palpate the trunk and extremities for abnormal
masses or swelling. When a mass is found, note the
• Palpate all external lymph nodes (Fig. 1-4). General- location, size, and consistency. Use calipers to accu-
ized lymphadenopathy usually indicates a systemic
rately measure the size of the mass. Determine which
disease (systemic fungal infection, immune-mediated
tissues are involved (dermal, epidermal, subcuta-
disease, or neoplasia), whereas local lymph node
neous, underlying tissue, etc.). Note whether the
enlargement usually indicates a localized tumor or a
mass is freely movable or attached to the underlying
regional infection. If enlarged lymph nodes are
muscle, fascia, or bone.
present, use calipers to measure and record the size
of the affected node or nodes. This information is
helpful in monitoring the patient’s response to Thorax
treatment (antibiotics or chemotherapy). • As previously described, evaluate the respiratory rate,
• The mandibular lymph nodes are located at the rhythm, and effort.
angle of the mandible, slightly cranial and ventral to
the parotid and submaxillary salivary glands. The
nodes are generally smooth and ovoid in contrast to Palpation
the irregular texture of the salivary glands. Practice • Palpate the thorax for evidence of fractured ribs, con-
distinguishing these lymph nodes from salivary genital malformations (pectus excavatum), subcuta-
glands. neous emphysema, and masses. Palpate the areas
Inguinal
Prescapular
Axillary
W0422-Ch001.qxd 11/10/05 4:39 PM Page 13
between the fourth and sixth intercostal spaces on • Increased resonance (tympany) is indicative of pneu-
either side of the thorax for the point of maximum mothorax, and decreased resonance (dull sounding)
intensity (PMI) of the heartbeat and for cardiac suggests pleural effusion, a diaphragmatic hernia, a
thrills. large pulmonary mass, or an area of consolidation.
• Attempt to compress the cranial thorax in cats to
See also Chapter 142.
help identify the presence of a mediastinal mass.
In a normal feline, the cranial thorax is easily
compressible. Abdomen
• Examine the external appearance of the abdomen
Auscultation for distention or asymmetry. If distention is apparent,
• Perform auscultation in a quiet room with a calm perform percussion to help determine if it is a result
patient. Have the patient standing during the exam- of peritoneal effusion, air (gastric dilatation or
ination so that the heart is in its normal position. volvulus), obesity, or a mass.
Evaluate the heart independently from the lungs. • Palpate the abdomen systematically proceeding in a
• Disregard sounds that are artifacts. These sounds cranial-to-caudal direction with the animal standing.
include rumbles secondary to shivering and crackles Palpate the trunk superficially for evidence of skin
created by the stethoscope rubbing against the hair. masses or hernias. In puppies and kittens, check for
Close the patient’s mouth for short periods of time evidence of umbilical or inguinal hernias. To palpate
to reduce upper respiratory noise. An additional abdominal organs, apply firm but gentle pressure. In
technique is to apply moderate pressure on either small animals, use a one-handed technique. With
side of the chest to help decrease motion caused by larger patients, two hands are needed, one on each
panting or shivering. side of the abdomen (Fig. 1-5). If the patient is
• Auscultate the heart initially over the PMI and iden- nervous or tense, try to get the patient to relax by
tify the first and second heart sounds. Characterize talking reassuringly and stroking its belly or sides just
the cardiac rhythm. Sinus arrhythmia is considered prior to palpation. Start again in a cranial-to-caudal
normal and is typified by increased cardiac rate direction just as you did with the superficial palpa-
during inspiration and decreased rate during expira- tion. Use a systematic method to attempt to identify
tion. Evaluate the femoral pulses for quality and each organ.
deficits while auscultating the heart. Note split heart
sounds, murmurs, and clicks. Auscultate all cardiac Stomach
valve areas, because some murmurs are localized, • Palpate the cranial abdomen for evidence of gastric
such as the mitral, aortic, and pulmonic on the left distention (see also Chapter 67). The normal
hemithorax and the tricuspid on the right (see also stomach is rarely palpable. Tympany indicates gastric
Chapter 142). dilatation or volvulus. Diagnosis and treatment
• Note muffled heart sounds that may be due to should be pursued aggressively. Overeating may
obesity, pleural effusion, pericardial effusion, tho- result in a doughy or fluid-filled stomach in the left
racic mass, or diaphragmatic hernia. side of the cranial abdomen.
• Pulmonary auscultation requires practice and persis-
tence. Normal bronchovesicular sounds may be Liver
increased, decreased, or normal. They may be inten-
sified in the nervous or tachypneic patient. These • The liver may be difficult to palpate in the normal
sounds are heard equally on both sides of the chest. patient (see also Chapter 71). The caudal edges are
Abnormally quiet or dull areas are suggestive of barely palpable, smooth, and well defined.
pleural effusion, pneumothorax, thoracic mass, and Hepatomegaly results in a liver that extends past
pulmonary consolidation. Crackles are abnormal dis- the costal arch. The edges may be rounded rather
continuous sounds resulting from popping open of than sharp. Palpation with the animal in lateral
small airways or air moving through airway secre- recumbency or standing on its hind legs may be
tions. Wheezes are abnormal continuous, musical helpful.
sounds resulting from passage of air through nar-
rowed or partially obstructed airways. Spleen
Percussion • The spleen is located in the mid-abdomen and may
not always be palpable (see also Chapter 25). If
• Percussion is a technique for evaluating the reso- splenomegaly is present, it is usually palpable. Deter-
nance (pitch and tone) of sound produced by a mine if the spleen is irregular or if a palpable mass is
series of quick taps of uniform force at various points present. Use gentle palpation on mid-abdominal
on the chest wall using a finger or a percussion masses. It is possible to rupture a splenic or hepatic
hammer. hematoma or hemangiosarcoma.
W0422-Ch001.qxd 11/10/05 4:39 PM Page 14
Urinary Bladder • In the male intact patient, palpate both testicles for
symmetry, firmness, and irregularity. If both testicles
• If the urinary bladder is moderately or markedly dis- are not present in the scrotum, examine the inguinal
tended, it can usually be palpated in the ventral- region for the presence of a retained testicle and
caudal abdomen (see also Chapter 79). The patient palpate the abdomen for masses.
does not usually resist palpation of the normal
bladder. Assess size, turgidity, and thickness of the See also Section 7.
bladder wall. The normal urinary bladder is thin
walled. Careful palpation may reveal cystic calculi. A Rectal Examination
painful, firm distended urinary bladder indicates
urethral obstruction. • A rectal examination often provides valuable infor-
mation during a physical examination.
Uterus • During a rectal examination, palpate the sublumbar
lymph nodes in the dorsal aspect of the pelvic canal.
• The normal uterus usually cannot be palpated (see Enlargement is usually suggestive of metastatic
also Chapter 90). If it is markedly enlarged, because neoplasia.
of pyometra or late pregnancy, the uterus is found in • Note the symmetry of the pelvis and the presence of
the mid- to-ventral abdomen, often extending from palpable fractures during the rectal examination.
the diaphragm to the pelvic inlet. The uterus often is This is always indicated in a trauma victim. Evaluate
tubular in shape with pyometra or late pregnancy. In abnormal masses in the pelvic canal for size, position,
mid-gestation, the individual fetuses may be palpated. and consistency.
In the pregnant cat, these fetuses may feel similar to • During the rectal examination, evaluate the perineal
the urinary bladder but will usually be present in and perianal regions for hernias or abnormal masses.
multiple numbers and feel slightly thicker walled • Evaluate the anal sacs for evidence of infection,
than the bladder. distention, or masses.
• Examine any fecal material obtained for amount,
Prostate consistency, color, and presence of blood or mucus.
• The prostate in intact male dogs can occasionally be Note the presence of foreign material such as bone
palpated in the caudal abdomen ventral to the colon fragments, gravel, cloth, or plastic.
and caudal to the urinary bladder (see also Chapter • Perform a rectal examination in all mature male dogs
84). If found in this location, evaluate the prostate for to evaluate the prostate. The normal prostate is
size, shape, and surface irregularities. bilobed (characterized by the presence of the median
raphe), symmetric, smooth, and nonpainful. If the
External Genitalia prostate is enlarged, it may extend slightly over the
brim of the pelvis or fall into the abdomen, as previ-
• In the female patient, palpate the mammary glands ously described for the palpation of the caudal
carefully for masses. If the history indicates a possi- abdomen.
bility of pregnancy or pseudopregnancy, gently • In female dogs, abnormal masses associated with the
express the nipples for signs of discharge or milk. In uterus or urethra may occasionally be detected on
the nursing bitch or queen, examine the mammary rectal palpation.
glands for abnormal swelling, firmness, or heat, as
seen with mastitis or abscessed glands.
• In the female patient, examine the vulva for confor-
Skin
mational abnormalities, swelling, or discharge. Deter- • Inspect the general appearance of the haircoat for
mine the color, consistency, and odor of the luster, fullness, and areas of hair loss. Note symmet-
discharge. Examine the vulvar mucous membranes ric alopecia as seen with endocrinopathies, such as
for evidence of jaundice, cyanosis, petechiae, or hyperadrenocorticism, hypothyroidism, or sex
ulceration for clues of systemic disease. In dystocia or hormone imbalances. Inspect areas of alopecia for
when a vaginal discharge is present, a vaginal exami- broken hairs as seen with pruritic or psychogenic
nation is indicated. Vaginoscopy may be required to conditions. Check for erythema as will be seen in
rule out the presence of vaginal masses. allergic or inflammatory conditions.
• In the male canine, examine the prepuce and penis. • When approaching a pet with a dermatologic
Retract the preputial sheath caudal to the bulb so problem, examine all areas of the body. Location of
that the entire penis can be examined for any signs skin lesions often aids in the diagnosis. For example,
of trauma or masses. Inspect the penis for jaundice, localized demodicosis causes patches of alopecia
cyanosis, petechiae, ulceration, or masses. Examine involving the head and forelegs. Sarcoptic mange
the tip of the feline penis for evidence of obstruction typically causes scaling and partial alopecia of the
(discoloration or the presence of plug material) if pinnae, elbows, and hocks. Do not overlook the inter-
indicated by the history. digital areas and the foot pads. Examine mucocuta-
W0422-Ch001.qxd 11/10/05 4:39 PM Page 16
neous junctions (lips, anus, vulva, preputial orifice, • Evaluate each coxofemoral joint range of motion and
etc.) for evidence of an immune-mediated disease. evidence of pain. Test for a positive Ortolani sign to
• Identify all skin lesions and categorize them as evaluate for hip laxity if the patient’s breed is at
primary or secondary. Primary lesions include risk for hip dysplasia (see Chapter 108 for more
papules, pustules, nodules, wheals, macules, and vesi- details).
cles. Common secondary lesions are scales, crusts, • If difficulty arises in localizing the lameness, always
ulcers, excoriations, lichenifications, hyperpigmenta- compare the results of palpation and manipulation
tions, and hyperkeratoses. of the affected limb with those on the contralateral
• Note evidence of external parasites. Large flakes and limb.
scales in a pruritic patient may indicate Cheyletiella
infestation. If fleas are not seen, search the patient Nervous System
for flea dirt, especially in the tail-head region. A flea As with the musculoskeletal system, a complete neuro-
comb is often helpful in discovering small amounts logic examination is not necessary unless specifically
of flea dirt. Repetitive combing may be necessary to indicated by the history or the general physical exami-
find small amounts of flea dirt in the flea allergy nation. The details of the neurologic examination are
dermatitis patient. While combing the patient, you discussed in Chapter 125. A brief overview of the basic
can educate the owner regarding flea control. procedures for the localization of lesions is provided
See also Section 5. here.
• Observe mental status and behavior as previously
Musculoskeletal System described.
• Initially evaluate the musculoskeletal system by • Evaluate the gait and posture while the patient is
walking and standing. Pay particular attention to
observing for lameness while the patient is in motion
strength, symmetry, and coordination.
both at a walk and at a trot. Observe the patient’s
posture with special attention to head carriage, head
• Always perform a complete cranial nerve examination
when evaluating neurologic problems (see Chapters
bobbing, arching of the back, or stilted gait. For fore-
125 and 126). This includes checking for a menace
limb lameness, an obvious downward bobbing of the
response, palpebral reflex, and pupillary light flexes.
head will be present as the sound leg makes contact
Note pupillary symmetry and ocular positioning.
with the ground.
Facial sensation can be tested by lightly touching the
• A complete musculoskeletal examination is not nec-
nasal mucosa with a hemostat. The presence of a gag
essary unless evidence of lameness or pain is noted in
reflex should have been noted during the oral exam.
the history or on initial observation of the patient.
• Gently manipulate the patient’s head dorsally, ven-
• Evaluate and compare postural reactions in all
limbs, including proprioception, “wheelbarrowing,”
trally, and to either side to look for evidence of pain
hopping, extensor postural thrust, and placing
or resistance. Palpate the vertebral column for signs
reactions.
of a pain response. Pressure applied to either side of
the dorsal spinal process of each vertebra may be
• Evaluate and compare spinal reflexes with the calm
patient in lateral recumbency. Important segmental
necessary to elicit pain (see Chapters 100, 128).
reflexes include the triceps, biceps, patellar, and
• If lameness is present, examine the affected limb
cranial tibial reflexes, as well as the flexor (with-
systematically to localize the area involved. First,
drawal) reflexes of the thoracic and pelvic limbs.
examine the foot for evidence of traumatized or
Evaluate the panniculus reflex by needle stimulation
abnormal toenails or nail beds. Evaluate each inter-
of the thoracic or lumbar skin (see Chapter 125).
digital area for erythema, swelling, or draining tracts,
which may be indicative of a foreign body. Palpate
• Evaluation of some parts of the neurologic examina-
tion is subjective. If you are unsure how the patient
each toe individually and note swelling or pain.
responded to a particular test, then repeat the test in
• Palpation proceeds proximally. Evaluate each long
question and compare the results. If the patient is
bone for pain, swelling, abnormal masses, or palpa-
hospitalized, the exam will need to be repeated at
ble fractures.
regular intervals to evaluate progression of the
• Evaluate each joint for evidence of effusion, soft-
disease and response to treatment.
tissue swelling, crepitation, or pain with flexion and
extension.
• In examining the stifle, note the position of the
patella in extension and flexion. If the patella is in its SUPPLEMENTAL READING
normal location, attempt to luxate it medially and lat-
erally. Extension of the stifle usually aids in mobiliz- Bistner SI, Ford R, Raffe M: Kirk and Bistner’s Handbook of Veteri-
nary Procedures and Emergency Treatment, 7th ed. Philadelphia:
ing the patella. Manipulate the stifle for evidence of WB Saunders, 2000, pp 284, 287.
a cranial drawer sign that indicates an anterior Bistner SI, Shaw D: Examination of the eye. Vet Clin North Am Small
cruciate ligament tear (see Chapter 110). Anim Pract 11:595, 1981.
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Crow SE, Walshaw SO: Restraint of dogs and cats. In Crow SE, Morgan, R: Handbook of Small Animal Practice, 3rd ed. Philadelphia:
Walshaw SO (eds): Manual of Clinical Procedures in the Dog and WB Saunders, 1997, p 1222.
Cat. Philadelphia: JB Lippincott, 1987, pp 3–14. Schaer M: The medical history, physical examination, and physical
Laflamme DP, Kealy RD, Schmidt DA: Estimation of body fat by body restraint. In Sherding RG (ed): The Cat: Diseases and Clinical
condition score. J Vet Int Med 8:154, 1994. Management, 2nd ed. New York: Churchill Livingstone, 1994, pp
McCurnin DM, Poffenbarger EM: Small Animal Physical Diagnosis 7–23.
and Clinical Procedures. Philadelphia: WB Saunders, 1991.
W0422-Ch002.qxd 11/10/05 4:40 PM Page 18
▼ Chapter
Anesthesia is an integral part of the practice of com- • Evaluate traumatized patients more extensively
panion animal medicine. In addition to surgical appli- because of the potential for blood loss, cardiac
cations, some form of anesthesia may be required for a arrhythmias (ventricular tachycardia), and thoracic
wide variety of procedures, such as radiography, trauma (pneumothorax).
endoscopy, cerebrospinal fluid collection, and bone • Evaluate abnormalities discovered after ausculta-
marrow aspiration. tion, percussion, palpation, and examination of
mucous membranes with ancillary tests, such as
▼ Key Point The keys to successful anesthesia include thoracic radiography and electrocardiography.
(1) an understanding of what is “normal” in the • The pertinent abnormalities associated with
various species; (2) a working knowledge of the various metabolic diseases are discussed in the
pharmacology of anesthetic drugs; and (3) a appropriate chapters of this text.
systematic evaluation and reevaluation of the • Weigh the animal. Estimate the lean body weight if
patient’s status (monitoring) during the period of the animal is obese to more accurately calculate
anesthesia. correct anesthetic drug doses.
• Determine packed cell volume and total plasma
protein to establish a baseline for reference if hem-
The understanding of what is “normal” comes with orrhage occurs. Check renal function with blood urea
experience. Several excellent texts describe the phar- nitrogen (BUN) or creatinine concentrations in
macology of anesthetic drugs (see “Supplemental older (>7 years) animals. Increases in BUN or creati-
Reading” at the end of this chapter). Monitoring is a nine values may dictate a more careful perianesthetic
matter of establishing a routine and maintaining the fluid management to prevent further renal dysfunc-
discipline to adhere to the routine. This chapter sug- tion (see Table 2-2).
gests some basic anesthetic techniques and protocols
that can be used successfully in small animal practice. Intravenous Catheterization
Place an IV catheter before induction of anesthesia to
provide a convenient pathway for the administration of
GENERAL PRINCIPLES drugs, to allow fluid or blood administration if required,
and to ensure access to the vascular space if an emer-
Preoperative Assessment (Table 2-1) gency occurs.
• A history of vomiting or a recent meal is an indica-
tion for postponing surgery or using techniques that Endotracheal Intubation
produce rapid induction, allowing rapid endotra-
A patent airway is essential to any anesthetic protocol.
cheal intubation that minimizes the potential for
aspiration of gastric contents. • Place a cuffed endotracheal tube in the trachea soon
• On an elective basis, withhold food 6 to 8 hours after induction of anesthesia.
before the administration of anesthetic drugs. • Alternatively, use drugs that maintain the swallowing
• Do not withhold water. reflex (ketamine or tiletamine/zolazepam).
• Potential problems discovered from the history • Clean, thoroughly rinse, and dry endotracheal tubes
include exercise intolerance or cough, as an indi- between uses. Sterilization of endotracheal tubes
cator of cardiorespiratory dysfunction; polyuria or between uses is not necessary on a routine basis. Use
polydipsia, as an indicator of endocrine or renal chemical sterilization or discard the tube if a known
dysfunction; or any other recent change in the pathogen is present. Glutaraldehyde is a safe disin-
animal’s physical status. fectant if the tubes are thoroughly rinsed following
• Perform a physical examination with emphasis on the sterilization.
cardiovascular and respiratory systems (Table 2-2 • See Table 2-3 for the suggested range of sizes of endo-
provides normal values). tracheal tubes for dogs and cats.
18
W0422-Ch002.qxd 11/10/05 4:40 PM Page 19
Anticholinergic
Atropine 0.02–0.04 0.02–0.04
Glycopyrrolate 0.005–0.010 0.005–0.010
Tranquilizer/Sedative
Acepromazine 0.05–0.20 0.1–0.3
Xylazine 0.3–0.8 0.5–1.5
Medetomidine 0.007–0.020 0.01–0.04
Diazepam 0.10–0.25 0.10–0.25
Midazolam 0.05–0.20 0.1–0.2
Analgesic
Morphine NR* 0.2–0.5
Oxymorphone 0.05–0.10 0.1–0.3
Fentanyl 0.002–0.005 0.004–0.008
Meperidine 0.4–2.0 1.0–4.0
Butorphanol 0.1–0.2 0.1–0.4
Nalbuphine 0.5–2.0 0.5–2.0
Buprenorphine 0.005 0.005
Hydromorphone 0.05–0.2 0.1–0.4
Anesthetic
Tiletamine/zolazepam (Telazol) 0.5–4.0 4–10
Thiopental 6–10 NR
Etomidate 1–4 NR
Propofol 2–6 NR
Combination
Acepromazine/oxymorphone 0.05–0.10/0.01–0.02 0.1–0.2/0.1–0.2
Acepromazine/butorphanol 0.05–0.10/0.1–0.2 0.1–0.2/0.1–0.2
Ketamine/acepromazine 2–5/0.05–0.10 5–10/0.1–0.2
Ketamine/xylazine 1–5/0.1–0.8 5–10/0.3–1.5
Ketamine/diazepam (50 : 50) 1 ml/10 kg NR
• Not an analgesic itself, but it may potentiate other • Produces profound cardiopulmonary depression,
drugs that are analgesics. including bradycardia, first- and second-degree atrio-
• Produces hypotension through an a-adrenergic ventricular blockade, catecholamine sensitization,
blockade, particularly in large doses. and decreased respiratory rate.
• Potentiates hypothermia. • Combine with an anticholinergic (atropine or glyco-
• Epinephrine reversal (i.e., hypotension after epi- pyrrolate), particularly if large doses are administered.
nephrine administration) can occur. • Do not use in patients with preexisting cardiac, liver,
• Calms excitable dogs. Aggressive dogs or cats may not or kidney disease or with shock.
become tractable. Combine with opioids or cyclo- • Reverse effects with yohimbine, tolazoline, or ati-
heximides to produce the desired effect (see Tables pamezole (see “Recovery and Reversal” for doses).
2-4 and 2-5). • Vomiting occurs in approximately 25% of dogs and
• Avoid in animals with epilepsy, shock, bleeding 50% of cats.
disorders (inhibition of platelet function), or liver • See Tables 2-4 and 2-5 for doses.
disease.
• Reduce the dose or choose another agent in stressed Medetomidine
or older animals because effects may be exaggerated.
Cats are calmed but usually still resist restraint.
• An a -adrenergic agonist that produces sedation with
2
Anticholinergic
Atropine 0.02–0.04 0.02–0.04
Glycopyrrolate 0.005–0.010 0.005–0.010
Tranquilizer/Sedative
Acepromazine 0.05–0.20 0.1–0.3
Xylazine 0.4–1.0 0.8–1.8
Medetomidine 0.01–0.03 0.03–0.08
Diazepam 0.10–0.25 0.10–0.25
Midazolam 0.05–0.20 0.1–0.2
Analgesic*
Oxymorphone 0.01–0.04 0.05–0.10
Butorphanol 0.05–0.20 0.1–0.3
Nalbuphine 0.5–1.5 0.5–1.5
Buprenorphine 0.005 0.005
Hydromorphone 0.05–0.1 0.1–0.3
Anesthetics
Ketamine 4–10 10–20
Tiletamine/zolazepam (Telazol) 0.5–4.0 4–12
Thiopental 6–10 NR†
Etomidate 1.0–4.0 NR
Propofol 2–6 NR
Combination
Acepromazine/oxymorphone 0.05–0.07/0.01–0.04 0.1–0.2/0.05–0.20
Acepromazine/butorphanol 0.05–0.07/0.07–0.15 0.1–0.2/0.1–0.2
Ketamine/acepromazine 4–8/0.05–0.10 7–15/0.1–0.2
Ketamine/xylazine 4–8/0.1–0.8 7–15/0.3–1.5
Ketamine/diazepam (50 : 50) 1 ml/10 kg NR
Carprofen 2 mg/kg twice daily or 4 mg/kg once daily orally (injectable 4 mg/kg SC once daily)
Deracoxib 3–4 mg/kg once daily orally for 7 days
Etodolac 10–15 mg/kg once daily orally
Ketoprofen 2.2 mg/kg IV, SC, or IM for dogs and cats, single dose
Meloxicam 0.1 mg/kg (0.2 mg/kg loading dose) once daily, SC, PO (cats: if given SC, dose of
0.3 mg/kg is used one time only)
Phenylbutazone 40 mg/kg daily in three divided doses for 2 days then reduce
Tepoxalin 10 mg/kg once daily orally
*Concentration required depends on fresh gas flow rate. The lower the flow rate, the higher the concentration required.
cardiovascular disease, particularly those with cardiac and endotracheal intubation. The injectable drugs and
conduction abnormalities. drug combinations previously described, with the pos-
• The combination of medetomidine (60–80 mg/kg), sible exception of ketamine/xylazine combinations, can
butorphanol (0.2 mg/kg), and ketamine (5 mg/kg) be used to induce anesthesia. Ketamine/xylazine com-
administered IM is a useful preanesthetic in cats that binations produce significant cardiopulmonary depres-
is sufficient for some surgery and is easily augmented sion that can be extreme when inhalant anesthetic
with inhalants. drugs are added.
Etomidate Equipment
• A nonbarbiturate hypnotic that can be used for short- Circle Anesthetic Systems
term IV anesthesia. • A carbon dioxide absorber removes carbon dioxide
• Produces a hypnotic state with little cardiovascular from the exhaled gas.
effect. • Exhaled gas is rebreathed, making the system an eco-
• Etomidate is expensive. Limit to patients with signi- nomic one.
ficant cardiovascular and respiratory disease. • Use 4 to 7 ml/kg/min as the minimum fresh gas flow
• Recovery can be stormy, with vomiting and muscle rate for oxygen. This rate matches the animal’s meta-
tremors. Premedicate the animal with sedatives or bolic need for oxygen. Increase the fresh gas flow rate
tranquilizers to minimize these effects. for oxygen to 10 to 20 ml/kg/min if nitrous oxide is
given. Add the nitrous oxide flow to the oxygen flow
Anticholinergics rate. The pop-off valve in the circle system needs to
be open to vent the excess gas at this flow rate.
• Used to reduce salivation, block vagal inhibition of
the heart, and quiet the digestive tract if indicated.
• Not innocuous. Respiratory dead space is increased Non-rebreathing Anesthetic Systems
(bronchodilation). Ventricular arrhythmias are more
likely to occur. • Bain and Modified Jackson Rees (Hudson RCI; Temec-
• Use if bradycardia occurs or is likely to occur. ula, California) (SurgiVet; Waukesha, Wisconsin).
• Not routinely indicated in anesthesia. Myocardial • Use for patients less than 2 to 4 kg, because less resis-
oxygen consumption is increased owing to tachycar- tance to respiration is produced.
dia. Secretions become more viscous. • Use a fresh gas flow of 1.5 times the minute ventila-
• Glycopyrrolate is more potent and has a longer dura- tion (approximately 150 ml/kg/min). Fresh gas flow
tion of action than atropine. It does not cross the rates are higher because the fresh gas removes
placental or blood-brain barrier. carbon dioxide from the system.
• Give IM, SC, or IV when expediency is important.
Atropine dose is 0.02 to 0.04 mg/kg. Glycopyrrolate Scavenging Equipment
dose is 0.01 mg/kg.
▼ Key Point Use of inhalation anesthetics mandates
the removal of expired and waste gases from the
ANESTHESIA FOR MAJOR PROCEDURES operating room environment.
Anesthesia for major procedures, requiring optimal • Exhaust waste gases using suction systems or vent
hypnosis, analgesia, and muscle relaxation for relatively them to the outside via a hole in an exterior wall.
long periods, usually incorporates the inhalant anes- • Directing gases to the floor is insufficient.
thetics (see Tables 2-7 and 2-8). Although inhalant • Use activated charcoal canisters as alternatives to
drugs can be given as the sole source of anesthesia, absorb halogenated compounds. This is not effective
injectable drugs are usually given to facilitate induction for nitrous oxide.
W0422-Ch002.qxd 11/10/05 4:40 PM Page 26
▼ Chapter
3 Emergency and Critical Care
Techniques and Nutrition
Shane W. Bateman / C. Anthony Buffington / Cheryl Holloway
This chapter describes commonly used techniques in • Needle holders, tissue forceps
emergency and critical care medicine. See appropriate • Monofilament skin suture appropriate to patient
chapters for information about diseases that require • Skin staples (optional)
critical care.
Technique
1. When the patient is semicomatose or moribund,
INTRAVENOUS CATHETERIZATION local anesthesia is not required. Otherwise, infil-
BY CUTDOWN trate small amounts of local anesthetic into the
aseptically prepared skin site.
Indications 2. In general, the lateral saphenous (canine) or
medial saphenous (feline) are easier to approach
▼ Key Point Venous access is required in every emer- than the cephalic veins. Jugular cutdown can also
gency situation. be performed with the same technique, but the vein
is deeper and may be more troublesome for
Perform venous cutdown when percutaneous venous inexperienced surgeons to find.
catheterization has been unsuccessful after one or two 3. After aseptic skin preparation and use of aseptic
attempts (depending on the urgency with which access technique, identify the vessel. In many situations
is required). Nonurgent venous cutdown can also be the vessel may not be visible even when occluded,
performed when numerous percutaneous catheteriza- so the anatomy of the vessel is important to under-
tion attempts have resulted in severe peripheral stand.
hematoma formation or thrombophlebitis. 4. Place the scalpel blade gently on the skin over the
vessel and, without cutting the skin but maintaining
Contraindications skin contact with the blade, pull the skin laterally to
the vessel (Fig. 3-1).
Relative contraindications include severe hemostatic 5. Incise approximately 1 to 1.5 inches parallel to the
dysfunction. However, occasionally such patients vessel.
require IV catheterization, necessitating an easily 6. Allow the skin to retract back into place over the
compressible location as the best choice for a cutdown vessel.
procedure. 7. The bluish hue of the vessel should be obvious if
the incision was made in a correct location. Move
Objective the skin to attempt to identify the vessel if it is not
Obtain vascular access for administration of fluid and immediately obvious. To differentiate the vessel
drugs. from underlying muscle bellies, the vessel should
blanch with minimal digital pressure; muscle bellies
will not.
Equipment 8. Hold the iris scissors with the thumb and index
• Local anesthetic finger in the finger rings with the tips of the scis-
• Scalpel handle and #10 or #15 blade sors pointing across the palm of your hand, not
• Iris scissors (very small sharp/sharp) extending out from the fingers. This allows the
• Thumb forceps shaft of the scissors to be perpendicular to the
• Curved mosquito hemostat patient and the vessel.
• Suitable size IV catheter (e.g., Surflo catheter, 9. Place the tips of the scissors as close to the vessel
Terumo Medical Corp.) wall as possible, apply gentle pressure to the tissue,
29
W0422-Ch003.qxd 11/10/05 4:41 PM Page 30
Contraindications
Presence of a severe coagulopathy is a relative con-
traindication. In general, with firm direct pressure for
prolonged periods, significant blood loss is not a
concern. The sample is most easily obtained when the
patient is in lateral recumbency; thus observe patients
with respiratory compromise carefully for worsening of
respiratory distress during the procedure and give sup-
plemental oxygen as required.
tibial crest
Objectives
• Obtain arterial blood for blood gas analysis
• Prevent hemorrhage
Equipment
Use either of the following:
• Dry heparin blood gas syringe
Figure 3-3. Anatomic locations for intraosseous access. • A heparinized regular syringe
W0422-Ch003.qxd 11/10/05 4:41 PM Page 32
Contraindications
Femoral a.
• Patients with severe deforming facial trauma
• Brachycephalic breeds with respiratory distress
• Severe thrombocytopenia or other coagulopathy
• Severe or protracted vomiting (if placing a feeding
tube)
B Objectives
Dorsal
metatarsal a. • Provide oxygen therapy using a nasal catheter
• Provide nutritional supplementation using a naso-
gastric tube
Equipment
• Nasal oxygen cannula or nasoesophageal or nasogas-
tric feeding tubes
• Topical ophthalmic local anesthetic
• Tape
• Needle holders and tissue forceps
Figure 3-4. A, Femoral artery puncture. B, Dorsal metatarsal • Monofilament skin suture appropriate to the patient
artery puncture. • Skin staples
W0422-Ch003.qxd 11/10/05 4:41 PM Page 33
Figure 3-5. Positioning for placement of nasal catheter. Figure 3-6. Finger trap suture pattern.
W0422-Ch003.qxd 11/10/05 4:41 PM Page 34
Equipment
• Scalpel handle and #10 or #15 blade
• Mayo scissors
• Large, curved Kelly or Carmalt hemostat
• Tracheostomy tube
• Monofilament suture material appropriate to patient
Technique
1. Position the patient in dorsal recumbency with the
head extended slightly off and over the edge of the
table or with the neck over a rolled towel or
sandbag.
2. Make one attempt to insert a large over-the-needle
Figure 3-7. Between-the-rings tracheostomy with stay suture
peripheral IV catheter into the trachea at the base placement.
of the neck close to the thoracic inlet to provide
oxygen to the patient while final preparations are
made.
3. Rapidly clip and aseptically prepared the skin.
4. The patient will need rapid IV anesthesia for the
procedure unless it is moribund.
5. Incise the skin from the larynx to the thoracic inlet.
6. Bluntly force the closed tips of Mayo scissors into
the first tissue plane, open and insert one tip into
the tissue plane created, then incise the tissue plane
to each end of the incision. Attempt to use the
sharp edges of the scissors to cut by advancing with
the blades open rather than “scissoring” through
the tissue.
7. Incise the sternohyoideus muscles (strap muscles)
in a similar way, exposing the trachea.
8. Identify the neurovascular bundle on each side and
bluntly insert a hemostat through the fascia dorsal
to the trachea, allowing it to be elevated into the
surgical incision. Figure 3-8. Through-the-rings tracheostomy with stay suture
9. Do not damage the vessels overlying the trachea. placement.
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12. Place stay sutures (3-0 or 4-0 silk) in the edges of devices add a small amount of increased resistance that
the tracheal incision. If a transverse incision was contributes to the work of breathing. In patients with
made, place stay sutures in the ventral-most aspect marginal muscle strength, this may be significant and
of the trachea and around the first proximal and lead to a vicious cycle of hyperthermia and increased
first distal ring. If a longitudinal incision was made, work of breathing.
place stay sutures around two adjacent rings, Monitor the patient’s temperature regularly. Routine
approximately 3 to 5 mm from the tracheal incision administration of saline into the tracheostomy site is not
and encompassing 2 tracheal rings on both sides of recommended. A poorly fitting tube and inappropriate
the incision. Leave the suture ends long. inflation of the cuff are the most common cause of
13. Insert the tracheostomy tube into the trachea. fibrosis and web formation as a long-term complication.
Several types of specialized tracheostomy tubes are
commercially available. Each has advantages and
disadvantages. A simple tracheostomy tube can also ABDOMINOCENTESIS
be easily constructed from an endotracheal tube
(Fig. 3-9). Indications
14. The most critical aspect of tube placement is the Physical examination or radiographic evaluation indi-
size and fit of the tube. If the tube exerts circum- cates moderate quantities of peritoneal effusion, and
ferential pressure on the tracheal mucosal, then cytological or chemical analysis of the fluid will assist in
significant pressure necrosis, scarring, or fibrotic the diagnostic process.
web formation are more likely to occur as a com-
plications. Choose a tube that fits loosely in the Contraindications
trachea with no major points of mucosal pressure.
Do not inflate the cuff unless positive pressure Severe coagulopathy is a relative contraindication
ventilation is required. depending on the value or benefit of obtaining a fluid
15. Suture the skin edges to allow easy access to the tra- sample. Relative contraindications to use of a blind
cheal incision when the tube needs to be changed. technique include a large abdominal mass; significant
organomegaly, particularly of a vascular organ such as
Postoperative Care and Complications the spleen, liver, or kidney; or distension of a hollow
viscus such as bowel or uterus. Consider ultrasono-
• Clean or replace the tube as necessary to maintain graphic guidance if available.
patency.
• Clean the “dirty tube” and allow it to soak in an Objectives
appropriate and safe antimicrobial solution, then
rinse carefully with sterile saline prior to the next • Aseptically obtain fluid from the abdominal cavity for
tube exchange. analysis and culture
• Do not apply suction to the tube. • Avoid trauma to abdominal organs
• Keep the animal well hydrated.
• Protect the skin around the tube with petrolatum Equipment
(Vaseline). • 22- to 20-gauge, 1- to 1.5-inch needle and syringe
If possible, use tracheostomy heat and moisture appropriate to patient size (e.g., 3- to 12-ml syringe)
exchange devices (HME) to maintain airway humidifi-
cation and thus decrease viscosity of secretions. These Technique
1. If possible, allow the patient to stand or be posi-
tioned in sternal recumbency to allow access to the
most dependent site on the abdomen. Alternatively,
place the patient in left lateral or dorsal recumbency.
2. The goal of the patient position and of the location
and direction of the abdominocentesis attempt is to
avoid the spleen, thus preventing hemorrhage that
will contaminate the sample.
3. Clip and aseptically prepare the skin. Local anes-
thetic can be infiltrated if desired.
4. Advance the needle and syringe through the skin
and withdraw the plunger of the syringe to create a
small amount of negative pressure in the syringe
prior to advancing the needle into the peritoneal
Figure 3-9. Tracheostomy tube construction from endotracheal cavity and away from the presumed location of the
tube. spleen.
W0422-Ch003.qxd 11/10/05 4:41 PM Page 36
quences and requires vigilant attention to the care and 3. Choose a needle or catheter of sufficient size and
maintenance of the drainage system. length appropriate to the situation and patient.
Ensure that the three-way stopcock is closed to the
atmosphere.
THORACOCENTESIS 4. Advance the sharp point of the needle or stylet
through the skin, then place a small amount of neg-
Indications ative pressure on the syringe. Advance the needle tip
cautiously until a slight “pop” through the parietal
Perform diagnostic thoracocentesis on all patients that
pleura is felt, which ideally is accompanied by pro-
present with symptoms of pleural space disease (rapid
ductive aspiration of air or fluid from the pleural
shallow breathing, respiratory distress, symmetrical or
asymmetrical dullness, or absence of lung sounds on space.
auscultation) as described in Chapter 142. Patients with 5. Use one of the following methods:
significant respiratory distress that are unsuitable can- a. If using a rigid metal device, attempt to reposition
didates for radiographic evaluation may also benefit the needle or stylet tip into the intercostal space
from diagnostic thoracocentesis. (parallel to the ribs with the bevel facing into the
chest) so that as the pleural cavity is drained and
Contraindications the lung expands closer to the chest wall, there is
less likelihood that the lung will be lacerated by
Patients with long-standing chronic effusions (particu- the needle tip (Fig. 3-10A).
larly cats with chylous effusion) may be at a higher risk b. Alternatively, advance the needle under the
for development of fibrosing (restrictive) pleuritis. cranial rib and flatten the needle against the
Inadvertent needle contact with, and subsequent lacer- caudal rib (perpendicular to the ribs with
ation of, the diseased pleura in this syndrome can the bevel facing into the chest). This method
produce significant and life-threatening pneumotho- should cause the cranial rib to be pushed gently
rax. Exercise extreme caution in using sharp instru- from the chest, again protecting the tip of the
ments to drain thoracic fluid in such patients. needle and preventing laceration of the lung
parenchyma (Fig. 3-10B).
Objectives c. In a third method, grasp the rigid shaft of the
• Evacuate fluid or air from the pleural space needle or stylet between the index finger and the
• Avoid iatrogenic pneumothorax or trauma to the thumb such that only the tip of the needle or
lungs, heart, and intercostal blood vessels stylet is within the pleural cavity. Guard the needle
or stylet firmly to prevent inadvertent advance-
Equipment ment into the thoracic cavity. As soon as a
“scratching” or “scraping” sensation is detected
• 19- or 22-gauge butterfly catheter, 18- to 22-gauge on the needle, immediately withdraw it to prevent
over-the-needle intravenous catheter, 18- to 22-gauge, inadvertent laceration of the lung (Fig. 3-10C).
1- to 1.5-inch needle, or metal stylet from 18- to 6. Gently reposition the needle or stylet or withdraw it
22-gauge over-the-needle catheter with catheter if there is lack of continuing production of fluid or
removed air from further attempts at aspiration.
• IV extension set 7. Drain as much as possible from the pleural cavity
• Three-way stopcock using the three-way stopcock, syringe, and collection
• Syringe basin (a second thoracocentesis may be required on
the contralateral chest wall in some cases).
Technique
1. Clip hair from the site and aseptically prepare the
skin. Many patients will tolerate the procedure Complications
without instillation of local anesthetic and often Patients with chronic fluid accumulations, especially
resent the injection of local anesthetic more than the with significant quantities of fibrin, may have significant
procedure. compartmentalization of fluid that is difficult to remove
2. The site of thoracocentesis will depend on whether with routine thoracocentesis. Ultrasound-guided
air or fluid is suspected to be causing respiratory dis- attempts may be more successful in collecting fluid
tress. If fluid is suspected, select a ventral location in from such patients; alternatively, consider a chest drain
intercostal spaces 3 to 7 approximately one third of (see the next section). Inadvertent laceration of lung
the distance between the costochondral junction and parenchyma resulting in pneumothorax is rare (except
the sternum. If air is suspected, select a dorsal loca- in fibrosing pleuritis patients) and can be managed with
tion in intercostal spaces 5 to 9 at the junction of the chest drain placement and intermittent or continuous
dorsal one third and ventral two thirds of the chest suction. Laceration of a coronary artery is an extremely
wall. rare complication and likely only if the position of
W0422-Ch003.qxd 11/10/05 4:41 PM Page 38
Objectives
• Aseptically place an indwelling thoracic drain tube
without causing iatrogenic trauma to thoracic viscera
• Minimize iatrogenic pneumothorax
• Place the tube so that it effectively drains pleural air
or fluid
A Equipment
• Scalpel handle with #10 or #15 blade
• Adson Thumb forceps
• Mayo scissors
• Needle holders
• Curved Kelly or Carmalt hemostat appropriate to the
size of the patient and tube
• Chest catheter or tube of appropriate size (two thirds
of the intercostal space) (Argyle trocar catheter or
B red rubber feeding tube)
• Monofilament skin suture material appropriate to
patient (i.e., 3-0 to 0)
Technique
1. Use either general anesthesia or heavy sedation
with local anesthesia and intercostal nerve blocks.
2. Pull the patient’s lateral chest wall skin cranially as
far as comfortably possible.
3. Clip the hair and aseptically prepare the skin from
the 5th to the 12th intercostal space. Use local anes-
thetic to infiltrate into the 7th or 8th intercostal
space at the junction of the dorsal one third and
ventral two thirds of the lateral body wall.
C 4. Incise the skin at the 10th intercostal space. Make
the incision approximately 5 mm longer than the
Figure 3-10. A, Needle position for parallel intercostal approach
to thoracocentesis. B, Needle position for perpendicular intercostal
diameter of the tube being placed.
approach to thoracocentesis. C, Needle position for subpleural 5. Using thumb forceps and sharply incise the subcu-
approach to thoracocentesis. taneous and latissimus dorsi muscle tissue. Do not
use excessive blunt dissection so that you have a
tight seal around the tube.
6. Clamp the thoracostomy tube tip 3 to 5 mm behind
the heart is significantly deviated within the thoracic the tips of the Kelly or Carmalt hemostat (Fig. 3-
cavity. 11A). Ensure that the open end of the tube is
clamped or plugged with a collection device. Alter-
natively, use an Argyle trocar catheter.
THORACIC CATHETER OR TUBE PLACEMENT 7. Premeasure the tube from the intercostal entry site
(seventh or eighth intercostal space) to the point
Indications where the elbow naturally overlies the sternum.
8. Place the clamped tube into the deepest part of the
Consider placing a thoracic catheter or tube in patients incision, ensuring that the hemostat is curved
with large volumes of air or fluid production that are toward the elbow and the tips are in the intercostal
not reasonably and effectively drained with intermittent space and not over a rib.
thoracocentesis. 9. Stand at the patient’s back and grasp the shaft
of the tube or hemostat with the nondominant
Contraindications hand, allowing one finger’s width between the
Significant coagulopathy is a relative contraindication patient and the bottom of the nondominant hand.
for this procedure. Severe trauma or instability of the Form a fist over the finger rings of the hemostat
chest wall at the proposed site is a contraindication to (or trocar catheter) with the dominant hand
nonsurgical placement of the catheter or tube. (Fig. 3-11B).
W0422-Ch003.qxd 11/10/05 4:41 PM Page 39
ventral 2/3
B
Figure 3-11. A, Position of thoracic tube in Kelly or Carmalt forceps. B, Technique for placement of thoracic tube.
W0422-Ch003.qxd 11/10/05 4:41 PM Page 40
10. Place the tube into the chest cavity at the seventh of a percutaneous endoscopically placed gastrostomy
or eighth intercostal space with a sharp, quick, and tube (PEG tube).
forceful motion.
11. Open the hemostat and slide the tube gently into Contraindications
the chest cavity while the hemostat is removed.
12. After inserting the tube to the premeasured length, Contraindications for esophagostomy tube placement
release the skin to slide caudally, forming a “tunnel” include megaesophagus or localized infection at the
over the tube as it exits the chest wall. desired tube insertion site. Coagulopathy is a relative
13. Place a purse-string suture in the skin around the contraindication. Consider severity of the hemostatic
tube. Leave both suture ends of approximately dysfunction and the urgency of nutritional support.
equal length.
14. Place a finger trap suture pattern to secure the tube Objectives
to the skin (see Fig. 3-6). Also, if desired to prevent • Provide nutritional supplementation using an
leakage around the subcutaneous portion of the esophageal catheter
tube, place a simple interrupted suture around the • Avoid excessive trauma to the esophagus
tube between its entry site in the skin and where it
enters the thorax.
15. Cover the skin-tube interface with copious amounts Equipment
of antibiotic ointment and bandage it into place. • Scalpel handle with #15 or #11 blade
• Large curved Kelly or Carmalt hemostat
• Appropriate red rubber feeding tube (size 14 Fr or
Postoperative Care and Complications larger)
• Use an Elizabethan collar if necessary to prevent tube • Monofilament skin suture appropriate to the
damage. patient
• Change the chest bandage every other day or more
often if necessary. Check tube position during Technique
bandage changes.
1. Commercially available customized esophagostomy
• Frequently check tube connection devices for leaks.
kits are available. If using a kit, follow the instruc-
• A small amount of subcutaneous air or fluid ventral
tions for placement that accompany the kit.
to the tube entry site may occur. However, consider
2. Anesthetize the patient and place in right lateral
replacing the tube in a new site if large amounts of
recumbency with an endotracheal tube in place.
fluid or air drain to the subcutaneous space.
3. Premeasure the tube to ensure that the tip of the
• Obtain thoracic radiographs if necessary to check
tube is in the distal esophagus (from the entry site
tube position. Reposition the tube if necessary.
to the eighth rib).
• Pull the chest tube when minimal fluid or air is
4. Clip and aseptically prepare the skin over the left
drained. The chest tube can create 1 to 2 ml/kg/24
neck caudal to the ramus of the mandible.
hours of pleural fluid.
5. Insert a curved hemostat into the mouth with the
• Remove sutures and pull the tube quickly and
curve pointed laterally. Use a mouth gag to facili-
smoothly from the chest. Submit the tube tip for
tate hemostat placement if necessary. Advance the
culture if indicated.
hemostat into the esophagus and palpate the tips of
• Apply antibiotic ointment and bandage the incision.
the hemostat on the left lateral neck.
6. Place the tips of the hemostats to the level of the
second to third cervical vertebral body and as far
dorsal from the jugular vein (furrow) as possible.
FEEDING TUBE PLACEMENT Push outward or upward to “tent” the skin of the
Nasal Feeding Tubes (Nasoesophageal, neck.
7. Have an assistant’s index finger and thumb grasp
Nasogastric) the tips of the hemostat and gently push down to
See “Nasal Catheter Placement” in this chapter. stretch the skin over the tips of the hemostat to hold
it firmly in place and prevent it from moving (Fig.
3-12).
Esophagostomy Tube Placement 8. Have the assistant make a stab incision directly over
the tips of the forceps, making contact with the
Indications metal tips with the scalpel blade. Do not remove
Enteral tube feeding is required for long-term home the blade until the tips of the hemostat penetrate
feeding in patients with good gastric motility and when the incision. The goal is to gently use the scalpel
longer anesthetic periods or expense precludes the use to enlarge the incision only until it permits exit
W0422-Ch003.qxd 11/10/05 4:41 PM Page 41
Forceps
Figure 3-12. Technique for esophagostomy
tube placement.
Angle of
mandible
Jugular
vein
of the hemostat. A large or ragged incision is not 12. Direct the end of the tube down the esophagus and
desirable. advance the tube as far as possible (Fig. 3-13).
9. Push the hemostat tips outward through the stab 13. Gently pull out the tube exiting the neck, and twist
incision. If resistance is felt, the blade of the scalpel while attempting to advance the tube in place into
can be “wiggled” slightly to allow the hemostat to the patient’s pharynx. The tube should straighten
penetrate. and “unkink.” If correct and unkinked placement
10. Open the jaws of the hemostat, place the distal tip has been achieved, the tube can be advanced and
of the feeding tube parallel to the tips, and clamp withdrawn smoothly from the esophageal incision
it into place. with little resistance.
11. Pull the tube through the mouth to the appropri- 14. Suture the tube to the skin using the finger trap
ate length and remove the clamp. suture pattern (see Fig. 3-6).
W0422-Ch003.qxd 11/10/05 4:41 PM Page 42
15. Verify correct tube placement using a portable urgency of nutritional support in the decision. Place-
capnograph (no visible waveform and end-tidal ment of the tube described later in this section is also a
carbon dioxide measured at 0 mmHg) or with relative contraindication in large-breed (especially deep-
lateral and ventrodorsal radiographic views of the chested) dogs because of the increased risk of inadver-
thorax before feeding. tent tube removal from the stomach, resulting from
excessive tension between the paracostal placement site
Postoperative Care and Complications and the stomach wall. Consider placement of a cus-
tomized tube with a large, nonremovable inner flange
• Keep the incision clean and covered with a light for these patients. Removal of such tubes must also occur
bandage or stockinette.
using an endoscope and cannot be accomplished per-
• See the nutrition section of this chapter for supple- cutaneously. The presence of neoplasia or severe disease
mentation guidelines.
of the stomach wall increases the risk of leakage and peri-
• If the tips of the hemostats remain slightly open tonitis and is a relative contraindication.
during creation of the stab incision, a strip of
esophageal mucosa may get trapped between the jaws Objectives
of the hemostats. When the tube is being pulled into
the esophagus from the skin, the strip of tissue will • Allow nutritional supplementation bypassing the oral
make it difficult to pull the tube back into the esoph- cavity and esophagus
agus until the tissue breaks or the tube dislodges from • Provide a leakage-free, chronic, indwelling gastric
the hemostats. tube
• Ensure that the hemostat tips are not opened until
they are completely free from the skin-esophageal Equipment
incision. • Gastrointestinal (GI) endoscope
• If the tube will not straighten or unkink during • Endoscopic grasping forceps
insertion of the tube down the esophagus, do the • Bard urologic catheter (18- to 24-Fr Pezzer mush-
following: room-tip model)
• Ensure that the tube tip is in the esophagus and • Sovereign over-the-needle IV catheter (14 gauge)
not the trachea. • Three-way stopcock and adapters
• Gently withdraw the tube from the neck incision • Vetafil suture, size 2-0 (3–5 feet depending on patient
and continue twisting. size)
• Realize that the tube is not large enough, so it has • #11 blade
insufficient tensile strength or memory to • 20-gauge, 1-inch needle
straighten or unkink (ensure that the tube is at • Scissors
least 14 Fr). • Hemostats
• If the jugular vein is lacerated, take the following • Stockinette (cut to fit for “sweater”)
steps:
• Apply direct pressure to the wound for several Technique
minutes to prevent blood loss.
1. Prepare the Pezzer catheter by removing the flared
• Extend the incision and isolate the jugular vein,
end and cutting the flared end into two pieces of
then ligate it above and below the laceration, sac-
approximately equal length. Make a long axis stab
rificing the vessel.
incision in the center of each piece large enough
Percutaneous Endoscopically to accommodate the diameter of the Pezzer
catheter. Advance the hemostats through the stab
Placed Gastrostomy Tube incision of one piece and pull the catheter through.
Indications Advance this “inner flange” piece down to the
mushroom tip. Some clinicians prefer to snip off
• Consider a PEG tube for any patient for which long- the nipple-shaped tip of the Pezzer catheter to
term (weeks to months) nutritional support is war-
reduce occlusion of the tube with food particles.
ranted. It is generally the feeding tube of choice for
Cut the shaft of the opposite end of the catheter at
long-term nutritional support when an endoscope is
an approximately 60 degree angle to leave a
available to assist in placement.
tapered tip.
• Use a PEG tube to bypass the oral cavity and
2. Place the anesthetized animal in right lateral recum-
esophagus.
bency, and clip and aseptically prepare a 10- to
14-cm2 area of the skin just caudal to the costal arch.
Contraindications 3. Insert an endoscope and distend the stomach with
Infection at the site of insertion is a contraindication. air. Gently palpate the distended stomach from the
Coagulopathy is a relative contraindication. Consider abdominal wall just caudal to the last rib using an
the severity of the hemostatic dysfunction and the extended finger. Observe using the endoscope to
W0422-Ch003.qxd 11/10/05 4:41 PM Page 43
ensure that the proposed exit site is positioned in exiting the body wall does not enter the stomach
the body of the stomach away from the pylorus. accidentally (Fig. 3-14B).
4. Quickly and forcefully insert the Sovereign IV 7. Withdraw the Sovereign IV catheter from the body
catheter percutaneously into the distended stomach wall. Place a hemostat on the body wall end of the
and observe using the endoscope. Withdraw the suture to prevent inadvertent pull-through into the
needle, leaving the catheter in place (Fig. 3-14A). stomach (Fig. 3-14C).
5. Thread Vetafil suture material through the catheter 8. Insert the luminal end of the suture through the
into the stomach. narrow end of the Sovereign IV catheter and
6. Using endoscopic grasping forceps, grasp the advance the catheter toward the patient’s mouth
Vetafil suture and withdraw the entire endoscope, (Fig. 3-14D).
along with the luminal end of the suture, out 9. Secure the pointed tip of the Pezzer catheter to the
through the mouth. Ensure the end of the suture luminal suture end using a horizontal mattress suture.
D
B
F G
Figure 3-14. Placement of percutaneous endoscopic gastrostomy (PEG) tube. A, Over-the-needle catheter is placed through the skin and
into the air-distended stomach; B, suture threaded through the catheter is grasped by endoscopic forceps and pulled out through the mouth
(C); D, over-the-needle catheter is threaded onto the suture, which is tied to the gastrostomy tube. (E) and subsequently pulled into the stomach
and out the gastric and body wall. The flange at the end of the gastrostomy tube should press snugly against the gastric mucosa. See text for
F and G.
W0422-Ch003.qxd 11/10/05 4:41 PM Page 44
10. Slide the Sovereign IV catheter back down the there is concern regarding obstruction because of
suture toward the Pezzer catheter and firmly seat the tip, retrieve it endoscopically.
the pointed tip and suture knot (if possible) • Alternatively, remove the tube percutaneously by
into the large flared end of the catheter (Fig. grasping and pulling the mushroom tip through the
3-14E). body wall while applying firm downward pressure to
11. Lubricate the IV catheter and the gastrostomy tube. stabilize the body wall. A blunt stylet (e.g., cotton-tip
12. Pull the percutaneous end of the suture until the applicator) can be placed inside the tube against the
IV catheter tip is through the skin surface. Fre- nipple tip to stretch the mushroom tip, making it
quently, the skin will need to be incised a few mil- easier to remove. The inner flange slides off the
limeters (cautiously using a #11 blade). Place firm mushroom tip and passes out the GI tract.
downward pressure around the exit site and pull • Once a strong seal has developed between the
the gastrostomy tube out through the body wall stomach and the body wall (at least 2–3 weeks), the
until the mushroom tip and inner flange are posi- Pezzer mushroom catheter can be replaced by any of
tioned against the gastric mucosa and the stomach a variety of low-profile or “button” gastrostomy tubes.
is pulled up against the body wall. Pull the tube out These are placed percutaneously into the stoma
gently and observe the position of the mushroom immediately following extraction of the original
tip using the endoscope to ensure correct place- Pezzer tube.
ment (Fig. 3-14F).
13. Slide the “outer flange” over the external end of the Complications
Pezzer catheter to ensure a snug fit to the patient’s
body wall. Secure the tube into place (Fig. 3-14G).
• The opening in the inner or outer flange may be too
small and may cause severe constriction of the tube
14. Wrap a small piece of tape circumferentially around and obstruction to feeding. Observe the tension on
the tube at the junction of the tube and the outer the catheter walls when the inner and outer flanges
edge of the outer flange to identify ideal position- are placed to prevent this complication.
ing and serve as a method for detecting inadvertent
flange movement or slippage.
• Inadvertent tube removal from the stomach wall can
result in leakage and peritonitis. Stomach wall
15. Remove the pointed tip of the catheter and the integrity because of disease and excessive tension on
suture material with scissors and place the three-way the stomach wall in large-breed dogs because of deep-
stopcock into the tube tip. Alternatively, place a chested conformation may contribute to this compli-
small, graduated Christmas tree adapter in the tube cation. Use caution when placing a tube in a gastric
tip. Place a cap on all openings of the stopcock or site suspected to have infiltrative disease. Consider
Christmas tree adapter. alternative tubes for large-breed deep-chested dogs.
16. Cut a 4 ¥ 4 gauze sponge on the folded edge and Inadvertent removal of the tube from the body wall
tuck around the feeding tube-skin interface. by the patient or by snagging on another object is not
17. Cut a sufficient length of stockinette and pull one a concern if the tube has been in place 10 to 14 days
end through so that both cut ends are together. Cut or more to allow fibrous seal or stoma formation.
holes near the folded end of the stockinette for the Tube replacement can occur through the same stoma
patient’s front legs and place the stockinette to if it is still patent, or a low profile tube (button tube)
protect the tube site. Tuck the free end of the tube can be considered.
under the stockinette to prevent inadvertent
removal.
• Tube obstruction with food can also be a complica-
tion. In general, mechanical removal or an attempt
18. Small amounts of water can generally be adminis- to advance the obstruction forward with a narrow
tered through the tube immediately, but delay diameter stylet is preferable to the use of chemical
feeding 12 to 24 hours to allow an appropriate dissolution methods.
fibrin seal to form around the insertion site.
develop learned aversions if the food is associated with • Use a muscle condition score (MCS) (Fig. 3-16) to
illness-related nausea or other negative sensations. quantify the assessment. Structural impediments to
Encourage owners of hospitalized patients to provide eating also may be identified during the examination.
whatever food is typically offered at home and to feed • Hypoalbuminemia, lymphopenia, and anemia are
the pet during hospitalization (many pets eat more will- nonspecific laboratory findings that can be associated
ingly for their owners than for strangers) when possible. with severe malnutrition. Decreased resistance to the
In some cases, however, patients cannot eat by them- passage of a needle for blood collection because of
selves and need more invasive approaches to nutrition loss of skin collagen also is a reasonably sensitive indi-
support. cator of peripheral protein depletion.
• Assess a serum biochemical profile to provide impor-
tant information regarding visceral organ function,
Nutritional Assessment which may influence the composition of the diet or
• If malnutrition is not present initially, reevaluate the the route of administration. For example, evidence
patient periodically during hospitalization to ensure of significant abnormalities of liver or kidney func-
that malnutrition does not develop secondary to an tion could indicate the need for protein restriction,
ongoing disease process, administered drugs or treat- and severe pancreatitis could necessitate parenteral
ments, persistent inability to eat, or inadvertent food administration of nutrients.
deprivation.
• Nutritional support is part of the primary therapy for Routes of Nutrient Delivery
malnourished patients and when voluntary food Oral Feeding
intake is impossible for prolonged periods.
• Oral feeding is the safest, least expensive, most ben-
eficial physiologically, and most convenient method
▼ Key Point Do not begin nutritional support until the of feeding; thus, use oral feeding whenever possible.
initial goals of fluid therapy—rehydration, elec- • Try nursing techniques to improve food intake (often
trolyte replacement, and normalization of acid- referred to as “coax-feeding”) before proceeding to
base status—have been achieved. more invasive methods.
• Attempt hand-feeding, petting or stroking, vocally
• The steps of nutritional assessment include a history reassuring the animal, offering food when the animal
(including a complete diet history), a physical exam- is outside of the cage (during a walk outside or in a
ination, and an evaluation of any supporting labora- quiet area of the hospital), warming the food to body
tory data. Increased risk for malnutrition is suggested temperature to enhance aroma, or offering a favorite
by a recent history of one or more of the following food.
clinical situations: • When new diets must be introduced to hospitalized
• Greater than 10% weight loss patients, offer 15 to 30 g of the food initially. If resis-
• Decreased food intake tance is observed, remove all food and attempt again
• Increased nutrient needs because of trauma or in 1 to 2 hours. If no intake is observed within
surgery another 1 to 2 hours, or if the food hardens, remove
• Increased nutrient losses resulting from vomiting, it immediately and offer a different food.
diarrhea, or burns • If the diet is intended for long-term patient manage-
• Acute exacerbation of a chronic disease problem ment, offering it after the patient is home and feels
• Obtain a diet history to determine the quality and better improves the probability of long-term accep-
appropriateness of the diet fed and the total daily tance and success.
intake of food. Ask if corticosteroids, cancer • If attempts to restore food consumption fail, try force-
chemotherapeutic agents, antibiotics, diuretics, or feeding using a syringe for 1 to 2 days. Force-feeding
other drugs that may adversely affect nutritional provides some nutrition, but the inconvenience and
homeostasis have been administered recently. the stress imposed on the patient during feeding limit
• Perform a thorough physical examination, including its usefulness.
assigning a body condition score (BCS) (Fig. 3-15). • A feeding tube also may be passed through the
• Underweight animals lose subcutaneous fat and mouth into the stomach for each feeding. Passing an
experience muscle wasting. Patients in a moderate or orogastric tube is relatively simple; limited restraint
overweight body condition also may be tissue and the opening of the animal’s mouth just enough
depleted but may not appear so because of an “over- to introduce the tube minimize the patient’s opposi-
coat” of fat. This situation occurs when muscle tissue tion to this procedure.
is broken down more quickly than is adipose tissue.
Affected patients usually can be recognized by a poor Enteral Routes
haircoat; easily pluckable hair; thin, dry skin; and • If the patient is too debilitated to tolerate repeated
abnormal prominence of the bones of the head. tube feedings, or if nutritional support is required for
W0422-Ch003.qxd 11/10/05 4:41 PM Page 46
BCS 1 Emaciated
BCS 2 Thin
BCS 3 Moderate
BCS 4 Stout
BCS 5 Obese
Figure 3-15. Body condition scoring. (Buffington CAT, et al: Manual of Veterinary Dietetics. St. Louis: WB Saunders, 2004.)
more than 2 days, place either a nasogastric or a • When access proximal to the stomach is not available
nasoesophageal tube (see the technique described in in patients with normal GI function, place a gastros-
“Nasal Catheter Placement”). Tube placement is tomy feeding tube. Surgical gastrostomies are the
simple, does not require anesthesia or sedation, and safest but the most expensive and difficult to place.
allows provision of fluid and nutrients for days to Alternatively, a feeding tube can be placed using an
weeks. endoscope or a blind placement device (see “Percu-
• If a nasal tube cannot be placed, or if a prolonged taneous Endoscopically Placed Gastrostomy Tube”).
course of feeding is anticipated, place an esophagos- Gastrostomy tubes can be maintained in patients for
tomy tube in patients that have a functional GI tract months with good nursing care.
and no history of vomiting or regurgitation (see • Rarely, a needle catheter jejunostomy or gastroje-
“Esophagostomy Tube Placement”). junostomy may be necessary when gastric atony, gas-
W0422-Ch003.qxd 11/10/05 4:41 PM Page 47
Bone
1 Marked or
severe muscle wasting
No muscle covering the temporal
bones, ribs, lumbar vertebrae,
and pelvic bones on palpation
“Overcoat syndrome”
Clinically, body condition score (BCS)
and muscle condition score (MCS) are
not directly related, because of the
“overcoat syndrome” (OS), which
occurs when an animal has less muscle
and more fat, making an MCS of 1 or 2
look relatively normal. We suspect OS when
the history and physical do not match.
Palpation is required for a diagnosis of
OS. Although some areas of the body
may feel relatively normal (as shown at
right), marked wasting is felt over bony
prominences.
Figure 3-16. Muscle condition scoring. (Buffington CAT, et al: Manual of Veterinary Dietetics. St. Louis: WB Saunders, 2004.)
troduodenal obstruction, neoplasia, regurgitation, or fed immediately postoperatively using the jejunal
vomiting prevent feeding using more proximal sites. tube, which can be removed from the gastrostomy
Jejunostomy tubes are typically placed at surgery. tube to permit gastrostomy feeding once motility
Patients requiring extensive surgical procedures of returns to the stomach.
the stomach, duodenum, pancreas, or hepatobiliary
system also can be fed in the immediate postopera- Nutrient Needs
tive period through these tubes.
Calories
• Small feeding tubes also can be threaded into the
jejunum through a surgically placed gastrostomy tube Provide hospitalized patients with their basal energy
at the time of surgery if the patient is not expected needs. Graphs of the basal energy needs of dogs and
to eat orally for a prolonged period. Patients can be cats over a range of body weights are presented in
W0422-Ch003.qxd 11/10/05 4:41 PM Page 48
Figure 3-17. These graphs were constructed using the Diet Selection
following equation: 97 kcal ¥ kg of body weight0.655 per day.
Use the exponential equation for patients weighing less • Choose an appropriate diet for the disease-related
than 2 kg or more than 50 kg. For animals weighing nutrient modifications required.
between 2 and 50 kg, a linear equation such as • Secondary factors include both size and location of
(30 ¥ kg body weight) + 70 = kcal/day can be used. the feeding tube.
These estimates are conservative and may be lower • Liquid diets specifically formulated for veterinary
than the energy needs of some patients during the use (e.g., CliniCare; Abbott Laboratories) are avail-
course of their disease. They are only initial guidelines, able and may be fed through a tube of any size. To
also intended to avoid adverse consequences of over- maximize success and minimize the risk of clogged
feeding. Provide slightly less food than needed to avoid tubes, feed only liquid diets through tubes smaller
the potential for overfeeding. The estimated energy than 12 Fr. Feed veterinary or commercial canned
needs of a patient can be converted to food needs by pet foods that have been processed in a blender
assuming that many canned foods contain approxi- (with water added as needed) through tubes larger
mately 1 kcal/g and that many dry foods contain than 12 Fr. Tables of veterinary foods are available
approximately 350 kcal/8 oz. If more accurate values in the Manual of Veterinary Dietetics (see “Supplemen-
are needed, consult the pet food’s manufacturer. tal Reading”) and at www.nssvet.org.
Protein Feeding
• In patients with no disease-related limitations on • Provide food or water soon after the patient recovers
protein intake, 7 to 10 g of protein per 100 kcal of from anesthesia.
energy is usually adequate. • Estimate and deliver fluids and nutrients in four to
six feedings over a 24-hour period.
• Patients with advanced liver and kidney disease
require careful use of limited amounts of high-quality • Give small volumes distributed over several meals
protein, probably in the range of 2 g (in dogs) to during the first 24 to 48 hours of feeding to
3 g (in cats) of a high-quality protein per kilogram of avoid overdistention of the stomach, vomiting, or
body weight per day. regurgitation.
• Monitor animals consuming these amounts or less for • In severely ill patients, use slow, constant administra-
signs of protein depletion. tion rates to help minimize incidents of diarrhea
and cramping and to maximize absorption of
Minerals and Vitamins the nutrients. Hang small volumes of liquid diet
(approximately a 12-hour supply) in fluid therapy
In addition to energy and protein, provide vitamin and bags or burettes for gravity-assisted constant-rate infu-
mineral intake near the National Research Council sion to minimize the possibility of “overdosing”
requirements for growth in the absence of a specific patients with the feeding solution during continuous
contraindication. feeding.
2000
1800
1600
Kilocalories per Day
1400
1200
1000
Kilocalories per Day
600
Figure 3-17. Basal energy requirements
500
800 of dogs and cats.
400
600 300
200
400 100
0
200 0 5 10 15 20 25 30
Body Weight - Pounds
0
0
0
0
0
0
0
0
0
0
0
0
10
20
30
40
50
60
70
80
90
0
10
12
13
14
15
16
17
18
19
20
11
• Flush tubes with water before and after each feeding trolled with insulin therapy as needed (see “Glucose
to avoid occlusion with food or mucus. Monitoring”).
• Diarrhea (usually small amounts of soft, pasty feces)
can occur in enterally fed patients. It is generally Calorie and Protein Content
more of a nuisance than a threat to the patient and
Estimate energy needs of PN patients as previously
usually results from rapid gastric emptying caused by
described. Attempt administration of nutrients at rates
overly rapid administration of a bolus meal. Reduce
exceeding resting energy needs only after the initial
the feeding rate and feed diets that contain fiber or
goal has proved tolerable for the animal. Provide 2.5 g
higher concentrations of fat (>50% of total kcal) to
of protein per kilogram of body weight. Restrict protein
delay gastric emptying.
intake to approximately 2 g/kg/day in animals with
severely compromised liver or kidney function.
Parenteral Nutrition
• Parenteral nutrition (PN), or intravenous feeding, Minerals and Vitamin Content
allows the provision of short-term metabolic and The macromineral portion of the solution is provided
immune system support to animals with severe GI by an amino acid-electrolyte solution. Zinc, copper,
disease or pancreatitis. Because PN therapy is rela- manganese, and chromium, as well as water-soluble vit-
tively expensive and is associated with more compli- amins, are routinely added to PN solutions. The essen-
cations than feeding through the GI tract, use enteral tial fatty acids, fat-soluble vitamins, and minerals
feeding whenever the GI tract can tolerate it. PN is necessary for prolonged PN therapy do not appear to
also not indicated when the patient’s prognosis is be necessary for the short-term PN more typically
hopeless. provided to veterinary patients.
• The high osmolality of PN solutions requires the use
of a central venous catheter inserted in the external Apparatus and Delivery
jugular vein or placed in a peripheral catheter and
advanced into a central vein. Proper insertion and • The apparatus required for PN administration
maintenance of the PN catheter is one of the keys to includes the solution, the solution container, an
successful PN therapy. Use aseptic technique when administration set, a 0.22-mm filter, a dedicated
placing the intravenous catheter. If well cared for, central venous catheter, and, preferably, an infusion
central vein catheters may be used for prolonged pump.
periods. Do not remove the catheter unless a specific • Provide PN at a rate intended to meet resting energy
indication for removal exists. needs by the end of the first 24 hours, then advance
to slightly higher rates of intake, if necessary, over the
▼ Key Point Once a catheter is placed and designated next 24 to 48 hours as patient tolerance allows.
for PN therapy, do not use it for other purposes,
such as drawing blood samples, administering Glucose Monitoring
medications, or measuring central venous pres- • During the initiation phase, measure blood glucose
sure. every 4 to 6 hours until stable. Once goals are
reached, monitor the patient as described subse-
Adverse drug-nutrient reactions and clogged quently. At the end of therapy, wean the patient from
catheters are serious potential complications of these the solution over 4 to 24 hours as tolerance permits
practices. by progressively halving of the infusion rate to avoid
hypoglycemia, particularly if insulin has been
Glucose Content infused. If the patient is able to eat, offer food and
• Formulate glucose-based PN solutions based on the record the food intake. As soon as signs of appetite
patient’s estimated nutrient needs. The most com- are observed, decrease the PN administration rate to
monly used PN solution for patients at Ohio State approximately half the previous rate to encourage
University contains 17.5% glucose. Glucose-based PN the animal to begin eating on its own.
solutions are filterable, bacteriostatic because of the
high osmolality, relatively easy to prepare, and rela- ▼ Key Point The most important monitoring parame-
tively inexpensive. On the other hand, their hyper- ter for patients receiving glucose-based PN is
osmolality necessitates central venous access, and blood glucose, which is monitored closely during
thrombophlebitis may result if solutions are infused initiation of therapy.
at high rates into small veins.
• Hyperglycemia, usually less than 600 mg/dl, is also • Treat patients when blood glucose concentrations
more common with glucose-based solutions than with exceed 250 mg/dl with intramuscular administration
lipid-based solutions. This has minimal pathophysio- of 0.25 U of regular insulin per kilogram of body
logic significance but needs to be monitored and con- weight every 4 to 6 hours as necessary. Insulin therapy
W0422-Ch003.qxd 11/10/05 4:41 PM Page 50
is not commonly required for dogs, although and treatment of sepsis. PN-related infections occur
consider it for cats during the first 36 hours to only rarely.
control hyperglycemia. Diabetic animals placed on
PN often require continuous infusions of higher- Returning to Normal Food Intake
than-expected quantities of insulin to control their
blood glucose concentration effectively. When insulin
• In general, discontinue assisted feeding when
patients begin eating a quantity of food that contains
is used, caution must be exercised with regard to the at least half of their calculated daily energy needs.
central venous catheter, which is presumed to be in Ideally, the weaning process should take place grad-
place continually. If insulin is given and then vascu- ually over at least a day or two before the feeding tube
lar access is lost, give a 5% glucose infusion through is removed or PN administration stopped.
a peripheral vein immediately to prevent severe
rebound hypoglycemia.
SUPPLEMENTAL READING
Complications of PN
The most common PN-related complications are Buffington CAT, Holloway C, Abood SK: Manual of Veterinary Dietet-
mechanical, technical, and related to glucose abnor- ics. St. Louis: WB Saunders, 2004.
malities. Use a strict protocol for prevention, diagnosis,
W0422-Ch004.qxd 11/10/05 4:43 PM Page 51
▼ Chapter
4 Radiographic and Ultrasonographic
Techniques
David S. Biller / Laura J. Armbrust
The purpose of the radiograph is to provide a lasting record of (short scale). Lowering the kVp increases the con-
maximum information. The sequence of the major operations trast, and raising the kVp reduces the contrast.
involved in transforming the altered morphology and tissue • To adjust the technique to alter film contrast while
density within a diseased animal into a two-dimensional, maintaining the same radiographic density, consider
black-and-white radiograph and then reaching a diagnosis the following:
is complex and includes the following steps: (1) making a • The mAs and the kVp have to be in balance.
properly exposed and positioned radiograph; (2) recording the • As the mAs increases, the kVp must decrease.
x-ray picture with the assistance of accessory equipment; (3) • As the kVp increases, the mAs must decrease.
reviewing radiographs in proper conditions and in a system- • Doubling radiographic density requires doubling
atic and detailed manner; (4) recognizing lesions—therefore the mAs or increasing the kVp by 10% in the 40- to
[requiring] a knowledge of normal radiographic anatomy 100-kVp range or 15% in the 100-kVp or greater
and its variation by age, species, and breed and the ability range.
to recognize and understand artifacts; and (5) evaluating
radiographic abnormalities with respect to clinical and Recommendations
laboratory findings. • The 300-mA machine may have adjustable mA stations
of 25, 50, 100, 200, and 300 and two (1 and 2 mm or
Dr. Peter Suter
smaller) focal spots.
• An ideal kVp range is 40 to 120 and is adjustable in
1 or 2 kVp per step.
X-RAY MACHINE • A timing device is necessary to control the duration of
an x-ray exposure. Modern x-ray machines have elec-
Milliampere-Second and Kilovolt Peak tronic timers with ranges that can control motion in
• mA (milliampere) ¥ seconds (time) = mAs (milliampere- the patient and prevent blurring. With a timed expo-
second), which affects the degree of blackness sure of 1/120 second, all significant motion is stopped.
(density) of the radiograph with no effect on con- • The line voltage compensator is automatic or manual.
trast. A direct relationship exists between mA and • The tube stand moves along the full length of the table
radiographic density. Time and mA both influence and has an adjustable height from 0 to 60 inches
the number of x-rays produced but have no effect (152 cm). The tube is able to rotate 90 degrees
on the penetrating ability of the beam. To quickly around the vertical axis and 180 degrees around the
check the adequacy of the mAs on a film, hold the horizontal axis.
film up to room light and place a white sheet of paper • The table is 5 to 6 feet in length with a top that has
about 1 inch behind the film. Place a finger between floating motion in four directions.
the film and the paper. If the finger can be readily • The collimator decreases scatter radiation and human
seen through the film in the black area (the most and patient exposure as it increases film quality.
exposed), increase the mAs. Always leave a clear margin of collimation on every
• kVp (kilovolt peak) is the only machine factor that influ- film. The collimator is lighted and has a centering
ences radiographic contrast and has some control mark. A high-quality, dial-adjustable, multileaf lead
over the amount of radiographic density (blackness). shutter collimator is highly recommended.
The contrast can be expressed as being low, which • Filters have the primary function of reducing patient
means that there are many shades of gray (long scale) radiation dose by removing scatter radiation and
between the extremes of black and white. The term increasing (mean beam energy) quality. Most x-ray
high contrast means that there are few shades of gray equipment has inherent filtration equal to 1.5- to
51
W0422-Ch004.qxd 11/10/05 4:43 PM Page 52
2.0-mm aluminum. Increased film quality can be machine. Many of the units use 110 volts. They are
obtained by adding an additional 2.0-mm aluminum reliable, with less downtime than single-phase
filtration. Total filtration must be at least 2.5-mm alu- machines. Their cost, at present, is greater than that
minum. of single-phase machines but most likely will decrease
• Grids consist of a flat plate with a series of lead foil in the future.
strips separated by transparent spacers. They are • For a list of x-ray machine manufacturers, see Table
made in various sizes and improve the diagnostic 4-1.
quality of radiographs by absorbing the greater part
of the scatter radiation. Position grids between the
patient and the cassette, usually under the table. Use ACCESSORY RADIOGRAPHIC EQUIPMENT
only for body parts thicker than 10 cm. The recipro-
cating grid (Potter-Bucky diaphragm) includes a Intensifying Screens
mechanism that moves the grid during exposure to The screen is a suspension of phosphor crystals in a
eliminate grid lines from the radiograph. This grid is binder. The phosphor in the screen converts x-ray
optional equipment but recommended for the best- photons into visible light, to which the film is more sen-
quality radiographs. sitive. A latent image is created by exposure of the film
• Grids can be classified in three ways: the lead to this light. This technique reduces x-ray exposure to
content (g/cm2), the number of lines per inch, and the patient by at least 10 times and the time of x-ray
the ratio of lead strip height to the space between exposure, thus decreasing the chance of blurring.
the lead strips. In general, high-ratio grids absorb
scatter better but are more expensive. More lines • Screen speed depends on the thickness of the phos-
per inch give better quality, because the lead strips phor layer, the size of phosphor crystals, and the effi-
are narrower and therefore lines become less ciency of phosphor crystals at absorbing x-rays and
prominent; however, they cost more. The most converting them to light.
common grid is an 8:1 with 103 lines per inch. • Screen classification varies because each company
• The higher the grid ratio, the more critical the x-ray has a slightly different system for labeling screen
tube alignment. Always stay within the focal zone of speed. Resolution ability of the screen is inversely
the grid. This is usually written on the grid and is 36 related to speed. Increased speed gives decreased res-
to 42 inches (90–105 cm) in most instances. olution. Have a technique chart available for each
• Exposure switches include the two-position exposure screen speed. Par speed is the starting point for com-
switch on the console and the two-position exposure parison of screens. High speed has a speed 2 times
foot switch, with a cord of sufficient length. that of par speed. Ultraspeed is 4 times par speed.
• High-frequency x-ray machines have a few advantages High detail speed is half that of par speed.
over single-phase x-ray machines. A 150-mA high- • Types of Screens
frequency generator can produce a quantity of • Calcium tungstate screens reduce the amount of
x-rays equal to that of a 300-mA, single-phase x-ray radiation necessary to expose film by 10 times com-
pared with film exposed without a screen. They are • Clean screens with the product recommended by the
also less expensive than rare-earth screens. Calcium manufacturer on a regular schedule (monthly) and
tungstate emits a broad spectrum of light in the whenever debris is noted on the radiographs.
ultraviolet and blue range.
• Rare-earth screens are more expensive than Film
calcium tungstate screens. The light emitted is in Radiographic film provides a permanent record con-
the ultraviolet, green, or blue range. The major taining the maximum amount of diagnostic information.
advantage of rare-earth over calcium tungstate
screens is that rare-earth screens are fast, because • Film is made of a light-sensitive emulsion, composed
of a more efficient production of light. Therefore, of gelatin and silver halide with other ingredients
they decrease the production of scatter, the expo- attached to a plastic (polyester) base. The silver
sure time, the radiation dose, the chance of motion halides are sensitive to light and change when exposed
and subsequent blurring, and the wear and tear on to light to produce a latent image. The process of
the x-ray tube. developing changes silver ions into black silver, thus
• System speed is the speed of film and screen in com- producing the radiographic image. Fixer removes all
bination. It is not an additive system. A very low unexposed silver from the film. The emulsion may be
system speed results when screens and films with dif- attached to one or both sides of the base. X-ray film
ferent color spectrum sensitivities are put together. may be most sensitive to direct x-ray exposure (non-
Ask the film dealer what system speed you have with screen film) or to blue, green, or ultraviolet light.
your particular screens and film. The higher the • Films vary in their contrast. Some films appear more
system speed number, the more sensitive the system black and white after exposure and development. Use
and the less radiation necessary to make an exposure. the film that is recommended by your screen manu-
System speeds can vary from 50 to 3200 and higher. facturer to match the spectrum of light produced by
The higher the system speed number, the less radia- your screens. Choose a film that results in the con-
tion to the patient and to personnel within the room; trast range most pleasing to you. Use a film that gives
however, the lower the system speed number, the you a system speed that results in quality radiographs.
better the resolution qualities. When you know the Make sure to match film, screens, and processing
system speed, changing the technique chart is chemicals.
simpler. If the system speed doubles, change the mAs • Film must be sensitive to the type of light emitted by
on the technique chart by half. If the system speed the screens in use. Film speed determines the amount
decreases by 50%, double the mAs on the technique of light required to produce an image on the radi-
chart. ograph. Fast film has large crystals (silver halide),
• Exposure time requires less exposure, and produces a grainy image.
Slow film has small crystals, requires greater expo-
sure, and produces a sharper image.
▼ Key Point Always use the shortest exposure times • Screen film is manufactured with crystals that are sen-
possible to eliminate blurring. sitive to fluorescent light. Nonscreen film is a direct
exposure–type film and is manufactured to be sensi-
• For thoracic radiographs, exposure times of 1/60 tive to x-rays. Nonscreen film requires 10 to 25 times
second or shorter stop the effects of respiratory and more radiation than screen film.
heart motion. • Film is available in both metric and nonmetric mea-
• For abdominal radiographs, employ exposure surements. The most common sizes used in small
times of 1/40 second or shorter to eliminate gas- animal practice are 8 ¥ 10 inches, 10 ¥ 12 inches, and
trointestinal motion. 14 ¥ 17 inches.
• For extremity radiographs, exposure times of 1/20 • X-ray film is sensitive not only to light and x-ray
second or shorter eliminate the effects of patient photons but also to humidity, chemicals, and physi-
motion. cal stress. Film is stored on end to reduce pressure on
• Rare-earth screens have a system speed that allows the the face of the film. High humidity causes film
shortest exposure times possible to eliminate motion fogging, and low humidity causes film static; there-
problems and to lower radiation exposure to patient fore, between 30% and 40% humidity is appropriate
and personnel. In general, when using a 300-mA for film storage. Storage temperature should not
machine and a 400 to 800 speed system, with an 8:1 exceed 50°F to 70°F (10°C to 21.1°C). Store the film
grid, good-quality radiographs are attainable even for away from developing chemicals and ionizing radia-
large-breed dogs. In a feline practice, a slower system, tion. Do not put pressure on the film when loading
such as a 100 to 250 speed system, provides excellent or unloading film.
quality. As the crystal size gets larger, the system gets • Film and screen companies are provided in Table
faster but resolution is reduced. 4-2.
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does not tell you if all mA stations are accurate, but If your mA stations and kVp settings are working
it does tell you if a particular station has a problem. correctly, each exposure has the same density but a dif-
ferent contrast range. Remember to employ density-
• A digital, electronic mA-checking device is the most changing factors when necessary.
accurate way to compare your mA stations.
Exposure Timer Check (Single-Phase Machine)
Kilovolt Peak Check
Use a spinning-top test tool. It can be purchased from
the same company as the machine (see Table 4-1) or
▼ Key Point The only accurate way to check the kVp
from an accessory company (see Table 4-3). This tool
is the Wisconsin test cassette ($1300; see Table
is inexpensive ($50) and easy to use. It is a flat metal
4-3 for sources).
spinning top with a hole in one side. The top is set
on a loaded cassette and spun. Take an exposure at
1
• The Wisconsin test cassette has many kVp settings /120 second. Move the top to another corner of the film,
listed on the front of the cassette. Under each of spin again, and expose at 1/60 second. This maneuver is
these settings is a certain amount of material to atten- repeated at 1/40 and 1/30 second. At 1/120 second, only one
uate the beam. After exposure and processing, this dot should be seen; at 1/60, two dots; at 1/40, three dots;
film provides information to determine if the kVp set- and at 1/30, four dots. If more or less dots are on the film
tings are accurate. than expected, the timer is not accurate.
• Another less accurate way to obtain a general check
of kVp accuracy is to vary mAs and kVp. Go through Line Voltage
all kVp settings, employing density-changing factors Line voltage is the amount of current coming into the
to keep the densities the same throughout all these machine. The amount of current may vary, depending
exposures. on electrical wiring, consistency of voltage in the area,
Example and usage of current on the same circuit in the partic-
100 mAs at 50 kVp 3.1 mAs at 81 kVp ular practice. Almost all machines used for small
50 mAs at 55 kVp 1.5 mAs at 90 kVp animals have a line voltage-check device. Some have a
25 mAs at 61 kVp 0.8 mAs at 99 kVp meter and a dial to adjust line voltage and do not permit
12.5 mAs at 67 kVp 0.4 mAs at 108 kVp exposure until the voltage is manually adjusted. Other
6.2 mAs at 74 kVp 0.2 mAs at 124 kVp machines have an automatic line voltage adjustment.
W0422-Ch004.qxd 11/10/05 4:43 PM Page 56
Almost all equipment in small animal practice uses 120 animal’s file number. Label the radiograph with right
volts (i.e., right out of the socket). or left, dorsoventral or ventrodorsal (DV/VD), a time
marker on contrast studies, and a Mitchell marker
when a horizontal beam is used. Basic types of per-
FILM PROCESSING manent marking systems are available:
• Lead letters and numbers in a holder with the hos-
Manual Processing pital or veterinarian’s name, placed on the cassette
during exposure.
Film developing is a chemical process and therefore
• Radiopaque marking tape (lead-impregnated
depends on both time and temperature.
tape). Information may be written on the tape, and
the tape is placed on the cassette before exposure.
Advantages and Disadvantages
• A darkroom printer transfers data from a card to
• Advantages the corner of the x-ray film that was shielded from
• Less expensive setup costs than those of an auto- radiation during exposure. This system requires
matic processor. cassettes with special windows. The film is removed
• No special electrical or structural changes are nec- from the cassette, and the corner of the film where
essary for the darkroom. it was blocked from light exposure is imprinted by
• Disadvantages exposing the patient information on a 5 ¥ 7-inch
• Valuable technician time to develop films and card onto the film.
maintain chemical baths (i.e., increased labor
costs). Silver Recovery
• Quality is not consistent, due to human error, com-
Recover silver from fixer solutions by either manual
pared with automatic processors.
or automatic systems. Fixer solutions may be sold to
• Longer time to prepare diagnostic films compared
companies for silver recovery. Alternatively, you may
with automatic processors.
purchase a system (metallic replacement process, elec-
trolytic recovery, or chemical precipitation) for silver
Accessories
recovery in your practice. Exposed developed and unde-
• Developing tanks veloped film may also be sold for silver recovery. Usually,
• Two stirring paddles the supplier of the x-ray films or processing solutions
• Two thermometers can be consulted to determine if silver recovery is fea-
• Film developing hangers of different sizes sible and who to contact.
• Chemicals
• Adjustable mixing valve for measuring water Procedure for Manual Film Processing
temperature
• Timer • Check temperatures, turn off room lights, use safe-
lights, and agitate (mix) solutions well.
• Dust-free drying cabinet or area
• Place the film on development hangers, making sure
all four corners are attached.
Darkroom Safelight
• Set and start time depending on the temperature in
Darkroom safelights must produce enough illumina- the developing tank.
tion in the darkroom so that a person can see to process • Place the hanger with the film into the developing
radiographic film (load and unload cassettes) without tank. Rap hard against the tank wall to dislodge air
unwanted density (fog) to the film. Safelights utilize a bubbles. Agitate by pulling film out of the developer,
wavelength of light different from that to which the film and let the developer drain to one lower corner.
is sensitive. A Wratten 6B filter is adequate for blue- Return film to the developer. Repeat agitation every
sensitive film. A GBX-2 filter is employed with green- minute. Manufacturers recommend a specific tem-
sensitive or both green- and blue-sensitive films. Usually, perature for the developed solution that they
15-watt bulbs are used with safelights. The safelight is produce, usually 68°F (20°C). Adjust for change
about 4 feet from the film-handling area. No system is in temperature (increased temperature, decreased
100% safe; therefore, expose the film no longer than time, and vice versa). The chemical manufacturer
necessary. can provide a time-temperature development chart.
• At the end of the developing time, remove the hanger • Good quality control
from the developer and drain over the rinse tank. • Smaller darkroom necessary
Agitate film in rinse water for 30 seconds. • Disadvantages
• Place the hanger with film in fixer at the end of the • Machine is expensive.
developing time. • Darkroom structural changes are expensive.
• Set the timer. Fixer time equals twice the develop- • Needs daily and weekly maintenance.
ment time. • Repairs can be expensive.
• Agitate film every 2 to 3 minutes while in the fixer. • Equipment includes processor, safelight, water for
• At the end of fixation time, remove film from fixer processing, chemicals, sponges to clean rollers of
and drain. processor, and processor cleaning solution.
• Place the hanger in wash water at the end of fixer • Tabletop film processors are easy to install (no special
time. plumbing or wiring). Different models process films
• Agitate after 2 to 3 minutes. as fast as 90 seconds or as long as 31/2 minutes. Most
• Wash for 15 to 30 minutes, depending on water flow are made for easy care and cleaning. They are rela-
and temperature in wash tank. tively inexpensive (from $3000 to $7000).
• Provide no less than four water changes per hour in • Large, hard-wired, 90-second film processors need
the wash tank. special plumbing and electrical wiring, but they
• At the end of the wash, remove from water and drain. are able to process many films. They need special
• Place film in a drier cabinet or hang up to dry. cleaning and repairs and are expensive ($15,000–
$25,000).
Automatic Processing • The more a processor is used, the fewer problems it
will have. It is made to be used on a 24-hour basis.
• Processors are a good investment for most veterinary Chemical buildup on rollers can cause film artifacts.
practices. New, small, tabletop models are priced from
$3500. Most of these processors develop an excellent Rollers age and crack if oxidized chemicals are left
quality film in 90 to 210 seconds. They can use cold on them.
water for processing; therefore, no special needs exist • Clean processors often.
for plumbing. They are also easy to maintain. • All processors need cleaning daily when not in use.
Take out the rollers and wash them down with a
sponge and water. Dry and replace the rollers.
▼ Key Point If your small animal practice is process-
ing 7 to 10 films a day, consider an automatic
Clean the chemical tanks. Once a month, clean
processor.
with processor cleaning solution. Cleaning a
processor takes about 15 minutes a day but saves in
wasted film and time.
• Advantages
• Highly repeatable results • Consider purchasing a processor with a standby
• Short waiting time for diagnostic films mechanism. This function helps conserve water,
• Ability to process large quantity of films quickly and energy, and chemicals.
accurately • Automatic processor companies are listed in Table
4-4.
Figure 4-1. Floor plan for a darkroom using manual (wet tank)
processing.
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3. Fill out the chart, according to the kVp per cm • Need to have computers and a software package to
increments. integrate with medical records
4. Take films at three different mAs values (0.8, 1.6, and
3.2 with rare earth; 5, 10, and 20 with calcium
tungstate). Continue selecting the mAs values until
an appropriate exposure has been made. Your table-
DIGITAL RADIOGRAPHY
top extremity chart is now complete. Employ this
Direct digital radiography (DR) uses specialized x-ray
chart for all extremities distal to and including the
equipment that has a digital imaging sensor. Once the
elbow and stifle.
image is transferred to the computer system, image
analysis and storage are similar to those previously listed
Nonscreen Film Technique Chart for CR.
• For the nonscreen film technique chart, the mAs in
your technique chart may vary up or down from the Advantages
example shown in Figure 4-5.
• A digital image is generated (these can easily be sent
to specialists if needed).
COMPUTED RADIOGRAPHY • Excellent image quality.
• Film, processor, and darkroom can be eliminated.
Computed radiography (CR) is an indirect digital
imaging technology in which a plate (which looks Disadvantages
similar to a cassette but is filmless) is used to record the • Currently more expensive than CR systems (cannot
image. A reader is required to extract the data, which be used with existing x-ray equipment).
is converted to a digital image and viewed on a com- • Few current systems allow horizontal beam
puter screen. CR utilizes standard x-ray machines. Com- radiography.
ponents of CR include both the hardware described • Need to have computers and a software package to
previously and the software (for display, storage, and integrate with medical records.
archiving). New technique charts must be developed
when switching from a traditional film-screen system to
CR. CR software allows image manipulation that can
adjust for exposure and contrast. Images can also be POSITIONING AND TECHNIQUE
drawn, and measurements can be taken.
Measuring for Radiographic Studies
▼ Key Point The ability of the viewer to appreciate • Measure all animals standing.
the image quality provided by CR depends on the • Measurements for the thorax, abdomen, and thora-
quality of the computer monitor. columbar spine are all taken at the same location
on the animal. Observe the animal from above,
Advantages taking the lateral measurement from the widest point
across the ribs. The DV/VD measurement is made
• A digital image is generated (these can easily be sent at the same point. The widest point is usually at the
to specialists if needed). thoracolumbar junction.
• Existing radiography equipment can be used.
• Measure the pelvis across the wings of the ilium. This
• Excellent image quality. is a very accessible area to measure, giving highly
• Initially less expensive than digital radiography. repeatable results. The same measurement is used for
• Film, processor, and darkroom can be eliminated. both the lateral and the VD.
Disadvantages • Measure extremities at the widest point.
• Make sure all personnel measure all areas at the same
• Still have to use an imaging plate point; otherwise, the technique will vary from one
• Need to purchase new plates and a reader study to the next.
Abdomen
Withhold food for at least 12 hours for optimal abdom-
inal radiographs. Encourage the animal to defecate
and urinate before being radiographed. Radiographs
include the diaphragm to the coxofemoral joints. For
large-breed dogs, this may require two 14 ¥ 17-inch films
for both the lateral and DV/VD views. Use a 1/40-second
or less exposure time to reduce motion; use a kVp in
the 70 to 90 range for maximum latitude. Figure 4-7. Positioning for dorsoventral or ventrodorsal thoracic
radiograph.
Sternum
Figure 4-6. Positioning for lateral thoracic radiograph. Figure 4-8. Positioning for lateral abdominal radiograph.
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Mediolateral (ML)
The animal is in lateral recumbency, with the down side
to be radiographed. Extend the leg about 45 degrees
from the vertebral column. Flex the opposite leg and
place it over the thorax. Pull the head and neck back so
that the cervical spine and trachea are not overlapping
the joint space.
Humerus
Caudocranial
The animal is in dorsal recumbency, with the legs
extended. Rotate the sternum away from the side being
radiographed. Center the x-ray beam at the mid-
humerus. The radiograph includes both the shoulder
and the elbow joints.
Mediolateral
Figure 4-9. Positioning for ventrodorsal abdominal radiograph. Place the animal in a position similar to that for the ML
view of the scapula and the shoulder joint. Center
the x-ray beam at the mid-humerus. The radiograph
includes both the shoulder and the elbow joints.
structures. The spoon can separate the colon from
the urinary bladder to demonstrate the uterus, for
example. Remember to reduce the kVp, because you Elbow Joint
are decreasing the thickness of the tissue being Craniocaudal
radiographed.
The animal is in sternal recumbency, with the elbow
Extremities joint in full extension. If the elbow cannot be com-
pletely extended, angle the x-ray beam 10 degrees to 20
For radiography of the extremities, the animal needs a degrees, craniodistal to caudoproximal.
clean, dry haircoat. Remove splints and bandages if pos-
sible. Place the limb to be radiographed closest to the Mediolateral
film. Employ a high-mAs, low-kVp (50–70) technique to
produce high-contrast radiographs. Collimate closely. The animal is in lateral recumbency, with the elbow
Use tabletop (nongrid) techniques on parts less than slightly flexed. Pull the opposite leg caudally. Center the
10 cm thick. Administer anesthesia or tranquilizers beam on the palpable medial epicondyle. The elbow is
whenever needed. Use positioning devices. Measure the in extreme flexion if identification of the anconeal
part to be radiographed over the thickest area. If the process is of importance.
part thickness varies greatly, two exposures (e.g., lateral
pelvis and femur) may be necessary. In the case of mod- Craniolateral-Caudomedial Oblique
erate variation, choose the greater measurement to set This aids in imaging of the lateral aspect of the medial
the exposure and “hot light” the slightly overexposed coronoid.
areas when reading the film. When long bones are
being radiographed, include the joints proximal and Antebrachium
distal.
Craniocaudal
▼ Key Point Radiograph the opposite limb for com- Place the animal in sternal recumbency. Extend the leg
parison to determine normal from abnormal. and position the elbow for a true craniocaudal projec-
tion. The film includes both elbow and carpus.
Scapula and Shoulder Joint
Caudocranial Mediolateral
The animal is in dorsal recumbency, with the sternum The animal is in lateral recumbency, with the leg in
rotated away from the side being radiographed. The leg the neutral position. Move the opposite limb caudally;
is fully extended. Center the x-ray beam at the mid- center the beam on the midshaft radius. It may be easier
scapula. For the shoulder joint, center the beam at the to obtain the radiograph if the elbow is slightly flexed.
point of flexion for the joint. Include the elbow and carpal joint on the film.
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Oblique Views • Ideal spinal survey studies are listed in Table 4-5.
Dorsolateral to palmar medial oblique and dorsomedial Cervical Spine
to palmar lateral oblique. Position the animal in dorsal
Measure at the caudal cervical spine for all views.
recumbency, then rotate 45 degrees in each direction
(lateral and medial) for the two oblique views.
Lateral View
Metatarsus and Digits For radiography, the spine must be parallel to the cas-
sette. In many cases, support the center of the neck
Position the animal as for the metacarpus and digits of with radiolucent positioning blocks (sponges). Place
the forelimbs. the head in a normal position (neither flexed nor
extended) relative to the neck. The head must be lateral
Spinal Positioning and Technique: because it controls the position of the proximal neck.
General Principles Pull the front legs back over the thorax to allow thin-
ning of the tissues over the caudal neck. The thorax
• Materials needed include sandbags, foam wedges, must be in the accurate lateral position because it con-
markers (right and left), and a Plexiglas trough to aid
trols the position of the caudal neck. Extending the
in positioning the animal without anyone in the room.
entire neck may help open up the caudal cervical disc
• Use general anesthesia or heavy sedation in all but
spaces. Include both occipital and cervicothoracic areas
the most subdued animals. Exceptions are suspected
on the radiograph.
fracture, congenital malformation with instability,
and other diseases in which the animal’s condition or
Ventrodorsal View
protective mechanisms that have maintained stability
will be compromised. The spine is not parallel to the cassette because of the
• Short-scale, high-contrast (high-mAs, low-kVp) tech- anatomic variation between the head and the thorax.
nique provides good detail. Use a grid and collimate The spine inclines away from the cassette at the thorax.
to include only the spine. Place the head in normal position (hard palate and
• At least two radiographic views of the area of interest dorsal nose at a 60 degree angle to the cassette). If the
are needed: lateral and VD. head is in a true VD position, an undesirable arch is pro-
Thoracolumbar Spine
Lateral View
The midplane of the entire body must be parallel to the
cassette. Most animals must have the sternum elevated
for good lateral views of the spine. Pull the front legs
cranially and the rear legs caudally to straighten the Nonscreen
spine. Extending the entire neck may help open up the packet
cranial thoracic disc spaces.
Figure 4-10. Positioning for dorsoventral occlusal (intraoral)
Ventrodorsal View radiograph of the skull.
The midplane of the entire spine must be perpendicu-
lar to the cassette. When the dorsal spines are promi-
nent, as in thin animals, radiolucent positioning blocks
may be beneficial. The body may be held by placing
tension on the legs.
Skull Radiography
• General anesthesia or deep tranquilization of the
patient is essential, if not specifically contraindicated
by the patient’s physical condition, to obtain radio-
graphs of good diagnostic quality.
Routine Skull
Lateral and DV views are used.
Figure 4-13. Positioning for the open-mouth lateral oblique Figure 4-15. Positioning for the open-mouth lateral oblique
(20∞ to 30∞) view of the frontal sinuses. (20∞ to 30∞) view of the mandible.
Central
Dental Arches beam
Mandible
DV, lateral, and lateral oblique (right and left).
Maxilla
DV occlusal, VD open mouth, lateral, and lateral
oblique (right and left).
• Use the technique described previously for catheter taken if needed. Follow-up radiographs may be
placement. helpful if a bolus of contrast material is retained
• Administer 3 to 5 ml/kg of positive-contrast medium. within the esophagus.
Complications Complications
• Fatal air embolism (rare cases). An increased risk • Aspiration.
exists with ulcerative or erosive cystitis. Carbon • Leakage of barium into mediastinum. Low osmolal-
dioxide is more soluble than room air in blood and ity, nonionic iodinated contrast medium (iohexol)
thus less likely to cause this problem. Air embolism may be indicated if perforation is suspected.
occurs immediately after the administration of nega-
tive-contrast medium. Place the animal in left lateral Gastrography
recumbency, and lower the head to maintain normal
blood circulation through the heart. The air is ▼ Key Point Before contrast studies of the gastroin-
trapped in the right ventricle. testinal tract, discontinue all drugs that may influ-
• Iatrogenic trauma (hematuria or rupture) and infec- ence motility.
tion (bacterial contamination or cystitis).
Technique
Urethrography
1. Fast patient 12 to 24 hours before the study.
• Retrograde positive-contrast study of the urethra 2. Give cleansing enema the night before and 3 to 4
using iodine. hours before the study, especially if complete upper
• Equipment includes catheter (Foley, metal, male gastrointestinal study is to be done.
dog), sterile gel, lidocaine, and water-soluble iodi- 3. Take plain films before the study. Then pass a
nated contrast medium. stomach tube for administration of contrast medium.
4. Obtain negative-contrast gastrogram (pneumogas-
Technique trogram) by administering 6 to 16 ml of room air
1. Evacuate the colon with an enema, if needed, before per kilogram of body weight using a stomach tube.
the study; take scout films before the study to evalu- Immediately take four views (right and left lateral,
ate technique and preparation. VD, and DV). This is often valuable in the diagnosis
2. Pass a urinary catheter into the distal urethra. Inflate of radiolucent foreign bodies.
the balloon if a Foley catheter is used (in distal 5. Obtain positive-contrast gastrogram using barium
urethra for female dogs or cats and proximal to the (suspension, 30% weight-to-volume) at a dose of 6
os penis in male dogs when possible). to 12 ml/kg (see Table 4-6). Administer through a
3. Administer 2 to 5 ml of 2% lidocaine before inject- stomach tube, and take films immediately (right and
ing contrast material to reduce urethral spasm. left lateral, VD, and DV). Use this procedure to doc-
4. Position male dogs with their legs drawn cranially. ument gastric displacement, certain gastric foreign
5. Administer 10 to 20 ml of contrast medium for male bodies, and gastric perforation. Barium begins
dogs and 5 to 10 ml for female dogs and cats. Inject leaving the stomach within 5 to 15 minutes. The
as a bolus and take radiographs during the last few stomach is emptied by 30 to 60 minutes in cats and
milliliters of injection. 1 to 2 hours in dogs.
6. A lateral radiograph may be sufficient, but subse- 6. A double-contrast gastrogram can be done as a
quent lateral and VD oblique views may be helpful. separate study or during an upper gastrointestinal
study. Give barium, 60% weight-to-volume at a dose
Complications of 1.5 to 3 ml/kg, and insufflate with room air at
10 ml/kg. Immediately take DV, VD, and right and
• Iatrogenic trauma and bacterial contamination left lateral films. This study is indicated in cases of
suspected gastric wall and mucosal lesions.
Esophagography
Technique Upper Gastrointestinal Study
1. Take survey cervical and thoracic radiographs. • Preparation requires a 12- to 24-hour fast and an
2. Position the animal in lateral recumbency. enema the night before and 3 to 4 hours before the
3. Administer contrast medium (see Table 4-6) (barium study.
sulfate suspension, Esophotrast, barium burger) • Use barium suspension, 30% to 60% weight-to-
slowly into the buccal pouch. volume, for routine studies (see Table 4-6). Dose is 8
4. Dose is variable (5–20 ml); use enough to induce to 16 ml/kg.
swallowing and coat esophagus. • Use iodinated contrast (ionic and nonionic) agents
5. Obtain radiographs following swallows. The lateral (see Table 4-6) with suspected perforation for quick
view is most informative; additional views can be determination of small intestine patency and location
W0422-Ch004.qxd 11/10/05 4:43 PM Page 72
Complications
• Seizures (incidence is reduced with new contrast RADIATION SAFETY
agents, e.g., iohexol)
• Exacerbation of clinical signs
Basic Radiation Safety
• Hyperesthesia The objectives of radiation safety are to obtain the
• Apnea during injection maximum amount of diagnostic information while
• Epidural injection will not negatively affect the health keeping the radiation exposure to personnel and
of the animal but negatively affects the quality of the animals to a minimum.
myelogram.
• Central canal filling occurs when the needle is placed ▼ Key Point The responsibility for radiation safety
through the center of the cord. It usually appears thin lies solely with the owners of the practice.
on radiograph and sharply defined in the normal
animal. Radiation protection in veterinary medicine is the
subject of the National Council on Radiation Protection
Interpretation and Measurements (NCRP) Report No. 36, titled Radi-
ation Protection in Veterinary Medicine. This report specif-
Lesions are divided into three categories (Fig. 4-21): ically outlines when radiation protection surveys are
1. Extradural, characterized by made. The report makes recommendations concerning
a. Displacement of the spinal cord tube housing, aluminum filtration, collimation types,
b. Narrowing or compression of the subarachnoid and centering devices. A special section discusses radi-
space ography with portable and mobile diagnostic equip-
c. Deviation of the subarachnoid space ment. All practices need a copy of this report. Other
d. Spinal cord may appear wide on opposite view NCRP reports that may be pertinent are No. 116, which
2. Intradural extramedullary, characterized by discusses protection devices and provides recommen-
a. Filling defect within the subarachnoid space dations for the maximum permissible dose (MPD); No.
(“golf tee” sign) 107, which explains the concept of ALARA (as low as
b. Possibly associated extradural or intramedullary reasonably achievable) for medical and dental person-
component nel; and No. 35, which discusses dental applications of
3. Intramedullary, characterized by diagnostic radiology.
a. Spinal cord widening in all views The MPD was established to keep the radiation expo-
sure of workers below a level at which adverse effects
might be observed during a lifetime and to minimize
the incidence of genetic effects in the entire popula-
tion. The MPD does not apply to animal patients, to
radiation emitted from natural background sources,
or to radiation therapy. The actual risk to an individual
Extradural Intradural Intramedullary exposed to MPD is small, but the risk is directly pro-
Extramedullary portional to the received dose. Therefore, radiation
exposure must be kept as low as possible. Radiation
can cause both tissue and genetic damage. The effects
of radiation can be demonstrated in a short time, or
they can be cumulative and not observed for a long
time.
Federal regulations regarding use of x-ray equipment
and radiation protection are published in the Code of
Lateral
Federal Regulations, available at university and public
libraries. Individual states publish radiation control
regulations that are reprinted from the state codes.
These regulations include information concerning
the licensing of x-ray machines, the licensing fee, and
the procedure to be followed in obtaining licensing.
The goal in diagnostic radiology is to obtain radi-
ographs with minimum exposure to both patient and
Ventrodorsal
personnel.
• However you choose to evaluate films, be consistent machines, but all produce a thin fan of x-rays that are
from case to case. directed through the patient and strike a row of radia-
• Knowledge of normal radiographic anatomy is tion detectors. The amount of radiation going through
essential. a specific part of the patient, and therefore reaching the
detector, is related to the density of the body part. Based
Radiographic Signs on numerous views of each part and the image density
of different areas, a computer is used with various algo-
• Radiopacity: Various radiographic opacities are caused rithms to form a cross-sectional, gray-scale image.
by the differential absorption of x-rays. The opacity Similar to radiographs, when looking at a CT: bone
of surrounding material also influences the observed = white, air = black, fat = dark gray, and soft tissues/fluid
opacity of a structure. The five radiopacities in = various shades of gray. Once the image has been
decreasing order (white to black) are those of metal, acquired, post-processing parameters can be adjusted to
bone, soft tissue (fluid), fat, and gas. Metal is the only optimize viewing of certain areas (i.e., bone, soft tissue,
one that is not a biologic opacity. lung, and brain). Thus, the term soft-tissue or bone
• Geometry: Size, shape, position, margination, and window is commonly used when evaluating CT images.
number. Often, the same study is viewed in multiple windows for
• Function: Excretion (intravenous urography), motility a complete evaluation. For example, a CT of the thorax
(upper gastrointestinal), patency, and integrity. Eval- would need to be viewed in a soft-tissue window (for the
uation of function often requires contrast medium mediastinum), a lung window (for the pulmonary
and multiple films. parenchyma), and a bone window (for the ribs and
spine). The adjustment in a bone versus a soft-tissue
window is made by changing the window width and
COMPUTED TOMOGRAPHY window level. The window width defines how many
shades of gray are seen over a given density of tissue
Computed tomography (CT) is a cross-sectional (providing a long or short scale of contrast). The
imaging technique that allows identification of struc- window level is the midpoint of the window width.
tures without the superimposition present with radi- CT studies are normally performed with slices in the
ographs. Like radiographs, CT uses x-rays to produce transverse (axial) plane through the area of interest.
an image. There are many different types of CT This information can then be used to reformat the area
W0422-Ch004.qxd 11/10/05 4:43 PM Page 77
of interest into a different plane (sagittal, coronal, or termed the Tesla. Low-field magnets are less than 0.5
oblique), therefore maximizing interpretation. Tesla, mid-field magnets are 0.5 to 1 Tesla, and high-
Common areas to use CT in veterinary medicine are field magnets are more than 1 Tesla. Although all types
the nasal cavity, middle ears, skull (bone changes or of magnets are utilized, the cost of the machine and the
trauma), skeletal (elbows and spine), thorax, abdomen, time needed to acquire the image depend on field
and areas of neoplasia (for surgical or radiation plan- strength. In general, high-field magnets are more
ning). Magnetic resonance imaging (MRI) is consid- expensive, but images are acquired more quickly than
ered best for soft-tissue structures, particularly the brain from low-field units.
and spinal cord. Images are acquired using different pulse sequences
(imaging acquisition parameters). These different
Advantages sequences are used because the signal intensity (appear-
ance of the image) will vary depending on primarily the
• The cross-sectional image is provided without water, fat, and mineral content of the area being
superimposition of structures, allowing more
accurate detection and assessment of the extent imaged. Typical sequences are termed T1-weighted, T2-
of disease. weighted, and proton density. There are a variety of fat
saturation techniques and variations in the sequences
• CT is considered better than MRI for evaluation of
that are also utilized. Contrast material is generally
bone abnormalities (MRI is best for soft tissue).
given to patients and the T1-weighted sequences are
Disadvantages repeated. The contrast material is a ferromagnetic sub-
stance that enhances signal intensity on T1-weighted
• Higher cost compared with radiographs (less expen- sequences.
sive than MRI).
• The animal must not move during the CT study, so Advantage
the patient must undergo general anesthesia in most
cases. • MRI is useful for areas that cannot be evaluated by
more conventional methods (radiographs or ultra-
sound) such as the central nervous system, particu-
larly the brain.
MAGNETIC RESONANCE IMAGING
Disadvantage
MRI is a cross-sectional imaging technique that is con-
sidered excellent for imaging soft tissues. CT is still con- • Limited access
sidered the best cross-sectional imaging modality when • High cost
assessment of bone is required. MRI utilizes a magnetic
field, radiofrequency (RF) waves, and the hydrogen
protons in the patient for creation of the images. The
equipment consists of a magnet, receiving coils, and ULTRASOUND
hardware and software of the control station.
Ultrasound is rapidly becoming an accepted imaging
MRI technology utilizes a magnet to polarize hydro-
modality in small animal practice. New and used equip-
gen atoms in the tissues and monitor the summation of
ment is available at reasonable prices, and usefulness
the spinning energies within living cells. When a patient
has increased to include ophthalmic, cardiac, abdomi-
is put in a strong magnet, some of the atoms become
nal, and reproductive disease diagnosis. It is a safe, non-
aligned with the magnetic field. If an RF pulse is sent
invasive diagnostic technique that provides information
into the patient, the vector direction of the hydrogen
about the internal architecture of organs within the
protons can be changed. As the atoms realign them-
abdomen and thorax. Functional information can also
selves with the magnetic field, they give off an RF pulse
be obtained with echocardiography. Ultrasound is not
that can be detected by the receiver coil. The amount
meant to replace diagnostic radiography but to com-
of RF signal given off and the time at which it is released
plement it. Ultrasound is operator dependent. The
are characteristic for certain tissues. This information is
quality of the image and the information gained are
again processed by a computer to provide a cross-sec-
directly related to the ability of the person doing the
tional image with various shades of gray. The shade of
study.
gray of a certain tissue depends on the acquisition para-
meters. In other words, fluid may be dark gray in one
acquisition and bright white in a different acquisition.
Equipment
Cortical bone and air will always be black with MRI. The major components of the diagnostic ultrasound
The images can be acquired in any plane without imaging system are pulser, transducer, receiver,
reformatting. memory, and display. Electrical pulses are produced by
There are different types of magnets, ranging from the pulser, and these drive the transducer. The trans-
low- to mid- to high-field units. The unit strength is ducer produces ultrasound pulses for each electrical
W0422-Ch004.qxd 11/10/05 4:43 PM Page 78
pulse it receives. The transducer also produces electri- • Mechanical: In a mechanical (sector) scanner, the
cal pulses for each ultrasound pulse (reflection) it sound wave is focused a certain distance from the
receives from tissues. The electrical pulses go to the transducer (focal point). The sound wave is within
receiver, where they are converted to information that focus for some distance on both sides of the focal
the memory can utilize. Information from the memory point (focal zone). Resolution is best within this fixed
drives the display, which produces an image. focal zone. The scanner contains moving parts.
Suppliers of ultrasound equipment are listed in Table • Electronic: These are linear or sector scanners with
4-8. no moving parts; therefore, they are more durable
than mechanical scanners. The beam is formed
by adding together many small beams from an array
Machines of small crystals. The scanner has variable (dynamic)
• Questions to consider before purchasing or leasing focusing. The focal zone therefore can be placed any-
ultrasound equipment: where in the image depth.
• What kind of scanning will I be doing (e.g., heart, • Image display
abdomen, real-time, B-mode, or M-mode)? • M-mode (motion-mode): Documents motion,
• How large or small are my patients? especially that of the heart (echocardiography). A
• Is someone in the practice willing to accept primary thin ultrasound beam is directed into the heart, is
responsibility for learning and doing the proce- reflected back, and then is shown on the screen as
dures? numerous moving lines. Motion is indicated along
• How much money can I invest? the side, and time is shown along the bottom of the
• There are multiple types of transducers screen.
• A linear array scanner produces a rectangular • B-mode (brightness-mode): Echoes are displayed
image and can be used to evaluate broad areas, as dots. The brightness of the dot changes with the
where no bony or gas-filled structures interfere. amplitude of reflection. The larger the reflection,
These scanners are usually less expensive. The the brighter the dot—no reflection, black dot. The
major drawback is the transducer contact zone, location of the dot corresponds to the location of
which makes intercostal and subcostal (heart, liver, the reflector in the body.
biliary tract, and right kidney) imaging difficult. • Real time: The image is continually updated during
• A sector scanner produces a pie-shaped image. A the entire examination. This permits direct obser-
smaller contact zone is used, which makes inter- vation of moving structures (e.g., heart or bowel
costal and subcostal imaging less difficult. peristalsis).
• New versus used equipment • Surgical table can be formed into a V-trough.
• New equipment purchase is ideal because some • Cardiac table (wood or Plexiglas) with holes so that
companies offer training (in-house or continuing the transducers may be brought up under the
education course) and a year-long warranty with recumbent patient. Lateral recumbency causes the
service and parts (in-house service or another unit heart to lie against the chest wall, providing an
is made available while your unit is serviced by the ultrasonographic window to the heart.
company). Manufacturer-reconditioned units may • Standoff pad to place between the transducer and the
provide a year-long or shorter warranty. The major skin for imaging superficial tissues.
disadvantage of new equipment obviously is the • Coupling gel is necessary to transmit sound from the
higher cost. transducer through the skin.
• A great deal of used equipment is available with the • Numerous brands are commercially available.
advent of newer technology. Older, used, outdated • Water-soluble, hypoallergenic gel is available.
equipment is being replaced with new equipment
based on new technology. The price of old equip-
ment is very attractive, sometimes as low as $1000. Image Storing
Although initial cost is low, some significant There are various methods of preserving the image for
expense may be required, including service, main- inclusion in the animal’s medical record:
tenance, transducers, and accessories. If the appro- • Polaroid camera—Heat-sensitive, thermal-paper re-
priate frequency transducers do not come with the corder
unit (often only 2- and 3-MHz transducers come • Multiformat camera—Can record multiple images on
with units that were used on human patients), the x-ray film
cost can increase 3 to 4 times to purchase 5- and • Videotape—Images are recorded, allowing evalua-
7.5-MHz transducers. tion by others at a later time
• Digital images or digital video
Transducers
• Transducers are available in a variety of frequencies Ultrasound Technique
(2–15 MHz). Low-frequency transducers provide
greater depth of penetration, but because of large • Patient preparation
wavelength, resolution is poorer. High-frequency • Tranquilization is usually not required, but the
transducers provide excellent resolution, but the patient must always be adequately restrained.
beam is rapidly attenuated in tissue. They are there- • The most common problem in obtaining good-
fore used to evaluate superficial tissues. quality images is poor transducer skin contact. Clip
the hair over the area to be imaged with a #40
• Use as high a frequency transducer as possible to
blade. Hair tends to trap air, acting as a barrier to
maximize resolution but still allow penetration to the
depth needed. the ultrasound. Clean the exposed skin to remove
dirt, oil, and debris before applying the coupling
• For transducer uses, see Table 4-9.
gel to help achieve the best image.
Ancillary Equipment • Patient positioning
• Most abdominal imaging is done from the ventral
This may include a guided biopsy attachment for the surface. Alternate scanning planes from lateral
transducer, calipers, a screen-labeling device, and an M- and lateral intercostal can be chosen to avoid gas.
mode/B-mode split screen. Portability of the machine When gas is a problem, gentle abdominal pressure
must also be considered. from the transducer usually displaces it.
• The heart is imaged through the intercostal spaces,
Ultrasonographic Accessories usually while the animal is in lateral recumbency.
• Positioners • Ultrasound image
• V-trough is easily constructed from wood or • It is a two-dimensional representation of a three-
Plexiglas. dimensional object.
• Ultrasound reflects the anatomy tomographically
(cross-sectionally).
Table 4-9. TRANSDUCER SELECTION • Ultrasound permits identification of internal organ
Transducer Type Use architecture.
• Image viewing
7.5 MHz Eye, feline heart and abdomen, small • Abdomen (Figs. 4-24 and 4-25)
canine abdomen (<25 lb), testicles
5.0 MHz Medium-size canine (<55 lb) heart and
• Cardiac
abdomen • Longitudinal scan: Cardiac base to the right
3.5 MHz Very large-breed canine heart and abdomen • Transverse scan: Pulmonary valve (outflow tract)
on the right of the screen
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Organ Echogenicity
• Rank of abdominal parenchymal organs from least to
Figure 4-24. Viewing a longitudinal (sagittal) ultrasound image.
most echogenic:
• Renal medulla
• Renal cortex
• Liver
• Spleen
• Prostate
• Renal sinus
Ultrasound Use
See respective chapters for ultrasound use in specific
diseases. See Table 4-10 for an overview of ultrasound
in various organs.
Interventional Ultrasound
• Uses
• Ultrasound-guided needle biopsy for histopathol-
ogy and culture
• Ultrasound-guided fine needle aspiration (FNA)
for cytology and culture
Figure 4-25. Viewing a transverse (axial) ultrasound image. • Cystocentesis to obtain urine (small bladder, diffi-
cult animals)
• Gallbladder aspiration for culture and cholangiog-
raphy
Principles of Interpretation • Abscess diagnosis and drainage
• Cyst diagnosis and drainage
Ultrasound Terminology • Renal pyelocentesis
• Anechoic: Area void of echoes (seen as black). • Equipment
• Hypoechoic: Lower level of echogenicity (darker) than • Real-time B-mode scanner
adjacent structures. • Transducer biopsy guide (or can be done
• Hyperechoic: Higher level of echogenicity (brighter) freehand)
than adjacent structures. • Needles, syringe, slides, culture medium, formalin
• Isoechoic: Level of echogenicity similar to adjacent containers
structures. • Sterile glove or transducer cover
• Complexly echogenic: Area of multiple echogenicities. • Sterile ultrasound gel or alcohol
• Ultrasonographic barriers: Highly reflective or absorp- • Sedatives, lidocaine
tive interfaces within the body that cause an almost • Patient preparation
complete attenuation of the sound beam. Examples • Complete an abdominal ultrasound examination.
include bone, mineral, and air. This barrier results in • Choose the site for FNA biopsy.
an absence of echoes deep to the interface (acoustic • FNA: Rarely need sedation; sterile preparation of
shadow). skin and transducer sterile glove cover.
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▼ Chapter
DECISION-MAKING CHECKLIST
Answer these questions to decide when fluid therapy is
needed:
• Does the patient have a form of shock that requires
fluid resuscitation?
• Does a serious deficit (or excess) of fluid or water
exist?
• Is there an anticipated loss of substantial fluid
volume?
• Are there serious electrolyte disturbances (excesses
or deficits)?
• Is there a serious disturbance in the acid-base
balance?
• Is there a serious disturbance in oncotic pressure or
excessive protein loss?
• Is there an immediate need for full nutritional
support with calories and protein?
• Does the patient have an anemia that may be affect-
ing oxygen delivery?
• Does the patient have a coagulopathy?
Answer these questions in order to provide appro-
priate fluid therapy: Figure 5-1. General decision tree for fluid therapy. (From Finco
DR: A scheme for fluid therapy in the dog and cat. J Am Anim Hosp
• What type(s) of fluids will be given? Assoc 8:178–180, 1972.)
• What volume of fluids will be given?
• How fast will fluids be given?
• Through what route will fluids be given?
• What, if any, supplements will be added to commer- INDICATIONS FOR FLUID THERAPY
cially available fluids?
• If more than one fluid type is being given, can they • Most commonly for resuscitation from shock syn-
be administered together? dromes and the correction of dehydration, hypo-
• If medications are to be administered with fluids, are kalemia, and metabolic acidosis
they compatible? • Less commonly for specific correction of other elec-
trolyte disturbances (sodium, potassium, chloride,
▼ Key Point If no laboratory testing is immediately calcium, or magnesium), acid-base disturbances
available, start correction of dehydration with (metabolic alkalosis or mixed acid-base disorders),
isotonic-balanced electrolyte solutions. and disorders of oncotic pressure
82
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Table 5-1. DAILY FLUID REQUIREMENTS FOR Table 5-2. DAILY FLUID REQUIREMENTS FOR
HOSPITALIZED NON-ANORECTIC DOGS* HOSPITALIZED NON-ANORECTIC CATS*
Total Daily Hourly Rate Total Daily Hourly Rate
Body Total Daily Fluid per of Total Body Total Daily Fluid per of Total
Weight Fluids Body Weight Daily Fluid Weight Fluids Body Weight Daily Fluid
(kg) (ml/day) (ml/kg/day) (ml/hr) (kg) (ml/day) (ml/kg/day) (ml/hr)
the owner about volume of intake (adipsia, hypodipsia, Skin Turgor Artifacts
polydipsia, or normal intake of water). Because volume
Many artifacts confuse interpretation of skin turgor.
of water intake may, in part, be a function stimulated by
food intake, note also the presence or absence of • Skin turgor of obese animals may appear normal
anorexia. Abnormal losses of body fluid may be deter- despite dehydration, owing to the large amounts of
mined from owner responses to questions about vomit- subcutaneous fat.
ing, diarrhea, polyuria, panting, excessive salivation, or • The skin of an emaciated animal with normal hydra-
other bodily discharge. The duration of these historical tion may fail to return to its normal position owing
signs and the magnitude of losses affect the magnitude to a lack of subcutaneous fat and elastic tissue. Con-
of clinically detectable dehydration. sequently, underestimating dehydration in obese
animals and overestimating dehydration in emaci-
ated animals can occur.
Physical Examination • Avoid testing cervical skin because redundant skin in
Physical examination provides general guidelines for the neck area confuses the result.
detecting dehydration but is subjective (see Table 5-3). • Skin turgor changes in longhaired animals are more
Signs of listlessness and depression may occur from difficult to detect than those in shorthaired animals.
dehydration but may be partially attributable to the • Differences in turgor assessment can occur in the
underlying disease or to concomitant electrolyte and same animal in the standing versus recumbent
acid-base abnormalities. As dehydration becomes more positions.
severe, decreased skin turgor, sunken eyes, dryness of
mucous membranes, tachycardia, diminished capillary ▼ Key Point Dehydration may be as much as 5% of
refill, and signs of shock may occur. An accurate and body weight loss in lean dogs and 10% or more
recent body weight, when available, can be used for in obese dogs before loss of skin turgor is
comparison to evaluate change in body weight as an detected.
indicator of body water change.
Other Physical Examination Artifacts
▼ Key Point An acute increase or decrease in an • Dry mucous membranes may occur in animals that
animal’s body weight often reflects acute gain or pant continually and in those given anticholinergics.
loss of body water. This is the most sensitive • Sunken eyes may be seen with catabolic diseases that
clinical tool for assessment of dehydration and decrease the soft tissue behind the globe or with
rehydration. An acute loss or gain of 1 kg is the atrophy of the muscles of mastication.
equivalent of losing or gaining 1 L of fluid.
▼ Key Point Assessment of fluid, electrolyte, and acid-
base status will frequently be in error if only the
Skin Turgor history and physical examination are available for
Skin turgor assessment during physical examination is interpretation. The more seriously ill an animal is,
important for estimating the percentage of body weight the more important evaluation of laboratory data
loss due to dehydration. Skin turgor is evaluated by becomes.
determining the time required for skin gently lifted
from the body to return to its original position (referred Laboratory Assessment of Dehydration
to as the skin pinch or skin tent). Normal skin pliabil-
ity (skin turgor) depends on hydration of the tissues in Packed Cell Volume and Total Plasma Protein
the area tested. Skin turgor is largely determined by Simple laboratory testing is helpful in evaluation of
hydration status of the interstitial tissues, although both intravascular hydration. Packed cell volume (PCV)
vascular and intracellular hydration also contribute. recorded in percentages (SI unit: L/L) and total plasma
Elastin and adipose within skin and subcutaneous protein (TPP) recorded in gm/dl (SI unit: g/L) can be
tissues will also influence the apparent skin turgor. rapidly and inexpensively determined using microhe-
Choose skin from the trunk as a test area. Avoid depen- matocrit tubes and a refractometer. These two tests
dent areas and skin from the neck. Normal skin returns require only a few drops of blood and can be taken by
immediately to its initial position when lifted a short dis- capillary action from a 25-gauge venipuncture. TPP
tance and released. Dehydrated skin shows varying concentration may be more helpful in the detection of
degrees of slow return to the original position. As dehy- dehydration than PCV. Increased TPP and PCV provide
dration progresses, the time required for the return of documentation for intravascular dehydration. Simulta-
the skin pinch to its initial position becomes greater. neous evaluation of PCV and TPP is recommended
The clinician assigns increasing percentages of dehy- in order to minimize interpretation errors due to pre-
dration to abnormal skin turgor of increasing severity existing anemia or hypoproteinemia. (Table 5-4) Addi-
(see Table 5-3). tional value is obtained when PCV and TPP are followed
W0422-Ch005.qxd 11/10/05 4:44 PM Page 87
TYPES OF FLUIDS AND THEIR SELECTION space to the interstitial and intracellular fluid spaces.
Thus they exert their greatest effect in rehydration or
Crystalloid Solutions replacement of prior fluid loss. Expansion of the vas-
Crystalloid fluids contain no large macromolecules, cular fluid space initially occurs, but with time, redistri-
allowing them to redistribute quickly from the vascular bution minimizes this effect.
Method 1
_________ml = Deficit = estimated % dehydration ¥ weight (kg), or
= estimated % dehydration ¥ weight (lb) ¥ 500
+
Method 2
_________ml = Deficit = estimated % dehydration ¥ weight (kg), or
= estimated % dehydration ¥ weight (lb) ¥ 500
+
5% Albumin 69 — — 20 —
25% Albumin 69 — — 100 —
6% Dextran-70 70 10–80 0.9% NaCl or D5W 40 0.5
6% Hetastarch 480 10–3400 0.9% NaCl 30 0.7
10% Pentastarch 260–280 10–1000 0.9% NaCl 40 0.4–0.5
Oxypolygelatin 30–35 5.6–100 Electrolyte Solution 45–47
Oxyglobin 200 65–500 Modified LRS 42 —
animal medicine, this group of fluids includes the blood higher size ranges and molar substitution ratios are
transfusion components that possess albumin and other more difficult to metabolize; thus these solutions tend
plasma proteins (whole blood and plasma). Indications to have a longer biological effect.
for use of blood component therapy are covered else-
where (see Chapter 22). • Synthetic colloids should rarely be utilized by them-
selves but are useful adjuncts to standard crystalloid
fluid therapy in several well-defined situations.
Concentrated Human Albumin
Patients with hypoproteinemia and lowered oncotic
In human medicine, 5% and 25% concentrated pressure are likely to benefit from continuous infu-
albumin products are also manufactured. Unconcen- sions of hydroxyethyl starch (hetastarch or pen-
trated natural colloids do not expand the vascular space tastarch) at doses of 20 ml/kg every 24 hours
except by the volume administered. Concentrated (cats—10–15 ml/kg every 24 hours) or more if
natural colloids will expand the vascular space by up needed. The measurement of COP is a useful moni-
to 5 times (25% albumin) their volume owing to their toring tool to determine infusion rate and end point.
impressive oncotic pressure. Concentrated human al- In addition, synthetic colloid solutions may play a
bumin products have been used with success in small valuable role in shock resuscitation (see the previous
animals, but their use carries risk of adverse reaction. section).
Most commonly, concentrated human albumin solu- • Patients with diffuse vascular injury to the pulmonary
tions are used when severe decreases (<12 mmHg) in vasculature and who are at risk for non-cardiogenic
colloid osmotic pressure (COP) are measured or the pulmonary edema formation may be very sensitive to
patient’s albumin concentration is severely decreased sudden elevations in intravascular volume. Thus if
(<1.5 g/L or <15 g/dl). increased oncotic pressure is desirable, continuous
infusion rather than bolus administration of colloids
Synthetic Colloids is recommended.
The commercially available synthetic colloids, which are ▼ Key Point Use synthetic colloids with caution, and
currently finding more frequent use in small animal at very reduced doses, in patients with congestive
medicine, are all complex polysaccharide molecules. heart failure and those with renal origin oliguria
The reported average molecular weight, COP, and or anuria as rapid volume expansion could be
molar substitution ratio of these molecules are listed in detrimental.
Table 5-7. The complex behavior and pharmacokinetics
of these molecules do not allow accurate prediction of • Of the three synthetic colloids mentioned in Table
actual biological behavior. As a result, the dose and 5-7, dextran 70 has the most potential to interfere
duration of administration of these solutions vary with with hemostasis. While clotting times become ele-
individual preference and the patient characteristics vated with use of the hydroxyethyl starches, clinically
and requirements. In addition, availability of these apparent hemostatic abnormalities are typically
products in some countries depends on national health not encountered if the recommended dosages are
and safety licensing. utilized.
In general, the smaller the average molecular weight, • Dextran 70 also carries a small risk of anaphylactic
the more potent the effect on intravascular expansion. reaction, whereas reactions to administration of
This is due generally to the higher COP of these solu- hydroxyethyl starches have not been reported. Con-
tions. Breakdown of synthetic molecules depends on sequently, and also as a result of the decreasing cost
their size (molecular size range) and the complexity of differential between dextrans and hydroxyethyl
branching (molar substitution ratio). Molecules with starch, dextrans are being used infrequently.
W0422-Ch005.qxd 11/10/05 4:44 PM Page 91
ations and continue for no longer than 3 to 4 hours and carbon dioxide (HCO3- + H+ Æ H2CO3 ∫ H2O
before the serum potassium is rechecked. + CO2).
• Animals with alkalosis and translocation of potassium • Patients that do not have adequate ability to exhale
may not require vigorous potassium supplementation CO2 formed in this reaction are at risk for worsened
if the alkalosis can be corrected rapidly. Potassium acidosis by administration of bicarbonate.
can rapidly return from the cells to the ECF.
• Animals with severe emaciation have reduced lean ▼ Key Point Patients with inadequate respiratory
body mass available for potassium uptake and should compensation for a metabolic acidosis or a mixed
be less vigorously supplemented with potassium in acidosis are at risk for worsened acidosis by
their fluids. administration of bicarbonate. Focus on fluid re-
• Reduced renal function and azotemia can lead to suscitation, if they are in shock, or investigate the
potassium retention and hyperkalemia during infu- cause of respiratory dysfunction. Re-evaluate acid-
sion of potassium-supplemented fluids, particularly if base status using blood gas analysis prior to
oliguria is present. Less vigorous potassium supple- administration of bicarbonate.
mentation and careful monitoring is indicated in this
situation. ▼ Key Point Do not add sodium bicarbonate to fluids
• Potassium chloride supplementation increases the that contain calcium (lactated Ringer’s solution), as
osmolality of fluids, particularly when high concen- calcium precipitates may occur.
trations are provided. For example, potassium sup-
plementation at 40 mEq/L increases the osmolality • Calculate alkali replacement from either the bicar-
of the fluid by 80 mOsm/kg, 40 Osm each from potas- bonate value reported on a blood gas analysis or the
sium and chloride. If the infused potassium enters total CO2 value on a serum biochemical profile. Total
cells or is excreted, this lessens the effects of the CO2 (mEq/L) can be substituted for bicarbonate in
osmolality. these calculations since the difference is usually only
1 to 2 mEq/L.
▼ Key Point Although potassium supplementation is
often beneficial, excessive supplementation can
result in death of the patient due to hyperkalemia. Methods for Calculating Bicarbonate Dose
Do not use potassium supplementation at higher • Assume that normal HCO is 24 mEq/L.
3
concentrations unless serum potassium concen- • Subtract measured patient HCO from 24, which is
3
tration can be measured on an urgent basis. equal to the HCO3 deficit in mEq/L.
Electrocardiographic monitoring may be needed
during supplementation of fluids with potassium Method A
in animals that are at risk for development of
hyperkalemia. • HCO deficit ¥ 0.6 ¥ body weight (kg) = “missing”
3
• Estimate of moderate acidosis: Give 6 mEq/kg bicar- be added to most commercially available fluid
bonate over 24 hours types. A loading dose of 30 mg/kg of magnesium
• Estimate of severe acidosis: Give 9 mEq/kg bicar- sulfate can also be administered over 20 minutes to
bonate over 24 hours 1 hour prior to beginning the lower rate of hourly
• In crisis situations requiring bicarbonate, administer supplementation.
0.5 to 1.0 mEq/kg of sodium bicarbonate over 5 to • Magnesium supplementation can be extremely
10 minutes and reevaluate. Electrocardiographic helpful in achieving and maintaining high normal
monitoring is recommended during the injection if levels of potassium when treating cardiac arrhythmias.
it is available. • Do not use magnesium supplementation in oliguric
patients as this is the primary route of excretion of
Precautions for Bicarbonate excessive amounts.
• Remember that along with bicarbonate, sodium is Dextrose Supplementation
administered, which can result in hypernatremia,
hyperosmolality, hypertension, overhydration, and If supplementation with dextrose is necessary, use
volume overload if the administered sodium is not varying amounts of 50% dextrose to achieve the desired
excreted. concentration or the percentage of dextrose in the final
• Overtreatment with alkali can result in alkalosis, solution.
paradoxical cerebrospinal fluid acidosis, shifts of • To increase the dextrose concentration by 2.5%,
ionized calcium, a shift of the oxyhemoglobin dis- add 25 g of dextrose or 50 ml of 50% dextrose to
sociation curve (decreasing oxygen unloading), and 1000 ml of stock solution (e.g., lactated Ringers
seizures. solution). Long-term supplementation of dextrose
through a peripheral vein should not exceed con-
Magnesium Supplementation centrations over 5%, as the hypertonicity can induce
significant phlebitis.
Magnesium has recently emerged as an important but • Indications include hypoglycemia due to sepsis,
seldom considered ion. It is a metabolic cofactor in hun- insulin overdosing, insulinoma, and liver disease.
dreds of metabolic functions, most importantly as a Dextrose supplementation at greater than 10% to
cofactor in the sodium-potassium pump (NaK-ATPase). 15% is necessary to provide sufficient calories for
Deficiencies in magnesium can thus lead to potassium anorectic animals.
loss from the body. Hypokalemia and hypomagnesemia
are often found concurrently in many ill or dehydrated
patients. Magnesium is lost alongside other cations
Vitamin Supplementation
when urinary and gastrointestinal losses result in de- The benefits of supplemental vitamins during par-
hydration. Inadequate intake in anorexic patients will enteral fluid therapy in cats or dogs are plausible but
exacerbate hypomagnesemia. not proven. Water-soluble vitamins can be conserva-
tively added to parenteral fluids without known harm
• As magnesium is primarily an intracellular ion, serum and may replenish rapidly depleted stores.
measurements are often not reflective of total body
stores. It is generally thought that low total serum • Dogs or cats in polyuric renal failure may benefit
magnesium is reflective of low total body magnesium from additional water-soluble vitamins in parenteral
status, but this is often a late finding. Ion-specific elec- fluids because of urinary losses of these vitamins.
trodes are more sensitive for detecting hypomagne- • Thiamine deficiency can be of clinical concern in cats
semia but are not in common use. and can develop during anorexia while on fluids, as
the storage period of thiamine is short.
▼ Key Point In patients with documented hypokale- • Initial signs of thiamine deficiency include ano-
mia, and especially hypokalemia that seems to be rexia, vomiting, and ataxia that can progress to
resistant to supplementation efforts, magnesium dilated pupils and tonic ventriflexion of the neck,
supplementation is indicated. In addition, patients which may be confused with seizures. True seizures
with diabetic ketoacidosis, congestive heart failure, can also occur. Death usually occurs within 24
and ventricular arrhythmias (and concurrent hypo- hours of onset of convulsions if the deficiency is not
kalemia) are likely to benefit from magnesium treated.
supplementation. • It is common practice to add 0.5 to 1.0 ml of water-
soluble multi-vitamins to each liter of fluids to
• Magnesium sulfate and magnesium chloride are the provide needed vitamins and to prevent thiamin
commonly available sources of magnesium. Magne- deficiency.
sium sulfate is preferred to prevent excessive chloride • B-complex vitamins are light sensitive, so the IV
administration. The dosage of magnesium sulfate fluid bag should be covered to prevent degenera-
supplementation is 2.5 to 5 mg/kg/hour and can tion. Fluids with B-complex vitamins added should
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also be replaced every 24 to 48 hours to maximize at a maintenance volume of 60 ml/kg/day (2.5 ml/
the potential benefits of vitamin supplementation. kg/hour). Approximately 1, 2, or 3 mg/kg/hour of
elemental calcium are provided by adding 10, 20, or
30 ml of 10% calcium gluconate, respectively, to each
Calcium Supplementation 250-ml bag of fluids.
• Calcium gluconate and calcium chloride can be sup- • Do not add calcium salts to fluid therapy prepara-
plemented in replacement and maintenance fluids tions that contain lactate, acetate, bicarbonate, or
for the correction of symptomatic hypocalcemia. phosphates, since calcium salt precipitates can occur.
Many small animals with low serum albumin will have • Alkalinizing fluid therapy containing sodium bicar-
low total serum calcium concentrations. Most of these bonate decreases ionized calcium and may expose
will not require calcium supplementation as the clinical signs of hypocalcemia in patients with bor-
ionized calcium is not usually as depressed as the total derline hypocalcemia; consequently, it should not be
calcium. When ionized calcium is substantially de- used.
creased, supplementation with calcium salts may be
required. Subcutaneous Injection
• The percentage of calcium contained varies widely by Never give calcium salts subcutaneously as severe skin
the specific calcium salt. There is no difference in necrosis and calcification have been observed in some
effectiveness of IV calcium salts to correct hypocal- patients, even when the calcium salts have been diluted
cemia when the dose is based on elemental calcium prior to subcutaneous administration.
content. Calcium gluconate is often chosen as the
calcium salt of choice because it is non-irritating if the Phosphorus Supplementation
solution is injected outside of a vessel. In contrast,
calcium chloride is extremely irritating to tissues but Hypophosphatemia is present when the serum
provides more elemental calcium in each milliliter of concentration is less than 0.8 mmol/L (2.5 mg/dl).
solution. Mild hypophosphatemia (0.65–0.80 mmol/L or 2.0–
2.5 mg/dl) is common and often transient. Hypophos-
phatemia often resolves quickly during therapy directed
Acute Infusion for Hypocalcemic Tetany at the underlying cause. Severe hypophosphatemia
(<0.48 mmol/L or <1.5 mg/dl) is uncommon but
• Tetany or seizures due to hypocalcemia require treat- can be life threatening, particularly when less than
ment with IV calcium salts. Calcium is administered
0.32 mmol/L (1.0 mg/dl). Use supplementation with
to effect at 5 to 15 mg/kg of elemental calcium (0.5–
phosphate salts when the serum phosphorus concentra-
1.5 ml/kg of 10% calcium gluconate) over a 10- to
tion is very low (<0.48 mmol/L or <1.5 mg/dl).
20-minute period.
• Monitor heart rate and electrocardiogram during ▼ Key Point Clinically significant hypophosphatemia
acute infusion of calcium salts. Bradycardia may that requires phosphate replacement therapy is
signal the onset of cardiotoxicity from an excessively most likely to be encountered in patients with dia-
rapid infusion rate of calcium. betic ketoacidosis 12 to 48 hours after initiation of
insulin therapy or in patients in whom enteral
▼ Key Point Treat severe symptoms of ionized nutrition is initiated after prolonged periods of
hypocalcemia (tetany and seizures) by administer- anorexia.
ing 0.5 to 1.5 ml/kg of 10% calcium gluconate intra-
venously over 10 to 20 minutes while observing a When necessary, sodium phosphate or potassium
continuous electrocardiogram. phosphate can be supplemented to replacement and
maintenance fluids for the correction of symptomatic
Continuous Intravenous Infusion or severe hypophosphatemia.
• Continuous IV infusion of calcium is recommended • Do not add phosphate salts to fluids that contain
from 60 to 90 mg/kg/day of elemental calcium (2.5– calcium.
3.75 mg/kg/hour) until oral medications provide • Treat only if hypophosphatemia is severe and a con-
control of serum calcium. Give initial doses in the current likely cause is present.
higher range to patients with more severe hypocal- • The dosage for phosphate supplementation is 0.01 to
cemia and decrease the dose according to calcium 0.03 mmol/kg/hour, intravenously, for 3 to 6 hours.
level achieved. Reduce the dose of IV calcium as oral • Severe cases may require prolonged supplementation
calcium salts and vitamin D metabolites become or higher dosages of phosphate (0.06–0.12 mmol/
more effective. kg/hour intravenously).
• Ten milliliters of 10% calcium gluconate provides 93 • Continue supplementation only until the serum
mg of elemental calcium. A convenient method to phosphorus concentration is greater than
infuse calcium is available when IV fluids are given 0.65 mmol/L (2.0 mg/dl).
W0422-Ch005.qxd 11/10/05 4:44 PM Page 95
• Avoid oversupplementation that can cause hyper- gases. When serum concentration of an electrolyte is
phosphatemia, hypocalcemia, tetany or seizures, elevated, choose a fluid for infusion that is devoid or
soft-tissue mineralization, hyperkalemia (if using low in that electrolyte concentration. When serum con-
potassium phosphate), and hypernatremia (if using centration of an electrolyte is low, choose a fluid for
sodium phosphate). infusion that contains high concentration of that elec-
trolyte or provide supplementation of that electrolyte to
the fluid. In some instances, supplemental electrolyte
GENERAL GUIDELINES FOR FLUID SELECTION can be given to prevent deficits (as previously men-
tioned for potassium). Evaluate final osmolality of fluids
Serum Sodium Level as a Guide for infusion following supplementation of base solu-
tions to ensure that they are appropriate, as supple-
Normal Sodium mentation of base solutions often results in
If the serum sodium concentration is normal, the unappreciated hyperosmolality.
animal has isotonic dehydration and needs replacement Selection of fluid type can be confusing when clini-
fluids that are nearly normal in serum sodium concen- cal problems dictate that disparate fluid types should be
tration and osmolality. Lactated Ringer’s solution, chosen; for example, use an acidifying solution (0.9%
Plasma-Lyte 148, Normosol-R, or 0.9% sodium chloride sodium chloride) in a patient that is severely acidemic,
would be appropriate selections. because high sodium content of this fluid is desirable.
Thus in these situations, identify the most severe
Hypernatremia problem and choose the initial fluid to address this
issue. Subsequently, as resolution of the most urgent
If the serum sodium concentration is elevated, the
problem is accomplished, correct secondary abnormal-
animal has hypertonic dehydration and needs more
ities. Fluid therapy is often dynamic, and changes of
water than salt for replacement (hypotonic fluid).
fluid type and additives are frequently needed over the
Choose fluids that are effectively hypotonic (5% dex-
course of therapy.
trose in water, 0.45% NaCl in 2.5% dextrose). Dextrose
solutions in 2.5% to 5% concentration are considered
effectively hypotonic because of rapid dextrose metab-
Preservatives
olism removing its contribution to osmolality. The mag-
nitude of the elevation in serum sodium and the ▼ Key Point Never use fluids containing preservatives
patient’s clinical status will determine whether dextrose of any kind for administration to cats, puppies, or
in water or dextrose in some concentration of saline small dogs because of the likelihood of severe
should be administered. Lowering of severe hyperos- toxic reactions.
molality and hypernatremia excessively rapidly can be
detrimental, particularly to the brain. A general guide- • Benzoic acid derivatives are commonly used in fluids
line is to allow sodium concentration to fall no faster for their antibacterial and antifungal effects. Cats are
than 0.5 mEq/L/hour or no more than 12 mEq/L in extremely susceptible to toxic effects from these com-
24 hours. Pure water without some electrolyte or pounds even at low doses. Benzyl alcohol at 0.9% is
glucose to add osmolality is not given as this can cause commonly added to multiple dose vials of sodium
severe problems with hemolysis and rapidly decreased chloride for injection.
serum osmolality. • Clinical signs of toxicity are mostly neurological,
and early signs include changes in behavior, appre-
Hyponatremia hension, aggression, hyperexcitability (light and
sound), salivation, marked ataxia, fasciculations of
If the serum sodium concentration is low, the animal the muscles of the head and ears, widely dilated non-
has hypotonic dehydration and needs additional responsive pupils, convulsions, coma, and death.
sodium relative to water. Hypertonic fluid infusion is
theoretically indicated, but clinically is not chosen
unless the hyponatremia and hyposmolality are very
severe and the patient is symptomatic. Isotonic fluids ROUTES OF ADMINISTRATION
are usually chosen for replacement since the kidneys FOR PARENTERAL FLUIDS
should excrete unnecessary water and reclaim needed
sodium. The route of fluid therapy depends on the nature of
the clinical disorder, its severity, its onset (acute versus
chronic), the nature and magnitude of ongoing losses,
Other Laboratory Abnormalities and the composition of fluids to be given. The avail-
Further selection of fluid type requires laboratory ability of personnel and equipment required for moni-
measurement of albumin, total protein, potassium, toring during IV therapy also influences decisions about
chloride, magnesium, calcium, phosphorus, and blood the appropriate route of administration.
W0422-Ch005.qxd 11/10/05 4:44 PM Page 96
Intraosseous Route ence will most likely be lost in the urine. In this situ-
ation, increased urine production is a misleading
• Provides rapid access to circulation when venous indicator of hydration status of the patient, so other
catheterization is not successful or possible. physical examination and laboratory parameters as
• Consider using in puppies and kittens and in emer- well as serial monitoring of the patient’s weight must
gency situations where immediate IV access is difficult. be considered.
• Blood and crystalloid solutions can be infused safely. • If fluid infusion can be observed for only part of the
• Catheterize the bone marrow of the femur, tibia, or day, give the 24-hour needs over the number of hours
humerus with a bone marrow or spinal needle and that personnel can watch the drip, then flush the
secure it in place (see Chapter 3 for technique). catheter with heparinized saline to maintain patency
until infusion resumes. If severe dehydration has
been corrected, give additional fluids subcutaneously
RATE OF FLUID INFUSION until the IV drip can be restarted the next day.
this technique, there is a tendency to overestimate • These pumps are especially useful for small dogs,
the actual fluid needs in an oliguric animal (result- cats, and animals receiving fluids supplemented with
ing in overhydration) and to underestimate the fluid potassium or other agents.
needs in an animal undergoing extensive diuresis
(resulting in failure to correct dehydration). Syringe Pumps
• Choose an observation interval (every 1–8 hours) Syringe pumps provide an extremely accurate method
and begin quantifying urine production. At the of administering small volumes of medication or fluid
end of the first interval, a new fluid rate is calcu- into a patient’s IV drip or directly into the IV catheter.
lated that will include the insensible losses for the
upcoming interval (22 ml/kg divided by the obser- • Sophisticated machines exist that allow complex
vation interval) and the measured sensible (urine) dosages (such as mg/kg/min) to be easily programmed.
losses from the previous observation interval. For • Drug administration errors because of mathematical
example, a 10-kg dog will be placed on ins and error can thus be eliminated, and rapid changes
outs every 6 hours. In the previous 6-hour period, to new dosing rates are easily and accurately
120 ml of urine was produced. The fluid amount accomplished.
to be given over the next 6 hours will be 120 cc plus • Most machines allow extremely accurate dosing of
insensible loss ({10 ¥ 22 = 37/6} ml) to equal 157 very small volumes (0.1–0.01 ml).
ml of fluid. • Refurbished machines are becoming more widely
• This type of close attention to fluid volume admin- available, making them cost effective for many
istration is of benefit in the initial management of practices.
critically ill animals, particularly when CVP and
renal status are uncertain.
• Remember that with this technique the volume of MONITORING EFFICACY OF FLUID THERAPY
fluid administered (ins) will exceed the volume of
fluid (urine) that is measured (outs) by the daily Perform a physical examination several times daily
insensible needs. If the patient is rehydrated, your during the initial fluid management to document rehy-
calculations are accurate, and no other source of dration, prevent overhydration, and detect contempo-
fluid loss exists, then the patient’s weight should rary fluid loss. The indicators of successful fluid therapy
remain static. are normalization of skin turgor, moistening of mucous
membranes, strengthening of pulses, increased perfu-
sion (decreased refill time), and increased alertness.
Infusion Pumps Table 5-9 provides guidelines to assess the success of
Infusion pumps provide an extremely accurate means fluid therapy, and Table 5-10 lists possible reasons dehy-
of administering IV fluids. dration has not been adequately corrected.
• Enter ml/hr or drops/min depending on the type of Body Weight
machine.
• Most are equipped with an alarm system that indi- • Increased body weight should occur during success-
cates if fluid flow is interrupted. ful rehydration. An acute gain or loss of 1 kg suggests
• New pumps are expensive (refurbished, used an increase or decrease of 1000 ml of body water
machines may be surprisingly affordable). (1 lb = 500 ml).
Body Weight ✓ ✓ ✓
PCV/TPP ✓ ✓ ✓
Urine Specific Gravity ✓ ✓ ✓
Electrolytes (Na, K, Cl) ✓ ✓
Bicarbonate (Total CO2) ✓ ✓
Electrocardiogram ✓ ✓
Blood Gas (ven ± art) ✓
Lactate ✓
Central Venous Pressure (CVP) ✓
Ionized Calcium (Ca)/Magnesium (Mg) ✓
OVERHYDRATION
• An anorexic animal, however, loses 0.1 to 0.3 kg of its
body weight per day per 1000 calories of daily caloric Overhydration rarely occurs as a spontaneous disorder;
requirement owing to tissue catabolism. Measure and it usually is iatrogenic following fluid therapy. Inability
record body weight accurately at least once daily. to excrete free water, which can occur in a variety of
renal and liver diseases and in congestive heart failure,
Packed Cell Volume and Plasma Protein predisposes a patient to overhydration.
• Follow PCV and TPP serially during fluid therapy. Clinical Signs
Decreases in both PCV and TPP suggest successful
intravascular rehydration (see Table 5-4). • Body weight increases above and beyond that ex-
pected to accomplish rehydration.
Central Venous Pressure • CVP is persistently elevated or increases suddenly.
• In difficult cases (particularly those with renal or • Increased volume and/or frequency of urinations
heart failure), monitor CVP to minimize chances of may be noticed as the patient attempts to rid the body
overloading the heart and causing pulmonary edema of excess water, but the volume excreted may not be
when administering fluids rapidly. sufficient to prevent overhydration.
• Monitor CVP with a jugular catheter, the tip of which • A gelatinous feel to the subcutaneous tissues may
is in the cranial vena cava or near the right atrium. precede the development of obvious peripheral
Normal CVP is 0 to 5 cm H2O. edema.
• A sudden increase in CVP during fluid therapy indi- • Pulmonary edema, manifested as lung crackles and
cates the inability of the cardiovascular system to tachypnea, may be detected.
accommodate the rate of fluid administration. • Vomiting, diarrhea, serous discharge from the nose
Reduce the rate of administration accordingly. and eyes, and chemosis can develop.
• A persistent increase in CVP following administration • Venous overdistension may also be noted.
of a fluid challenge indicates adequate volume ex-
pansion of the patient. Patients with mild or moder- Laboratory and Radiographic Findings
ate degrees of hypovolemia will have a rapid return • Progressive decreases in PCV and total protein may
to baseline CVP following fluid challenge. be measured (see Table 5-4).
• Signs of overhydration, unfortunately, can still occur • Radiographs may reveal increased lung density com-
even without a change in CVP. patible with pulmonary edema; cardiac enlargement
or pulmonary venous distension may be noted if con-
Electrolyte and Acid-Base Status gestive heart failure is imminent.
• Closely monitor all animals receiving fluid therapy. Treatment
Determine serial serum electrolyte values and acid-
base status in severely dehydrated animals receiving • Immediate correction may be difficult when renal or
fluid therapy at least every 12 to 24 hours. Ideally, cardiac function is impaired.
animals that had serum electrolyte deficiency or • Discontinue all IV infusions, and give furosemide
excess or severe acid-base disturbances will show from 2 to 4 mg/kg IV. Give another dose of
improvement toward normal values after appropriate furosemide (4–8 mg/kg IV) if no diuresis is seen
therapy. within 15 minutes.
• Follow electrolyte determinations and acid-base • Morphine may be considered as a treatment to
status in those cases that had initially normal values increase compliance of pulmonary vessels.
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▼ Chapter
6 Pain Management in
the Surgical Patient
Richard M. Bednarski
Like anesthesia, the perioperative assessment of pain • Nociception: The sensing and ascending neural trans-
and the provision of analgesia have become an integral mission of a noxious stimulus. Nociception that is
part of companion animal medicine. Regardless of the centrally processed can be interpreted as pain.
type of medical or surgical procedure performed, pain • Somatic pain: Pain caused by activation of nociceptors
management must be considered a part of the peri- within the skin and musculoskeletal tissue. This is
anesthetic drug plan. usually described in people as sharp and localized
when associated with superficial tissue and dull or
▼ Key Point The keys to developing a successful peri- aching when associated with deeper tissues.
anesthetic analgesia plan include (1) understand- • Visceral pain: Pain that is poorly localized and
ing basic concepts of pain transmission and described by people as a pressure-like or squeezing
modulation; (2) recognizing and differentiating the sensation. It is associated with activation of nocicep-
signs of pain; (3) gaining a working knowledge of tors within a body cavity.
the pharmacology of analgesic drugs and tech- • Neuropathic pain: Pain related to nervous system
niques associated with their use; and (4) knowing damage. This is usually described in people as a
how to integrate these drugs and techniques into burning sensation.
a perianesthetic plan. • Acute versus chronic pain: Acute pain is the normal
response to an inciting stimulus, such as the pain
A multimodal approach to analgesia is generally resulting from surgical stimulation, trauma, or
more effective than reliance on a single drug or tech- thermal injury. Perioperative analgesic plans are for-
nique. One or multiple sites in the anatomic pain mulated to minimize this type of pain. Chronic pain
pathway are targeted. A multimodal approach involves persists longer than that associated with healing of an
choosing more than one drug or technique from the acute condition or that associated with a malingering
available categories of analgesic drugs. These are op- condition. Perianesthetic analgesia can temporarily
ioid analgesics, nonsteroidal anti-inflammatory drugs alleviate this type of pain.
(NSAIDs), local anesthetics, alpha-2 agonists, and dis- • Preemptive analgesia: The concept of administering
sociative N-methyl-D-aspartate (NMDA) receptor antag- analgesic drugs to prevent central sensitization of
onists. Several texts describe in detail the pharmacology pain pathways (see below). Often erroneously
and techniques associated with these drugs (see “Sup- referred to as simply administering analgesics
plemental Reading”). This chapter suggests some peri- preoperatively.
operative analgesic protocols and techniques that can
be used commonly in small animal practice.
PAIN PATHWAYS
DEFINITIONS • Transduction: Tissue injury releases chemical media-
tors (prostaglandins, histamine, and cytokines) that
• Pain: Pain is defined as an unpleasant sensory and can activate nociceptors. Continued nociceptive
emotional experience associated with actual or stimulation sensitizes the nociceptors (peripheral
potential tissue damage. The inability to communi- nociceptive sensitivity), resulting in hyperalgesia
cate in no way negates the possibility that an individ- (increased response to a painful stimulus) and allo-
ual is experiencing pain and is in need of appropriate dynia (pain from a normally non-painful stimulus)
pain relieving treatment. localized to the area of insult.
• Nociceptor: Specialized sensory nerve endings that
respond to the mediators of tissue damage. These ▼ Key Point NSAIDs and local anesthetics can block
mediators are mechanical, thermal, and chemical. or modify transduction. Preventing or reducing
100
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Side Effects
• Regardless of the pain score, use common sense. If a
given procedure would cause you pain, then admin- • Bradycardia is the most common cardiovascular side
ister perioperative analgesic therapy. If you think the effect. Respiratory depression can occur during
animal is experiencing pain, administer analgesia. general anesthesia but is not generally an issue in
awake animals.
• Prolonged opioid administration (days) can result in
ANALGESIC DRUGS AND TECHNIQUES urinary retention and the need to periodically ex-
(Tables 6-4 to 6-8) press the bladder or insert a urinary catheter.
• Opioids can induce dysphoric behavior (vocalizing
and pacing) that can be confused with pain behavior.
General Principles Opioid-induced dysphoria can be treated using
• Consider preemptive analgesia as a part of every anes- small incremental boluses of naloxone (1–2 mg/kg),
thetic plan. an opioid antagonist.
• Consider multimodal analgesic therapy with some
combination of opioid, NSAID, local anesthetic, Opioid Agonist-Antagonist (Butorphanol)
NMDA-receptor antagonist, and alpha-2 agonist for and Partial Agonist (Buprenorphine)
more painful procedures (see Table 6-2) or for
animals with higher pain scores. These two drugs are generally considered less potent
analgesics than the opioid agonists. They are controlled
• Analgesic drugs and techniques are compatible with
substances and are subject to state and federal
general anesthesia. As with anesthetic drugs, their
selection should be influenced by preoperative regulations.
patient status (see Chapter 2).
• Assess postoperative pain using a pain scoring system Duration of Action
(see Table 6-3) and treat for pain whenever indicated. • Butorphanol lasts up to 2 hours in a cat but less than
• Do not rely on drugs used to induce and main- 1 hour in a dog.
tain anesthesia (propofol, thiopental, isoflurane, or • Buprenorphine is effective up to 8 hours. Onset of
sevoflurane) to provide preemptive analgesia or action is relatively slow (30 minutes), so it is not
postoperative control of pain. useful for immediate pain relief.
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Table 6-4. OPIOID DRUGS FOR TREATING PAIN IN DOGS AND CATS
Drug Dog Dose Cat Dose Duration of Comments DEA
(mg/kg) (mg/kg) Action (hr) Schedule
(IV, IM, SC) (IV IM, SC)
*CRI, constant rate infusion; usually preceded by a bolus dose to rapidly achieve therapeutic plasma concentration. Use lower end of infusion rate in cats.
†Duration of action after epidural use is up to 24 hours for morphine and buprenorphine.
Table 6-5. OTHER SEDATIVE AND ANESTHETIC DRUGS FOR TREATING PAIN IN DOGS AND CATS
Drug Dog Cat Duration Comments DEA
Dose Dose of Action Schedule
Ketamine CRI*: 2–10 mg/kg/min CRI*: 2–10 mg/kg/min Duration Subanesthetic dose, useful III
of infusion as analgesic adjunct when
given with other analgesics
Epidurally: 2 mg/kg diluted
in sterile 0.9% NaCl;
1 ml/4.5 kg body weight
Xylazine 0.1–0.2 mg/kg IV, 0.1–0.2 mg/kg IV, <1 hr Sedation accompanies —
IM IM analgesia, not recommended
if cardiovascular compromise
present
Medetomidine 2–10 mg/kg IV, 10–20 mg/kg IV, 1–2 hr Sedation accompanies —
IM IM analgesia, not recommended
if cardiovascular compromise
present
Morphine/lido- CRI*: 0.2/3.0/0.6 mg/ 0.2/3.0/0.6 mg/kg/hr Duration of Useful as an adjunct to Morphine: II
caine/ketamine† kg/hr infusion inhalation anesthesia in
and several dogs, compatible with Ketamine: III
hours beyond other perioperative
analgesics and anesthetics
Administration
Table 6-6. NONSTEROIDAL ANTI-
INFLAMMATORY DRUGS FOR TREATING PAIN • Buprenorphine is effective and well accepted orally
IN DOGS AND CATS in cats. It is useful for “at home” administration.
• Buprenorphine can be used epidurally (see Table
Drug Dog Cat 6-4).
Dose (mg/kg) Dose (mg/kg)
Ovariohysterectomy, castration, Parenteral opioid and or alpha-2 agonist Any opioid listed in Table 6-4 is acceptable as long
cystotomy, exploratory as part of preanesthetic regimen; NSAID as attention is given to dosing interval. For
laparotomy or any elective immediately pre- or post-surgery. For cats, onychectomy, also perform local nerve block of
surgical procedure with oral buprenorphine continued for 1–3 feet. Continue analgesic support for at least 24
minimum to moderate tissue days post-surgery hours post-surgery.
trauma
Fractures and severe soft Parenteral opioid agonist as part of the Maximum analgesia is needed. Combinations
tissue trauma† premedication plus one or more of the involving several categories (multimodal) are most
following: epidural opioid for rear limb useful. For example, preoperative opioid pre-med
fractures, abdominal procedures, and with an epidural opioid, CRI opioid, or opioid
perineal surgery; local anesthetic nerve combination. Continue postoperative analgesia for
blocks for maxillectomy, mandibulectomy, at least 48–72 hours.
or thoracotomy; Fentanyl patch applied
12–18 hours preoperatively; CRI‡ of
morphine, fentanyl, lidocaine, or
ketamine; CRI of a morphine, lidocaine,
and ketamine combination.
Arthritis NSAID Use only if normal liver and kidney function are
present. Follow manufacturer’s recommendations
for pre- and post-administration patient evaluation.
*Refer to drug tables for choice of specific drugs and dosing regimens. For procedures requiring general anesthesia, these recommended drugs are given peri-
operatively as part of the anesthetic plan (see Chapter 2). Pain treatment protocols depend on drug availability and the availability of qualified personnel to
administer controlled drugs. Depending on the pain score, additional analgesic drugs may need to be administered.
†Tissue trauma of increasing magnitude requires relatively high doses and multimodal therapy using more than one category of drug.
‡CRI, constant rate infusion.
W0422-Ch006.qxd 11/10/05 4:46 PM Page 105
• Ropivacaine (0.2%) or bupivacaine (0.25%); 1 to • Slowly inject and withdraw the needle.
2 mg/kg divided among the five intercostal spaces • The appropriate dose (mg/kg) is delivered in a 1 ml/
4.5 kg volume.
Epidural Anesthesia or Analgesia
For surgery of the caudal abdomen, tail, perineum, or Lidocaine Constant Rate (IV) Infusion
anus. • Can be used as an adjunct to other analgesic therapy.
• Opioids, local anesthetics, alpha-2 agonists, and ket- • Better for soft tissue pain rather than orthopedic.
amine have all been injected into the epidural space • Dosage = 20 to 60 mg/kg/min, IV
for analgesia (see Tables 6-4, 6-5, and 6-7). • Begin with mid-range dosage for dogs. Cats may
• Local anesthetics produce a dose related sensory and develop cardiovascular depression from lidocaine
motor blockade (epidural anesthesia). infusion.
• Opioids, alpha-2 agonists, or ketamine induce dose-
related analgesia with minimal motor blockade Nonsteroidal Anti-inflammatory Drugs
(epidural analgesia).
These drugs traditionally have been used to treat
chronic pain and to reduce inflammation as a result of
Area Blocked
their inhibition of the cyclooxygenase (Cox) 1 and 2
• Caudal abdomen, tail, perineum, and anus enzymes. Cox 1 is the normally present constitutive
enzyme, and Cox 2 is induced during inflammation.
Anatomy and Landmarks Both enzymes may be involved in normal renal
• The lumbo-sacral space is located on the midline on function.
a line drawn between the left and the right cranial- • They potentiate the action of opioid analgesics.
dorsal iliac spines. • Injectable NSAIDs can be administered immediately
• Palpate the spinous process of vertebrae L7 and the before or after surgery. Oral NSAIDs can be
median sacral crest. The space is located midway prescribed postoperatively. NSAIDs do not produce
between these structures. sedation.
• The spinal cord ends at L7 in the dog and between • They can cause gastrointestinal ulceration, liver, and
L7 and S1 in the cat. kidney damage, and they should be used cautiously if
at all in animals with hypotension, gastrointestinal, or
Technique renal disease.
• Position the animal in lateral or sternal recumbency. • Do not use NSAIDs with corticosteroids.
• Clip hair and do an aseptic preparation. Surgical
gloves should be worn when performing the proce-
dure. SUPPLEMENTAL READING
• A 22-gauge, 1- to 3-inch spinal needle is inserted on
the midline. Advance the needle through the yellow Gaynor JS, Muir WW: Handbook of Veterinary Pain Management. St.
ligament until a sudden loss of resistance is felt as the Louis: CV Mosby, 2002.
Mathews KA (ed): Veterinary Clinics of North America: Management
needle enters the epidural space. Depth of insertion of Pain. Philadelphia: WB Saunders, 2000.
will vary from 0.5 cm in a cat to 7 cm in a large-breed Thurmon JC, Tranquilli WJ, Benson GJ: Lumb and Jones’ Veterinary
or obese dog. Anesthesia, 3rd ed. Philadelphia: Williams & Wilkins, 1996.
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▼
Section
2 Infectious Disease
Robert G. Sherding
▼ Chapter
Proposed changes in vaccination protocols for com- Then, in March 2003, the American Animal Hospi-
panion animals, the safety of licensed vaccines, and tal Association (AAHA) Canine Vaccine Task Force
advances in vaccine technology are among the most released its Guidelines on canine vaccination. In that
important issues practicing veterinarians face as we document, 3-year booster intervals in adult dogs are rec-
enter the 21st Century. While many would argue that ommended for distemper, parvovirus, adenovirus-2,
these are already issues, the future promises to be espe- and parainfluenza virus.
cially challenging as the vaccines we use and the proto- In 2004, some vaccine manufacturers announced
cols we recommend undergo unprecedented change. results of challenge studies verifying the ability of their
canine distemper, parvovirus, and adenovirus-2 com-
bination vaccines to protect dogs against virulent
HISTORICAL BACKGROUND challenge, thereby validating the recommendations out-
lined in the canine vaccination guidelines.
Prior to 1998, vaccination recommendations were
limited to the Compendium of Animal Rabies Preven-
tion and Control, published annually by the National FUTURE VACCINATION ISSUES
Association of State Public Health Veterinarians (at
www.nasphv.org). In 1998, the American Association of It is important to remember, however, that despite the
Feline Practitioners (AAFP) published the first report of controversy over 3-year booster intervals for some vac-
an Advisory Panel on Feline Vaccines recommending cines, there are several strategic issues justifying the
that adult cats be vaccinated every 3 years, rather than need for veterinarians to reassess recommendations for
annually, against feline parvovirus (panleukopenia). Reac- the selection and use of vaccines. Included among these
tion to this report was profound. Veterinarians through- issues are vaccine safety profiles, profound variation in
out North America voiced concerns that anything other exposure risk of individual dogs and cats, and changes
than annual vaccination of adult cats against pan- in vaccine technology (e.g., recombinant vaccines).
leukopenia was inappropriate, irrational, and quite pos- These issues will take on even more importance in the
sibly detrimental to the health of the cat population. In future as new vaccines continue to be introduced and
December of 2000, the same Advisory Panel published a as more veterinarians question the need for and safety
second iteration of the Guidelines for Feline Vaccina- of these products.
tion. In that report, the Panel expanded the “every 3 The introduction of so many vaccines in the past 10
year” booster recommendation to include feline her- years, and the promise of more to come, justify the need
pesvirus-1, feline calicivirus, and panleukopenia. for the veterinary profession to critically address which
107
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For any vaccine preceded by “+,” see defining criteria in Table 7-2.
NOTE: All intranasal B. bronchiseptica vaccines also contain parainfluenza virus; some also contain canine adenovirus-2.
NOTE: In some States or municipalities, annual rabies vaccination may be required.
Table 7-2. DEFINING CRITERIA FOR MODERATE-RISK CANINES (APPLIES TO MOST DOGS)
B. Bronchiseptica Vaccination Is Indicated If
Dog is ever boarded in a commercial kennel
Dog requires occasional grooming
Dog regularly has supervised walks/runs outside with likelihood of contact with other dogs
Parainfluenza* Vaccination Is Indicated If
Dog is ever boarded in a commercial kennel
Dog requires occasional grooming
Dog regularly has supervised walks/runs outside with likelihood of contact with other dogs
Leptospira Vaccination Is Indicated If
The dog is 12 wks of age or older
Dog has opportunities for unsupervised outdoor activities
Cases of leptospirosis are known to have been confirmed in the area†
Dog has access (supervised or otherwise) to areas inhabited by “reservoir” hosts (e.g., opossum, skunk, raccoon, vole) or other domestic
animals such as cattle, pigs, or horses
Lyme Borreliosis Vaccination Is Not Indicated Unless
Dog will travel to known endemic areas (Northeast or upper Midwest) and will spend time outside
Lyme borreliosis cases have been diagnosed (via IDEXX Snap 3Dx or Western Blot analysis) in the community
Dog is not receiving any form of topical tick preventative (e.g., fipronil)
Table 7-3. ANNUALIZED VACCINATION PROTOCOL FOR DOGS AT LOW RISK OF EXPOSURE
Age at Vaccination Vaccine Age at Vaccination Vaccine
For any vaccine preceded by “+,” see defining criteria in Table 7-4.
Note: All intranasal B. bronchiseptica vaccines also contain parainfluenza virus; some also contain canine adenovirus-2.
Note: In some states or municipalities, annual rabies vaccination may be required.
Table 7-4. DEFINING CRITERIA FOR LOW-RISK CANINES (ONLY CORE VACCINES NEED
BE ADMINISTERED)
B. Bronchiseptica Is Not Indicated Because
Dog is never boarded in a commercial kennel
Grooming is not an issue
Dog lives exclusively indoors
Dog has no exposure to other dogs (or it occurs rarely)
Parainfluenza* Vaccination Is Indicated If
Dog is ever boarded in a commercial kennel
Dog requires occasional grooming
Dog regularly has supervised walks/runs outside with likelihood of contact with other dogs
Leptospira Canicola, L. Icterohemmorhagiae, L. Pomona, and L. Grippotyphosa Vaccinations Are Not Indicated Because
There is no exposure to other dogs
There is no opportunity for unsupervised outdoor activity
The dog lives exclusively indoors
Leptospirosis is not known to occur in the area
Lyme Borreliosis Vaccination Is Not Indicated Because
Dog does not reside in a known Lyme borreliosis endemic area
Dog does not travel to known endemic areas
Dog neither lives in or travels into a known tick-vector area
Dog is reliably treated with topical flea and tick preparation
Dog has never known a tick and never will
Table 7-5. ANNUALIZED VACCINATION PROTOCOL FOR DOGS AT HIGH RISK OF EXPOSURE
Age at Vaccination Vaccine Age at Vaccination Vaccine
For any vaccine preceded by “+,” see defining criteria in Table 7-6.
Note: All intranasal B. bronchiseptica vaccines also contain parainfluenza virus; some also contain canine adenovirus-2.
Note: In some states or municipalities, annual rabies vaccination may be required.
Table 7-7. ANNUALIZED VACCINATION PROTOCOL FOR CATS AT MODERATE RISK OF EXPOSURE
Age at Vaccination Vaccine Age at Vaccination Vaccine
For any vaccine preceded by “+,” see defining criteria in Table 7-8.
Table 7-8. DEFINING CRITERIA FOR MODERATE-RISK FELINES (APPLIES TO MOST CATS)
FeLV Vaccine Is Indicated If
Cat lives indoors predominately, but not exclusively, and
Cat is less than 6 months of age, and
Cat is known to occasionally have contact with other cats of unknown health status, or
Other cats in the household are known to be FeLV infected, or
Other cats live in the household but are of unknown FeLV status, or
Other cats in the household are known to roam at will, or
Owner may bring stray cats into the household
Bordetella Bronchiseptica and Chlamydophila Felis Vaccines Are Not Indicated If
Cat is an adult (current literature suggests that clinical B. bronchiseptica infections are most likely to occur in kittens), and
Cat does not have exposure to other cats, and
Any other cats in the household are known to be strictly indoor cats, and
Owner is unlikely to bring stray cats into the household
Rabies Vaccination in Cats
Is not required by many states and municipalities; however, in accordance with the Feline Vaccination Guidelines, rabies is a Core vaccine
and is highly recommended for all cats.
Table 7-9. ANNUALIZED VACCINATION PROTOCOL FOR CATS AT LOW RISK OF EXPOSURE
Age at Vaccination Vaccine Age at Vaccination Vaccine
For any vaccine preceded by “+,” see defining criteria in Table 7-10.
Note: Although administration of rabies vaccine to cats may not be required by state or local statutes, it is recommended for all cats, regardless of risk.
W0422-Ch007.qxd 11/10/05 4:46 PM Page 113
Table 7-10. DEFINING CRITERIA FOR LOW-RISK FELINES (PROTOCOL CENTERS AROUND
CORE VACCINES)
FeLV and FIV Vaccines Are Not Indicated If
Cat is known to be a strictly indoor cat, and
Any other cats in the household are known to be both FeLV and FIV-free and were tested within the last 12 months, and
Other cats in the household are known to be strictly indoor cats
Owner does not bring stray cats into the household
Bordetella Bronchiseptica and Chlamydophila Vaccines Are Not Indicated If
The cat is an adult (current literature suggests that clinical B. bronchiseptica infections are most likely to occur in kittens), and
The cat does not have exposure to other cats, and
Any other cats in the household are known to be strictly indoor cats
Owner does not bring stray cats into the household
Rabies Vaccination in Cats
Is not required by many states and municipalities; however, in accordance with the Feline Vaccination Guidelines, rabies is a Core vaccine
and is highly recommended for all cats.
Table 7-11. ANNUALIZED VACCINATION PROTOCOL FOR CATS AT HIGH RISK OF EXPOSURE
Age at Vaccination Vaccine Age at Vaccination Vaccine
For any vaccine preceded by “+,” see defining criteria in Table 7-12.
Note: Chlamydia psittaci has been renamed Chlamydophila felis (the name on vaccine label may not reflect the new classification).
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▼ Chapter
8 Feline Leukemia Virus
Robert G. Sherding
115
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under optimal temperature and moisture conditions. • Antitumor response is mediated by antibody directed
Heat, drying, detergents, and disinfectants readily against FeLV-associated antigens on the surface of
destroy FeLV. FeLV-induced neoplastic cells.
• In most transiently infected cats, the latent stage of dysfunction has been associated with immune-mediated
infection eventually is eliminated uneventfully within and autoimmune diseases.
6 to 9 months as part of the normal recovery process,
but it sometimes can take a year or more. Latent Nonspecific Clinical Signs
infection persists indefinitely in an estimated 10% of
“recovered” cats. Presenting clinical signs that are common in FeLV-
• The clinical significance of FeLV latency is the rare infected cats include weight loss, fever, dehydration,
possibility of reactivation to a replicating infection, oculonasal discharge, anemia, diarrhea, stomatitis, and
either spontaneously or in response to immunosup- lymphadenopathy.
pression (e.g., corticosteroid-induced). In addition,
reactivation of infection in latent-infected queens ▼ Key Point The majority of FeLV-infected cats are
may rarely transmit FeLV to kittens in utero or during asymptomatic at the time they are identified on
nursing. routine screening tests during wellness exams.
• Latent infected cats have minimal risk of developing
FeLV-related disease. They also have minimal risk of Lymphoma and Leukemia
being contagious to other cats, except for the rare
occurrences of reactivation mentioned above. FeLV can be a primary cause of lymphoma, leukemia,
and myelodysplasia. For additional information regard-
Persistent Infection ing diagnosis and treatment of these neoplastic condi-
tions, see Chapters 26 and 27. In the mid-1970s, 70% of
Cats with persistent or “progressive” FeLV infection cats with lymphoma and leukemia were FeLV positive.
have generalized lymphoid, bone marrow, and poly- Virus-negative alimentary lymphoma was uncommon.
glandular infection with persistent cell-associated However, with the decline in prevalence of FeLV
viremia and continuous shedding of virus. This wide- infection, FeLV-negative lymphomas now comprise 85%
spread replicating FeLV infection persists for the to 90% of the lymphomas seen in cats, and alimentary
remainder of the cat’s life with only rare exceptions. lymphoma is the predominant form. Some of these
• Persistent infection eventually leads to fatal FeLV- FeLV-negative lymphomas have molecular evidence of
related disease in most cats after a variable disease- FeLV provirus, but most feline lymphomas are now
free interval. The mortality rate in persistent caused by factors other than FeLV.
FeLV-positive cats is 30% at 6 months, 60% at 2 years,
and 90% at 4 years. Alimentary Lymphoma
• Persistent infection will develop in approximately
• Mesenteric lymph nodes—Palpable enlargement
10% to 30% of unvaccinated cats that receive con-
tinuous heavy exposure, such as living in an end-
• Stomach—Vomiting, anorexia, and weight loss
emically infected household. In this situation, kittens
• Intestine—Diffuse infiltrative thickening of the
intestinal wall or palpable obstructing mass (weight
less than 4 months of age are most susceptible, and
loss, vomiting, diarrhea, and inappetence)
the persistent infection rate can reach 70% in this
group.
• Liver—Diffuse hepatomegaly or nodular tumor
masses within the liver (icterus, weight loss, vomiting,
• Vaccination prevents persistent infection in many
and abnormal liver tests)
cats. Reducing the risk of exposure combined with
vaccination has greatly decreased the prevalence of
• Spleen—Diffuse splenomegaly
persistent FeLV infection.
▼ Key Point FeLV-negative alimentary lymphoma
affecting middle-aged and older cats (mean age of
CLINICAL DISEASE SYNDROMES 8 years) is now the predominant form of lym-
phoma in cats.
The clinical manifestations of FeLV are attributable to
the oncogenic, cytopathic, and immunosuppressive Mediastinal Lymphoma
effects of the virus. FeLV-induced neoplasia can be lym-
Characterized by a cranial mediastinal mass due to lym-
phoid or myeloid. Degenerative and cytopathic effects
phoma of the mediastinal lymph nodes or thymus.
on various cells include bone marrow cells (anemia,
neutropenia, thrombocytopenia), lymphocytes (T lym- • Pleural effusion (dyspnea)
phocyte depletion, lymphoid atrophy, lymphoid hyper- • Tracheal compression (dyspnea, cough)
plasia), intestinal cells (enteritis), and the fetus and • Esophageal compression (dysphagia, regurgitation)
placenta (abortion, stillbirth). The immunosuppressive • Sympathetic trunk impingement (Horner’s
effects of FeLV cause profound immunodeficiency, syndrome)
resulting in susceptibility to a wide variety of oppor- • Decreased cranial thoracic compressibility
tunistic infections. In addition, FeLV-related immune • Mass palpable at thoracic inlet
W0422-Ch008.qxd 11/10/05 4:45 PM Page 118
▼ Key Point ELISA and other IC screening tests detect Witness FeLV Synbiotics Membrane rapid
soluble FeLV antigen in serum or plasma (antigen- immunomigration
ViraCHEK/FeLV Synbiotics Microwell ELISA
emia). The IFA test detects intracellular virus in ASSURE/FeLV Synbiotics Saliva wand and tube
circulating leukocytes and platelets (cell-associated ELISA
viremia), indicating bone marrow infection. SNAP FeLV IDEXX Membrane ELISA
SNAP FIV/FeLV IDEXX Membrane ELISA (also
Combo tests for FIV)
Indications for FeLV Testing
The American Association of Feline Practitioners rec- ELISA, enzyme-linked immunosorbent assay; FeLV, feline leukemia virus;
ommends that the FeLV status of all cats should be FIV, feline immunodeficiency virus; IC, immunochromatographic.
W0422-Ch008.qxd 11/10/05 4:45 PM Page 121
The IFA test is a confirmatory test performed by com- Polymerase Chain Reaction Testing
mercial labs to detect FeLV p27 antigen within the cyto-
PCR is a highly sensitive confirmatory test that detects
plasm of circulating neutrophils and platelets on blood
FeLV nucleic acid sequences in blood, bone marrow, or
smears. A positive IFA indicates established FeLV infec-
biopsy specimens. PCR requires special laboratory
tion involving the bone marrow.
expertise and a validated assay; thus, PCR is not yet widely
• The IFA test is very specific for FeLV and is highly cor- available. Improper sample handling or technique can
related with persistent infection and the results of readily cause inaccurate results with PCR assays.
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• For routine blood testing, PCR has no significant Prevent sharing of food and water dishes, litter pans,
advantage over conventional FeLV tests; however, and any other item that could be a source of cross-
PCR may be helpful for determining the true status contamination. Vaccinate all uninfected cats, but it is
of cats with discordant results on conventional important to recognize that vaccination alone will not
tests. prevent infection in all cats.
• PCR may be useful for detecting latent (non- • Spay or neuter FeLV-infected cats. This prevents
replicating but reactivatable) FeLV infection. mother-to-kitten transmission in utero or via infected
milk. It also reduces roaming, aggression, and other
Virus Isolation stressful behaviors of sexually intact cats.
Isolation of FeLV by culturing the virus from blood or
bone marrow is a confirmatory test used primarily in General Health Care
research and is not readily available for clinical use. It • Feed cats a nutritionally balanced and complete
is the preferred “gold standard” for validating the accu- feline diet. Do not cats feed raw meat, uncooked eggs,
racy of other testing methods. Bone marrow culture can or unpasteurized milk, because the risk of food-borne
be used to detect latent, non-replicating, but reactivat- bacterial and parasitic infections is higher in
able FeLV infection. immunocompromised cats.
• Provide optimal wellness care, including parasite
Neutralizing Antibody Tests control, core vaccinations, dental care, and a thor-
ough semi-annual physical examination with a CBC,
Serum neutralizing antibody titers are of limited use-
blood chemistry profile, urinalysis, and fecal exami-
fulness in the diagnosis or clinical evaluation of FeLV
nation. This facilitates early detection and treatment
infection. A positive titer merely indicates prior expo-
of FeLV-related conditions.
sure to FeLV through infection or vaccination, but a
titer does not confirm current active infection. Vaccine-
• Diagnose and treat secondary infections that arise
because of immunosuppression promptly and
induced antibody titers do not correlate well with the
aggressively.
level of protective immunity.
• Avoid using corticosteroids and other immunosup-
pressive drugs except when clearly indicated.
TREATMENT
Antiviral Therapy
There is no proven effective treatment for FeLV, Antiviral drugs are intended to directly inhibit virus
although various immune modulator and antiviral infection and replication. Many anti-retroviral drugs
drugs have been used. The quality of life and possibly developed for humans are not suitable for treatment of
longevity of FeLV-infected cats are enhanced by general cats because of excessive toxicity, prohibitive cost, or
health care, palliative therapy, and treatment of sec- lack of availability. Protease inhibitors developed for
ondary infections that arise. humans are species specific and not effective in cats.
Two antiviral agents that may have a role in treating
General Recommendations FeLV are interferons and zidovudine (AZT). Cats
treated with antiviral drugs remain FeLV positive.
When a cat is found to be FeLV positive, optimize
general wellness care for the cat and take measures to
prevent the spread of infection to other cats. FeLV- Interferons
infected cats can live for months to several years, espe- Recombinant forms of interferon given parenterally in
cially healthy carriers identified on routine screening high doses can have both antiviral and immunomodu-
tests. The decision to treat or euthanize a cat with FeLV latory effects.
infection is an individual decision based on factors
other than just the results of FeLV tests. Feline Interferon-Omega
Recombinant feline interferon-omega (rFeIFN-w)
Preventing the Spread of Infection (Virbagen Omega, Virbac) has become available in
• Confine FeLV-infected cats indoors to prevent the Europe, and preliminary results look promising for
spread of infection to other cats and to reduce the treatment of FeLV. A placebo-controlled study in 81
cat’s exposure to infectious agents carried by other FeLV-infected cats showed significant benefit in survival
animals. rate, clinical signs, and hematologic parameters with
• If the cat lives in a multi-cat household, test all other rFeIFN-w given at 1,000,000 U/kg SC daily for 5 con-
cats and separate infected and uninfected cats. It is secutive days in three cycles beginning on day 0, 14, and
especially important that FeLV-infected cats be iso- 60. No serious adverse effects were seen. Expense could
lated from kittens, because they are most susceptible. be prohibitive for some owners.
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Kittens less than 4 months of age are most suscepti- sarcoma. However, the risk of vaccine-associated
ble; thus, keep kittens isolated from other cats to mini- sarcoma may be greater than the risk of FeLV infec-
mize the risk of FeLV infection. tion in well-controlled catteries and for indoor pet
cats where the prevalence of infection is virtually non-
Vaccination existent today.
Adjuvanted and non-adjuvanted inactivated parenteral
vaccines and a canary pox-vectored transdermal vaccine Efficacy
are currently available for prevention of FeLV. The pros • In general, many vaccinated cats that are exposed to
and cons of FeLV vaccination are controversial, but FeLV develop transient viremia and sometimes latent
overall, FeLV vaccine is considered a “non-core” vaccine infection despite vaccination; however, most vacci-
that is used according to an individual benefit-risk nated cats apparently are protected against persistent
assessment of each patient (see Chapter 7). viremia and therefore against FeLV-related disease.
• As a general guideline for discussing vaccination
Indications expectations with animal owners, expect 70% to 90%
• Vaccination is recommended for cats with potential of vaccinated cats older than 4 months of age to be
risk of exposure to FeLV, especially kittens. This protected against persistent FeLV infection.
should include cats allowed outdoors, cats living in
multi-cat households with infected cats, or cats Control in Multi-cat Households and Catteries
exposed to other cats of unknown status.
• Vaccination is not recommended for mature cats with Control in FeLV-Positive Catteries
minimal to no risk of exposure, such as cats restricted The following “test and removal program” is highly
to closed, indoor, FeLV-negative environments. effective for eliminating FeLV from a household or
cattery:
▼ Key Point Vaccination is most indicated for cats
living in multi-cat households (and shelters) with • Test all cats on the premises for FeLV (up to 30% may
frequent exposure to new cats and for outdoor cats
be persistently infected), and remove or strictly
at risk of contact with other cats of unknown health
isolate all confirmed FeLV-positive cats.
status. • Quarantine the cattery so that there is no movement
of new cats into the cattery.
Administration • Vaccinate all FeLV-negative cats.
• Clean and disinfect the premises.
• If vaccination is deemed appropriate, administer two • Clean and disinfect or replace food and water dishes,
doses of vaccine 3 to 4 weeks apart, beginning as early litter pans, bedding, and toys.
as 8 weeks of age, followed by an annual booster (see • If infected and uninfected cats are separated but
Chapter 7). Give FeLV vaccines subcutaneously in the remain in the same household or facility, caretakers
lateral aspect of the distal left rear limb. must take special precautions to prevent cross-
• FeLV testing at or before the first vaccination is highly contamination.
recommended. There is no proven beneficial or • Retest all cats every 1 to 3 months and continue to
detrimental effect from vaccinating a cat for FeLV remove any confirmed FeLV-positive cats.
that already is infected. • Once all cats on the premises have had negative
results on two successive tests 3 months apart, the
Adverse Vaccine Effects cattery is considered “FeLV free.”
• Acute side effects are infrequent and include local • Then isolate all new incoming cats and test as
swelling or pain, transient listlessness or fever, and described in the following section.
injection site granuloma. Acute hypersensitivity signs
(face and paw edema, vomiting, diarrhea, collapse) Control in FeLV-Negative Catteries
occur rarely. These effects are attributable mostly to
The following precautions should be taken for incom-
adjuvants.
ing cats:
• Inflammatory nodules occasionally develop at the
vaccination site. These can develop into vaccine- • Obtain incoming cats from a source with a negative
associated sarcomas in some cats weeks to years later FeLV history.
(incidence is 1 per 10,000 vaccines). Excise or biopsy • Screen incoming cats with ELISA; if test results are
vaccination site lesions if they persist more than 3 negative, vaccinate and then hold them in isolation
months, are larger than 2 cm, or increase in size 1 for 3 months (in case they were recently exposed and
month post-injection. are incubating FeLV).
• For cats at risk of exposure, the benefits of FeLV • After a second ELISA-negative result at the end of the
vaccination far outweigh the risk of injection site 3-month quarantine, new cats can join the cattery.
W0422-Ch008.qxd 11/10/05 4:45 PM Page 125
• ELISA-positive results should be confirmed by IFA or virus in unowned free-roaming cats. J Am Vet Med Assoc
repeat ELISA; however, in cattery situations, the safest 220:620–622, 2002.
Levy JK, Crawford PC: Feline leukemia virus. In Ettinger SJ (ed): Text-
course is to consider any cat that has been ELISA pos- book of Veterinary Internal Medicine, 6th ed. St. Louis: Elsevier,
itive at any time as too risky to allow into the cattery. 2006, pp 653–659.
Levy JK, Richards J, Edwards D, et al: 2001 Report of the American
Association of Feline Practitioners and Academy of Feline Medi-
cine Advisory Panel on Feline Retrovirus Testing and Management.
J Feline Med Surg 5:3–10, 2003.
SUPPLEMENTAL READING Levy JK, et al: Feline retrovirus testing and management, Compend
Contin Ed Pract Vet 23:652, 2001.
de Mari K, Maynard L, Sanquer A, et al: Therapeutic effects of recom- McCaw DL, Boon GD, Jergens AE, et al: Immunomodulation therapy
binant feline interferon-omega on feline leukemia virus (FeLV)- for feline leukemia virus infection. J Am Anim Hosp Assoc 37:356,
infected and FeLV/feline immunodeficiency virus (FIV)-coinfected 2001.
symptomatic cats. J Vet Intern Med 18:477–482, 2004. Richter KP: Feline gastrointestinal lymphoma. Vet Clin North Am
Elston T, Rodan I, Flemming D, et al: 2000 Report of the American Small Anim Pract 33:1083–1098, 2003.
Association of Feline Practioners and Academy of Feline Medicine Rojko JL, Hardy WD Jr: Feline leukemia virus and other retroviruses.
Advisory Panel on Feline Vaccines. Available at http://www. In Sherding RG (ed): The Cat: Diseases and Clinical Management,
aafponline.org. 2nd ed. Philadelphia: WB Saunders, 1994, p 263.
Hartmann K: Feline leukemia virus infection. In Greene CE (ed.): Sparkes AH: Feline leukaemia virus and vaccination. J Fel Med Surg
Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis: Elsevier, 5:97, 2003.
2006, pp 106–132. Torres AN, Mathiason CK, Hoover EA: Re-examination of feline
Lee IT, Levy JK, Gorman SP, et al: Prevalence of feline leukemia virus leukemia virus: Host relationships using real-time PCR. Virology
infection and serum antibodies against feline immunodeficiency 332:272–283, 2005.
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▼ Chapter
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Assays using PCR are not yet sufficiently reliable or Immunofluorescent Antibody Test
standardized to be recommended for routine clinical
diagnosis. • Available in some commercial laboratories
• Accuracy comparable to ELISA tests but less
convenient
Indications for Feline Immunodeficiency
Virus Testing Western Blot Test
• When cats are sick • Detects antibodies against specific viral proteins, and
• Healthy cats not previously tested is considered the “gold standard” for confirming
• Newly adopted cats ELISA-positive results
• Cats with potential exposure, such as bite wounds • Available in research and commercial laboratories
from any cat of unknown FIV status
• Before vaccinating cats with FIV vaccine
• Annual retesting of cats with high risk of exposure, Assays to Detect Virus
such as cats living with an FIV-positive cat or going • Virus isolation and PCR assays can be used to detect
outdoors unsupervised FIV in the blood, tissues, or body fluids of infected
cats.
Assays for Antibody
PCR Assay
▼ Key Point A confirmed positive FIV antibody test • FIV is difficult to detect reliably by PCR because of
indicates persistent, lifelong FIV infection, except wide genetic variability among field strains and
when interpretation is unclear because of anti- because of low virus levels in blood during the pro-
bodies induced by prior FIV vaccination or because longed asymptomatic latent phase of infection when
of passively acquired maternal antibodies in young most testing is performed.
kittens (<6 months of age). • PCR assays would theoretically be useful in place of
the antibody tests for early detection of infection
• Seroconversion usually occurs within 4 to 6 weeks prior to seroconversion and for diagnosis of terminal
after exposure; however, this is highly variable and it stages of infection when antigen levels may be high
can take up to 6 months for FIV antibodies to appear and antibody levels are depressed. Virus assays could
in some cats. also be used as an alternative to antibody testing in
• Maternal FIV antibodies acquired from colostrum in vaccinated cats.
nursing kittens can cause positive test results in unin- • Based on the rate of false-positive and false-negative
fected kittens up to 6 months of age; thus, reevaluate results, commercial PCR assays for FIV are generally
all positive kittens at 2-month intervals until 6 months too unreliable to be recommended. Although PCR
of age to determine whether they are infected or assays are promising for the future, currently avail-
not. able commercial assays are not yet adequately stan-
dardized or validated. In addition, it is uncertain
▼ Key Point Regardless of whether a positive or neg- whether PCR assays detect all field strains of FIV
ative test result is obtained for FIV antibody, all found in cats.
kittens younger than 6 months of age must be
retested after they reach 6 months of age to deter- Virus Isolation
mine their actual status.
• Virus isolation (culture) is a valuable research tool
but is too impractical for use as a clinical diagnostic
ELISA Antibody Test aid.
• ELISAs are sensitive, accurate, and considered the
preferred screening tests for FIV.
• ELISAs are simple and rapid enough for convenient TREATMENT
in-office or point-of-care screening, such as SNAP
FIV/FeLV Combo (IDEXX) that tests simultaneously ▼ Key Point No currently available treatment is effec-
for FIV antibodies and FeLV antigen. tive for eliminating FIV once infection is estab-
• Occasional false positives occur; thus, confirm all pos- lished; thus, assume that confirmed infections are
itive ELISA results by Western blot or IFA at a com- lifelong and incurable.
mercial lab.
• False-negative results can occur in the early stages of • Even though FIV is incurable, healthy FIV-positive
acute infection before seroconversion has occurred cats can live for years before developing clinical signs,
or rarely in the terminal stages of immunodeficiency and symptomatic cats often can be managed for
when antibody levels can fall below detectable levels. months to years with supportive care, antiviral
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therapy, immune modulators, and antibiotics as results look promising for treatment of feline
needed to control secondary infections. leukemia virus and possibly FIV. Treatment with
• The goal of therapy in FIV is to decrease the virus rFeIFN-w (Virbagen Omega, Virbac) is given at
load with antiviral therapy or to increase the host 1,000,000 U/kg SC daily for 5 consecutive days in
immune response through immune modulator drugs. three cycles beginning on day 0, 14, and 60. Expense
Although some studies have shown clinical improve- will be prohibitive for some owners.
ment in sick FIV-positive cats with these treatments, • A parenteral high dose (100,000–1,000,000 U/kg) of
there is little or no evidence that immune modulation recombinant human interferon-alpha (rHuIFN-a)
and antiviral therapy benefit health or increase (Roferon, Hoffman-LaRoche; Intron-A, Schering-
longevity in otherwise healthy FIV-infected cats. Plough) may initially decrease virus load, but this is
unlikely to be effective long term because cats
Specific Antiviral Therapy develop antibodies against the human protein after 6
to 7 weeks that inhibit the drug’s activity.
• Current and future antiretroviral therapies devel-
oped for human immunodeficiency virus (HIV) may
Other Antiviral Drugs
or may not be applicable to cats. Many of these drugs
have not been suitable for treatment of FIV because • Stampidine, an experimental nucleoside reverse tran-
of excessive toxicity, lack of efficacy, prohibitive cost, scriptase inhibitor, shows promise as a future treat-
or lack of availability. ment for FIV. In a preliminary study in chronically
FIV-infected cats, stampidine given orally significantly
Zidovudine decreased the virus load with minimal side effects.
• Zidovudine, a nucleoside reverse transcriptase • Protease inhibitors are a class of drugs that are fre-
inhibitor also known as AZT, is the most well-studied quently used to treat humans with HIV; however,
antiviral for treating FIV infection. In cats infected protease inhibitors developed for HIV are species
with FIV, zidovudine inhibits viral replication, specific and not effective against FIV.
decreases virus burden, improves immunologic para-
meters (such as the CD4/CD8 ratio), reduces clinical
Immune Modulator Therapy
disease, and increases survival time. One placebo- • Immune modulators are intended to stimulate the
controlled study showed regression of FIV stomatitis. compromised immune function of FIV-infected cats.
Clinical improvement in various other FIV-related Anecdotal reports of clinical improvement with these
manifestations is reported. agents have not been substantiated by controlled
• Give zidovudine (Retrovir, GlaxoSmithKline) at studies; thus, conclusive evidence of efficacy is
dosages of 5 mg/kg PO or SC q12h. Compound oral lacking.
AZT in gelatin capsules or flavored syrup. Dilute • Immune modulator agents that have been used to
injectable AZT in 5 ml of isotonic sodium chloride to treat FIV include low-dose oral human interferon-
reduce local irritation. alpha (Roferon, Hoffman-LaRoche; Intron-A,
• Zidovudine has been well tolerated in cats treated for Schering-Plough; 30 units PO, daily on alternate
over 2 years. However, the drug is myelosuppressive, weeks), bovine lactoferrin (40 mg/kg PO q24h),
so monitor the complete blood count for non- acemannan (Carrisyn, Carrington Labs), Propioni-
regenerative anemia. Mild anemia in the first weeks bacterium acnes (ImmunoRegulin; ImmunoVet), and
of treatment is common and usually resolves. If Staphylococcus protein A (SPA).
the packed cell volume (PCV) drops below 20%, dis-
continue treatment until PCV recovers (usually 2–3 General Supportive Therapy
weeks), then restart at half the original dose. • Use antibiotics to treat cats with FIV-related bacterial
• Unfortunately, mutation of the virus allows drug- infections, using culture and sensitivity guidance
resistant strains to emerge after several months of whenever possible. Response to antibiotics can be
therapy. dramatic in some cases.
Interferon
• For palliative treatment of stomatitis, use metroni-
dazole (10 mg/kg PO q12h) and clindamycin
• Recombinant forms of interferon given parenterally (12.5 mg/kg PO q12h). Stomatitis may also improve
in high doses can have both antiviral and with the immunotherapeutic agent, bovine lacto-
immunomodulatory effects. Feline interferon-omega ferrin (40 mg/kg PO or topically q24h), zidovudine
and human interferon-alpha have both been shown (see “Specific Antiviral Therapy”), or anti-inflamma-
to significantly inhibit replication of FIV, but feline tory doses of prednisolone (5 mg/cat PO q12h). Full-
interferon-gamma has no antiviral effect and actually mouth dental extraction is required in refractory
enhances FIV replication. cases.
• Recombinant feline interferon-omega (rFeIFN-w) • Use fluid therapy and nutritional support as indi-
has become available in Europe, and preliminary cated by the patient’s needs.
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• Keep FIV-positive cats indoors to prevent exposure of • Immediately prior to vaccinating any cat for FIV, first
the immunosuppressed cat to infectious diseases determine that the FIV antibody test is negative.
carried by other animals and to decrease the spread
of FIV to other cats. ▼ Key Point FIV antibodies from vaccination and
• Continue routine vaccinations in FIV-positive cats, infection are indistinguishable; thus, cats vacci-
although killed products are preferred. Studies have nated for FIV will be positive for FIV antibodies for
shown FIV does not interfere with the response to at least 12 months, thereby eliminating the diag-
vaccination until the terminal stages. nostic usefulness of FIV antibody tests.
• Avoid the use of griseofulvin to treat dermatophytes
in FIV-positive cats because of an increased risk of • Kittens born to vaccinated queens will be positive for
griseofulvin-induced neutropenia. passively acquired FIV antibodies for up to 12 weeks.
• An effective vaccine for HIV in humans has yet to be
developed despite intensive efforts. New vaccine
PROGNOSIS strategies are under development for both HIV and
FIV. The natural host immune response to FIV infec-
Healthy FIV-positive cats can live for several years before tion is almost never effective, and what is needed
developing clinical signs. Even symptomatic cats can live to elicit protective immunity is not yet understood.
for months to years with good quality of life. In one This suggests that conventional approaches to
study of FIV-positive cats, 18% died in the first 2 years vaccine development may not be successful for these
and another 18% had progression of clinical signs; lentiviruses.
however, more than 50% remained asymptomatic for
the 2-year follow-up period.
SUPPLEMENTAL READING
PREVENTION Bienzle D, Reggeti F, Wen X, et al: The variability of serological and
molecular diagnosis of feline immunodeficiency virus infection.
Can Vet J 45:753–757, 2004.
Prevent Exposure Burkhard MJ, Dean GA: Transmission and immunopathogenesis of
FIV in cats as a model for HIV. Curr HIV Res 1:15–29, 2003.
▼ Key Point The best prevention for FIV is to prevent DeMari K, Maynard L, Sanquer A, et al: Therapeutic effects of recom-
cats from roaming freely outdoors. binant feline interferon-omega on feline leukemia virus (FeLV)-
infected and FeLV/feline immunodeficiency virus (FIV)-coinfected
symptomatic cats. J Vet Intern Med 18:477–482, 2004.
• Spay and neuter cats that go outdoors to reduce Hartmann, K: Feline immunodeficiency virus infection and related
roaming and fighting behavior. diseases. In Ettinger SJ (ed): Textbook of Veterinary Internal Med-
• Prevent exposure to high-risk cats, such as stray and icine, 5th ed. St. Louis: Elsevier, 2006, pp 659–662.
feral cats or untested outdoor cats. Levy JK: CVT update: Feline immunodeficiency virus. In Bonagura JD
(ed): Kirk’s current veterinary therapy XIII small animal practice.
• Keep infected cats indoors and isolated from unin- Philadelphia: WB Saunders, 2000, p 284.
fected cats to reduce the risk to other cats. The risk Levy JK, Crawford PC, Slater MR: Effect of vaccination against feline
of transmission among housemates that do not fight immunodeficiency virus on results of serologic testing in cats. J Am
is considered low but possible. Vet Med Assoc 225:1558–1561, 2004.
• Spay and neuter FIV-positive cats. It is especially MacDonald K, Levy JK, Tucker SJ, et al: Effects of passive transfer of
immunity on results of diagnostic tests for antibodies against feline
important to remove FIV-infected females from immunodeficiency virus in kittens born to vaccinated queens. J Am
breeding programs. Vet Med Assoc 225:1554–1557, 2004.
Proceedings of the Sixth International Feline Retrovirus Research
Vaccination Symposium, Amelia Island, FL, December 2–5, 2002.
Sellon RK, Hartmann K: Feline immunodeficiency virus infection. In
• A killed, adjuvanted, dual-subtype, whole-virus FIV Greene CE (ed): Infectious Diseases of the Dog and Cat, 3rd ed.
vaccine is currently available that contains FIV sub- St. Louis: Elsevier, 2006, pp 132–144.
Uckun FM, Chen CL, Samuel P, et al: In vivo antiretroviral activity of
types A and D (Fel-O-Vax FIV, Fort Dodge). The stampidine in chronically feline immunodeficiency virus-infected
range of crossprotection against the other natural cats. Antimicrob Agents Chemother 47:1233–1240, 2003.
subtypes of FIV is uncertain. Until additional evi- Uhl EW, Heaton-Jones TG, Pu R, Yamamoto JK: FIV vaccine devel-
dence of efficacy in the field becomes available, FIV opment and its importance to veterinary and human medicine: A
vaccination is not recommended as a core vaccine for review: FIV vaccine 2002 update and review. Vet Immunol
Immunopathol 90:113–132, 2002.
cats.
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▼ Chapter
Feline infectious peritonitis (FIP) is a progressive and Pathogenesis of Feline Infectious Peritonitis
highly fatal systemic disease of cats caused by feline
coronavirus. Feline coronavirus most frequently causes ▼ Key Point FIP-causing coronaviruses are genetic
inapparent enteric infection with fecal shedding mutants of harmless enteric FCoV.
of virus. Mild enteritis and diarrhea are seen rarely
(see Chapter 14). A mutation of feline coronavirus • It was previously thought that cats were infected by
during intestinal replication enables it to infect two similar but distinct coronaviruses, the innocuous
macrophages and cause FIP. Despite its name, the feline enteric coronavirus and the deadly FIP virus,
lesions of FIP are widespread and not restricted to but these are now considered phenotypic variants
the peritoneum. Effusive and non-effusive forms of (biotypes) of the same virus. The non-mutated
FIP occur. Since its recognition in the 1950s, FIP enterotropic FCoV typically causes a clinically inap-
has been one of the most studied diseases of cats, parent infection of intestinal epithelial cells with fecal
yet a definitive diagnostic test, an effective treatment, shedding of virus. During replication in the cat’s
and a reliable vaccine are lacking. With the decline intestinal tract, FCoV mutates frequently, especially in
in prevalence of feline leukemia virus from vaccination, kittens, and this sporadically results in critical genetic
FIP has become the deadliest infectious disease of mutations that enable FCoV to infect and replicate in
cats. macrophages.
132
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• Natural immunity to FCoV is poorly understood but ▼ Key Point Most cats with FIP come from catteries
is presumed to be cell mediated rather than antibody
and shelters.
mediated. Circulating FCoV antibodies can actually
enhance progression of the disease.
• Any factor that increases FCoV replication in the
intestines of an infected cat will increase the proba-
bility of the virus mutating to a form that can cause
EPIDEMIOLOGY FIP. Thus, viral load, stress, immune impairment, cor-
ticosteroids, surgery, and concurrent disease (e.g.,
Prevalence feline leukemia virus or feline immunodeficiency
virus) can be risk factors for FIP.
• FCoV is ubiquitous in cats worldwide. In many • Inherited genetic susceptibility to FIP is a factor in
regions, 50% of cats are positive for coronaviral anti-
some purebred cats and in cheetahs.
bodies (i.e., seroprevalence). The majority of these
seropositive cats represent current or past inapparent
infection with non-mutated FCoV. Only some of these Transmission
develop into mutated FIP-causing infections; thus, • FCoV is primarily excreted in feces from cats with
the prevalence of FIP is much lower. inapparent enteric infection. Healthy carriers often
• The prevalence of FCoV infection is highest in cats shed FCoV in their feces for at least 10 months, and
confined in crowded groups, such as catteries, shel- some cats shed persistently for many years, possibly
ters, and multiple cat households, where the sero- for life. One-third of healthy FCoV-seropositive cats
prevalence ranges from 50% to 90%. are actively shedding virus. In high-density endemic
• In endemic catteries where the seroprevalence catteries, up to 60% of healthy cats may be shedding
approaches 90%, most FCoV-infected cats remain virus at any given time.
healthy and only 5% develop FIP. • FCoV is usually inactivated in 24 to 48 hours at room
• The seroprevalence of FCoV in free-roaming feral temperature, but the virus can survive up to 7 weeks
and stray cats is 12% to 15%. The lower prevalence is in dried fecal debris; thus, environmental contami-
presumed to relate to less social interaction and less nation with small particles of used litter is an impor-
exposure to fecally excreted virus than cattery cats. tant source of infection. Contaminated surfaces, food
• The seroprevalence in single-cat households is 15% and water dishes, and human clothing, shoes, and
or less. hands can act as fomites. Most disinfectants and
• In a large survey of North American veterinary teach- detergents easily destroy FCoV.
ing hospitals, FIP was diagnosed in 1 of every 200 new • Transmission to uninfected cats most frequently
feline accessions. This population mostly represents occurs through oronasal contact with virus-
sick cats seen by veterinarians. containing feces or contaminated material from the
• FCoV can infect most wild felids, including the lion, environment. Contaminated litter and dust particles
cougar, cheetah, jaguar, leopard, bobcat, sand cat, deposited on the fur are ingested during normal
caracal, serval, and lynx. Cheetahs are especially sus- grooming activity.
ceptible to developing FIP.
• Abdominal effusion is confirmed by radiography, over the surface and infiltrating throughout the renal
ultrasonography, or abdominocentesis, and the cortex.
results of fluid analysis are highly indicative of FIP • Extensive renal involvement occasionally causes
(see “Diagnosis”). renal failure with polyuria-polydipsia and azotemia
(increased blood urea nitrogen [BUN] and serum
Thoracic Effusion (Pleuritis) creatinine).
• Proteinuria is a frequent laboratory finding in renal
• Dyspnea, tachypnea, and exercise intolerance are the FIP. In addition, large quantities of circulating
major presenting signs because lung expansion is immune complexes may lead to subclinical glomeru-
restricted by compression from fluid in the pleural lonephritis with any of the other forms of effusive and
space. non-effusive FIP.
• Cats with pleural effusion may prefer a sitting or
sternal recumbent posture to facilitate breathing. Liver Disease
Increased respiratory distress may occur with exercise,
with physical restraint in the hospital, or with reposi- • Pyogranulomatous hepatitis (hepatomegaly, jaun-
tioning in lateral recumbency (i.e., orthopnea). dice, and signs of hepatic failure) may occur in FIP.
• Thoracic effusion may cause muffled heart and lung • The most consistent laboratory abnormalities are
sounds on auscultation and hyporesonance and a bilirubinuria and hyperbilirubinemia. Mild to mod-
horizontal fluid line on thoracic percussion. erate elevations of serum liver enzymes (alanine
• Thoracic effusion is confirmed by radiography or tho- aminotransferase, alkaline phosphatase) and serum
racocentesis (see Chapter 164). The results of fluid bile acids also may occur.
analysis are highly indicative of FIP (see “Diagnosis”).
Disease in Other Abdominal Organs
Pericardial Effusion • Pyogranulomatous lesions may cause palpable
• Pericardial effusion due to fibrinous pericarditis may enlargement of the visceral lymph nodes, spleen, or
occur in FIP, with or without other effusions. In one omentum.
survey, FIP was the second most frequent cause of • Pyogranulomatous enterocolitis may cause diarrhea
feline pericardial effusion, accounting for 14% of and diffuse or masslike intestinal thickening, espe-
cases. cially in the ileocecocolonic region.
• Pericardial effusion in FIP does not usually cause • Pancreatic involvement can occasionally cause pan-
overt clinical signs. It may be suspected from auscul- creatitis and, rarely, diabetes mellitus.
tation (muffled heart sounds), thoracic radiography,
or electrocardiography, and it is confirmed by Ocular Disease
echocardiography (see Chapter 151). • Ocular lesions of FIP are usually bilateral and affect
the vascular tunic or uvea (uveitis). Lesions may
Non-effusive (Dry) Form of Feline sometimes cause blindness.
Infectious Peritonitis • Manifestations of exudative anterior uveitis (iridocy-
clitis) may include miosis, aqueous flare, keratic fi-
▼ Key Point The non-effusive (dry) form of FIP is brinocellular precipitates, hypopyon (“mutton-fat”
characterized by multifocal pyogranulomatous deposits of cells and fibrin), hyphema, anterior
inflammation and necrotizing vasculitis in various chamber adhesions (synechia), corneal edema, and
organs, such as the abdominal viscera (e.g., liver, deep neovascularization of the cornea (see Chapter
spleen, kidneys, pancreas, and intestines), eyes, 136).
central nervous system (CNS), and lungs. • Chorioretinitis from posterior uveal involvement
is detected by ophthalmoscopic examination and
Pyogranulomas appear as multiple discreet or coa- may include perivascular cuffing, exudative retinal
lescing gray-white nodular masses of variable size on the detachment, and retinal hemorrhages (see Chapter
surface and within the parenchyma of affected organs. 138).
These are often mistaken for tumors. Effusion is often
minimal or absent. The specific organs affected and the Neurologic Disease
degree of resulting organ failure determine the pre-
senting clinical signs.
• Multifocal pyogranulomatous meningoencephalitis
and myelitis are frequent in FIP. Inflammatory lesions
are perivascular and often involve the meningeal and
Kidney Disease ependymal layers. In one report, 29% of cats with FIP
• Pyogranulomatous nephritis causes the kidneys to developed neurologic signs. In a retrospective survey
become palpably enlarged, firm, and irregular of 286 cats with neurologic disease, lesions indicating
(“lumpy”), associated with pyogranulomas scattered FIP of the CNS were found in 16%. In another large
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survey, FIP was the most common spinal disease in Intestinal Biopsy
cats.
• The neuroanatomic distribution of the lesions deter-
• Intestinal biopsy shows nonspecific lesions of villous
tip injury, with stunting and fusion of villi.
mines clinical signs; some of the most common are
ataxia, tremors, vestibular dysfunction, seizures,
• Immunofluorescence or immunohistochemical stain-
ing for viral antigen in intestinal biopsies is confir-
posterior paresis, hyperesthesia, and behavioral
matory.
changes. The relentless progression and multifocal
nature of the signs are characteristic features of
neural FIP. DIAGNOSIS OF FELINE INFECTIOUS
• Neuropathies occasionally involve the cranial nerves
PERITONITIS
(e.g., trigeminal or facial) or peripheral nerves (e.g.,
brachial or sciatic).
The diagnosis of FIP is usually suspected from clinical
• Cats with neural FIP often develop secondary hydro-
signs and the results of routine laboratory evaluations
cephalus when the inflammatory process obstructs
(see Table 10-1). There is no single reliable confirma-
the flow of cerebrospinal fluid (CSF). In one study of
tory test for FIP; thus, base the clinical diagnosis of FIP
24 cats with neural FIP, 75% had hydrocephalus.
on the combined results of well-chosen laboratory
Dilatation of the ventricular and central canal system
evaluations (e.g., hematology, serum chemistry, cyto-
is identified on computed tomography (CT) and
logy, serology, and virology), diagnostic imaging, and
magnetic resonance imaging (MRI) scans. Meningeal
histopathology (Table 10-2).
enhancement also is seen on MRI.
• The diagnosis of neural FIP depends on CSF analysis ▼ Key Point Clinical signs and laboratory abnormali-
(see the section on diagnosis). ties in cats with FIP are not specific for the disease;
however, collectively these may provide strong cir-
Pulmonary Disease cumstantial evidence for a presumptive diagnosis
• Pyogranulomatous pneumonia can be found in cats of FIP.
with FIP on thoracic radiographs or at necropsy, but
in most cases this is clinically silent or only causes a
Routine Laboratory Evaluations
mild cough. • Hematology often reveals nonspecific abnormalities
• This appears radiographically as a diffuse, poorly reflecting the chronic inflammatory response, such
defined, patchy or nodular interstitial pulmonary as nonregenerative anemia, neutrophilic leukocytosis
infiltrate. or leukopenia, and stress lymphopenia.
• Total serum protein and serum globulins (especially
Reproductive Disease gamma and alpha2) are increased by the chronic
immune stimulation in 70% of non-effusive cases and
• Testicular enlargement caused by pyogranulomatous 50% of effusive cases, whereas serum albumin is often
orchitis has been reported in FIP. decreased. One study showed that a decreased serum
• Contrary to what has been speculated in the past, albumin-to-globulin ratio (A/G < 0.8) indicates a
FCoV is not directly associated with cattery repro- high probability of FIP (92% positive predictive
ductive problems, neonatal deaths, or birth of weak value); while an A/G > 0.8 suggests that FIP is unlikely
or “fading” kittens. (61% negative predictive value). Serum protein elec-
trophoresis is usually not necessary.
• Serum chemistries may detect involvement of abdom-
DIAGNOSIS OF ENTERIC inal organs such as the liver (increased serum liver
FELINE CORONAVIRUS enzymes, bilirubin, and bile acids), kidneys
(increased creatinine and BUN), or pancreas
Fecal Virus Detection (increased pancreatic lipase immunoreactivity).
• Non-mutated FCoV infection is characterized by per- • Urinalysis findings may include proteinuria or
sistent viral replication in enterocytes and fecal shed- bilirubinuria.
ding of virus. Active fecal shedding of FCoV can be • Disseminated intravascular coagulation sometimes
confirmed by reverse transcription polymerase chain develops in FIP, resulting in prolonged coagulation
reaction (RT-PCR) assay of feces (see the later section times, decreased platelets, and increased fibrin
on RT-PCR assay) or by electron microscopy of feces. degradation products (see Chapter 23).
False negatives occur with both of these diagnostic
techniques. Diagnostic Imaging
• The quantity of fecal virus can fluctuate, so ideally Diagnostic imaging is useful for identifying organ sites
feces should be checked daily for 4 to 5 consecutive of involvement in FIP. Imaging also facilitates procure-
days before determining a cat is a non-shedder. ment of diagnostic fluid or biopsy specimens.
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A/G, albumin-to-globulin ratio; ALP, alkaline phosphatase; ALT, alanine transaminase; BUN, blood urea
nitrogen; CNS, central nervous system; CT, computed tomography; FCoV, feline coronavirus; FIP, feline
infectious peritonitis; GI, gastrointestinal; MRI, magnetic resonance imaging; PLI, pancreatic lipase
immunoreactivity; RT-PCR, reverse transcription polymerase chain reaction.
flecks or strands of fibrin. The fluid gets frothy when Coronaviral Antibody Tests
shaken because of its high protein concentration,
and it may clot when refrigerated. Testing for coronaviral serum antibodies is informative
• FIP fluid has a high protein concentration, approach- as an epidemiological screening tool and as a diagnos-
ing that of plasma, ranging from 4 to 10 g/dl. Effu- tic aid for FCoV and FIP if a reliable laboratory is used
sive FIP is highly likely if the total fluid protein is and the results are interpreted properly.
more than 3.5 g/dl and the globulin portion is
greater than 50%. The A/G is usually less than 0.8. A Principles of Feline Coronavirus-Antibody Testing
gamma globulin percentage of greater than 32% by
fluid protein electrophoresis is also highly indicative ▼ Key Point A positive coronaviral antibody test
of FIP. An A/G ratio of greater than 0.8, or an means only that a cat has been exposed to some
albumin percentage greater than 50%, indicates that coronavirus at some time.
a disease other than FIP is highly likely.
• FIP fluid usually has a nucleated cell count ranging • Serology does not provide a definitive diagnosis of
from 1,000 to 20,000 cells/ml, which is low compared FIP because the antibodies in cats infected with harm-
with other exudates. less non-mutated FCoV are not distinguishable from
• The cytologic pattern of FIP fluid is pyogran- the antibodies in cats with FIP. A large percentage of
ulomatous exudate. The predominant cells are the healthy cat population is seropositive for FCoV
well-preserved (non-degenerate) neutrophils and antibodies, and most of these cats never develop FIP.
macrophages with variable numbers of plasma cells In addition, seropositivity does not distinguish active
and lymphocytes. from past infection.
• Additional evaluations on effusions can include assay • Antibodies to the related non-FCoVs (e.g., CCV and
for anti-FCoV antibodies (see “Coronaviral Antibody TGEV) crossreact with FCoV antibodies, lowering
Tests”) and RT-PCR assay to detect coronaviral specificity further.
nucleic acid (see the later section on PCR assay). • Seroconversion after initial exposure to FCoV takes 1
Antibody and RT-PCR assays on effusions may have to 3 weeks.
higher diagnostic value than serum testing.
• Staining macrophages in effusions for intracellular ▼ Key Point A positive coronaviral antibody test does
FCoV antigen using either immunofluorescence or not confirm a diagnosis of FIP, and the absence of
immunohistochemistry is the most definitive con- FCoV antibodies does not rule out a diagnosis of
firmatory test for effusive FIP, with 100% positive FIP.
predictive value (see “Immunofluorescence and
Immunohistochemistry”). • Many commercial diagnostic labs measure FCoV-anti-
body titers; however, methodologies are variable;
Cerebrospinal Fluid and Aqueous of the Eye thus, results cannot be compared between labs. For
example, whether a feline or non-feline viral antigen
• Analyses of CSF for neural FIP and aqueous fluid is used in the test procedure will influence the
from the anterior chamber of the eye for ocular FIP titer values that indicate the lowest and highest titer
have high diagnostic value. Both the protein con- levels.
centration and the nucleated cell count (neutrophils, • Use a reliable commercial diagnostic laboratory
macrophages, lymphocytes) are increased in the CSF that measures quantitative FCoV-antibody titer
of most cats with neural FIP (see Table 10-2) and in levels. Avoid using rapid in-office enzyme-linked
the aqueous humor of cats with intraocular FIP. immunosorbent assay (ELISA) tests that merely
• CSF and anterior chamber fluid can also be evaluated report positive or negative results without titer
for the presence of anti-FCoV antibodies (see the fol- quantification—this is less useful than titer informa-
lowing section). In FIP, the ratio of CSF or ocular anti- tion, and these tests give less consistent results than
bodies to serum antibodies is generally much higher conventional serologic tests.
than the ratio of CSF or ocular total protein to serum • Commercially available ELISA tests for detection of
total protein. antibody to the 7b gene have been marketed as “FIP-
• A PCR assay of CSF and anterior chamber fluid for specific tests.” However, mutation of this gene is not
coronaviral nucleic acid is not as useful (see the specific for FIP, and this test has no advantage over
section on PCR assay). conventional serologic assays.
• Serum or plasma samples for FCoV antibody testing
▼ Key Point Neurologic FIP is highly likely in cats that can be refrigerated or stored at -20∞C without affect-
have the combination of progressive neurologic ing the test.
signs (especially if multifocal), increased CSF • FCoV antibodies also can be measured in effusions,
protein and leukocytes (especially neutrophils), CSF, or anterior chamber fluid (aqueous). Some
and hydrocephalus on imaging. studies suggest that these are more diagnostically
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Positive Antibody Test Results ▼ Key Point Interpret the RT-PCR test with other clin-
ical findings, and do not use this as the sole basis
A positive FCoV-antibody titer in a cat can indicate any for diagnosis of FIP.
of the following:
• Clinical FIP caused by a mutant variant of FCoV • The RT-PCR viral assay is used to detect coronaviral
• Healthy carrier of non-mutant FCoV nucleic acid in blood, fluids, tissue, or feces.
• Recovered from previous FCoV infection • A positive result indicates the presence of FCoV, but
• Seroconversion to other non-FCoVs it does not distinguish between the mutated, FIP-
• False-positive as a result of recent vaccination producing variants and non-mutated FCoV. Viremia
occurs not only in FIP but also in healthy FCoV
Guidelines for Interpretation carriers. One study found that up to 80% of cats
in endemic catteries can be viremic and RT-PCR–
▼ Key Point Coronaviral-antibody titers are not suffi- positive, and this was not predictive of FIP. Thus, RT-
ciently specific to be used as a definitive diagnos- PCR by itself is not a reliable confirmatory diagnostic
tic test. A positive titer, no matter how high, does test.
not confirm a diagnosis of FIP.
▼ Key Point PCR assays do not distinguish between
• In healthy cats, the height of the antibody titer cor- mutated and non-mutated FCoV.
relates with the virus replication rate in the intestine,
the likelihood of fecal shedding, and the amount of • In general, effusions and tissue specimens are more
virus shed in the feces. likely than blood to be positive in cats with FIP.
• In general, low titers have the least diagnostic value. Plasma is more sensitive than serum. The lowest yield
• The highest measurable titer level for the assay used is in CSF and urine, so these are not recommended
by the lab is highly suggestive of FIP but is still not for routine PCR testing.
confirmatory by itself. One study found 94% proba- • Fecal RT-PCR can be used to document fecal shed-
bility of FIP at the highest titer level. ding of FCoV, especially in healthy cats as a compo-
• Rising antibody titers are not helpful because they are nent of a cattery control program. Evaluate feces
seen in healthy cats with non-mutated FCoV, and daily for 4 to 5 consecutive days. Retesting over
titers fluctuate unpredictably in both FIP and aviru- several months is required to identify chronic persis-
lent infections. tent shedders.
• Healthy carriers of non-mutated FCoV living in • A false-negative RT-PCR results from degradation of
endemic cattery and multicat environments tend to sample RNA and poor laboratory technique. The
have higher titers than individual pet cats; thus, high primers used also may not detect all strains of FCoV.
titers might be less meaningful in cattery cats. • Samples for PCR require careful handling to avoid
Less than 10% of cattery cats with titers ever develop invalid results. Keep samples frozen and assay them
FIP. as soon as possible for optimal results.
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and does not achieve systemic levels, but it may exert • Persistent drug-induced anorexia is a frequent
immunomodulating activity on oropharyngeal lym- problem when these drugs are given daily. An alter-
phoid tissue leading to cytokine release. native is pulse administration, using a large dose of
the drug once every 2 to 3 weeks. In this way, a few
Palliative Medical Therapy days after each dose the appetite usually rebounds
and is maintained between treatment cycles.
Some cats transiently improve with supportive care com- • Regardless of the regimen chosen, if no response is
bined with palliative medical therapy using a high dose noted within the first 2 to 4 weeks, consider the
of corticosteroid, with or without a cytotoxic alkylating therapy ineffective and either modify or discontinue
agent such as chlorambucil or cyclophosphamide it. If a positive response occurs, continue the treat-
(Table 10-3). ment indefinitely.
• Corticosteroids and alkylating drugs have no effect
on the virus, but by virtue of their anti-inflammatory Supportive Treatment
and immunosuppressive effects, they are aimed at These measures may improve quality of life and possi-
controlling the widespread immune-mediated in- bly survival time.
flammatory reaction that occurs in FIP.
• These drugs may adversely affect cellular immunity • Minimize stress as an exacerbating factor.
mediated by T lymphocytes and macrophages and • Perform intermittent body cavity drainage of effusion
thus have the potential to promote the viral infection. as needed to relieve dyspnea.
• Give parenteral fluid therapy.
• Give nutritional support (via tube-feeding tech-
▼ Key Point Only use immunosuppressive drugs to niques; see Chapter 3).
treat overt FIP. In healthy FCoV carriers and • Give aspirin (10 mg/kg q72h) to inhibit platelet
seropositive cats, these drugs could have the aggregation caused by vasculitis.
unwanted effect of promoting the onset of FIP. • Give antibiotics as needed to control complicating
bacterial infections.
• The principal side effects of alkylating drugs are • Treat anterior uveitis with topical corticosteroids and
anorexia and bone marrow suppression; thus, atropine (see Chapter 136).
monitor a complete blood count periodically (see • Give blood transfusions (for severe nonregenerative
Chapter 26 for more details on the use of these drugs). anemia).
Immunomodulator and antiviral Feline interferon-omega (Virbagen 1 million U/kg SC q48h until remission, then weekly
Omega)
Immunomodulator Human interferon-alpha (Roferon, 30 units PO q24h for 7 days on alternating weeks
Intron-A)
Anti-inflammatory and Prednisone 2–4 mg/kg, q24h, PO
immunosuppressive
Immunosuppressive† Chlorambucil (Leukeran) or ‡ 20 mg/m2, every 2–3 wks, PO
Cyclophosphamide (Cytoxan) 2–4 mg/kg, 4 days each week, PO, or 200–300 mg/m2,
every 2–3 wks, PO
Platelet aggregation inhibitor Aspirin 10 mg/kg, q72h, PO
Ozagrel HCl 5 mg/kg, q12h, SC
Topical ophthalmic for uveitis Prednisone acetate (1%) 2–3 drops/eye q6h
Atropine (1%) 1–3 drops/eye up to q6h for mydriasis
Supportive treatment Minimize “stress” —
Parenteral fluid therapy As needed to maintain hydration
Nutritional therapy via tube feeding See Chapter 3
Body cavity drainage (thoracentesis) As needed to relieve dyspnea
Blood transfusion As needed for severe anemia
Antibiotics for complicating infections Dosage based on the drug
*Cats most likely to respond are in good physical condition, are eating, and are free of neurologic signs, severe anemia, and feline leukemia virus or feline
immunodeficiency virus infections.
†For conversion of body weight to body surface area (m2), refer to conversion tables in Chapter 26.
‡Choose only one of these two alkylating agents, and combine with a corticosteroid.
W0422-Ch010.qxd 11/10/05 4:50 PM Page 142
• Isolate queens 1 to 2 weeks pre-partum so that queens Bradshaw JM, Pearson GR, Gruffydd-Jones TJ: A retrospective study
can give birth and nurse kittens in isolation from of 286 cases of neurological disorders of the cat. J Comp Pathol
131:112–120, 2004.
other cats in the cattery. Elston T, Rodan I, Flemming D, et al: 2000 Report of the American
• Wean the kittens early and remove them from the Association of Feline Practioners and Academy of Feline Medicine
mother at 5 to 6 weeks of age, coinciding with the Advisory Panel on Feline Vaccines. Available at http://www.
time when maternal-derived immunity dissipates, aafponline.org.
Gunn-Moore DA, Gruffydd-Jones TH, Harbour DA: A reverse
then keep the litter of kittens isolated from all other transcriptase-polymerase chain reaction (RT-PCR) of blood
cats until at least 16 weeks of age. samples from healthy cats and cats with clinical feline infectious
• Maintain strict quarantine procedures to prevent peritonitis. Vet Microbiol 62:193–205, 1998.
environmental or fomite transfer of FCoV. Haijema BJ, Volders H, Rottier PJ: Live, attenuated coronavirus
• Confirm seronegativity at 12 to 16 weeks of age or vaccines through the directed deletion of group-specific genes pro-
vide protection against feline infectious peritonitis. J Virol
prior to moving kittens to a new home to document 78:3863–3871, 2004.
effectiveness. Hartmann K: Feline infectious peritonitis. Vet Clin North Am Small
• The disadvantages of this approach are that it Anim Pract 35:39–79, 2005.
requires facilities for isolation and quarantine and Hartmann K, Binder C, Hirschberger J, et al: Comparison of differ-
ent tests to diagnose feline infectious peritonitis. J Vet Intern Med
that early weaning may adversely affect social devel- 17:781–790, 2003.
opment of the kittens. Pedersen NC, Addie D, Wolf A: Recommendations from working
groups of the International Feline Enteric Coronavirus and Feline
Infectious Peritonitis Workshop. Feline Pract 23:108–111, 1995.
SUPPLEMENTAL READING Rohrbach BW, Legendre AM, Baldwin CA, et al: Epidemiology of
feline infectious peritonitis among cats examined at veterinary
medical teaching hospitals. J Am Vet Med Assoc 218:1111–1115,
Addie DD, Jarrett O: Use of a reverse-transcriptase polymerase chain 2001.
reaction for monitoring the shedding of feline coronavirus by Shelley SM, Scarlett-Kranz J, Blue JT: Protein electrophoresis on effu-
healthy cats. Vet Record 148:649–653, 2001. sions from cats as a diagnostic test for feline infectious peritonitis.
Addie DD, Jarrett O: Feline coronavirus infections. In Greene CE J Am Anim Hosp Assoc 24:495, 1988.
(ed): Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis: Vennema H, Poland A, Foley J, Pedersen NC: Feline infectious peri-
Elsevier, 2006, pp 89–103. tonitis virus arises by mutation from endemic feline enteric coro-
Addie DD, Paltrinieri S, Pedersen NC: Second international feline navirus. Virology 243:150–157, 1998.
coronavirus/feline infectious peritonitis symposium: Recommen- Weiss RC: Feline infectious peritonitis and other coronaviruses. In
dations from workshops of the second international feline coro- Sherding RG (ed): The Cat, Diseases and Clinical Management,
navirus/feline infectious peritonitis symposium. J Feline Med Surg 2nd ed. New York: Churchill Livingstone, 1994, pp 449–477.
6:125–130, 2004.
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▼ Chapter
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populations are 5% to 10% for pet cats, 20% for cal disease caused by FHV and FCV is usually self-
show cats, and 40% for colony cats. limiting within 5 to 10 days; however, some cats take 3
• FCV is highly resistant with survival outside the weeks to recover. See Table 11-1 for a comparison of the
host of 8 to 10 days, causing a high risk of fomite clinical manifestations of FHV and FCV.
transmission.
• The preferred disinfectant is a 1:32 dilution of 5% Feline Herpesvirus
sodium hypochlorite (bleach).
• FHV has an affinity for conjunctival, nasal, and upper
Chlamydophila felis airway (laryngotracheal) epithelium. Multifocal
epithelial necrosis at these sites causes rhinitis, tra-
• Primarily shed from conjunctival secretions; pro- cheitis, laryngitis, and conjunctivitis. FHV can also
longed shedding up to 18 months has been docu- cause nasal turbinate necrosis and osteolysis.
mented after experimental infections
• Signs include sneezing, lacrimation, serous to muco-
• Survives for several days in conjunctival discharges purulent naso-ocular discharge, cough, hypersaliva-
• Inactivated by lipid solvents, detergents, and 1:1000 tion, and loss of voice.
quaternary ammonium
• Corneal involvement causes keratitis and herpetic
ulcers. Ulcers can have a punctate, oval, or branch-
Bordetella bronchiseptica ing (dendritic) pattern (see Chapter 134).
• B. bronchiseptica can be isolated from many healthy • Infection during pregnancy may result in abortion or
cats, indicating a widespread subclinical carrier state. in a severe generalized form of infection in newborn
Prolonged oronasal shedding for at least 19 weeks kittens, characterized by fatal encephalitis or focal
after experimental infection has been documented. necrotizing hepatitis. Neonates also may develop
panophthalmitis (ophthalmia neonatorum) that can
permanently damage the eyes.
CLINICAL SIGNS • Secondary bacterial complication of the lesions may
worsen and prolong FHV disease. Bacterial pneumo-
Typical clinical signs of feline URI are sudden onset of nia is a serious complication in young kittens.
anorexia, depression, fever, and naso-ocular discharge. • Extensive turbinate damage may lead to fibrosis and
Other signs specific to each etiologic agent are detailed stenosis of the nasal passages and predispose the
in the following sections. Illness is more severe in young patient to chronic rhinitis.
kittens and milder in previously vaccinated cats. Clini- • Ulcerative skin lesions are seen infrequently.
tion probably does not induce crossprotection • In housing facilities for cats, avoid overcrowding,
against all FCV strains. provide adequate ventilation (10 or more air changes
• FHV and FCV vaccines: Initially give kittens at least two per hour), maintain a warm nonfluctuating temper-
doses 3 weeks apart (usually 9 and 12 weeks of age or ature, control humidity at approximately 50%, and
every 3–4 weeks until 12 weeks of age), then revacci- provide separate cages or pens with solid partitions
nate 1 year later and revaccinate every 3 years there- and separate food and water dishes.
after (see Chapter 7). Do not use MLV vaccines in • To prevent fomite transmission, clean and disinfect
pregnant cats. cages (1:32 sodium hypochlorite bleach solution)
• Chlamydophila and Bordetella vaccines: These are not and minimize cross-contamination by personnel.
recommended for routine use but may be considered • Identify cats infected with Bordetella or Chlamydophila,
for cats in high-risk multicat environments (see and treat them with oral doxycycline and topical
Chapter 7). Vaccine efficacy and duration of immu- tetracycline ophthalmic ointment.
nity are not well established.
Control in Endemic Breeding Catteries
Vaccine Side Effects
• In endemic catteries, kittens lose their maternal
• Local reactions and injection site sarcomas have been immunity at 5 to 7 weeks of age and often become
associated with adjuvanted killed vaccines. infected by virus shed from carrier adults, especially
• Transient fever, arthralgia, and myalgia can be seen their own lactating mother.
after MLV vaccines. • To boost maternal antibody levels in kittens, vaccinate
• Mild postvaccinal sneezing and oculonasal discharge queens before breeding or during pregnancy. Only
are common after intranasal vaccination. Oronasal use inactivated vaccine in pregnant cats.
exposure to the viral strains in injectable MLV vac- • Move queens into isolation 3 weeks before giving
cines by inadvertent aerosolization or licking from birth to prevent exposure of newborn kittens to car-
the haircoat also can cause clinical disease with sneez- riers in the colony.
ing, oculonasal discharge, and oral ulcers. • Wean kittens early at 4 to 5 weeks of age and raise
• MLV vaccines that are produced in feline kidney them in isolation to reduce risk of acquiring infection
cell culture systems contain renal antigens that from a carrier mother.
may stimulate anti-kidney antibodies in vaccinated • Use intranasal vaccine in kittens starting at 6 weeks
cats; however, the significance of this is not yet of age, because it can induce local protection rapidly
known. despite the presence of interfering maternal anti-
body. Maintain isolation until 1 week after the last
Control in Catteries and Shelters dose of vaccine at 12 weeks.
• Vaccinate all cats against FHV and FCV. When faster • When possible, avoid using confirmed or suspected
immunity is needed (such as in outbreaks), use carriers in breeding programs, especially queens with
intranasal vaccine. In catteries apparently free of res- a history of producing infected litters.
piratory disease, consider using a killed injectable
vaccine to avoid introducing an MLV strain into the
group. SUPPLEMENTAL READING
• Avoid incoming cats from infected sources. Isolate
cats with signs of illness. Binns SH, Dawson S, Speakman AJ, et al: A study of feline upper res-
piratory tract disease with reference to prevalence and risk factors
• FHV and FCV are perpetuated in catteries by virus for infection with feline calicivirus and feline herpesvirus. J Feline
shed from subclinical carriers and spread by contact, Med Surg 2:123, 2000.
fomite, and aerosol transmission. Elston T, Rodan I, Flemming D, et al: 1998 Report of the American
Association of Feline Practioners and Academy of Feline Medicine
▼ Key Point Subclinical shedders of respiratory Advisory Panel on Feline Vaccines. J Am Vet Med Assoc
212:227–241, 1998.
viruses are prevalent. Cats free of signs of disease Ford RB, Levy JK: Infectious diseases of the respiratory tract. In Sherd-
are not necessarily free of infection, even if they ing RG (ed): The Cat: Diseases and Clinical Management, 2nd ed.
have been well vaccinated. New York: Churchill Livingstone, 1994, p 489.
Gaskell R, Dawson S, Radford A: Feline respiratory disease. In Green
CE (ed): Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis:
• When introducing a new cat, there is always a risk Elsevier, 2006, pp 146–154.
that the incoming cat is a subclinical carrier that can Geissler K, Schneider K, Platzer G, et al: Genetic and antigenic het-
be the source for an outbreak. Vaccinate and then erogeneity among feline calicivirus isolates from distinct disease
isolate all incoming cats for 3 weeks. This protects manifestations. Virus Res 48:193, 1997.
the incoming cat from viruses in the cattery and pro- Hurley KF, Sykes JE: Update on feline calicivirus: New trends. Vet Clin
N Am Small Anim 33:759–772, 2003.
tects the cattery from a new cat that might be incu- Maggs DJ, Nasisse MP, Kass PH, et al: Efficacy of oral supplementa-
bating a viral infection or undergoing stress-induced tion with L-lysine in cats latently infected with feline herpesvirus.
shedding. Am J Vet Res 64:37, 2003.
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Nasisse MP, Dorman DC, Jamison KC, et al: Effects of valacyclovir in Scott FW, Geissinger C: Duration of immunity in cats vaccinated with
cats infected with feline herpesvirus-1. Am J Vet Res 58:1141, 1997. an inactivated feline panleukopenia, herpesvirus, and calicivirus
Pedersen NC, Elliott JB, Glasgow A, et al: An isolated epizootic of vaccine. Feline Pract 25:12, 1997.
hemorrhagic-like fever in cats caused by a novel and highly virulent Scott FW, Geissinger CM: Long-term immunity in cats vaccinated with
strain of feline calicivirus. Vet Microbiol 73:281–300, 2000. an inactivated trivalent vaccine. Am J Vet Res 60:652, 1999.
Pedersen NC, Hawkins KF: Mechanisms of persistence of acute and Stiles J: Feline herpesvirus. Vet Clin N Am Small Anim Pract 30:1001,
chronic feline calicivirus infections in the face of vaccination. Vet 2000.
Microbiol 47:141, 1995. Stiles J, McDermott M, Willis M, et al: Comparison of nested poly-
Pesavento PA, MacLachlan NJ, Dillard-Telm L, et al: Pathologic, merase chain reaction, virus isolation, and fluorescent antibody
immunohistochemical, and electron microscopic findings in natu- testing for identifying feline herpesvirus in cats with conjunctivitis.
rally occurring virulent systemic feline calicivirus infection in cats. Am J Vet Res 58:804, 1997.
Vet Pathol 41:257–263, 2004. Sykes JE, Browning GF, Anderson G, et al: Differential sensitivity of
Radford AD, Gaskell RM, Dawson S: Feline viral upper respiratory culture and the polymerase chain reaction for detection of feline
disease. In King LG (ed): Textbook of Respiratory Disease in Dogs herpesvirus-1 in vaccinated and unvaccinated cats. Arch Virol
and Cats. St. Louis: Elsevier, 2004, p 271–283. 142:65, 1997.
Radford AD, Sommerville L, Ryvar R, et al: Endemic infection of a cat
colony with a feline calicivirus closely related to an isolate used in
live attenuated vaccines. Vaccine 19(31):4358, 2001.
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▼ Chapter
12 Canine Infectious Tracheobronchitis
(Kennel Cough)
Robert G. Sherding
▼ Key Point Canine ITB is commonly spread in dogs • Mild, serous, or mucopurulent naso-ocular discharge
that are confined in high-density facilities with can be seen.
poor ventilation (e.g., boarding kennels, animal • Typically, affected dogs continue to eat, remain active
shelters, pet shops, veterinary hospitals, and lab and alert, and are nonfebrile. In severe cases,
animal facilities). anorexia, depression, and fever may be present.
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• Complicating bacterial pneumonia and even rare • Serology (paired acute and convalescent titers)
fatalities can occur with severe disease, especially in can demonstrate viral exposure but has limited
mixed infections in young or unvaccinated puppies usefulness.
from crowded environments such as pet shops and
animal shelters.
• Clinical course: Clinical signs usually last 7 to 14 days TREATMENT
in uncomplicated cases.
Because many of the principles of treatment for bron-
chitis and bacterial pneumonia can be applied to dogs
DIAGNOSIS with ITB, refer also to Chapters 162 and 163.
cated ITB (no fever or evidence of bronchopneumo- booster is not well established; however, immunity for
nia), the cough can be such a nuisance and source of CAV-2 and CPIV is expected to last for at least 3 years,
discomfort for owner and patient that antitussives are whereas immunity for Bordetella may be only 6 months
often needed for relief. or less.
• Examples: Hydrocodone (0.22 mg/kg PO q6–12h) • For Bordetella, a booster is recommended 1 to 2 weeks
and butorphanol (0.55–1.1 mg/kg PO q6–12h). prior to known exposure (e.g., boarding or showing)
• Over-the-counter human cough medicines (dex- if the dog has not been vaccinated within the previ-
tromethorphan, guaifenesin) are not effective for ous 6 months.
treating ITB.
Kennel Prevention
Corticosteroids • Avoid overcrowded, high-density confinement.
• Use anti-inflammatory dosages of corticosteroids • Isolate infected (coughing) animals. In recovered
(prednisolone 0.25–0.5 mg/kg PO q12h) as needed animals, ITB viruses may be shed for 1 to 2 weeks,
to control refractory cough in uncomplicated ITB. and Bordetella and mycoplasmas may be shed for 3
Limit use to 5 days or less, and do not use in dogs months or longer.
with bronchopneumonia. • Use caretaker hygiene to prevent fomite spread.
• Ensure proper kennel ventilation (at least 12 air
Bronchodilators changes per hour; 15–20 is optimal).
• Efficacy of bronchodilators in ITB is not established, • Use disinfectants such as sodium hypochlorite
(Clorox), chlorhexidine (Nolvasan), and benzalko-
but these may reverse reflex bronchoconstriction
nium Cl (Roccal-D).
triggered by airway irritation, thereby reducing dis-
comfort and cough.
• Examples: Theophylline, aminophylline, albuterol,
PUBLIC HEALTH CONSIDERATIONS
and terbutaline (see Chapter 162 for dosages).
Humans are potentially susceptible to B. bronchiseptica,
Supportive Care especially if immunocompromised; however, the risk of
• Provide adequate fluid intake, airway humidification, acquiring infection from an infected pet is considered
nutritional support, and rest. minimal.
▼ Chapter
13 Canine Distemper
Robert G. Sherding
Canine distemper is a severe, highly contagious viral dis- outside of the host. It is readily destroyed by drying
ease of dogs and other carnivores with profound effects and by most disinfectants, such as phenols and qua-
on the respiratory tract, gastrointestinal tract, nervous ternary ammonium.
system, and lymphoid tissue. It is seen worldwide.
PATHOGENESIS
ETIOLOGY AND EPIDEMIOLOGY
The pathogenesis and severity of disease is affected by
Canine distemper virus (CDV) is an RNA Morbillivirus the viral strain and dose, the animal’s age, and the effec-
in the Paramyxoviridae family. It is closely related to tiveness of the host’s immune response.
human measles virus.
Stages of Infection
Epidemiology • Day 1: Airborne exposure leads to infection of tissue
• Distribution: Enzootic worldwide. macrophages of the upper respiratory tract.
• Incidence: All ages can be affected; however, the inci- • Days 2 to 4: Infection spreads to local lymphoid tissues
dence is highest in young dogs (2–6 months of age), of the tonsils, retropharyngeal lymph nodes, and
especially unvaccinated puppies that are exposed fol- bronchial lymph nodes.
lowing the loss of passive immunity from maternal • Days 4 to 6: Widespread infection of systemic lym-
colostral antibodies. phoid tissues involves the liver, spleen, abdominal
• Host susceptibility: Domestic dogs and many wild car- lymph nodes, and lamina propria of the gastroin-
nivores, including the following: testinal tract. This corresponds to a transient fever
• Canidae family—Fox, dingo, coyote, wolf, jackal spike and the onset of lymphopenia caused by viral
• Mustelidae family—Ferret, mink, weasel, marten, damage to T and B lymphoid cells.
skunk, badger, otter • Days 6 to 8: Viremia occurs.
• Procyonidae family—Raccoon, kinkajou, coati • Days 8 and 9: The virus is disseminated to epithelial
• Large Felidae—Cheetah, lion, jaguar, margay, ocelot tissues (epitheliotropism) and the central nervous
• Others—Bear, panda, hyena, mongoose system (CNS) (neurotropism).
• Days 9 to 14: The subsequent outcome varies depend-
Transmission ing on the host’s immune response and can include
recovery, severe multisystemic clinical disease, or CNS
• Infected animals shed virus in all body secretions and localization.
excretions.
• The primary route of infection is by inhalation of the Host Immune Response
virus from aerosolized secretions or from fomites.
• The greatest opportunity for spread occurs where • If the immune response fails to develop by days 9 to
dogs are kept in groups (e.g., pet shops, kennels, 14, the outcome is rapid, widespread dissemination
animal shelters, and research colonies). of the virus to skin; glandular and epithelial organs,
• Transplacental transmission is a rare source of dis- such as the respiratory and gastrointestinal tracts;
temper in neonates. and the CNS, causing acute encephalomyelitis. The
• Viral shedding usually ceases 1 to 2 weeks after recov- results are multisystemic signs, a second fever spike,
ery; therefore, “carrier state” transmission is not a and a high mortality rate, especially in young
big problem. Shedding for 60 to 90 days has been puppies.
reported but is rare. • If the immune response is sluggish or partial, multi-
• The virus is labile in the environment, usually surviv- systemic signs are mild or absent and recovery occurs;
ing only a few hours and no more than a few days however, CNS localization can result in chronic
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Gastrointestinal System
• Vomiting and diarrhea are the result of acute DIAGNOSIS
gastroenteritis.
▼ Key Point A presumptive diagnosis of canine dis-
Eyes temper is based on typical clinical signs in a young
dog (2–6 months of age) with a history of inade-
• Keratoconjunctivitis results in serous to mucopuru-
lent ocular discharge. quate vaccinations and possibility of exposure to
the virus.
• Chorioretinitis results in hyperreflective fundic
lesions of retinal atrophy.
• Optic neuritis or serous retinal detachments results In suspected cases of distemper, perform a complete
in blindness. blood count to assess leukocyte responses and thoracic
radiographs to assess pneumonia. In dogs presenting
with neurologic disease suspected to be due to CDV, use
Nervous System routine cerebrospinal fluid (CSF) analysis to distinguish
Acute encephalomyelitis predominantly destroys gray CDV infection from other diseases. The presence of a
matter (neurons), whereas subacute or chronic non- CDV-specific antibody in CSF can confirm the diagno-
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sis but requires a special laboratory. Special virology • Polymerase chain reaction (PCR) assays have been
techniques can help substantiate a diagnosis of distem- used to test peripheral blood monocytes and tissues
per; however, this is not practical or necessary in for CDV. These tests appear to be highly sensitive and
most clinical situations, and false-negative results are specific under experimental conditions, but they are
common. not yet readily available for clinical use.
Hematology
• Lymphopenia (beginning with the initial fever TREATMENT
spike).
• Neutrophilic leukocytosis occurs later (associated There is no effective antiviral treatment for CDV; there-
with secondary bacterial complications such as fore, treatment is supportive and symptomatic. When-
pneumonia). ever possible, treat distemper in an isolation facility to
• Distemper inclusions are seen rarely in circulat- prevent aerosol exposure of other hospitalized animals.
ing lymphocytes, monocytes, neutrophils, and
erythrocytes. Symptomatic Treatment
• Give broad-spectrum antibiotics (extended-spectrum
Thoracic Radiography cephalosporin, fluoroquinolone, etc.) for secondary
• Diffuse interstitial pneumonitis is seen early. bacterial infection, especially pneumonia (see
• A diffuse alveolar and bronchial pattern, air bron- Chapter 163).
chograms, and lobar consolidation are seen later with • For pneumonia, give antibiotics for secondary bacte-
secondary bacterial bronchopneumonia. rial infection, maintain hydration with parenteral
fluid therapy, and perform chest coupage (see Chap-
Cerebrospinal Fluid Analysis ters 162 and 163).
• For vomiting and diarrhea, restrict food intake and
• CSF may have increased cells (mostly lymphocytes) administer antiemetics (see Chapter 67) and antidiar-
and/or protein, but normal findings do not rule out rheals (see Chapter 69) as necessary.
CDV (see Chapters 125 and 126). • For seizures, give a single dose of dexamethasone
• The presence of a CDV-specific antibody in CSF in (1–2 mg/kg IV) for CNS edema, and consider anti-
greater concentration than serum is diagnostic of convulsant therapy using phenobarbital, diazepam,
CDV, but not all cases have CSF antibodies. or potassium bromide (see Chapter 127).
• Provide general supportive care, such as eyes and
Serology nose kept clear of discharges; nutritional support;
and adequate fluid intake or parenteral fluid therapy.
• A single positive immunoglobulin G (IgG) titer is of
no benefit, because it does not distinguish current Prognosis
infection from previous vaccination or exposure.
• The demonstration of a rising serum neutralizing an • Mortality rate varies but is highest in young puppies,
antibody titer or a CDV-specific IgM titer is suggestive especially those with high fever, severe multisystemic
but not diagnostic of recent CDV infection. disease, severe pneumonia, or progressive neurologic
disease.
Virology • The neurologic deficits caused by CDV are often pro-
gressive and irreversible. It is justified to recommend
Various methods are available for demonstrating the euthanasia for patients with progressive neurologic
virus or viral antigen in cells or tissues; however, with signs that are severe and incapacitating.
any of these procedures negative results do not rule out
CDV. ▼ Key Point Do not be too optimistic with the owner,
even with mild cases of distemper. The disease
• Intracytoplasmic viral inclusion bodies can some- is often progressive despite therapy; and even
times be detected in peripheral blood cells, epithelial
animals that seem to be recovering can have a
cells (cytology specimens), or biopsies, but inclusions
delayed onset of progressive, incapacitating
are absent in many cases.
neurologic disease.
• Viral antigen can be identified by immunohisto-
chemistry or fluorescent antibody techniques in cells
from blood, CSF, cytology specimens (e.g., conjunc-
Client Education
tival scraping or tracheobronchial aspirate), or • Discuss the multiplicity of signs, likelihood of pro-
frozen tissue specimens. gression, and guarded to poor prognosis.
• Virus isolation is difficult and expensive, and it mostly • Advise owners to isolate their animal from others to
uses postmortem tissues. prevent spread of infection.
W0422-Ch013.qxd 11/10/05 4:48 PM Page 157
• Educate the client about proper immunization pro- • Measles virus vaccine is not as protective as CDV
cedures for future reference. vaccine, but a single IM dose can be used to provide
• Recommend routine disinfection procedures and a temporary, partial protection in the presence of inter-
1-week waiting period before bringing another dog fering maternal antibodies in young puppies 4 to 12
onto the premises. weeks of age who are in high-risk environments. This
must be followed by CDV vaccine after 12 weeks of
age.
PREVENTION • Rarely, postvaccinal encephalitis has occurred from 7
to 15 days after MLV distemper vaccination, primar-
Passive Maternal Antibody ily in neonatal puppies (<4 weeks of age); in severely
ill, stressed, or immunocompromised dogs; or in very
• The neonatal pup acquires passive immunity against young puppies infected with parvovirus.
CDV from its dam. Most of this maternal-derived anti-
body (Ab) comes from colostrum absorbed during
nursing in the first few hours after birth.
• Maternal Ab protects most pups until after weaning
SUPPLEMENTAL READING
and then gradually disappears between 8 and 14
American Animal Hospital Association Canine Vaccine Task Force:
weeks of age. Executive summary and 2003 canine vaccine guidelines and rec-
• When present, maternal Ab interferes with the ommendations. J Am Anim Hosp Assoc 39:119, 2003. Full report
response to vaccination; however, in most dogs it available at http://www.aahanet.org.
decreases to a level that allows successful immuniza- Frisk AL, Konig M, Moritz A, et al: Detection of canine distemper virus
nucleoprotein RNA by reverse transcription PCR using serum,
tion by 12 weeks of age. whole blood, and cerebrospinal fluid from dogs with distemper. J
Clin Microbiol 37:3634, 1999.
Vaccination Greene CE, Appel MJ: Canine distemper. In Greene CE (ed): Infec-
tious Diseases of the Dog and Cat, 3rd ed. St. Louis: Elsevier, 2006.
▼ Key Point CDV vaccination is highly recommended Koutinas AF, Polizopoulou ZS, Baumgaertner W, et al: Relation of clin-
ical signs to pathological changes in 19 cases of canine distemper
for all dogs, and the efficacy of recombinant and encephalomyelitis. J Comp Pathol 126:47–56, 2002.
modified live virus (MLV) vaccines is considered Mouzin DE, Lorenzen MJ, Haworth JD, King VL: Duration of sero-
high. Vaccinate puppies at 6 to 8 weeks, 9 to 11 logic response to five viral antigens in dogs. J Am Vet Med Assoc
weeks, and 12 to 14 weeks of age. Give the first 224:55–60, 2004.
Shin YJ, Cho KO, Cho HS, Kang SK, et al: Comparison of one-step
booster 1 year later and additional boosters every
RT-PCR and a nested PCR for the detection of canine distemper
3 years thereafter (see Chapter 7). virus in clinical samples. Austral Vet J 82:83–86, 2004.
W0422-Ch014.qxd 11/10/05 4:47 PM Page 158
▼ Chapter
14 Intestinal Viruses
Robert G. Sherding
158
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loops that are painful and distended with fluid and caused by bone marrow disruption from the virus.
gas. The severity of the leukopenia is generally propor-
• Hypothermia, hypovolemic shock, icterus, hemor- tional to the severity of the clinical illness. A rebound
rhagic diathesis (disseminated intravascular coagula- neutrophilia is a positive indicator of impending
tion), and pulmonary edema because of acute recovery.
respiratory distress syndrome may develop terminally • The hematocrit is variable. The PCV is often normal
in cases complicated by bacterial septicemia, endo- but can be moderately decreased (especially after
toxemia, and SIRS. rehydration with fluids) in some dogs because of
• Death may occur in severe cases, particularly in very intestinal hemorrhage. In some dogs, the PCV can be
young puppies and in the highly susceptible breeds, elevated initially because of hemoconcentration from
and is usually attributable to dehydration, electrolyte dehydration.
depletion, endotoxic shock, or overwhelming bacte-
rial sepsis associated with severe leukopenia. Septic Serum Chemistries
puppies often develop hypoglycemia.
• The severity of clinical illness may be increased by Serum chemistry abnormalities are variable and non-
factors such as stress, overcrowded or unsanitary specific. Findings may include electrolyte abnormalities
kennel conditions, secondary bacterial infection, and (most frequently hypokalemia), prerenal azotemia,
concurrent diseases such as canine distemper, hypoglycemia, hypoalbuminemia, increased bilirubin,
coronavirus, salmonellosis, campylobacteriosis, and and increased liver enzymes (alanine transaminase and
intestinal parasitism (e.g., nematodes or giardia). alkaline phosphatase).
• In susceptible mature dogs, mild or inapparent infec-
tion that results in seroconversion without obvious Abdominal Radiography
clinical signs is common. Gas and fluid distention of the gastrointestinal (GI)
• In utero or postnatal infection can cause acute tract due to generalized ileus is frequent in parvoviral
neonatal myocarditis in neonatal puppies that did enteritis and must be differentiated from small intesti-
not receive maternal antibodies. However, this form nal obstruction (e.g., foreign body or intussusception).
of perinatal parvoviral infection is rare because most Carefully palpate the abdomen to help rule out
nursing puppies receive abundant maternal antibod- mechanical obstruction, including complicating intus-
ies from colostrum. Signs of parvoviral myocarditis susception. Barium contrast radiography often reveals
include dyspnea caused by acute heart failure, mucosal irregularity (corrugation or scalloping) and
sudden death caused by arrhythmias, and sometimes prolonged transit time.
delayed-onset chronic congestive heart failure caused
by chronic myocardial fibrosis. Serology
oratories) and ASSURE-Parvo Test (Synbiotics), or replacement of ongoing losses. Two to three times
the rapid immunomigration assay, such as Witness normal maintenance levels are often required. Con-
CPV (Synbiotics). These tests are sensitive and tinue fluid therapy until vomiting ceases and oral
accurate. intake resumes.
• Consider that false-positive results are occasionally • Add potassium (20–30 mEq/L) to IV fluids to control
seen on these CPV immunoassays 5 to 12 days fol- hypokalemia.
lowing vaccination with modified live virus (MLV) • Add dextrose to IV fluids at a 2.5% solution to control
vaccines. False-negative results occur rarely when complicating hypoglycemia of sepsis. Monitor serum
fecal antigen is bound to neutralizing antibodies or glucose and increase to 5% if needed to maintain
viral shedding stops early. serum glucose from 120 to 160 mg/dl.
• Other methods for detecting fecal excretion of par- • Consider supplementing magnesium according to
vovirus, such as hemagglutination, latex agglutina- guidelines in Chapter 5, as magnesium is often defi-
tion, electron microscopy (EM), virus isolation, and cient in severe cases of parvoviral enteritis.
polymerase chain reaction (PCR) assay, are less con- • Infuse colloid solution (e.g., hetastarch) at 20 ml/kg,
venient for routine clinical use because they require IV, if infusion of balanced crystalloid solution
a commercial or research laboratory. does not restore hemodynamic stability or if serum
albumin drops below 2 g/dl.
Necropsy • Avoid administration of fluids by the subcutaneous
route, especially in dogs with severe leukopenia,
Necropsy diagnosis of parvovirus is based on identifica- because this has been associated with secondary infec-
tion of the characteristic intestinal lesions of necrosis of tion, cellulitis, and skin necrosis at administration
the intestinal crypt cells with secondary villous collapse sites.
and dilatation of the crypts with necrotic debris. • Monitor fluid therapy by tracking body weight, phys-
Myeloid degeneration and widespread lymphoid deple- ical parameters, urine output, estimates of ongoing
tion also are seen. Parvovirus can be demonstrated in fluid losses (vomitus, diarrhea), and hematocrit and
frozen tissue samples by immunofluorescence and in total plasma protein. Also evaluate serum potassium
fixed specimens by PCR. concentration daily and adjust potassium level added
to IV fluids accordingly.
Treatment Antibiotics
The treatment of parvovirus is mainly supportive and
similar in most ways to the treatments used for other • Administer bactericidal, broad-spectrum antibiotics
to control bacterial complications. Initially, adminis-
types of severe gastroenteritis. The intensity of the treat-
ter antibiotics parenterally.
ment depends on the severity of the signs. In dogs with
fully developed clinical signs, withhold food and water • Use cefazolin or ampicillin in mild cases.
for 12 to 24 hours to rest the GI tract, administer IV • Use cefazolin, ampicillin, or penicillin combined with
an aminoglycoside (e.g., gentamicin or amikacin) or
crystalloids to replace fluid and electrolytes, and give
a fluoroquinolone (e.g., enrofloxacin) in severe and
parenteral antibiotics to control bacterial complica-
leukopenic cases. Fluoroquinolones may damage
tions. Initiate therapy whether or not definitive tests are
joint cartilage in young, growing pups. If an amino-
done or while awaiting the return of results.
glycoside is used, maintain hydration to prevent
nephrotoxicity and monitor the urine daily for casts
Fluid Therapy and proteinuria as early indicators of nephrotoxicosis.
• Consider a third-generation cephalosporin (e.g., cef-
▼ Key Point The cornerstone of treatment for CPV tiofur; Naxel) combined with clindamycin in dogs
infection is IV fluid and electrolyte therapy. with severe life-threatening bacterial sepsis.
• When feeding is resumed, give small, frequent feed- • Dexamethasone (2–4 mg/kg IV) can be used as a
ings of a bland and digestible diet, such as a com- single dose to treat septic shock.
mercial GI diet or cooked skinless chicken and rice, • Flunixin meglumine (Banamine), a nonsteroidal
until GI function appears to have recovered. The anti-inflammatory drug, is an alternative to cortico-
transition back to regular feeding should be gradual. steroids as a single injection to treat septic shock.
Beware of gastric ulceration; do not give repeated
doses or combine with corticosteroids.
Antiemetics • Equine-origin, antiendotoxin hyperimmune serum
• For frequent or persistent vomiting associated with (Septi-Serum, Immvac) is intended to bind and neu-
delayed gastric emptying that sometimes occurs in tralize endotoxin, but efficacy is uncertain.
parvoviral infection, administer metoclopramide, a
dopaminergic antagonist, at 0.5 mg/kg every 8 hours Immunotherapy
SC or most effectively as a constant rate infusion of 1
to 2 mg/kg every 24 hours diluted in IV fluids. The following experimental treatments have been used
• For gastritis, control gastric acid secretion with an H2 for CPV infection:
receptor blocker, for example, ranitidine (Zantac; • Recombinant human granulocyte colony-stimulating
2 mg/kg IV, q8–12h), or famotidine (Pepcid; factor (rhG-CSF) has been used to treat other causes
0.5 mg/kg IV, q12–24h). of neutropenia, but studies have failed to show
• If these are unsuccessful for controlling vomiting, con- improved survival or any beneficial effects in par-
sider the broad-spectrum phenothiazine antiemetic, voviral neutropenia.
chlorpromazine (0.5 mg/kg SC or IM, q6–12h), but • Recombinant human bactericidal/permeability-
not until dehydration has been corrected because increasing protein is used to treat human SIRS, but
phenothiazines have a hypotensive effect. Avoid the in a preliminary study in dogs with CPV enteritis it
use of metoclopramide and chlorpromazine together did not decrease circulating endotoxin or improve
because they can produce central nervous system exci- survival.
tation and, rarely, seizures. • Recombinant feline interferon-omega (rFeIFN-w)
• For persistent vomiting that is refractory to (Virbagen Omega, Virbac), 2.5 million U/kg IV, daily
other treatments, give ondansetron (Zofran; 0.1– for 3 consecutive days, decreased the severity of
0.2 mg/kg slow IV, q6–12h), a serotonin-antagonist enteritis and improved survival in dogs with CPV
antiemetic. enteritis in preliminary studies. This product is cur-
• Avoid the use of anticholinergics in parvoviral enteri- rently available in France but needs further study as
tis because they can worsen GI hypomotility. a treatment for CPV.
• CCV is considered of minor importance as a cause of • Serology can provide only a retrospective diagnosis
enteritis in dogs. via demonstration of a fourfold or greater rise in
• CCV is shed subclinically for months postinfection in serum antibody titer in paired sera (at the time of
chronic carriers and spreads rapidly by fecal-oral illness and 2–6 weeks later).
transmission. The incubation period is 1 to 4 days.
• CCV is closely related to feline coronavirus (see Chapter
Treatment
10). Cats experimentally infected with CCV develop
enteritis and sometimes feline infectious peritonitis. Treat coronaviral enteritis with nonspecific supportive
measures such as fluid therapy and dietary restriction
Clinical Signs for 12 to 24 hours. Antibiotics are not necessary. Most
dogs recover rapidly, although occasionally diarrhea
• CCV rarely causes clinical disease, and when signs do persists 3 to 4 weeks. Rare fatalities have been reported,
occur they are typically mild and self-limiting. Acute
especially in neonates and mixed infections involving
diarrhea is the most frequent clinical sign. This may
CPV or enteropathogenic bacteria.
be accompanied by mild anorexia, depression, and
vomiting. The character of the diarrhea varies from
soft to watery and sometimes contains mucus. Bloody Prevention
diarrhea and fever are infrequent.
• The signs are mild and easily confused with various • Killed (inactivated) and modified-live CCV vaccines
are commercially available; however, the efficacy,
other nonspecific causes of mild diarrhea of brief
duration of immunity, and benefit from these prod-
duration.
ucts is questionable. Thus, CCV vaccination is not
routinely recommended for most dogs (see Chapter
▼ Key Point Most CCV infections are subclinical;
7). The CCV vaccine may be considered in selected
however, occasional epizootics of severe enteritis
situations in which exposure risk is high, such as in
have occurred, primarily in puppies associated
show and field trial dogs and kenneled (boarded)
with kennels and dog shows.
dogs.
Diagnosis • In general, immunity to coronaviruses is brief and
is mediated by local (immunoglobulin A) immunity
Consider coronaviral enteritis in dogs with an acute rather than the serum antibodies that would result
onset of signs of gastroenteritis, especially if other dogs from a parenteral vaccine. Parenteral vaccination
on the premises are affected. Because coronaviral does not prevent CCV infection, but it may reduce
enteritis is usually non-fatal and the only treatment intestinal replication of virus and minimize clinical
is supportive, definitive laboratory confirmation is not signs.
needed for effective case management except to
document an epizootic outbreak. Coronaviral enteritis
should, however, be distinguished from parvoviral infec-
tion, a more serious systemic infection.
CANINE ROTAVIRUS
(infertility), fetal death, fetal mummification, abortion, • Both attenuated (MLV) and inactivated (killed) FPV
or stillbirth. vaccines are available, but MLV vaccines are more
effective and produce a more rapid onset of immu-
Diagnosis nity. This can be an important consideration in high-
risk environments such as shelters, where cats are
Feline panleukopenia usually is diagnosed presump- housed in groups. Side effects associated with adju-
tively on the basis of typical clinical signs and leukope- vants in killed vaccines are avoided when MLV vac-
nia in a susceptible (unvaccinated) kitten. cines are used. Parenteral and intranasal MLV
vaccines are available.
▼ Key Point Profound leukopenia (total leukocyte • Vaccinate kittens for FPV at least twice 3 weeks apart
count often <500/ml) is frequent and usually lasts 2 (usually 9 and 12 weeks of age) or every 3 to 4 weeks
to 4 days before rebounding during recovery. The until 12 weeks of age. Give the first booster 1 year
degree of leukopenia is proportional to the sever- later and additional boosters every 3 years thereafter
ity of clinical illness. (see Chapter 7). Annual revaccination as recom-
mended by manufacturers is not needed because
antibody titers and resistance to FPV challenge persist
• Serum chemistry abnormalities are nonspecific 3 years or more after vaccination.
and occur inconsistently but can include electro-
lyte depletion (especially hypokalemia), prerenal
• Give two doses of vaccine, 3 to 4 weeks apart, for
primary vaccination of adult cats.
azotemia, and increased bilirubin and liver enzymes.
• If leukopenia persists more than 5 days or is accom-
panied by severe nonregenerative anemia, consider ▼ Key Point Use only killed FPV vaccine in pregnant
the panleukopenia-like syndrome that is associated cats and in kittens younger than 4 weeks of age.
with feline leukemia virus infection (see Chapter 8). MLV vaccine given perinatally can infect the
Other panleukopenia “look-alike” diseases include unborn fetus or the neonatal cerebellum.
acute salmonellosis, acute bacterial sepsis with endo-
toxemia, and GI foreign body with perforation and
peritonitis (e.g., linear foreign body).
• Presumptive serologic diagnosis is based on paired FELINE CORONAVIRUS
neutralizing antibody titers. Definitive diagnosis
requires fecal PCR or virus isolation, but these are not Etiology
routinely available in clinical practice. Feline coronavirus is a ubiquitous enteric virus in the
• Necropsy diagnosis is based on lesions of severe cat population that invades the epithelium of the villous
necrosis of intestinal crypts. tip, resulting in villous atrophy and mild enteritis. A
mutant variant of feline coronavirus causes feline infec-
Treatment tious peritonitis (see Chapter 10).
• The treatment for feline panleukopenia is similar to
that for canine parvoviral enteritis, mainly non- ▼ Key Point Feline coronavirus is shed in the feces of
specific supportive treatment such as intensive fluid many normal cats, and a high percentage of cats
therapy, parenteral antibiotics, antiemetics, nursing are seropositive, indicating that inapparent infec-
care, and restriction of dietary intake followed by tion is extremely prevalent.
enteral or parenteral feeding.
• In young kittens with panleukopenia, the mortality
rate is high (50–90%). A guarded prognosis is justi- Clinical Signs
fied until impending recovery is indicated by cessa- • In young kittens, especially those 4 to 12 weeks of age,
tion of vomiting and diarrhea, return of appetite to feline coronavirus causes an acute onset of mild
normal, return of body temperature to normal, and enteritis with diarrhea. Feces are soft to fluid and
rebound leukocytosis. However, serious complica- rarely contain mucus and blood.
tions that frequently indicate an impending fatal • Diarrhea is infrequently accompanied by vomiting,
outcome include hypothermia, septic shock, over- low-grade fever, anorexia, and lethargy.
whelming bacterial infection, jaundice, and dissemi- • Clinical signs are usually mild and self-limiting within
nated intravascular coagulation. 2 to 4 days. Rare fatalities have been seen in kittens.
• In a small percentage of infected carrier cats, muta-
Prevention tion of this coronavirus enables the virus to infect
macrophages, leading to systemic dissemination and
▼ Key Point Vaccination is highly effective for pre- fatal feline infectious peritonitis (see Chapter 10 for
vention of feline panleukopenia. a detailed discussion of FIP).
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Diagnosis
FELINE ASTROVIRUS
Serology can identify a convalescent rise in coronaviral
antibody titer. Subclinical coronavirus infection is wide- Etiology
spread in cats; thus, seropositivity does not distinguish
active and past infection. EM and PCR can be used to Very little is known concerning this viral agent, but
identify active shedding of coronavirus in fresh feces, a few reports have identified astroviruses in the
but sensitivity is low with both of these diagnostic feces of cats with diarrhea, and mild diarrhea was
techniques. reproduced experimentally in kittens. A survey of
British cats determined a seroprevalence of less than
Treatment 10%. Astrovirus infections in other species are limited
to infection of the mature villous epithelial cells of the
Uncomplicated coronaviral enteritis is usually self- intestinal mucosa. Transmission is by the fecal-oral
limiting. Routine supportive measures such as fluid route.
therapy and dietary restriction may be beneficial.
▼ Chapter
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and skunks. These animals may survive and shed virus Molecular Techniques
for extended periods.
Rabies virus genomic RNA can be detected in brain
tissue using molecular techniques such as polymerase
Diagnosis chain reaction (PCR) and hybridization techniques.
These are generally reserved for specimens with ques-
▼ Key Point Rapid laboratory confirmation of animal tionable DFA results.
rabies is essential so that exposed humans can
receive proper prophylaxis as early as possible. Treatment
Definitive diagnosis requires laboratory testing of
postmortem tissues. Rabies is almost always fatal in domestic animals.
Because of the extreme public health danger, treatment
is not warranted; therefore, quarantine or euthanize all
Antemortem tests for rabies are too unreliable to be
animals suspected of rabies, and notify local health
recommended; thus, always evaluate postmortem tissue
department authorities.
specimens for diagnosis, especially the brain. For labo-
ratory analysis of brain and salivary tissue for the pres-
ence of rabies virus or antigen, submit the animal’s head
Prevention in Dogs and Cats
chilled on wet ice in a leak-proof container, along with Rabies prevention requires vaccination and preventing
appropriate information and biohazard labeling. Spec- pets from having contact with wild animals.
imens can be stored by refrigeration but not freezing,
because thawing will ruin the specimen for subsequent Vaccination
virus detection.
▼ Key Point Vaccinate all dogs, cats, and ferrets
Direct Fluorescent Antibody Test against rabies in accordance with local public
health regulations and the Compendium of Animal
This is the test of choice used by most laboratories for Rabies Prevention and Control, published annually
rapid, reliable confirmation of rabies antigen in tissues. by the National Association of State Public Health
Brain tissue is most often used for routine testing, but Veterinarians (available at www.nasphv.org).
salivary glands can also be evaluated. The direct fluo-
rescent antibody (DFA) procedure has also been used • Vaccinate as early as 3 months of age and 1 year later,
for antemortem detection of rabies antigen in skin biop- then booster every 3 years in accordance with the
sies; however, a high percentage of false-negative results product recommendations. Maternal antibodies
limits the usefulness of the skin test. from vaccinated females will protect neonates until 3
months of age. Immunity is not fully developed until
Histopathology 28 days after the initial rabies vaccination.
This older, less sensitive test identifies intracytoplasmic • Side effects: Adjuvants may cause local soreness, lame-
neuronal inclusions called Negri bodies, which are ness, fever, lethargy, palpable inflammatory nodules,
found in 75% of rabid dogs but rarely in cats. and rarely, injection-site sarcomas in cats. The rare
neurologic complications of earlier attenuated
(modified live virus [MLV]) vaccines are no longer a
Mouse Inoculation Test problem because only inactivated and recombinant
This is a backup confirmatory test in which DFA- rabies vaccines are currently available in the United
positive brain suspensions are inoculated intracere- States. In other countries where MLV vaccines are
brally into mice; the mice then are sacrificed and their available, only use MLV vaccines that are derived
brains are examined by DFA testing 5 to 6 days postinoc- from high egg passage or cell culture.
ulation. The correlation between DFA and mouse • Rabies serum titers may not correlate with protection
inoculation tests is reportedly 99.9%. and should not be used to determine the need for
booster vaccination.
Tissue Culture Inoculation Test • Do not vaccinate wild animals or hybrids against
rabies, even if they are kept as pets. The safety and
This test is similar to the mouse inoculation test except efficacy of parenteral rabies vaccination in wildlife
that cell cultures are inoculated and then examined by and hybrids (wild animal–domestic animal cross-
DFA testing 24 to 72 hours later. breds) have not been established, and no vaccines are
licensed for these animals.
Monoclonal Antibody Techniques
These techniques are used to identify specific antigenic
Postexposure Management
variants of rabies virus and to differentiate vaccine virus Report all human and animal exposures to the local
strains from wild-type strains in DFA-positive brains. public health authorities. Recommendations for dogs
W0422-Ch015.qxd 11/10/05 4:55 PM Page 170
and cats exposed to rabies (bitten by a known rabid • Vigorously cleanse the wounds of an exposed human
animal or a wild animal that is unavailable for testing) with copious amounts of soap and water to reduce
are as follows: virus in the wound. Ethanol (70%) and benzalko-
nium chloride (1–4%) are acceptable rabicidal dis-
• In a previously vaccinated dog or cat that has been infectants. Depending on the circumstances, public
exposed, revaccinate immediately and keep under
health authorities will decide immediately whether
the owner’s control for 45 days to observe for illness
postexposure prophylaxis is indicated. Previously
suggestive of rabies.
immunized humans generally receive two doses of
• In an unvaccinated dog or cat that has been exposed,
vaccine (on days 0 and 3), whereas non-immunized
recommend immediate euthanasia for examination
humans are given five doses of vaccine (on days 0, 3,
of tissues. If euthanasia is not allowed by the owner,
7, 14, and 28) and rabies immunoglobulin.
strict isolation is required for 6 months with vaccina-
tion either at entry or 1 month before release. If
illness suggestive of rabies develops during isolation,
immediate euthanasia and testing for rabies is PSEUDORABIES
required.
Etiology
Prevention in Humans • Pseudorabies is a herpesvirus that predominantly
Approximately 15% of humans untreated after a bite infects pigs (also called Aujeszky’s disease and mad
from a known rabid animal become infected. Once itch). Most mammals are susceptible (but not
signs develop in a human, rabies is almost always fatal; humans), and infections are seen sporadically in dogs
thus, prevention is essential. and cats in areas where the disease is enzootic in pigs.
• Pseudorabies in dogs and cats is almost always a direct
Pre-Exposure Prevention result of ingestion of contaminated raw pork. Direct
contact with pigs shedding virus in nasal secretions
• For pre-exposure prevention in humans in high-risk and saliva is rarely a source of infection.
situations (e.g., veterinarians and their employees), • The virus invades nerve endings in the pharynx and
immunization with human diploid cell vaccine travels by way of nerve fibers to the brain, where it
(HDCV) or another vaccine approved by the causes acute fatal panencephalitis.
Food and Drug Administration is recommended.
Contact your state health department for specific Clinical Signs
recommendations.
Pseudorabies in dogs and cats causes an acute disease
Animal Bites to Humans: that is almost always fatal within 3 to 5 days of exposure.
Initial signs may include depression and inactivity or
For management of animals that bite humans, follow anxiety and restlessness. The most characteristic sign
the Compendium of Animal Rabies Prevention and (but not seen in every case) is intense pruritus, espe-
Control, published annually by the National Association cially involving the head and neck regions, that leads
of State Public Health Veterinarians (available at to excoriation and self-mutilation. Other signs may
www.nasphv.org). include fever, diarrhea, vomiting, copious hypersaliva-
tion, various cranial neuropathies, ataxia, and seizures.
▼ Key Point Immediately notify local public health Progressive depression, dyspnea, coma, and death
authorities when an animal bite to a human has follow shortly thereafter. Death occurs within 48 hours
occurred or whenever there is the possibility of from the onset of clinical signs.
contact with a rabid animal.
▼ Key Point Suspect pseudorabies in a dog or cat
• When a healthy pet dog or cat has bitten a human, with acute onset of violent, frantic scratching and
the owners must confine and observe the animal for self-mutilation around the face, head, neck, and
10 days. During confinement, the animal must be iso- ears, especially if there is a history of exposure to
lated from contact with other animals and confined pigs or of ingestion of raw pork in an endemic area.
in an escape-proof enclosure or building except for
leash walking under owner control. Any signs of
illness in the confined animal must be reported to
Diagnosis
local public health authorities. • The clinical presentation of pseudorabies is indistin-
• When a wild animal or a feral or stray dog or cat with guishable from rabies and is similar to other forms of
unknown vaccination status has bitten a human, encephalitis.
regard the animal as potentially rabid and sacrifice it • It is virtually impossible to make a definitive ante-
immediately for laboratory examination of tissues mortem diagnosis of pseudorabies in dogs and cats.
under the guidance of local public health officials. Routine hematologic and serum chemistry evalua-
W0422-Ch015.qxd 11/10/05 4:55 PM Page 171
tions are normal. Cerebrospinal fluid may show non- Hanlon CA, Childs JE, Nettles VF, et al: Recommendations of the
specific increases in protein and mononuclear cells Working Group on Rabies, Article III: Rabies in wildlife. J Am Vet
Med Assoc 215:1612–1618, 1999.
suggestive of viral encephalitis. The serologic tests Hanlon CA, Smith, JS, Anderson, GR, et al: Recommendations of the
used in pigs are not diagnostically useful in dogs and Working Group on Rabies, Article II: Laboratory diagnosis of
cats. rabies. J Am Vet Med Assoc 215:1444–1446, 1999.
• Postmortem diagnosis is based on specialized testing Hanlon CA, Niezgoda MN, Rupprecht CE: Postexposure prophylaxis
for prevention of rabies in dogs. Am J Vet Res 63:1096–1100, 2002.
of unfixed brain tissue for virus using immunofluo- Jay MT, Reilly KF, DeBess EE, et al: Rabies in a vaccinated wolf-dog
rescent, virus isolation, animal inoculation, or mole- hybrid. J Am Vet Med Assoc 205:1729–1732, 1994.
cular techniques. Routine histopathology may show Krebs JW, Mandel EJ, Swerdlow DL, et al: Rabies surveillance in the
characteristic viral inclusion bodies. United States during 2003. J Am Vet Med Assoc 225:1837–1849,
2004.
McQuiston J, Yager PA, Smith JS, et al: Epidemiologic characteristics
Treatment of rabies virus variants in dogs and cats in the United States, 1999.
No effective treatment is known. J Am Vet Med Assoc 218:1939–1942, 2001.
Position on canine hybrids. In Directory and Resource Manual.
Schaumburg, IL: American Veterinary Medical Association, 2002,
Prevention pp 88–89.
Tepsumethanon V, Lumlertdacha B, Mitmoonpitak C, et al: Survival
To prevent pseudorabies in dogs and cats in endemic of naturally infected rabid dogs and cats. Clin Infect Dis
areas, prevent direct contact with pigs and never feed 39:278–280, 2004.
raw pork. An effective vaccine is not available. Vaughn JB, Gerhardt P, Paterson J: Excretion of street rabies virus in
saliva of cats. J Am Med Assoc 184:705, 1963.
Vaughn JB, Gerhardt P, Newell KW: Excretion of street rabies virus in
saliva of dogs. J Am Med Assoc 193:363–368, 1965.
SUPPLEMENTAL READING
Rabies Pseudorabies
Hagemoser WA, Kluge JP, Hill HT: Studies on the pathogenesis of
Barnes HL, Chrisman CL, Farina L, Detrisac CJ: Clinical evaluation pseudorabies in domestic cats following oral inoculation. Can J
of rabies virus meningoencephalomyelitis in a dog. J Am Anim Comp Med 44:192–202, 1980.
Hosp Assoc 39:547–550, 2003. Monroe WE: Clinical signs associated with pseudorabies in dogs. J Am
Compendium of Animal Rabies Prevention and Control 2005; Vet Med Assoc 195:599–602, 1989.
National Association of State Public Health Veterinarians; Vandevelde M: Pseudorabies. In Greene CE (ed): Infectious Diseases
http://www.nasphv.org/83416/83301.html of the Dog and Cat, 2nd ed. Philadelphia: WB Saunders, 1998, p
Greene CE, Dreesen DW: Rabies. In Greene CE, ed: Infectious Dis- 126.
eases of the Dog and Cat, 3rd ed. St. Louis: WB Saunders, 2006.
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▼ Chapter
172
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confirmed by postmortem PCR assay of brain tissue. the virus has been demonstrated in lung and kidney
The seroprevalence in dogs and cats in endemic areas of tissue of cats. However, the clinical significance of this
North America appears to be low. Oral transmission virus in cats is not yet known. Most if not all infections
of West Nile virus can occur in cats through ingestion in cats appear to be subclinical. In humans, Hantavirus
of infected rodents. is a life-threatening zoonotic infection that causes
hemorrhagic fever, renal syndrome, or pulmonary syn-
Bornavirus drome, depending on the strain of virus. The virus is
transmitted in aerosolized rodent excrement and rarely
Bornavirus is a neurotropic virus that mostly infects by rodent bites.
horses and sheep, but it also causes a rare but fatal neu-
rologic disease in cats and dogs, especially in central Feline Foamy Virus
Europe and Japan. Non-suppurative meningoen-
cephalomyelitis (especially gray matter) causes progres- This feline Spumavirus is in the retrovirus family and
sive neurologic signs of ataxia, circling (dogs), paresis, was formerly known as feline syncytium-forming virus.
behavior changes, salivation, hyperesthesia (cats), loss Infection with this virus is very common in cats, with
of vision, and seizures. The diagnosis is based on post- seroprevalence as high as 90% in some cat populations.
mortem demonstration of Bornavirus in brain tissue This feline retrovirus is ubiquitous and has been studied
using PCR. The reservoir of infection is unknown, but for over 3 decades, but it has yet to be associated with
transmission is presumed to be vector-borne. Human clinical disease in cats except for early studies that
infections also occur. found a statistical link to feline chronic progressive
polyarthritis.
Other Vector-Borne Viruses Feline Spongiform Encephalopathy
Dogs and cats are susceptible to several viruses that are
Feline spongiform encephalopathy (FSE) is a fatal neu-
transmitted by arthropods, such as mosquitoes and
rologic disease that has primarily been seen in cats in
ticks. In most cases these viruses target other host
Great Britain and a few other European countries since
species; dogs and cats are merely incidental hosts
the 1990s concurrently with the European outbreak of
that seroconvert after subclinical infection. Examples
bovine spongiform encephalopathy (BSE). The etiology
of vector-borne viruses that can infect dogs and/or
of FSE is considered to be the same prion, or self-
cats include equine togaviruses (Eastern, Western and
replicating protein, that causes BSE in cattle or scrapie
Venezuelan equine encephalitis), flaviviruses (St. Louis
in sheep. Cats are probably infected through ingestion
encephalitis, louping ill, yellow fever, and others), bun-
of table scraps or prepared cat foods that contain
yaviruses (e.g., Rift Valley fever), and orbiviruses
prion-infected meat from cattle, sheep, or goats. After
(African horse sickness and blue tongue).
a prolonged incubation period, cats with FSE deve-
lop neurologic signs (e.g., behavior changes, ataxia,
Influenza Viruses tremors, salivation, and hyperesthesia) that slowly
The avian influenza virus strain H5N1 that has caused progress to death. There is no effective treatment. The
fatal human infections in Asia also can infect cats and diagnosis is based on distinctive gray matter vacuolation
cause fatal pneumonia. Infection occurs through and fibril deposits in the brain at necropsy. The occur-
contact with or ingestion of infected poultry. Under rence of FSE is expected to decline now that strict reg-
experimental conditions, horizontal cat-to-cat transmis- ulations are in place for control of BSE and scrapie.
sion has been shown. Zoonotic cat-to-human transmis-
sion has not been ruled out.
SUPPLEMENTAL READING
Paramyxoviruses
Infectious Canine Hepatitis
Hendra virus in horses in Australia and Nipah virus in
pigs in Malaysia are fatal zoonotic respiratory diseases Greene CE: Infectious canine hepatitis and canine acidophil cell
hepatitis. In Greene CE (ed): Infectious Diseases of the Dog and
that can be experimentally transmitted to cats. Fruit Cat, 3rd ed. St. Louis: Elsevier, 2006.
bats are the endemic reservoirs for these paramyxo-
viruses. Antibodies to human mumps paramyxovirus Canine Herpesvirus
have been found in dogs, but experimental inoculation
of dogs with mumps virus have been inconclusive. Carmichael LE, Greene CE: Canine herpesvirus infection. In Greene
CE (ed): Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis:
Elsevier, 2006.
Hantavirus in Cats Miyoshi M, Ishii Y, Takiguchi M, et al: Detection of canine herpesvirus
DNA in the ganglionic neurons and the lymph node lymphocytes
Hantavirus is endemic worldwide in rodent reservoirs. of latently infected dogs. J Vet Med Sci 61:375, 1999.
Serologic evidence of Hantavirus infection in cats has Morresey, PR: Reproductive effects of canine herpesvirus. Com-
been found in North America, Europe, and Asia, and pendium Contin Educ Pract Vet. 26:804–810, 2004.
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▼ Chapter
17 Rickettsiosis, Ehrlichiosis,
Anaplasmosis, and Neorickettsiosis
Robert G. Sherding
178
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may still be found on the dog (or may have been • Using the indirect fluorescent antibody (IFA) sero-
recently removed by the owner); however, a negative logic test, a serum titer of >1:128 is presumptive evi-
tick history by no means excludes RMSF. dence of RMSF; however, dogs often have a negative
Clinical findings in dogs with acute RMSF can titer when tested early in the disease (first 5 days). A
include any of the following: definitive diagnosis is established by a fourfold rise in
paired titers (2–3 weeks apart); or based on a single
• General signs: Fever, anorexia, lethargy, vomiting/ titer of >1:1024 at 7 days or more after the onset of
diarrhea, weight loss, and generalized lymphade-
clinical signs.
nopathy.
• Polyarthritis: Poorly localized joint and muscle pain
• The prevalence of seropositivity is higher than the
prevalence of the clinical disease and must be con-
and lameness.
sidered when interpreting titers. This is due in part
• Ocular signs: Schleral and conjunctival hyperemia
to cross reactivity with nonpathogenic tickborne Rick-
and petechiae; retinal vasculitis and hemorrhages;
ettsia spp. High titers can persist for up to 1 year after
and anterior uveitis and hyphema.
successful treatment or recovery from the disease,
• Neurologic signs: Hyperaesthesia, tetraparesis, ataxia,
which also must be considered.
vestibular signs, stupor, and seizures.
• Cutaneous vasculitis: Hyperemia, edema, and
• Rapid confirmation of the diagnosis can be estab-
lished by PCR identification of rickettsial DNA in
petechial-to-ecchymotic hemorrhages (face, distal
an EDTA blood sample or in tissues. Prior antibiotics
extremities, scrotum, ventral abdomen); and skin
can cause a false-negative PCR result.
necrosis and gangrene in severe cases.
• Pneumonitis: Cough, tachypnea, dyspnea, and exer-
• The direct immunofluorescence test can confirm the
diagnosis by detecting rickettsial antigens in fresh or
cise intolerance.
paraffin-embedded tissues, especially skin, as early as
• Myocarditis: Cardiac arrhythmias or sudden death.
3 to 4 days post-inoculation. Skin biopsies obtained
• Other signs: Icterus, orchitis, bleeding (epistaxis,
with local anesthetic and a biopsy punch can be used.
melena, and hematuria), or oliguric renal failure.
A positive result is highly specific for RMSF; however,
false-negative results occur in up to 30% to 40% of
cases (low sensitivity).
Laboratory Findings
• Frequent hematologic findings include mild-to-mod-
erate thrombocytopenia (>80% of cases), leukocyto- Treatment
sis with a left shift, toxic granulation of neutrophils, • Doxycycline (5–10 mg/kg, PO or IV, q12h) for 14
monocytosis, and mild anemia. Rare findings are days is the drug of choice for treating dogs with
transient leukopenia (early) and overt disseminated RMSF. Tetracycline (22 mg/kg PO q8h), enrofloxacin
intravascular coagulation (DIC) (late). Anti-platelet (3 mg/kg, SC or PO, q12h), or chloramphenicol
antibodies have been demonstrated in natural and (15–25 mg/kg, PO, IM, or IV, q8h) given for 14 days
experimental canine RMSF infections. have also been effective for treating dogs with RMSF.
• Biochemical abnormalities, which reflect vascular • Initiate supportive therapy as needed, but use
injury and organ damage, can include hypoalbumin- extreme caution with fluid therapy because vascular
emia, increased serum liver enzymes, hyperbiliru- damage predisposes the patient to severe edema.
binemia, azotemia, hyponatremia, hypochloremia,
hypercholesterolemia, and metabolic acidosis.
• Synovial fluid is typical of neutrophilic polyarthritis, ▼ Key Point Do not delay treatment of dogs sus-
and cerebrospinal fluid has a mild increase in protein pected of having RMSF. Initiate doxycycline while
and cells (neutrophils). awaiting confirmatory diagnostic tests to prevent
development of complications such as fatal central
nervous system (CNS) disease, cardiovascular col-
Diagnosis lapse, oliguric renal failure, or gangrene.
Suspect RMSF in dogs residing in endemic areas
that present with an acute, rapidly progressive febrile
illness and a recent history of tick infestation. The diag-
Prognosis
nosis of RMSF can be confirmed by serum antibody The prognosis is good when treatment is instituted
titers and polymerase chain reaction (PCR) assays that promptly. Clinical response should occur within hours
are readily available to practicing veterinarians through of initiating appropriate drug administration. The mor-
the Vector Borne Disease Diagnostic Lab at North tality rate is high if an ineffective antibiotic is used or
Carolina State University. Submission requirements treatment is delayed until the disease is advanced. Dogs
and forms are available at www.cvm.ncsu.edu/docs/ with severe CNS signs may die within hours, before
tickbornediseaselab.html. treatment takes effect.
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months to years, dogs with persistent E. canis infection Serology by Indirect Fluorescent Antibody
develop a variety of chronic vague illnesses accompa-
nied by lymphoreticular hyperplasia and bone marrow Serologic testing for E. canis antibodies using IFA is
dysfunction. highly sensitive and reliable for presumptive diagnosis
of canine ehrlichiosis.
• Clinical signs can be mild or severe, and may include
weight loss, fever, spontaneous bleeding (petechiae • Antibody titers >1:64 are considered indicative of
and ecchymoses, epistaxis, melena, hematuria, prior or active infection.
hyphema), pallor due to anemia, generalized lym- • Diagnostic titers may not be detected until 2 to 4
phadenopathy, splenomegaly, hepatomegaly, uveitis weeks after infection; thus, some dogs develop clini-
(anterior uveitis, chorioretinitis, retinal hemorrhages cal signs before developing a positive titer. Most dogs
or detachments), meningoencephalomyelitis (ataxia, with clinical signs are seropositive.
paresis, seizures, stupor, vestibular signs, etc.), poly- • Antibodies to one Ehrlichia species may or may not
arthritis, and intermittent limb edema. cross react with other species. E. canis titers are posi-
tive in most dogs with E. chaffeensis infection, but only
• Chronic-phase ehrlichiosis may be more severe in
half of dogs with E. ewingii infection.
German shepherds and Doberman pinschers.
• Hematologic findings can include nonregenerative • Ehrlichia antibody titers do not confer protection
anemia, thrombocytopenia, leukopenia, or all three against reinfection. Titers persist for at least 9 to 12
(pancytopenia), due to bone marrow hypoplasia; months after treatment or recovery.
lymphocytosis (occasionally composed of atypical
or large granular lymphocytes); bone marrow Serology by Enzyme-Linked Immunosorbent Assay
and splenic plasmacytosis; and occasional Coombs’- An ELISA-based test kit (SNAP 3Dx; IDEXX) for detect-
positive hemolytic anemia. ing E. canis antibodies is available as a rapid point-of-
• Other laboratory findings include hyperglobulinemia care screening test for canine ehrlichiosis. This tests
caused by polyclonal (or less often monoclonal) gam- simultaneously for heartworms and Borrelia burgdorferi,
mopathy; hypoalbuminemia; proteinuria; and a pos- hence the name “3Dx”.
itive test for anti-nuclear antibodies (ANA). In some
cases severe protein-losing nephropathy is associated • The SNAP 3Dx is calibrated to be positive at an IFA
with immune-complex glomerulonephritis. titer of >1:500. Limited studies have shown good cor-
relation with IFA testing; the reported sensitivity is
71% to 95%, and the specificity is 99%.
▼ Key Point Clinical signs, physical findings, and lab- • This assay is intended for E. canis and does not detect
oratory abnormalities in dogs with chronic ehrli- other Ehrlichia infections.
chiosis may resemble multiple myeloma or chronic
lymphocytic leukemia.
Polymerase Chain Reaction Testing
Diagnosis PCR for detection of Ehrlichia DNA in EDTA blood can
be used to definitively diagnose canine ehrlichiosis and
Canine ehrlichiosis must be differentiated from various to identify the infecting Ehrlichia species. Always use
other infectious and immune-mediated diseases that PCR in conjunction with serologic testing, not in place
can present with similar clinical signs. The diagnosis of of it.
canine ehrlichiosis can be confirmed by cytologic visu-
alization of organisms in blood or cytology specimens, • False-negative PCR blood tests can occur, especially
and by serum antibody titers and PCR assays that are in animals treated recently with antibiotics.
available to practicing veterinarians through the Vector • In some dogs, splenic and bone marrow aspirates
Borne Disease Diagnostic Lab at North Carolina State have been PCR positive when blood was PCR
University. Submission requirements and forms are negative.
available at www.cvm.ncsu.edu/docs/tickbornedisease-
lab.html. Blood culturing for Ehrlichia is not available Cytology
except in research labs because it is difficult and expen-
Identification of intracellular Ehrlichia organisms
sive and growth takes up to 8 weeks.
(morulae) in peripheral blood leukocytes (buffy coat
smears) is confirmatory; however, this is a time-
consuming and highly insensitive means of diagnosis.
▼ Key Point A confirmed diagnosis of Ehrlichia is a
marker for exposure to ticks and the infectious • Morulae can also be seen in bone marrow cells, cere-
agents they transmit. Consider using a serologic brospinal fluid leukocytes, joint fluid leukocytes, or
tick panel to test for other concurrent tick-trans- fine-needle aspirates of the spleen or lymph nodes.
mitted infections, such as Anaplasma, Rickettsia, • Plasmacytosis also is frequently prominent in cyto-
Bartonella, Borrelia, and Babesia. logic specimens from dogs with ehrlichiosis.
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Diagnosis Diagnosis
Confirmation is based on finding granulocytic morulae, The diagnosis is based on serology, PCR, or blood cytol-
demonstrating a rising serum antibody titer in paired ogy. See Chapter 22 for a discussion of the differential
sera, or PCR detection of A. phagocytophilum DNA (avail- diagnosis of thrombocytopenia. A. platys and E. canis
able through the Vector Borne Disease Diagnostic Lab often infect dogs concurrently; thus, consider evaluat-
at North Carolina State University; www.cvm.ncsu. ing dogs for both agents.
edu/docs/tickbornediseaselab.html).
• Serologic testing by IFA detects antibodies against
A. platys after 2 to 3 weeks. A. platys does not cross
Treatment react serologically with E. canis, A. phagocytophila, or
Dogs with anaplasmosis respond rapidly to doxycycline N. risticii.
(5–10 mg/kg, PO, q12h for 14–21 days) or tetracycline • PCR detection of A. platys DNA is confirmatory.
(22 mg/kg PO q8h for 21 days). PCR is available through the Vector Borne Disease
Diagnostic Lab at North Carolina State University;
Prevention and Public Health www.cvm.ncsu.edu/docs/tickbornediseaselab.html.
Prevention of A. phagocytophilum depends on minimiz- • A. platys organisms (morulae) are occasionally visual-
ing tick exposure, using an effective tick preventative ized within platelets as blue inclusions in Giemsa-
product on a regular basis, and routinely checking dogs stained blood smears; however, this is too insensitive
for ticks and removing them promptly. Infected ticks to be used as the only diagnostic test.
can transmit A. phagocytophilum to humans, but there is
no evidence of direct transmission of Anaplasma infec- Treatment
tion from animals to people. E. platys infection is effectively eliminated by doxycy-
cline (5–10 mg/kg, PO, q12h for 14 days) or tetracy-
cline (22 mg/kg PO q8h for 14 days).
CANINE CYCLIC THROMBOCYTOPENIA
(Anaplasma platys) Prevention
Prevention of A. platys infection depends on minimiz-
Etiology ing tick exposure, using an effective tick preventative
Canine cyclic thrombocytopenia is cause by A. platys product on a regular basis, and routinely checking dogs
(formerly E. platys), a bacterial organism that only repli- for ticks and removing them promptly.
cates in platelets.
• It is presumed that A. platys is transmitted by ticks, but
the specific tick species are not known. Experimen- NEORICKETTSIOSIS
tally the brown dog tick, Rhipicephalus sanguineous, did
not transmit A. platys. (Neorickettsia risticii)
• In the United States, A. platys infection is reported
most frequently in the Southeast and Gulf Coast Etiology
states. One study of dogs in Louisiana found a sero- Neorickettsia risticii, the agent that causes equine
prevalence of 40% in thrombocytopenic dogs and Potomac Horse Fever (formerly E. risticii), can also
50% in healthy kennel dogs. infect dogs and cats, but its clinical importance and the
extent of its pathogenicity is not yet known. Feline
Clinical Signs and Laboratory Findings neorickettsiosis is discussed under Feline Ehrlichia-Like
A. platys appears to be minimally pathogenic and is not Diseases.
associated with clinical signs in most dogs. Thrombocy-
topenia develops at 10 to 14 day intervals in association • The vectors that transmit N. risticii infection are
trematodes (flukes) that use snails and aquatic insects
with cyclic A. platys bacteremia. Thrombocytopenic
as intermediate hosts. Dogs and cats are presumably
episodes are generally incidental findings in seemingly
infected by ingesting free-living trematode stages
healthy dogs. Uveitis was reported in one infected dog.
in standing water, or by ingesting snails or aquatic
• Thrombocytopenia is moderate to severe, with a insects that are parasitized by N. risticii-infected
nadir as low as 20,000 to 50,000 platelets/ml. Platelet trematode metacercariae.
aggregation is also impaired. However, signs of spon- • N. risticii has a tropism for monocytes and
taneous bleeding are rare. enterocytes.
• Other laboratory findings can include mild normo- • Experimentally, inoculation of N. risticii induces sub-
chromic-normocytic nonregenerative anemia, leukope- clinical infection or mild clinical illness in dogs and
nia, hypoalbuminemia, and hyperglobulinemia. cats.
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▼ Chapter
Lyme borreliosis is a polysystemic, tickborne disease • In the United States, over 90% of clinically affected
caused by the spirochete Borrelia burgdorferi. The disease dogs are found in the northeastern coastal states and
has been associated with polyarthritis in dogs, cattle, Wisconsin and Minnesota. Within endemic regions,
horses, and humans. Infection is widespread in the there are focal areas of high and low prevalence. The
United States, and is endemic in the northeastern coastal seroprevalence in dogs in highly endemic areas com-
states and the upper Midwest. Infection also occurs monly reaches 50% to 90%, and 60% to 80% of the
worldwide and is prevalent in areas of Europe. Borre- ticks in these areas may harbor Borrelia spirochetes.
liosis is transmitted to animals and people by deer ticks. The seroprevalence in Southern and Western states
is less than 4%.
• 95% of seropositive dogs are asymptomatic.
ETIOLOGY
Transmission
Lyme borreliosis in dogs and humans is caused by at
Dogs are infected through the bite of an infected tick.
least 6 subspecies of the Borrelia burgdorferi sensu lato
The primary vectors of Lyme borreliosis are Ixodes spp.
complex. The strain that primarily causes borreliosis in
ticks, also called black-legged or deer ticks. These hard
North America is Borrelia burgdorferi senso stricto. These
ticks are small (2–3 mm) 3-host ticks that have a 2-year
eubacteria are spiral-shaped, flagellated, gram-negative
life cycle with larval, nymph, and adult stages.
spirochetes that are related to Leptospira, except they do
not survive as free-living organisms outside of the host. • In the Northeast, Southeast, and Midwest regions
B. burgdorferi is easy to isolate from vector ticks but of the United States, Borrelia burgdorferi is carried by
not from clinically affected patients. The organisms are Ixodes scapularis (formerly designated I. dammini). In
microaerophilic and have special growth requirements. California and other western states, I. pacificus is the
The outer membrane of the spirochete can undergo carrier. Various other Ixodes ticks are involved in
antigenic variation during the course of infection, Europe and Asia. Other species of ticks and biting
which enables the organism to evade the host’s immune insects such as flies and mosquitoes can carry Borre-
response and cause persistent infection. Antigenic vari- lia spirochetes, but these are not a significant source
ation may limit the effectiveness of vaccines. of transmission.
Dogs in endemic areas are commonly co-infected • Deer support the adult stage of I. scapularis but are
with other tickborne agents, especially Anaplasma phago- not usually infected by the spirochete. Mice and
cytophila (see Chapter 17), and mixed infections may other small rodents are the main reservoirs of borre-
contribute to the pathogenesis and severity of disease in liosis because they maintain the larval and nymphal
some cases. stages of I. scapularis and can become infected with
the spirochete. Migratory birds may be important
Prevalence reservoirs because they have the ability to transmit
ticks and spirochetes over long distances. Dogs are
▼ Key Point The risk of Borrelia burgdorferi infection incidental hosts.
correlates with the prevalence of infected ticks in • Western I. pacificus ticks are less efficient as vectors
an area and the likelihood of being bitten by a because they prefer to feed on lizards that contain
vector tick. borreliacidal factors.
• Direct transmission between dogs is unlikely. Unin-
• Borreliosis commonly affects dogs that have recre- fected dogs housed with infected carrier dogs for 1
ational exposure to tick-infested vegetation in year did not become infected. In utero transmission
endemic areas, especially outdoor sporting and is not likely. Iatrogenic transmission by blood trans-
hunting dogs. fusion is a possibility.
186
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(ELISA) or immunofluorescent antibody (IFA) tech- • Evaluate animals with a negative titer and clinical
niques. These do not differentiate between antibodies signs suggesting borreliosis for immune-mediated
from natural exposure and vaccination. The C6 anti- causes of polyarthritis (see Chapter 124).
body test and Western blot analysis are more specific for
natural exposure. ▼ Key Point Routine ELISA and IFA tests are highly
sensitive screening tests, but they have poor speci-
ELISA and IFA Antibody Titers ficity and thus are not suitable as confirmatory
The antibody titer detected by ELISA or IFA increases tests.
by 4 to 6 weeks after exposure, which is almost always
before the onset of clinical signs; thus, ELISA or IFA C6 Antibody Test
titers are acceptable screening tests for Lyme borrelio- This test uses a synthetic C6 peptide as the antigen for
sis in unvaccinated dogs. Unfortunately, reliability and detecting C6 antibodies against the highly conserved
reproducibility of results vary between different com- invariable region 6 (IR6) of the outer surface protein
mercial laboratories. (Osp) of B. burgdorferi. C6 antibodies are formed in
response to natural exposure, but not in response to
▼ Key Point Routine ELISA or IFA serologic testing vaccination.
does not differentiate between dogs with active
Lyme disease and those with persistent antibodies • The C6 antibody test is highly specific (99% speci-
from earlier exposure or vaccination. ficity) for B. burgdorferi. The test does not crossreact
with antibodies from prior Lyme vaccination or non-
Positive Titer specific antibodies against other spirochetes (e.g.,
Leptospira), thus eliminating the major causes of false-
• In an endemic area, a positive titer can be an inci- positives seen with traditional whole-cell ELISA and
dental finding resulting from prior infection. Anti- IFA tests.
body titers after natural exposure persist for years. • The C6 antibody test is more sensitive than tradi-
Other causes of positive titers include prior vaccina- tional whole-cell ELISA for detecting early infections,
tion, crossreactivity to other noncausative organisms detecting infections even as early as 3 weeks post-
(e.g., nonpathogenic Borrelia strains, Leptospira spp., exposure, before clinical signs develop. This test may
oral spirochetes), and nonspecific reactions seen in also be more sensitive for detection of certain strains
other inflammatory conditions. of Borrelia, such as those found in Europe.
• Positive titers have a low predictive value for the
development of clinical disease. In one study seropos- ▼ Key Point The C6 antibody test (SNAP 3Dx) distin-
itive dogs were observed for 20 months, and less than guishes between natural exposure and vaccine-
5% developed clinical joint disease. induced antibodies.
▼ Key Point A positive Borrelia antibody test indi- • An ELISA-based test kit for C6 antibodies (SNAP 3Dx;
cates exposure, but it does not prove that the IDEXX) is available as an in-office screening test
clinical signs are caused by borreliosis. for Lyme borreliosis. The kit simultaneously tests
for heartworms and Ehrlichia canis, hence the name
• Paired titers (to identify a rising titer) are not helpful, “3Dx”. The manufacturer recommends a two-tiered
and high titers can persist for years, even after testing approach, first using the in-office SNAP 3Dx
treatment. test kit as the qualitative screening test for C6 anti-
• Because dogs do not develop clinical disease before bodies. Positive results are then further characterized
the rise in immunoglobin G (IgG) antibody, differ- with a quantitative C6 antibody test on a serum sample
entiation of immunoglobin M (IgM) and IgG is not sent to a reference laboratory.
useful. In addition, IgM titers persist for many • The quantitative C6 antibody test correlates with Bor-
months and do not indicate recent exposure. relia load. In seropositive healthy dogs, a high level of
• In cases suspected of neuroborreliosis, a high cere- C6 antibody may help to determine if treatment is
brospinal fluid (CSF)-to-serum antibody titer ratio warranted, although additional studies are needed to
has been suggested as an indicator of central nervous confirm this.
system (CNS) antibody production and active neural • In seropositive dogs with clinical borreliosis, the
infection. quantitative C6 antibody level can be measured prior
to treatment and then used to monitor response to
Negative Titer the therapy. The C6 antibody level usually declines by
• False-negative antibody titer results are rare; thus, a 3 months after successful antibiotic treatment.
negative titer in an animal with clinical signs rules out Current recommendations are to reevaluate the test
Lyme borreliosis with high probability. at 3 and 6 months after treatment.
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▼ Chapter
19 Systemic Bacterial Infectious Diseases
Robert G. Sherding
A large number of bacteria can infect dogs and cats. • Wild animal populations serve as reservoirs of infec-
This chapter focuses on leptospirosis, brucellosis, and tion that persistently shed Leptospira organisms and
bartonellosis. Chapter 18 is devoted to Lyme borrelio- contaminate the environment. Suburban “backyard”
sis. Other infectious diseases caused by bacteria are sum- wildlife such as raccoons, skunks, squirrels, voles, and
marized in Table 19-1, and most are described in the other rodents may be especially important sources of
respective organ-system chapters. Bordetella bronchiseptica infection.
is associated with the canine infectious tracheobron- • Exposure usually occurs by mucocutaneous contact
chitis (see Chapter 12). Mycoplasma haemofelis and with Leptospira organisms in the environment, most
Mycoplasma haemominutum are hemotropic infections importantly contaminated surface water, but also
(see Chapter 22). Mycobacterial infections are associ- food, bedding, soil, vegetation, or fomites. The
ated with chronic skin disease (see Chapter 39). Actin- organisms penetrate mucosa or abraded skin. In
omycosis and nocardiosis are causes of pyothorax (see addition, transplacental, venereal, and bite-wound
Chapter 164). Tetanus and botulism cause severe neu- transmission can occur.
romuscular dysfunction (see Chapters 128 and 130,
respectively). Salmonellosis, campylobacteriosis, yersin- Prevalence
iosis, and Clostridium perfringens and Cl. difficile primar- Canine leptospirosis appears to be a reemerging disease
ily involve the intestinal tract (see Chapter 69). with increasing prevalence, especially involving serovars
L. grippotyphosa and L. pomona. Middle-aged, male, large-
breed outdoor dogs that live in peri-urban areas are
LEPTOSPIROSIS most commonly affected; however, all dogs are at risk.
The incidence is highest in late summer and early fall.
Etiology Infection rates increase after wet periods of rainfall and
flooding.
Leptospira are filamentous, motile, spirochete bacteria
that infect many wild and domestic animals and
Pathogenesis
humans. Over 200 leptospiral serovars have been
described. A universal feature of pathogenic serovars Leptospiremia occurs 4 to 12 days post-infection. The
is the ability to colonize the proximal renal tubules primary targets in leptospirosis are the kidneys and the
resulting in a prolonged renal carrier state and urine liver. Vasculitis and disseminated intravascular coagu-
shedding. lopathy (DIC) may result from widespread acute
In North America, canine leptospirosis is most fre- endothelial injury.
quently caused by serovars of Leptospira interrogans
(serovars L. icterohaemorrhagiae, L. canicola, L. pomona,
• Leptospira preferentially infect renal tubule epithe-
lium, often causing acute tubular injury and renal
and L. bratislava) and Leptospira kirschneri (serovar L. failure. Renal colonization and urine shedding are
grippotyphosa). Serovar L. autumnalis may also be emerg- prolonged, continuing for months to years after clin-
ing in some regions. ical recovery.
• Leptospira can injure hepatocytes, resulting in hepa-
Transmission tocyte dysfunction, cholestasis, acute hepatic necro-
sis, jaundice, and occasionally chronic hepatitis and
▼ Key Point Infection is spread by recovered animals hepatic fibrosis (especially L. grippotyphosa).
that shed Leptospira organisms in their urine for • Infection typically is subclinical in vaccinated
months to years after infection. (immune) dogs and in nearly all cats.
191
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AGID, agar-gel immunodiffusion; DIC, disseminated intravascular coagulation; ELISA, enzyme-linked immunosorbent assay; IFA, indirect fluorescent antibody;
MA, microscopic agglutination; PCR, polymerase chain reaction.
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crossreactivity and/or background titers from prior Polymerase Chain Reaction Test
vaccination.
PCR detection of leptospiral DNA in blood, urine,
or tissues is highly sensitive and specific. It detects in-
Combined Immunoglobulin Titers fection earlier than serology, and may be useful for
identifying subclinical urine shedding. Unfortunately,
Combined immunoglobulin M (IgM)-immunoglobulin validated PCR assays are not yet readily available to the
G (IgG) enzyme-linked immunosorbent assay (ELISA) clinician.
titers differentiate the early IgM antibody response of
acute infection from the later IgG response that is seen
with recovery, prior infection, or vaccination. Although Treatment
the combined IgM-IgG ELISA helps to identify natural Effective treatment requires general supportive therapy,
infection in vaccinated dogs, it does not distinguish treatment of the leptospiremic phase of infection, fol-
between different serovars. The ELISA test is not as lowed by treatment of the leptospiruric carrier phase of
readily available as the MA test. infection. With intensive management, survival rates of
• The IgM titer becomes positive within the first week 75 to 90% can be expected. Most dogs recover com-
of infection (before the MA test) and peaks at 2 pletely, but residual chronic renal failure is a potential
weeks. outcome.
• The IgG titer becomes positive 2 to 3 weeks after • For supportive care: Administer intensive fluid and
infection and persists for months. electrolyte therapy (see Chapter 5) and, depending
on clinical findings, initiate appropriate treatment
for acute renal failure (see Chapter 77), acute hepatic
Identification of Leptospiral Organisms failure (see Chapter 71), and DIC (see Chapter 23),
Leptospirosis can be confirmed by identification of Lep- as recommended in other chapters in this book. Olig-
tospira organisms by microscopy and culture. These tests uric renal failure and fulminant DIC are life-threat-
are most useful for confirming positive serologic tests, ening complications of leptospirosis that often need
and only positive results are meaningful. Because of low the most immediate attention and intensive care.
detection rates, negative results never exclude the pos-
sibility of leptospirosis. In addition, antibiotics rapidly ▼ Key Point The antibiotics of choice are penicillin
eliminate the organisms from blood and urine so they derivatives for terminating leptospiremia, and
will be undetectable by culture. Polymerase chain reac- doxycycline for eliminating leptospiruria.
tion (PCR) identification of leptospiral DNA may be a
more reliable means of documenting infection. • For leptospiremia: Initially give parenteral antibi-
otics, such as penicillin G (25,000–40,000 units/kg IV,
q12h) or ampicillin (22 mg/kg IV, q6–8h). Once
Microscopic Identification vomiting resolves, switch to oral amoxicillin (22 mg/
• Darkfield microscopy is used to detect leptospires on kg PO, q8–12h) and continue treatment for 2 weeks.
a wet mount of fresh urine. Accuracy is highly oper- • For leptospiruria: To eliminate the renal carrier state
ator dependent, and the high rate of false positives once amoxicillin treatment has been completed, give
and false negatives makes this an unreliable test. doxycycline (5 mg/kg PO q12h) for 2 weeks. Other
• Leptospira organisms can sometimes be identified in alternatives for treating the carrier state include
urine or in tissues (e.g., by kidney and liver biopsy or macrolides (erythromycin, azithromycin), fluoro-
cytology specimens) using Giemsa or silver stains, quinolones, or aminoglycosides (avoid in dogs with
immunohistochemical staining, or fluorescent anti- renal impairment).
body techniques. • For caretaker precautions, see the “Public Health”
section.
Culture
Prevention
Culture for Leptospira is technically difficult and has a
Because wild animal reservoirs harbor and shed lep-
low detection rate; thus, it is rarely used for clinical diag-
tospiral organisms that contaminate the environment,
nosis. The organisms are fastidious and may take several
prevention of exposure is not a realistic expectation.
weeks to grow. The preferred specimen is fresh urine
Routine vaccination for leptospirosis helps to decrease
taken by cystocentesis prior to administration of
the incidence and severity of canine leptospirosis and
antibiotics. In hydrated dogs, a low dose of furosemide
to reduce the zoonotic risks to pet owners.
(0.5 mg/kg, IV) prior to urine collection may optimize
the recovery rate. Collected urine must be alkalinized • Bivalent Leptospira bacterins (L. canicola and L. ictero-
to >pH 8 and transported in special media. haemorrhagiae) have been widely used for routine
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or chorioretinitis (vitreal haze, retinal lesions or The TAT titer is more specific than the RSAT, but
detachment). because of false positives the TAT is not considered
• Meningoencephalitis: This is very rare and not well definitive (titers 1 : 50 to 1 : 100 are suspicious; titers
characterized. ≥ 1 : 200 are highly suggestive).
• Glomerulonephritis: This is seen as subclinical pro-
teinuria without azotemia. Agar Gel Immunodiffusion
The agar gel immunodiffusion (AGID) is a sensitive and
Diagnosis specific test for antibodies to either cell wall or cyto-
plasmic antigens of B. canis. The cytoplasmic-antigen
▼ Key Point Consider brucellosis in all canine AGID has the best specificity and is the preferred sero-
infertility evaluations and bitches with late-term logic confirmatory test for diagnosis of brucellosis.
abortion. AGID is available at some commercial and state diag-
nostic laboratories.
• Routine CBC, urinalysis, and serum chemistries are
normal except for occasional hyperglobulinemia. Other Serologic Tests
• Lymph node cytology reveals nonspecific reactive
hyperplasia. Indirect fluorescent antibody (IFA) and ELISA titers for
• Semen abnormalities—more than 80% of sperm B. canis have high specificity and are used as confirma-
are morphologically abnormal (immature sperm, tory tests (titers of 1 : 50 to 1 : 100 are suspicious; titers
deformed acrosomes, swollen midpieces, detached ≥ 1 : 200 are diagnostic).
tails, head-to-head agglutination); increased semen
leukocytes; and aspermia in advanced cases. Bacterial Culture
Serology • A positive Brucella culture is definitive evidence
of infection. Whole blood is the preferred culture
▼ Key Point The diagnosis of brucellosis is a 2-step specimen because of the characteristically prolonged
process. First, use a screening serologic test for bacteremia of brucellosis. Urine, semen, vaginal
presumptive diagnosis, then confirm positives discharges, and aborted fetal tissues also can be
with a high-specificity serologic test, a blood cultured.
culture, or, ideally, both. • Negative cultures never rule out brucellosis because
the bacteremia can be intermittent or transiently sup-
Because other bacteria elicit antibodies that crossreact pressed by antibiotics. Use a serologic test such as the
with B. canis, false-positive results are common with RSAT to screen for infection, and then use blood
agglutination tests. Hemolysis (hemoglobin) also causes cultures for confirmation.
false-positive results. False-negative titers are rare, but
can result from sequestration of infection or recent ▼ Key Point Although positive serologic tests are
antibiotics. In recent infections, it can take up to 4 indicative of active brucellosis, a positive blood
weeks to seroconvert; thus, when screening dogs for culture is the gold standard for definitive diagno-
entry into a breeding kennel, a negative test result on sis and should be used whenever possible for
day 1 and again after 4 weeks is required. confirmation.
possible that the Bartonella isolated from cats with these the positives. False negatives are uncommon except
conditions is coincidental rather than causative, or it when bacteremia is transiently suppressed by prior
may be a cofactor with other infections. antibiotics. False positives are rare.
Diagnosis Treatment
Blood culture, blood PCR, and serologic testing can be The optimal treatment for eliminating Bartonella infec-
used to evaluate the Bartonella infection status of cats, tion in cats has not been established. Infection is
and these diagnostic procedures are readily available extremely refractory to antibiotics because of the intra-
to practicing veterinarians through the Vector Borne cellular location of the bacteria. In most cats, antibiotics
Disease Diagnostic Lab at North Carolina State Univer- transiently suppress the bacteremia without curing the
sity. Submission requirements and forms are available at infection. Relapse of bacteremia typically occurs several
www.cvm.ncsu.edu/docs/tickbornediseaselab.html. weeks after discontinuation of antibiotics. Thus, treat-
ment is only indicated for cats with clinical disease
▼ Key Point Diagnostic testing is only indicated in attributable to bartonellosis.
cats suspected of clinical bartonellosis. Routine
testing of healthy cats for Bartonella infection is
▼ Key Point Treatment of healthy Bartonella-infected
not currently recommended.
cats is not recommended and usually ineffective.
Serology merely indicates exposure and the possibil-
ity of infection. Only culture and PCR can prove active The following antibiotics have been suggested for
infection. Most cats that have negative results on these clinical bartonellosis in cats. Use one or more antibi-
tests are not actively infected. In some cats, however, otics for a minimum of 6 weeks (after informing the
bacteremia can be intermittent, resulting in occasional owner of the uncertainty of antibiotic efficacy). Follow-
false negatives with culture and PCR. ing treatment, evaluate blood cultures at 4- to 8-week
intervals for at least 3 to 4 months to detect relapse.
Serology • Macrolides (e.g., azithromycin, 7.5–10 mg/kg PO
Serologic testing is based on IFA or ELISA procedures q12h)
for detection of antibodies against B. henselae. Serology • Fluoroquinolones (e.g., enrofloxacin, 2.5 mg/kg
has limited diagnostic value because a positive titer q12h PO; caution: higher doses can cause retinal
(>1 : 64) does not distinguish between prior exposure degeneration and blindness in cats); can be used
and active infection. In cats with acute illness (i.e., alone or in combination with amoxicillin
recent infection), paired titers over 2 to 3 weeks may be • Doxycycline (10 mg/kg PO q12h), or amoxicillin-
required to document seroconversion. Pre-adoption clavulanate (15 mg/kg PO q12h), have also been
serologic testing of kittens and young cats may be used, but are considered less effective options.
useful, especially when the prospective owner is
immunocompromised, because seronegative cats are Prevention
unlikely to be infected. However, some false negatives
occur with serology (up to 10% of seronegative cats may ▼ Key Point Rigorous flea control is the most effec-
have bacteremia). tive prevention against Bartonella infection in cats.
Prevention of Bartonellosis in
• B. henselae and other Bartonella spp. in dogs are trans-
mitted primarily by fleas. Cats are the primary reser-
Immunocompromised Pet Owners voir host for B. henselae and B. clarridgeiae; rodents are
Recommend that immunocompromised people avoid the main reservoir for B. elizabethae, and squirrels for
cats less than 1 year of age and cats with a history of flea B. washoensis.
infestation. Flea-free adult cats kept in a flea-controlled • The seroprevalence of B. henselae in dogs is highest in
environment are least likely to infect people. Acquisi- the flea-dense southeastern United States (10% of
tion of a new cat from a private owner or breeder is healthy pet dogs and 28% of sick dogs), but only 1%
preferable to adoption of a stray or shelter cat. In addi- to 2% of dogs in many other areas.
tion, seronegative cats are less likely to have bacteremia
and thus are less of a potential risk, although not all Clinical Signs
seronegative cats are free of infection (see “Serology”
Dogs experimentally infected with B. vinsonii (berkhoffii)
section). Immunocompromised people should con-
develop persistent bacteremia and immunosuppres-
sider the following recommendations.
sion, but they have minimal clinical signs except for
• House cats indoors to lessen the potential for flea transient fever. Dogs with natural infection can be per-
exposure. sistent subclinical carriers for months to over a year.
• Use flea control products regularly (see “Prevention” Various clinical conditions are emerging in associa-
section). tion with canine bartonellosis, and this list is expand-
• Wash hands after handling cats. ing. Most of these have been implicated by serologic
• Avoid rough play to reduce accidental cat scratches. and PCR evidence, but a definitive causative relation-
• Cleanse cat-inflicted skin wounds immediately, and ship is unproven. Some of these conditions may be the
seek medical advice. result of mixed infections with multiple tickborne
• Do not restrain cats or pull cats from cat carriers. pathogens.
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• Valvular endocarditis (especially aortic valve) and to practicing veterinarians through the Vector Borne
myocarditis, mostly in large breed dogs, leads to Disease Diagnostic Lab at North Carolina State Univer-
arrhythmias, murmurs, syncope, sudden death, con- sity. Submission requirements and forms are available at
gestive heart failure, and systemic thromboembolism. www.cvm.ncsu.edu/docs/tickbornediseaselab.html.
The mortality rate is high.
• Prolonged or intermittent fever of unknown origin • B. vinsonii (berkhoffii) antibody titers of >1:64 indicate
exposure and potentially active infection. Because
• Granulomatous rhinitis; epistaxis; mucopurulent
the seroprevalence of B. vinsonii (berkhoffii) in the
nasal discharge
general dog population is low (<5% of dogs), clini-
• Granulomatous lymphadenitis
cally sick dogs with significant titers are presumed
• Granulomatous hepatitis
to be actively infected and are treated. Dogs with
• Granulomatous meningoencephalitis
Bartonella endocarditis usually have very high titers
• Anterior uveitis; chorioretinitis
(>1 : 512).
• Peliosis hepatis is characterized by vascular prolifera-
• Isolation of Bartonella spp. from blood cultures in
tion and multifocal, blood-filled cystic spaces in the
dogs is rarely successful; thus, PCR detection of Bar-
liver. This distinctive lesion has also been seen in
tonella DNA is the preferred confirmatory test for
immunocompromised humans with disseminated
canine bartonellosis. PCR testing can be done on
bartonellosis.
blood or fresh, frozen, or paraffin-embedded tissue
• Immune-mediated diseases
specimens.
• Immune-mediated hemolytic anemia
• Immune-mediated thrombocytopenia
▼ Key Point Mixed tick-transmitted infections are
• Polyarthritis
common in dogs residing in high-prevalence
• Protein-losing nephropathy
areas. Consider testing all Bartonella-positive dogs
• Cutaneous vasculitis
for other tickborne infections, such as Ehrlichia,
• Positive anti-nuclear antibody (ANA) test
Anaplasma, Rickettsia, Babesia, and Borrelia
burgdorferii.
▼ Key Point Consider Bartonella infection in dogs
with aortic valve endocarditis, unexplained granu-
Blood Culture
lomatous disease, unexplained epistaxis, or immune-
mediated disease. B. vinsonii (berkhoffii) is very difficult to culture from
infected dogs compared with B. henselae in cats; thus,
blood cultures are unreliable for diagnosing most dogs
Diagnosis with clinical bartonellosis.
The diagnosis of canine bartonellosis is based on serol-
ogy and PCR assay in dogs with compatible clinical Treatment
findings. Initiate antibiotic therapy in seropositive and/or PCR-
positive dogs with clinical signs attributable to Bartonella
Nonspecific Clinical Findings infection. The optimal treatment for canine bartonel-
• Hematologic findings in dogs with clinical bartonel- losis has not been established, but antibiotics that
losis may include anemia, thrombocytopenia (in half achieve high intracellular levels are recommended. In
of cases), eosinophilia (in one third of cases), mono- dogs, bacteremia is not as persistent or as likely to
cytosis, and neutrophilic leukocytosis. Some dogs relapse as in cats. Effective treatment is indicated by a
have proteinuria. drop in the Bartonella titer after 3 to 6 months.
• ANA tests are positive in 10% of dogs infected with
• Treat severe or life-threatening clinical disease (e.g.,
B. vinsonii (berkhoffii) alone, and in 45% of dogs with
endocarditis or meningoencephalitis) with an initial
B. vinsonii (berkhoffii) combined with Ehrlichia canis or
combination of a parenteral aminoglycoside (e.g.,
other tickborne pathogens.
amikacin) and a penicillin derivative (e.g., amoxi-
• Diagnostic imaging can detect some of the lesions
cillin or ampicillin). After 1 to 2 weeks, continue for
listed under “Clinical Signs.” In particular, echocar-
an additional 4 weeks with one of the antibiotics
diographic aortic valve lesions are found consistently
below.
in dogs with Bartonella endocarditis.
• Aspiration cytologies and biopsies may occasionally
• Treat less severe or chronic disease with a macrolide
(e.g., azithromycin) or a combination of a fluoro-
reveal intracellular bacteria that stain positive with
quinone and amoxicillin. Doxycycline can also be
silver stain within macrophages and lymph nodes.
used, but is not considered as effective. Continue
antibiotics for at least 4 to 6 weeks.
Serology and PCR Assay • Azithromycin (7.5–10 mg/kg PO q12h)
The diagnosis of canine bartonellosis is based on serum • Enrofloxacin (5 mg/kg q12h PO) plus amoxicillin-
antibody titers and PCR assays that are readily available clavulanate (15 mg/kg PO q12h)
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• Doxycycline (10 mg/kg PO q12h) tion of aerosolized sputum. Dogs are infected more
• Rifampin can be added in refractory cases than cats. Pulmonary infection is most common.
• M. bovis infection results from ingestion of unpas-
Prevention teurized milk, uncooked meat, or offal from infected
cattle or wildlife such as deer. Cats are infected more
▼ Key Point Rigorous flea and tick control is the most commonly than dogs. The intestinal tract and abdom-
effective prevention against Bartonella infection in inal viscera are usually involved.
dogs. • M. avium is ubiquitous in the environment, and infec-
tion results from contaminated water and soil, or
Reduce the risk of exposure to Bartonella spp. by limit- infected poultry feces or carcasses. Siamese cats and
ing access to tick-infested areas. Use an effective long- basset hounds seem to have a genetic predisposition,
acting topical flea and tick preventative at least monthly and immunosuppression may play a role in some
on dogs residing in flea and tick-infested areas, such as animals.
one of the following: • M. microti and M. microti-like are rodent pathogens
that occasionally infect cats that hunt prey.
• Fipronil/methoprene (Frontline Plus; Merial)
• Imidacloprid/permethrin (Advantix; Bayer); for
dogs only (permethrin is toxic in cats). Clinical Signs
• Amitraz tick collar (Preventic; Virbac) plus topical Clinical signs are usually chronic and reflect the site of
permethrin for fleas granulomatous lesions.
▼ Key Point Do not use dogs that are seropositive for • Cutaneous: Dermal nodules and non-healing wounds
Bartonella spp. as blood donors. with draining fistulous tracts, and regional lym-
phadenopathy.
Public Health • Pulmonary: Occurs mostly in dogs with M. tuberculo-
sis. Granulomatous pneumonia and hilar lym-
Dogs have very rarely been implicated as the source of phadenopathy cause signs of fever, weight loss, and
human Bartonella infections; however, dogs are capable chronic cough.
of carrying ticks or fleas that could transmit Bartonella • Intestinal: Occurs mostly in cats with M. bovis.
spp. to people. Granulomatous transmural enteritis and mesenteric
lymphadenopathy cause anorexia, vomiting, diarrhea,
weight loss, blood loss anemia, and peritoneal effusion.
MYCOBACTERIOSIS • Disseminated: This is typical of M. avium infections
that cause widespread granulomatous lesions in
The categories of mycobacterial infection in dogs and lymph nodes, liver, spleen, other abdominal viscera,
cats are (1) the systemic or tuberculous form, (2) the thorax, CNS, eyes (uveitis), and bone.
opportunistic form, and (3) the lepromatous form
(feline leprosy). Each of these is caused by a different Diagnosis
variety of mycobacterial species. This section describes
systemic tuberculous mycobacteriosis. Chapter 39 is • Leukocytosis and hyperglobulinemia may be seen.
devoted to opportunistic mycobacterial infections and • Diagnostic imaging may identify granulomatous
abdominal masses, pulmonary lesions, effusions,
feline leprosy, which are primarily cutaneous infections
internal lymphadenopathy, or bone lesions.
characterized by ulcerating skin nodules and draining
fistulous tracts. • A presumptive diagnosis is established by finding
acid-fast bacteria in cytologies or biopsies of lesions.
Intracellular bacteria with clubbed shape and beaded
Etiology appearance are typical and most abundant in M.
Mycobacteria are environmentally resistant, non- avium infections.
spore–forming, aerobic, acid-fast, gram-positive bacteria • Definitive diagnosis and speciation require culture or
that infect a wide range of animals worldwide, includ- PCR. Mycobacteria that cause systemic mycobacte-
ing dogs, cats, and humans. Mycobacteria cause per- riosis are slow-growing and culturing may take up to
sistent intracellular infection leading to chronic 6 weeks. The advantage of PCR is more rapid results.
granulomatous inflammation. Systemic tuberculous
mycobacteriosis (i.e., classic tuberculosis) in dogs and ▼ Key Point Intradermal tuberculin testing is incon-
cats is usually caused by infection with M. tuberculosis, M. sistent and unreliable in dogs and cats.
bovis, or M. avium, with sporadic reports of M. microti,
M. microti-like, and M. simiae. Treatment
• M. tuberculosis infection is an inverse zoonosis trans- Generalized systemic or tuberculous mycobacteriosis
mitted from infected humans to pets through inhala- is resistant to treatment and has a poor prognosis.
W0422-Ch019.qxd 11/10/05 4:53 PM Page 202
Treatment requires a minimum of 6 months of multi- tion of contaminated food, carrion, or water. Infected
drug therapy, and some cases require lifelong therapy. animals develop intracellular infection of macrophages
Drug toxicity and expense are often limiting factors. and hematogenous dissemination.
Hartmann K, Greene CE: Diseases caused by systemic bacterial infec- Feline Plague
tions. In: Ettinger SJ (ed): Textbook of Veterinary Internal Medi-
cine (6th Ed). St. Louis: Elsevier, 2005, pp 616–631. Eidson M, Thilsted JP, Rollag OJ: Clinical, clinicopathologic, and
pathologic features of plague in cats: 119 cases (1977–1988) 199:
Bartonellosis 1191–1197, 1991.
Orloski KA, Lathrop SL: Plague: a veterinary perspective. J Am Vet
Breitschwerdt EB: Canine bartonellosis. In: Ettinger SJ (ed): Textbook Med Assoc 222:444–448, 2003.
of Veterinary Internal Medicine (6th Ed). St. Louis: Elsevier, 2005,
pp 636–637. Tularemia
Chomel BB, Boulouis HJ, Breitschwerdt EB: Cat scratch disease and
other zoonotic Bartonella infections. J Am Vet Med Assoc 224: Feldman KA: Tularemia. J Am Vet Med Assoc 222:725–730, 2003.
1270–1279, 2004. Woods JP, Panciera RJ, Morton RJ, et al: Feline tularemia. Compend
Guptill L: Bartonellosis. Vet Clin Small Anim Pract 33:809–825, 2003. Contin Educ Pract Vet 20:442-457, 1998.
Guptill L, Wu CG, HogenEsch H, et al: Prevalence, risk factors and
genetic diversity of Bartonella henselae infections in pet cats in
four regions of the United States. J Clin Microbiol 42:652–659, Mycobacterial Infections
2004.
Hartmann K, Greene CE: Diseases caused by systemic bacterial infec-
Henn JB, Liu C-H, Kasten RW, et al: Seroprevalence of antibodies
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against Bartonella species and evaluation of risk factors and clinical
cine (6th Ed). St. Louis: Elsevier, 2005, pp 616–631.
signs associated with seropositivity. Am J Vet Res 66:688–694, 2005.
▼ Chapter
20 Systemic Mycoses
Robert G. Sherding
The four classical systemic mycoses of dogs and cats are Pathogenesis
histoplasmosis, blastomycosis, coccidioidomycosis, and
cryptococcosis. • Histoplasmosis primarily invades the lung and then
spreads to the mononuclear phagocyte system (liver,
spleen, etc.). The incubation period is 12 to 16 days.
▼ Key Point Systemic mycoses are not contagious Widespread hemolymphatic dissemination can occur
diseases. Infection results from contact with organ- to virtually any tissue or organ system. Infection
isms in the environment, especially through causes a granulomatous response.
inhalation. • The outcome of infection is influenced by level of
exposure; host cell-mediated immunity; age of the
Fungal infections with a predilection for individual host (clinical disease is most common in young
organ systems are discussed elsewhere; thus, for deep animals <4 years of age); breed (highest prevalence
cutaneous fungal infections see Chapter 40, for der- in sporting and hound breeds because of higher
matophytosis see Chapter 42, for intestinal pythiosis see exposure risk); and immunosuppressive factors (cor-
Chapter 69, and for nasal aspergillosis see Chapters 160 ticosteroids may enhance dissemination).
and 163.
Clinical Signs
▼ Key Point Histoplasmosis, blastomycosis, and coc- Inapparent subclinical infections are common. The
cidioidomycosis are endemic to defined regions of clinical forms of histoplasmosis are pulmonary, intesti-
North America (Fig. 20-1). nal, and disseminated (multisystemic).
Subclinical Infection
An inapparent, self-limiting infection confined to the
HISTOPLASMOSIS respiratory tract is the most common outcome of
natural infection. The aftermath of this form is some-
Etiology times identified radiographically as multiple, discrete,
• Histoplasmosis is caused by Histoplasma capsulatum, calcified interstitial foci in the lungs (inactive encapsu-
a dimorphic soil-dwelling fungus found in many lated or healed lesions). Calcified tracheobronchial
temperate and subtropical regions of the world. lymph nodes are seen less often.
In North America, the disease is most prevalent in
the river valley regions of the central United States, Acute Pulmonary Infection
especially in areas bordering the Mississippi, Ohio,
Acute pulmonary histoplasmosis is characterized by
and Missouri Rivers and their tributaries (see Fig.
severe fulminant granulomatous pneumonia with signs
20-1). Both dogs and cats are susceptible.
of cough, tachypnea, dyspnea, abnormal lung sounds,
• At ambient temperatures, soil enriched by decom-
fever, and severe malaise. Death from hypoxemia may
posing nitrogenous matter (e.g., bird feces or bat
occur despite treatment. The radiographic findings are
guano) provides an ideal growth medium for the
diffuse or nodular interstitial pulmonary infiltrates,
mycelial phase of Histoplasma. The principal route of
often with patchy coalescing alveolar densities and mod-
infection is by inhalation of airborne spores (conidia)
erately enlarged tracheobronchial lymph nodes.
and mycelial fragments in windblown soil; however,
intestinal infection via ingestion also may occur.
At body temperature (37°C), Histoplasma organisms
Chronic Pulmonary Infection
transform into a yeast phase that causes a facultative Chronic pulmonary histoplasmosis is more common
intracellular infection of macrophages. than the acute form and is characterized by chronic
205
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Disseminated Infection
Extrapulmonary dissemination causes a variety of clini-
cal signs depending on the organs involved. Most cats
Coccidioidomycosis develop this disseminated form of histoplasmosis. The
mononuclear phagocyte system is a common site of
dissemination. Manifestations can include anorexia,
depression, fever, weight loss, and pulmonary involve-
ment combined with any of the following:
• Bone marrow—Nonregenerative anemia
• Lymph nodes—Peripheral or abdominal lymphade-
nopathy
• Liver—Hepatomegaly, icterus, ascites
• Spleen—Splenomegaly
• Peritoneum—Omental masses, mesenteric adhesions,
nodular or granular serosal surfaces
Histoplasmosis
• Eyes—Exudative anterior uveitis, multifocal granulo-
matous chorioretinitis, optic neuritis
• Central nervous system (CNS)—Ataxia, seizures
• Skin—Cutaneous and subcutaneous nodules that
ulcerate or fistulate, drain or crust over
• Bone—Lameness and bone pain associated with pro-
Figure 20-1. Geographic distribution of blastomycosis, coccid- liferative or lytic bone lesions (osteomyelitis)
ioidomycosis, and histoplasmosis in North America. • Oral cavity—Oral and lingual ulcers
Diagnosis
granulomatous pneumonia (diffuse or multifocal) with Consider histoplasmosis on the basis of clinical signs
marked perihilar tracheobronchial lymphadenopathy in animals from endemic areas. The results of routine
that compresses the bifurcation of the trachea and laboratory evaluations are variable and nonspecific.
mainstem bronchi. Clinical signs include chronic Radiographic findings in the pulmonary form are often
cough, exercise intolerance, and mild dyspnea with vari- highly suggestive of a mycotic disease such as histoplas-
able weight loss and fever. Radiographically, massive mosis. Identification of the Histoplasma organisms by
enlargement of the perihilar tracheobronchial lymph cytology, biopsy, or culture is necessary for definitive
nodes and variable linear or nodular interstitial infil- diagnosis. Serology is unreliable.
trates are seen.
Hematology
Intestinal Infection
• Normocytic-normochromic nonregenerative anemia
Intestinal histoplasmosis is a common extrapulmonary frequently results from chronic inflammation, dis-
form in dogs but not cats, and it may represent primary semination of Histoplasma into the bone marrow,
infection by ingestion. The colon, the small intestine, intestinal blood loss, or hemolysis.
or a combination of both can be affected by extensive • Neutrophilic leukocytosis or neutropenia with a left
granulomatous thickening of the bowel wall and shift and monocytosis can be seen, and occasionally
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grows on blood agar from 30∞C to 37∞C. Use a diag- • Dogs are considered highly susceptible to blastomy-
nostic laboratory instead of in-clinic culturing, because cosis, and the canine infection rate in endemic areas
fungal growth is potentially infectious for humans and is 10 times the human infection rate. Young (<5
poses a biohazardous risk to personnel. years) male, large-breed dogs are infected most fre-
quently, especially pointers, hounds, and other sport-
Treatment ing breeds, probably because of increased exposure
through outdoor activities. Blastomycosis is rare in
Refer to the “Antifungal Therapy” section at the end of cats.
this chapter for specific treatment regimens and drug
dosages.
Clinical Signs
• Itraconazole is the treatment of choice for histoplas-
mosis that is not immediately life-threatening. Treat Pulmonary and disseminated forms of infection are
for a minimum of 4 to 6 months and at least 1 to 2 seen. Nonspecific signs of fever, anorexia, weight loss,
months beyond clinical resolution. and depression are common. Signs may be acute (days)
• Itraconazole plus amphotericin B is preferred for treat- or chronic (weeks to months).
ing severe, rapidly progressive infections, preferably
using lipid-complexed amphotericin to allow higher Pulmonary Infection
doses with less toxicity. Combined therapy is followed Lung lesions are present in 85% of cases. Cough,
by azole therapy alone for 2 to 4 months and at least tachypnea, and dyspnea are typical presenting signs.
1 to 2 months beyond clinical resolution. Respiratory manifestations can include the following:
• Fluconazole may not be as effective as itraconazole, but
it can be used for refractory ocular and neurologic • Diffuse interstitial pyogranulomatous pneumonia
infections because of its better penetration of the eyes • Perihilar tracheobronchial lymphadenopathy
and CNS. • Alveolar infiltration and consolidation
• Ketoconazole is less effective than itraconazole (espe- • Solitary mediastinal or lung masses
cially in cats), and it has more side effects; however, • Pleural effusion
it can be used if other antifungal drugs are cost pro-
hibitive for the owner. It also can be combined with Disseminated Infection
amphotericin B. Extrapulmonary dissemination is common in blastomy-
• Corticosteroids can be used with antifungal therapy to cosis, especially to the peripheral lymph nodes (50% to
reduce perihilar lymphadenopathy when it is causing 60% of cases), skin (40%), eyes (40%), bone (20%),
significant tracheobronchial obstruction. Only use and to a lesser extent CNS, male genitalia, oral cavity,
if needed, and do not use for prolonged periods nasal cavity, and abdominal viscera.
because corticosteroids can worsen fungal infections
or facilitate dissemination. • Cutaneous: Solitary or multiple circumscribed, raised
ulcerating pyogranulomas; fistulas that drain pus or
bloody fluid; deep abscesses (cats); paronychia; and
regional lymphadenopathy
BLASTOMYCOSIS • Ocular: Anterior uveitis, chorioretinitis, retinal de-
tachment, panophthalmitis, lens rupture, cataracts,
Etiology secondary glaucoma, and blindness
• Blastomyces dermatitidis is a dimorphic soil-dwelling • Bone: Osteomyelitis of distal limbs, with lameness and
fungus with a geographic distribution in the central, adjacent soft tissue swelling
mid-Atlantic, and southern Great Lakes regions of • CNS: Most often in cats as seizures, dementia, blind-
the United States, especially areas bordering the ness, or ataxia
Mississippi River and its tributaries and along the • Genital: Pyogranulomatous orchitis and epididymitis
St. Lawrence River region of the United States and in 16% of intact male dogs; also prostatitis
Canada (see Fig. 20-1). The organisms reside in
sandy, acidic soil near water. Most infected dogs live
within 1/4 mile of water. Diagnosis
• Inhalation of airborne spores (conidia) is the primary Consider blastomycosis on the basis of clinical signs in
source of infection and leads to mycotic pneumonia. animals from endemic areas. The results of routine
In addition, focal skin infection can occur from direct laboratory evaluations are variable and nonspecific.
cutaneous inoculation through a wound. In tissues Radiographic findings in the pulmonary form are often
the fungi become budding yeast. Extrapulmonary dis- highly suggestive of mycotic infection. Serology pro-
semination is common in blastomycosis, especially vides a presumptive diagnosis, but identification of Blas-
involving lymph nodes, skin, eyes, bones, and CNS tomyces organisms is necessary for definitive diagnosis,
(cats). The incubation period is 1 to 3 months. usually by cytology.
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Hematology and Serum Chemistries brospinal fluid (CSF), or pleural effusion. Any
routine cytology stain can be used.
• Typical findings are neutrophilic leukocytosis, mono-
cytosis, lymphopenia, and mild nonregenerative • Blastomyces in tissues appear as thick-walled, extra-
anemia. cellular yeast bodies (5–20 mm) with broad-based
budding.
• Serum chemistries are usually unremarkable except
for mild hypoalbuminemia, hyperglobulinemia, and
occasional hypercalcemia (10% of cases). ▼ Key Point Blastomyces organisms are usually
plentiful and easily identified in lesions by cytol-
ogy; thus, cytology is the initial confirmatory test
Diagnostic Imaging of choice.
Radiography, ultrasonography, computed tomography
(CT), and magnetic resonance imaging (MRI) are • The inflammatory pattern in blastomycosis is pyo-
useful for evaluating the lungs and suspected dissemi- granulomatous (macrophages and non-degenerate
nation sites and for guiding collection of cytology and neutrophils). Special stains such as PAS, GMS, and
biopsy specimens. Gridley may be used to identify fungal organisms.
phadenopathy. In cases with cardiac involvement, and lifelong azole therapy may be required to
pericardial effusion or pulmonary edema may be prevent relapses.
seen.
• Dissemination to bone is common in dogs, especially • Treat with one of the oral azoles (ketoconazole,
to the distal aspects of long bones, resulting in mul- itraconazole, or fluconazole) for at least 8 months
tifocal osteoproliferative and, less often, lytic lesions. and a minimum of 4 months beyond clinical resolu-
The spine can also be involved. tion. Use fluconazole to treat animals with CNS
involvement.
Serology • Amphotericin B lipid complex is indicated for fulmi-
nant infections and animals that do not tolerate azole
A reasonably reliable presumptive diagnosis can be drugs.
based on the detection of antibodies against Coccidioides. • Lufenuron, a chitin synthesis inhibitor licensed for
The tube precipitin test, which detects the early control of fleas in dogs and cats, does not appear to
immunoglobulin M (IgM) response, and the comple- be an effective antifungal agent despite initial anec-
ment fixation test, which detects the later and sustained dotal reports.
immunoglobulin G (IgG) response, are the traditional
serologic tests. The newer immunodiffusion (AGID)
and enzyme-linked immunosorbent assay tests for CRYPTOCOCCOSIS
detecting Coccidioides-specific IgM and IgG are more
reliable. Cryptococcosis is the most common systemic fungal
• The early IgM response becomes positive 2 weeks disease of cats and is more prevalent in cats than in
post-exposure and persists for 4 to 6 weeks. However, dogs.
in some dogs, IgM titers may persist for months and
can be detected simultaneously with high IgG titers, Etiology
usually indicating dissemination or recrudescence. • Cryptococcosis is caused by Cryptococcus neoformans, a
• The later IgG response is detected after 8 to 12 weeks. saprophytic yeast found in many regions of the world
High IgG titers (≥1 : 64) usually indicate severe pul- and throughout North America or by C. gattii in
monary or disseminated disease. Australia and various subtropical regions. High con-
centrations of Cryptococcus can be found in pigeon
Polymerase Chain Reaction droppings and in areas where pigeons and other birds
A sensitive and specific polymerase chain reaction roost. Infection is acquired by inhalation of the yeast
(PCR) for detecting Coccidioides DNA is expected to organisms or basidiospores from the environment.
facilitate the diagnosis of this disease once the test • The organisms are budding yeasts (4 to 7 mm) that
becomes available for clinical use. possess a uniquely prominent polysaccharide capsule.
This thick capsule is essential to the pathogenicity
of Cryptococcus because it inhibits plasma cell function,
Cytology and Biopsy phagocytosis, leukocyte migration, and complement.
Definitive diagnosis depends on identifying the large The capsule also allows the organisms to stand out in
Coccidioides spherules (20–200 mm) in affected tissues stained cytology preparations for easy identification
using cytology or biopsy; however, spherules are often and is the basis for the cryptococcal capsular antigen
sparse and difficult to find. Lesions show pyogranulo- diagnostic test (see the related “Diagnosis” section).
matous inflammation. • Dissemination from the nasal cavity can occur by
hematogenous spread or by direct extension through
Culture the cribriform plate to the CNS or through the nasal
bones to the paranasal soft tissues and skin.
Coccidioides can be cultured on routine fungal media;
however, special facilities are required because Coccid- Clinical Signs
ioides spores are a serious biohazard for humans and
pose a substantial risk to laboratory personnel. Cryptococcosis can cause localized nasal infection or
disseminated infection. Anorexia and depression are
common, but fever occurs infrequently (<25% of the
Treatment cases); in fact, temperatures exceeding 37∞C inhibit
Refer to the “Antifungal Therapy” section at the end of Cryptococcus.
this chapter for specific treatment regimens and drug
dosages. ▼ Key Point In cats, Cryptococcus has a predilection
for the nasal cavity, where the inhaled organisms
▼ Key Point Disseminated coccidioidomycosis is dif- initially deposit and cause granulomatous rhinitis
ficult to cure, especially when bones are involved, and sinusitis.
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Culture
Diagnosis
Cryptococcus can be cultured on Sabouraud’s dextrose
Consider cryptococcosis on the basis of clinical signs, agar from the same specimen sources as cytology;
especially in cats. The results of routine laboratory eval- however, growth can take from a few days up to 6 weeks,
uations and radiography are variable and nonspecific. thus limiting the diagnostic usefulness of cultures.
Serology provides a presumptive diagnosis, but identifi-
cation of Cryptococcus organisms by cytology, biopsy,
or culture is required for definitive diagnosis. In most Treatment
cases cytology is a quick and easy way to confirm the See the following section on “Antifungal Therapy” for
diagnosis. dosages and additional details.
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• Fluconazole is the treatment of choice for crypto- ▼ Key Point The oral triazole, itraconazole, is the
coccosis. It is effective but costly. It has excellent single-agent treatment of choice for most systemic
penetration into the CNS and eyes, which are the fungal infections that are not immediately life
preferred cryptococcal dissemination sites. threatening.
• Itraconazole is effective in most cases. It is slightly less
effective, but more affordable than fluconazole. Fluconazole has the best penetration of the CNS,
• Ketoconazole is not as effective as either of the other eyes, and prostate and thus may be the preferred treat-
azole drugs, and side effects are more frequent. ment when these areas are involved, especially in
• Amphotericin B is highly effective for cryptococcosis, cryptococcosis.
but it is inconvenient (parenteral route) and has
more adverse effects (especially nephrotoxicity). Oral
▼ Key Point Regardless of the treatment regimen, the
flucytosine can be given concurrently. unpredictable response in the disseminated forms
of mycotic disease requires a guarded prognosis,
▼ Key Point Monitor treatment response with the
cryptococcal capsular antigen test. especially if the CNS is involved.
Aspergillosis Aspergillus Inhalation Worldwide Fever, draining tracts, German shepherds; Itraconazole
spp. lymphadenopathy, cytology (septate plus ABLC
uveitis, chorioretinitis, hyphae); culture
dissemination to bone,
kidney, liver, spleen,
CNS, etc.
Sporotrichosis Sporothrix Puncture Worldwide Draining skin/subcutis Cats > dogs; Itraconazole
schenckii wounds, pyogranulomas; cytology (oval or (note:
bites, lymphadenopathy; cigar-shaped zoonotic
scratches dissemination to yeast); culture considerations)
abdomen, lung, eyes,
CNS, etc.
Pythiosis Pythium Waterborne Gulf Coast Cutaneous form: Non- Dogs > cats; Aggressive
insidiosum (warm); U.S., South healing wounds, young, male large- surgical
cutaneous America, invasive ulcerated and breed working dogs; resection
or GI Southeast draining skin/subcutis eosinophilia, anemia, followed by
inoculation Asia, masses, nasopharyngeal hyperglobulinemia; itraconazole
Australia lesions (cats) abdominal imaging plus
GI form: Chronic vomiting (masses); serum terbinafine
and diarrhea, GI ELISA; biopsy
bleeding, transmural (GMS+ stain, broad
granulomatous GI poorly septate
masses, GI obstruction, hyphae) with culture,
mesenteric PCR, and
lymphadenopathy immunohistochem-
istry
Lagenidiosis Lagenidium Waterborne Gulf Coast Multifocal skin/subcutis Young large-breed Aggressive
spp. (warm); and nodular lesions with dogs; biopsy surgical
cutaneous southeast ulcers and draining (GMS+ stain, broad resection
inoculation U.S. tracts, lymphadenopathy, poorly septate followed by
(damaged hind limb edema; hyphae) with culture, itraconazole
skin sites) lesions in aorta, vena PCR, and plus
cava, lung, mediastinum immunohistochemistry terbinafine
Zygomycosis Basidiobolus Cutaneous Ubiquitous Conidiobolus: Ulcerative Biopsy (GMS+ stain, Aggressive
spp.; inoculation saprophytes nasal, nasopharynx, and broad poorly surgical
(damaged palate lesions; septate hyphae) resection
skin sites); multifocal skin and with culture followed by
inhalation subcutis draining itraconazole
nodules
Conidiobolus Basidiobolus: ulcerative
spp. draining skin lesions
with GI and lung
lesions
Phaeohypho- Numerous Traumatic Ubiquitous Granulomas of skin, Biopsy (septate Surgical
mycosis (see implantation saprophytes subcutis, nasal, CNS, hyphae with resection or
Chapter etc. melanin) itraconazole
40)
Candidiasis Candida Commensal Ubiquitous Fever, neutropenia, Cytology (oval Itraconazole
albicans mucosal commensals non-healing oral and yeasts); culture; plus ABLC;
yeasts; GI mucosal ulcers, biopsy of tissue correct
proliferate skin lesions, myositis, invasion underlying
with osteomyelitis, predisposing
immuno- nephritis, factors
suppression, microabscesses, signs
mucosal referable to organs
damage affected
ABLC, amphotericin B lipid complex; CNS, central nervous system; ELISA, enzyme-linked immunosorbent assay; GI, gastrointestinal; GMS, Gomori
methenamine silver stain; PCR, polymerase chain reaction.
W0422-Ch020.qxd 11/10/05 4:50 PM Page 215
• Avoid concurrent use of other potentially nephro- to a total cumulative dose of 24 to 27 mg/kg. Dilute
toxic medications with AMB. in 5% dextrose to a concentration of 1 mg/ml and
• Always follow the package insert instructions for infuse over 1 to 2 hours.
reconstituting and handling AMB products. • For cats: Give ABLC at 1 mg/kg, IV, q48h (3 times
• AMB is available in its original formulation as deoxy- weekly), for a total of 12 treatments to a total cumu-
cholate suspension and in three newer lipid-based lative dose of 12 mg. Dilute and infuse as for dogs.
and liposomal formulations.
Renoprotective Measures
▼ Key Point Lipid-based formulations of ampho-
tericin B minimize the risk of nephrotoxicity, thus • Evaluate a urinalysis and renal function (serum cre-
allowing higher doses and increased efficacy. atinine, blood urea nitrogen [BUN]) before initiating
AMB therapy, and monitor these frequently during
treatment (once or twice weekly). In general, the
Dosage and Administration earliest evidence of a renal effect is decreased urine-
Amphotericin B protocols are designed as a series of specific gravity. This is followed by abnormal numbers
three infusions per week until a cumulative dose is of renal cells and casts in fresh urine sediment, and
achieved, with interruption of therapy if azotemia eventually azotemia may develop.
occurs. Amphotericin B therapy is combined and fol-
lowed with long-term oral azole therapy in most cases. ▼ Key Point If BUN exceeds 50 mg/dl or serum cre-
atinine exceeds 2.5 mg/dl during amphotericin
Amphotericin B Deoxycholate therapy, suspend treatment until azotemia resolves.
Azotemia is reversible in most cases.
• IV in dogs: Give amphotericin B (Fungizone, ER
Squibb) at dosages of 0.5 to 1.0 mg/kg, IV, q48h (3 • Always ensure that the patient is well hydrated prior
times weekly), to a total cumulative dose of 6 to to each dose of AMB.
10 mg/kg. Each dose can be given as a 10-minute • Consider the slow IV infusion method whenever pos-
bolus; however, infusion in 5% dextrose over 2 to 6 sible. Give AMB diluted in 250 to 500 ml of 5% dex-
hours is preferred to reduce nephrotoxicity (see trose solution by slow IV infusion over a period of 2
“Renoprotective Measures”). to 6 hours.
• IV in cats: Give amphotericin B at dosages of 0.25 to • Other measures used less often to enhance renal
0.50 mg/kg, IV, q48h (3 times weekly), to a total blood flow and glomerular filtration rate include
cumulative dose of 4 to 8 mg/kg. Infuse as for dogs. pretreatment sodium diuresis (0.9% sodium chloride,
• Subcutaneous protocol: A daily dose of 0.5 to 0.8 mg/kg 10 to 20 ml/kg, IV, over 1 to 3 hours prior to AMB);
is added to 0.45% saline with 2.5% dextrose solution concurrent administration of mannitol (0.5–1.0 g/kg,
(400 ml for cats, 500 ml for dogs <20 kg, and IV); furosemide (2 mg/kg, IV); or dopamine (3 to
1,000 ml for dogs >20 kg) then given SC q48h (3 times 10 mg/kg/min, by constant-rate IV infusion).
weekly) to a total cumulative dose of 10 to 20 mg/kg.
• Combination protocol: When amphotericin B is used
with itraconazole or other azole, use the low end of Adverse Effects
the daily and cumulative dosage ranges for ampho-
tericin B.
• The major adverse effect of AMB is dose-related
nephrotoxicity caused by a combination of reduced
renal blood flow (arteriolar vasoconstriction) and
Lipid-Complexed Amphotericin B direct renal tubular injury. Although there is consid-
• Lipid-complexed amphotericin B reduces the risk of erable individual variation in susceptibility to nephro-
nephrotoxicity up to 10-fold. Preferential uptake of toxicity, most animals treated with AMB show some
lipid complexes by phagocytic cells delivers high con- degree of renal dysfunction and azotemia. Nephro-
centrations of drug to target sites of inflammation toxicity is less of a risk with lipid-complexed AMB but
and organs such as the liver, spleen, and lung, while still is a possibility.
renal uptake is decreased; thus, higher doses can be • Other side effects of AMB include thrombophlebitis
used with less risk of renal injury. (local irritant effect), fever, anorexia, nausea or vom-
• Formulations include lipid complexed (Abelcet, iting, hypokalemia, hypomagnesemia, distal renal
Enzon), colloidal dispersion (Amphotec, Sequus), tubular acidosis, cytopenias, cardiac arrhythmias, and
and liposome encapsulated (AmBisome, Fujisawa). perivascular irritation if extravasated. For infusion-
Of these, amphotericin B lipid complex (ABLC) has associated nausea and fever, pretreat with an antihis-
been used most often in dogs and cats and is the least tamine such diphenhydramine.
expensive. • Local irritation and sterile abscesses occasionally
• For dogs: Give ABLC at dosages of 2 to 3 mg/kg, IV, occur with the subcutaneous protocol, especially if
q48h (3 times weekly), for a total of 9 to 12 treatments the AMB concentration is >20 mg/L.
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Pharmacology Voriconazole
• Ketoconazole depends on hepatobiliary metabolism Voriconazole (Vfend, Pfizer) is a derivative of flucona-
and excretion, and it is distributed widely except in zole with greater potency and broader spectrum of activ-
the CNS, eye, prostate, and testes. ity against many fungal pathogens, including invasive
• Acidity is required for optimal absorption of keto- aspergillosis. It has excellent oral and IV bioavailability.
conazole; thus, avoid concurrent use of drugs such as
H2 blockers that inhibit gastric acid secretion. Posaconazole
• Bioavailability is increased and nausea and vomiting Posaconazole (Noxafil, Schering-Plough) is a derivative
are minimized when ketoconazole is given with food. of itraconazole with greater potency and broader spec-
trum of activity against aspergillosis and molds.
Dosage and Administration
The oral dosage of ketoconazole (Nizoral, Janssen), Ravuconazole
ranges from 10 to 30 mg/kg/day. Divide this total daily
Ravuconazole (Bristol-Myers Squibb) is a fluconazole
dose into two or three doses for better GI tolerance.
derivative with extended half-life.
Give with food. Continue ketoconazole for at least 1 to
2 months beyond clinical resolution.
Flucytosine
• For dogs: Give 10 to 15 mg/kg, q12h, PO with food.
• For cats: Give 5 to 10 mg/kg, q12h, PO with food, or Flucytosine (Ancobon, Roche) is an antimitotic, anti-
a total dose of 50 mg, q24h. Cats generally are more fungal drug used exclusively for its synergism with
susceptible to the side effects of ketoconazole. If tol- amphotericin B in the treatment of cryptococcosis.
erance is a problem in a cat, administer a dosage of Flucytosine is most useful for CNS involvement, because
20 mg/kg on alternate days or switch to a different it attains 60% to 80% of serum concentration in CSF.
drug. Use this drug only in combination with amphotericin B
• Combination protocol: For severe infections, use because fungal resistance develops rapidly if it is used
amphotericin B in combination with ketoconazole alone.
for the first few weeks or use itraconazole. • The dosage in dogs and cats is 25 to 50 mg/kg, PO,
q6–8h.
Adverse Effects • Side effects are common, including anorexia, vomit-
• The most common immediate side effects of keto- ing, diarrhea, cytopenias caused by bone marrow
conazole are anorexia, vomiting, and diarrhea. Mini- suppression, and mucocutaneous drug eruptions (in
mize these GI side effects by dividing the daily dose dogs).
and administering the drug with food.
• Longer-term side effects may include hepatotoxicity Terbinafine
(hepatomegaly, elevated serum liver enzymes,
icterus), weight loss, and haircoat changes (lighten- Terbinafine (Lamisil, Sandoz) is an allylamine drug that
ing of color, alopecia). Because of hepatic effects, it blocks synthesis of ergosterol in the fungal cell mem-
is advisable to monitor serum liver enzymes monthly brane. The main indication is for treatment of der-
during treatment. The liver, GI, and haircoat reac- matophytosis and cutaneous fungal infections. It has
tions are usually reversible with reduction in dose. not been well evaluated in systemic mycoses of dog and
• Ketoconazole inhibits adrenal and testicular steroido- cats. Terbinafine (5 to 10 mg/kg, PO, q24h) combined
genesis. In dogs, but not cats, ketoconazole dimin- with itraconazole has reportedly been beneficial in
ishes serum testosterone and cortisol while increasing some dogs and cats with pythiosis and lagenidiosis (see
serum progesterone. Ketoconazole is embryotoxic Chapter 40). Potential side effects include GI, hepatic,
and teratogenic and thus should not be used in preg- and cutaneous reactions.
nant animals.
agent for Coccidioides and other systemic mycoses Gerds-Grogan S, Dayrell-Hart B: Feline cryptococcosis: A retrospec-
despite initial anecdotal reports of its use in dogs. tive evaluation. J Am Anim Hosp Assoc 33:118–122, 1997.
Greene CE: Antifungal chemotherapy. In Green CE (ed): Infectious
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pneumocandins, for example, caspofungin (Canci- 540–545.
das, Merck), micafungin, and anidulafungin. These Greene RT: Coccidioidomycosis. In Greene CE (ed): Infectious
are potent broad-spectrum antifungal drugs with Diseases of the Dog and Cat (3rd ed). St. Louis: Elsevier, 2006, pp
596–606.
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carinii. These agents are very costly and considered study (1984–1993). J Vet Intern Med 9:86, 1995.
investigational only at this time. Future indications Hodges RD, Legendre AM, Adams LG, et al: Itraconazole for the treat-
for use of these drugs in dogs and cats will need to ment of histoplasmosis in cats. J Vet Intern Med 8:409, 1994.
be determined. Jacobs GJ, Medleau L, Calvert CC, et al: Cryptococcal infection in cats:
Factors influencing treatment outcome, and results of sequential
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Johnson LR, Herrgesell EJ, Davidson AP, et al: Clinical, clinicopatho-
logic, and radiographic findings in dogs with coccidioidomycosis:
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Legendre AM, Rohrbach BW, Toal RL, et al: Treatment of blastomy-
no practical means of prevention in endemic areas. cosis with itraconazole in 112 dogs. J Vet Intern Med 10:365, 1996.
High concentrations of Histoplasma can be found in Malik R, Dill-Macky E, Martin P, et al: Cryptococcosis in dogs: A ret-
chicken and bat excreta, and Cryptococcus is found in rospective study of 20 consecutive cases. J Vet Med Mycol 33:291,
high concentrations in pigeon excreta; thus, exposure 1995.
Malik R, Wigney DI, Muir DB: Cryptococcosis in cats: Clinical and
to these sources should be avoided. Systemic mycoses mycological assessment of 29 cases and evaluation of treatment
are not contagious diseases between animals. using orally administered fluconazole. J Vet Med Mycol 30:133,
Although humans can be infected from the same 1992.
environmental point sources as animals, zoonotic trans- Medleau L, Jacobs GJ, Marks MA: Itraconazole for the treatment of
mission from animals to humans does not occur except cryptococcosis in cats. J Vet Intern Med 9:39, 1995.
Mitchell M, Stark DR: Disseminated canine histoplasmosis: A clinical
very rarely by direct inoculation of an open wound with survey of 24 cases in Texas. Can Vet J 21:95, 1980.
infected material from an animal. Vaccination for these O’Brien CR, Krockenberger MB, Wigney DI, et al: Retrospective study
mycoses is not available. of feline and canine cryptococcosis in Australia from 1981 to 2001:
195 cases. Med Mycol 42:449–460, 2004.
Schulman RL, McKiernan BC, Schaeffer DJ: Use of corticosteroids
for treating dogs with airway obstruction secondary to hilar
lymphadenopathy caused by chronic histoplasmosis: 16 cases
SUPPLEMENTAL READING (1979–1997). J Am Vet Med Assoc 214:1345–1348, 1999.
Stickle JE, Hribernik TN: Clinicopathological observations in dissem-
Arceneaux KA, Taboada J, Hosgood G: Blastomycosis in dogs: 115 inated histoplasmosis in dogs. J Am Anim Hosp Assoc 14:105, 1978.
cases (1980–1995). J Am Vet Med Assoc 213:658, 1998. Taboada J, Grooters AM: Systemic mycoses. In Ettinger SJ (ed): Text-
Armstrong PJ, DiBartola SP: Canine coccidioidomycosis: A literature book of Veterinary Internal Medicine (6th ed). St. Louis: Elsevier,
review and report of 8 cases. J Am Anim Hosp Assoc 19:937, 1983. 2006, pp 671–690.
Davidson AP: Coccidioidomycosis and aspergillosis. In Ettinger SJ Wolf AM, Belden MN: Feline histoplasmosis: A literature review and
(ed): Textbook of Veterinary Internal Medicine, 6th ed. St. Louis: retrospective review of 20 new cases. J Am Anim Hosp Assoc 20:995,
Elsevier, 2006, pp 690–699. 1984.
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▼ Chapter
21 Toxoplasmosis and Other Systemic
Protozoal Infections
Robert G. Sherding
The protozoa that infect dogs and cats can be classified Toxoplasma cysts (bradyzoites). Sources include
broadly into those that disseminate and cause systemic uncooked meat (or meat scraps scavenged from
disease and those that primarily live in the intestinal garbage) or hunted prey (mice, birds).
tract. This chapter describes toxoplasmosis, the most
important systemic protozoal infectious disease in • Ingestion of raw or undercooked meat (especially
pork) is an important source of toxoplasmosis in dogs
North America, and other emerging systemic protozoal
and humans.
infections—neosporosis, hepatozoonosis, and leishma-
niasis. These and other systemic protozoal infections • Ingestion of tachyzoites passed in milk can cause
lactogenic infection in nursing kittens. Ingestion of
are summarized in Table 21-1, including trypanosomia-
tachyzoites in raw (unpasteurized) milk, especially
sis, babesiosis, cytauxzoonosis, encephalitozoonosis,
from goats, is a rare source of infection.
acanthamebiasis, and pneumocystosis.
Protozoa that parasitize erythrocytes, such as Babesia
spp. and Cytauxzoon felis, are discussed in Chapter 22. Ingestion of Fecal Oocysts
Enteric protozoal infections (coccidiosis, giardiasis, Food, water, and soil contaminated with cat feces con-
tritrichomoniasis, amebiasis, and balantidiasis) are dis- taining sporulated Toxoplasma oocysts are potentially
cussed in Chapter 69. important sources of infection for intermediate hosts
such as humans, dogs, livestock, and rodents.
TOXOPLASMOSIS • Compared with carnivorous feeding, this is a rela-
tively minor source of infection in the primary host,
Etiology the cat.
• Oocysts can be transported from defecation sites in
Toxoplasma gondii is an obligate intracellular protozoan soil by cockroaches, flies, and earthworms.
parasite with worldwide distribution. The feline species
is the definitive host for this coccidium, but most
warm-blooded animals can be infected as intermediate Transplacental Infection
hosts, including dogs and humans. Only cats complete When a pregnant animal or human becomes infected
the coccidian life cycle with intestinal replication and during gestation, Toxoplasma tachyzoites can cross
passage of oocysts in the feces. the placenta and infect the unborn fetus, resulting
• Serologic surveys estimate that over 30% of cats and in severe or fatal disease (see under “Public Health
humans are seropositive and presumed infected. Considerations”).
• Seroprevalence in cats increases with age, and it is • For this reason, toxoplasmosis has major public
higher in male and domestic shorthaired cats. health significance in humans.
• In dogs and cats, congenital toxoplasmosis is uncom-
Routes of Transmission mon, but it is a potential cause of abortion, stillbirth,
Warm-blooded vertebrates can be infected by ingestion and neonatal mortality.
of any of the three life stages of the parasite (see the
next section) or transplacentally. Stages of Infection
The three stages of Toxoplasma infection are (1) intesti-
Ingestion of Tissue Cysts nal replication (cats only), (2) acute dissemination
Cats are mainly infected through the ingestion of meat and intracellular replication, and (3) chronic tissue
and animal tissues (carnivorism) that contain dormant encystment.
219
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Leishmaniasis Leishmania Endemic in Disease primarily in dogs: General: Origin from Caution: Zoonotic
infantum North Chronic diffuse skin endemic country or (indirectly)
(sand fly American hyperkeratosis (dry scaling), U.S. foxhound kennel; See text for
vector, foxhounds, dry brittle haircoat, skin hyperglobulinemia, dosages
bloodborne) Mediterranean nodules, mucocutaneous hypoalbuminemia, —Sodium
region, Central ulcers, fever, muscle proteinuria, azotemia, stibogluconate
and South atrophy, weakness, elevated serum liver (from CDC)
America, Asia, cachexia, anorexia, enzymes, anemia —Meglumine
Africa inactivity, vomiting, Specific: antimonite
diarrhea, lymphadenopathy, —Identify organisms by —Allopurinol
splenomegaly, uveitis, cytology (e.g., bone —Amphotericin
conjunctivitis, bleeding marrow) B
(epistaxis, melena), —PCR assay Prognosis: Fair to
glomerulonephritis, —Serology: Not as sensitive good for
polyarthritis or specific remission but
poor for cure
American Trypanosoma Southern U.S. Disease primarily in dogs: General: Endemic region, Caution: Zoonotic
trypanosomiasis cruzi (rarely), Acute myocarditis (fever, abnormal cardiac (indirectly)
(Chagas disease) (reduviid Central and weakness, sudden collapse, evaluations (radiography, Investigational
“kissing” South America fatal tachyarrhythmias), ECG, echocardiography) per CDC:
bug vector, chronic cardiomyopathy Specific: —Nifurtimox
bloodborne) (after 1–3 years, heart —Identify organisms in (Lampit, Bayer):
failure, ascites, pleural blood (direct or buffy 2–7 mg/kg POq6h
effusion, edema), coat smear) or lymph for 3–5 mo
lymphadenopathy, node aspirates —Benznidazole
splenomegaly, —Serology: Exposure or (Ragonil, Roche):
meningoencephalitis active 5 mg/kg PO q24h
—PCR assay for >2 mo
Prognosis: Good in
acute cases; poor
in chronic cases
Hepatozoonosis Hepatozoon U.S. (Gulf Disease primarily in dogs: General: Endemic region, For H. americanum
americanum Coast states, Episodic fever, cachexia, mild anemia, severe (see text):
(U.S only) Texas, chronic myositis and neutrophilic leukocytosis, —Clindamycin
(tickborne), Oklahoma), periosteal bone widespread periosteal —Trimethoprim-
Hepatozoon canis Brazil, Europe, proliferation (reluctance bone proliferation sulfadiazine
(worldwide) Asia, Africa to move, general muscle Specific: Identify organisms —Pyrimethamine
(tickborne) pain, atrophy), bloody in blood smear (in WBC) —Decoquinate
diarrhea, ocular discharge or in muscle biopsy (most For H. canis (see
reliable test) text):
—Imidocarb
dipropionate
Prognosis: Good
for remission but
poor for cure
Babesiosis Babesia Dog: B. canis, Hemolytic anemia (pallor, General: Regenerative anemia Dogs:
canis, B. gibsoni depression, weakness, (often Coombs’ positive), —Imidocarb
Babesia (U.S. and jaundice, hemoglobinuria, thrombocytopenia dipropionate
gibsoni, worldwide) fever, splenomegaly), Specific: (Imizol, Glaxo
etc. (tick Cat: B. felis, weight loss, subclinical —Identify organisms in Wellcome): 5.0–
vector, etc. (Africa, carrier Giemsa-stained smears of 6.6 mg/kg SC or
bloodborne) Asia, South capillary blood (from ear IM, two doses 14
America) or toenail) or splenic days apart
aspirate —Phenamidine
—Serology: IFA titer > 1:80 isethionate
is positive (Oxopirvedine,
—PCR assay Merial): 15 mg/kg
SC q24h ¥ 2 days
—Diminazene
aceturate (Berenil
10%, Ganaseg):
3.5 mg/kg IM
once, then repeat
in 14 days
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Cats:
—Primaquine
phosphate:
0.5 mg/kg IM
once
Prognosis: Good
but relapses are
common
Cytauxzoonosis Cytauxzoon U.S. (south- Disease in cats only: General: Free-roaming in a —Imidocarb
felis (tick central and Anorexia, depression, wooded area dipropionate
vector, southeastern high fever, anemia, Specific: (Imizol): 5 mg/kg
blood- states) jaundice, congestion and —Identify organism in IM, two doses 14
borne) edema (of lungs, spleen, blood smear (ring-shaped days apart
liver), shock, death in less RBC inclusions) or —Diminazene
than 1 week cytology of bone marrow, aceturate
lymph node, or spleen (Berenil): 2 mg/kg
—PCR assay IM, two
doses 7 days apart
Prognosis: Poor
Encephalitozoonosis Encephalitozoon U.S. (rarely), Neonatal disease in kennels: General: Nonregenerative No treatment
cuniculi Europe, South Stunted growth, acute anemia, azotemia, pyuria, known
(oronasal Africa nephritis (renal failure) hematuria, elevated CSF
exposure and encephalitis protein and mononuclear
to urine (depression, muscle cells
spores or spasms, ataxia, seizures, Specific:
ingestion blindness, aggression, —Identify spores in gram-
of infected paralysis) stained urine sediment
tissues) —Serology and PCR
Acanthamebiasis Acanthamoeba U.S. (very Disease in dogs only: Leukopenia; no diagnostic —No established
species rare; Pneumonia (fever, cough, test available (identify treatment protocol
(water, epizootics dyspnea, nasoocular organisms in lung —Trimethoprim-
sewage, seen in discharge), encephalitis biopsies) sulfonamide:
soil) greyhounds) (ataxia, seizures), mimics 30 mg/kg PO q12h
canine distemper
Pneumocystosis Pneumocystis —Worldwide Dogs (mostly miniature General: Neutrophilic —Trimethoprim-
carinii (rare in dogs dachshunds): Acute or leukocytosis, diffuse sulfadiazine:
(airborne) and cats) chronic pneumonia in radiographic alveolar and 15–30 mg/kg PO
—Predisposition immunocompromised interstitial lung densities q8–12h for 2–3
in miniature dogs (non-febrile, exercise Specific: Identify organisms weeks
dachshunds intolerance, dyspnea, dry in lung cytology or —Pentamidine
with cough, weight loss) biopsies (Giemsa and isethionate
immunodeficiency methenamine silver stains) (Lomidine,
syndrome Merial): 4 mg/kg
IM q24h for 2–3
weeks
Prognosis: Fair to
guarded
CDC, Centers for Disease Control and Prevention; IFA, immunofluorescent antibody; PCR, polymerase chain reaction; RBC, red blood cell; WBC, white blood
cell.
Intestinal Replication and Oocyst Shedding clinical signs are usually absent until after oocyst
shedding is over and the cat enters the next stage of
This is also called the sporozoite stage. When cats
infection.
ingest the meat of an infected intermediate host, the
encysted Toxoplasma bradyzoites are liberated by the • Infection by oocyst ingestion is a less important
cat’s digestive enzymes and invade the intestinal epithe- source in cats, but when it does occur, subsequent
lial cells. Replication within the intestinal epithelium shedding of oocysts is delayed for 3 weeks or more
results in fecal excretion of millions of oocysts begin- and is much less pronounced.
ning 3 to 10 days after exposure and continuing for 1 • Excreted oocysts are oval-shaped, 10 ¥ 12 mm in size,
to 3 weeks. Except for occasional transient diarrhea, and unsporulated (uninfective). To become infec-
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• Interpretation: A fourfold rise in the IgG titer in paired • Specimens to consider (depending on sites of
specimens over a 2- to 3-week period is indicative of involvement) include lung bronchoalveolar lavage
active infection. Both specimens must be measured (BAL), liver aspirates, lymph node aspirates,
together in the same test run to avoid assay variation. body cavity fluids, CSF, and aqueous humor by
oculocentesis.
▼ Key Point A single, high serum IgG Toxoplasma • Disadvantage: Tachyzoites are often sparse and diffi-
antibody titer is not diagnostic of active infection, cult to find; thus, sensitivity of detection is generally
no matter how high the titer level. low. However, in experimentally infected cats, BAL
was a reasonably effective method of diagnosis.
Antibody Titers in Cerebrospinal
Fluid and Aqueous Humor Detection of Oocysts in Feces
The diagnosis of CNS and ocular toxoplasmosis is aided Fecal oocysts are rarely detected because most cats are
by evaluating the local production of Toxoplasma-specific past the transient stage of oocyst shedding by the time
IgG and IgM antibodies in CSF or aqueous humor using clinical signs occur (see under “Stages of Infection”);
the calculated antibody coefficient (C-value), which dis- thus, this is not a suitable method for diagnosis of clin-
tinguishes true local production of Toxoplasma antibod- ical toxoplasmosis.
ies from inflammatory leakage. This can be combined • Procedure: Use Sheather’s sugar centrifugation-
with PCR assay for Toxoplasma DNA in CSF or aqueous flotation (Sheather’s solution: 500 g of table sugar,
humor. Specimens must be collected prior to glucos- 320 ml of distilled water, and 6.5 g of phenol crystals
teroid therapy. Aqueous humor and CSF assays are avail- melted in a hot water bath). Make a fecal suspension
able at the Veterinary Diagnostic Laboratory (College with 5–10 g of feces and water, then centrifuge one
of Veterinary Medicine, Colorado State University, Fort part fecal suspension with two parts Sheather’s solu-
Collins, CO 80523). tion for 10 minutes at 1000 g and examine one to two
ÈT . gondii antibody (aqueous or CSF)˘ drops from the meniscus.
ÍÎ ¥ Total antibody (serum) ˙˚ • Disadvantages: Oocysts are small, easily overlooked,
C - value = and morphologically indistinguishable from certain
È T . gondii antibody (serum) ˘ other coccidia (Hammondia spp., Besnoitia spp.)
ÍÎ¥ Total antibody (aqueous or CSF)˙˚ without specialized animal inoculation studies.
Nevertheless, assume coccidian oocysts 10 ¥ 12 mm
• C-value of 1 to 8 is suggestive of ocular or CNS toxo- in size in feline feces to be Toxoplasma until proved
plasmosis. otherwise.
• C-value of >8 is conclusive evidence of local ocular or
CNS antibody production. ▼ Key Point Detection of fecal oocysts is not a
reliable diagnostic test for clinical toxoplasmosis
▼ Key Point The combination of antibody titers because oocyst shedding occurs only briefly and
(especially IgM) and PCR assay on aqueous humor usually ends before clinical signs begin.
or CSF is the most accurate way to diagnose ocular
or CNS toxoplasmosis. Treatment
Polymerase Chain Reaction and Antigen Assays Toxoplasmosis can be treated with clindamycin,
trimethoprim-sulfonamide, or azithromycin. Localized
• PCR assay can be used to detect T. gondii DNA in ocular infection is most responsive. Approximately 60%
blood, CSF, or aqueous humor. The PCR assay in of animals with generalized toxoplasmosis recover with
blood can be positive in cats with and without clini- treatment; thus, the prognosis is guarded. Mortality rate
cal disease; thus, a positive PCR by itself does not is highest in neonates and in animals that are severely
confirm clinical toxoplasmosis. immunosuppressed.
• Toxoplasma antigen can be detected in cats initially
1 to 4 weeks after exposure and then intermittently ▼ Key Point Clindamycin is the initial drug of choice
for up to 1 year. This does not distinguish active from for treating clinical toxoplasmosis, and it pene-
past infection and thus has no advantage over anti- trates the blood-brain and blood-eye barriers. It
body titers. also reduces oocyst shedding.
• For uveitis, use 1% prednisone drops topically every sure to oocysts is very unlikely from petting cats or from
6 to 8 hours for 2 weeks. cat licks, bites, and scratches.
Prevention in Cats ▼ Key Point Because of the way cats defecate, bury
their feces, and keep their haircoats clean, trans-
Prevent cats from ingesting tissue cysts in meat and prey mission of Toxoplasma oocysts to humans by
animals. touching and caring for a pet cat is very unlikely.
• Do not feed cats raw meat, viscera, or bones, and do
not allow them to scavenge these from garbage. • The question often is raised, how dangerous is a
• Do not allow cats to ingest raw (unpasteurized) milk, healthy pet cat with a positive Toxoplasma antibody
especially from goats. titer? Most seropositive cats and cats with clinical tox-
• Do not allow cats to roam free where they can hunt oplasmosis have completed oocyst shedding by the
prey (mice, birds) for food. time they develop a positive titer. Repeat exposure of
• Do not allow cats to eat transport vectors (cock- a seropositive cat results in little or no shedding.
roaches, flies, earthworms). • Most cats that are shedding infective oocysts are
seronegative and preclinical. Seronegative cats are
non-immune and would be more likely to shed
Public Health Considerations oocysts if exposed, thus posing a greater risk to its
Toxoplasmosis is an important zoonosis in humans. owner than a seropositive cat.
Infection in immunocompetent people is inapparent or
causes a self-limiting, flu-like illness. Infection during ▼ Key Point Serologic testing of healthy cats for Tox-
pregnancy can cause fetal toxoplasmosis, leading to still- oplasma antibodies has little public health benefit
birth or severe ocular or CNS disease. Approximately and is not recommended.
10% of people with AIDS develop toxoplasma
encephalitis from reactivation of encysted bradyzoites. Environmental Control Measures
• Control the stray cat population to reduce contami-
Preventive Measures in Humans nation of the environment, soil, and water with
Prevention of human infection is based on avoiding oocysts. Cats that defecate in the soil are likely to be
ingestion of sporulated oocysts in the environment or the same cats that must hunt for their food and
tissue cysts in undercooked meat. Contaminated drink- thereby have a high risk of infection.
ing water has caused some outbreaks. • To reduce entry of Toxoplasma into the food chain,
prevent cats from roaming where food-producing
▼ Key Point Pregnant women and severely immuno- animals and livestock feed are kept. Pork is the most
compromised people should avoid contact with likely source of cyst ingestion in people in the United
soil, cat feces, litter boxes, and raw meat. States.
• Clinical disease has not been seen in cats, but exper- • Clindamycin (15 mg/kg PO q12h) for 28 days
imentally infected kittens develop encephalomyelitis • Trimethoprim-sulfadiazine (15–20 mg/kg PO q12h)
and polymyositis. combined with pyrimethamine (0.5 mg/kg PO q12h)
• N. caninum has worldwide economic importance as a for 28 days
major cause of abortion in dairy cattle.
Treat all littermates of infected puppies. The prognosis
Clinical Signs for dogs with severe neurologic involvement is grave,
and animals that recover usually have residual neuro-
Multifocal, progressive neuromuscular signs predomi- logic deficits.
nate as a result of non-suppurative encephalomyelitis,
polyradiculoneuritis, and fibrosing polymyositis. Prevention and Public Health
• Clinical signs can include hind-limb paresis and • Do not breed dogs with a history of whelping infected
ataxia progressing to ascending paralysis, hind-limb puppies.
extensor rigidity, and muscle atrophy and contrac- • Avoid glucocorticoids in seropositive dogs because of
ture. Dysphagia and masticatory muscle involvement the potential for activating encysted infection.
can be seen. • Neospora is seroprevalent in white-tailed deer; thus, do
• Less common manifestations include myocarditis not let dogs have access to deer carcasses.
(arrhythmias), pneumonia (fever, dyspnea, cough), • Do not allow dogs to have access to bovine placental
ulcerative or pruritic dermatitis, chorioretinitis, and tissues (afterbirth) or aborted fetuses.
multifocal intra-abdominal dissemination (hepatitis, • Because Neospora infection has a large economic
pancreatitis). impact as a cause of bovine abortion, prevent dog
feces from contaminating livestock feed and water.
▼ Key Point Subclinically infected bitches can trans- • Neospora caninum antibodies have been detected in
mit Neospora in utero to successive litters of people, but it is not yet clear whether Neospora is a
puppies. Congenital neosporosis is particularly cause of zoonotic disease.
severe and often leads to in utero or neonatal
puppy mortality.
replicate until cysts rupture, eliciting a severe pyogran- most pronounced on the pelvis, long bones of the
ulomatous inflammatory response and disseminating limbs, and vertebrae. The periosteal lesions may
more organisms to form new cysts. appear as smooth, lamellar thickening of the bone or
irregular proliferations.
▼ Key Point American hepatozoonosis is a chronic
debilitating illness characterized by waxing and Diagnosis
waning fever, extreme leukocytosis, polymyositis,
proliferative periosteal bone lesions, and severe ▼ Key Point Muscle biopsy is the most reliable
cachexia. means of confirming American hepatozoonosis.
In contrast, H. canis has relatively low pathogenicity; • Definitive diagnosis is based on visual identification
clinical signs are absent or mild in many infected dogs. of tissue stages of H. americanum organisms, which are
Severe disease is mostly limited to dogs with concurrent most reliably found in skeletal muscle biopsies and
disease or immunosuppression. Muscle and periosteal rarely in circulating leukocytes on Giemsa-stained
involvement do not occur with H. canis, but organisms blood smears. In contrast, blood smears are usually
are frequently seen in circulating leukocytes. diagnostic for H. canis infection.
• An ELISA-based serologic test for H. americanum has
Clinical Signs a sensitivity of 93% and specificity of 96%.
Clinical signs begin within 4 weeks of ingesting an
infected tick and continue to wax and wane as more Treatment
organisms are released into muscle tissue, exacerbating No treatment has been found to effectively eliminate H.
myositis, muscle pain, and fever. americanum from infected tissues in dogs. However, the
• Fluctuating fever (>104∞F) and lethargy following treatment has been shown to prolong survival
• Myalgia, stiffness, lameness, painful gait, reluctance and control clinical signs for extended periods, even
to move years. Pain and fever improve within 48 hours of initi-
• Hyperesthesia over the paraspinal muscles ating treatment.
• Progressive weight loss, weakness, and muscle • For H. americanum, use the combination of clin-
atrophy damycin (Antirobe) (10 mg/kg PO q8h), trimetho-
• Mucopurulent ocular discharge with each flare-up prim-sulfadiazine (Tribrissen or Ditrim) (15 mg/kg
• Transient bloody diarrhea PO q12h), and pyrimethamine (Daraprim) (0.25 mg/
• Possible protein-losing glomerulonephropathy (due kg PO q24h) for 2 weeks to establish remission; and
to immune complex glomerulonephritis or amyloi- follow this with decoquinate (Deccox, Alpharma)
dosis) in advanced cases (10–20 mg/kg PO q12h, mixed with food) for 2 years
and possibly lifelong to maintain remission and
Laboratory and Radiographic Findings prevent relapses. Decoquinate, an anticoccidial live-
The presumptive diagnosis of hepatozoonosis in dogs stock feed additive, decreases recurrences by inhibit-
from endemic areas is based on the combination of ing development of the organisms released from
typical clinical signs (fever, pain, and muscle wasting), tissue cysts, thereby preventing repeated cycles of
extreme leukocytosis, typical serum chemistry abnor- reinfection and illness.
malities, and characteristic periosteal bone lesions on • Use nonsteroidal anti-inflammatory drugs as needed
radiographs. for pain and fever.
• Avoid corticosteroids because they can worsen the
• The most characteristic hematologic finding is disease.
extreme neutrophilic leukocytosis (mean 75,000 to • For H canis, imidocarb dipropionate (Imizol) (5–
85,000/ml; range 20,000 to 200,000/ml), consisting of 6 mg/kg IM or SC, two doses 2 weeks apart) is highly
mostly mature neutrophils with a mild left shift. Mild effective and considered the drug of choice. It may
normocytic-normochromic nonregenerative anemia be effective for H. americanum. Pretreatment with
is also common. The platelet count is usually normal atropine (0.04 mg/kg SC), 30 minutes prior to imi-
to increased. Dogs with thrombocytopenia should be docarb injections, reduces the parasympathomimetic
evaluated for other concurrent tick-borne infections side effects of imidocarb.
(see Chapter 17).
• Common serum chemistry abnormalities are
Prevention and Public Health
increased alkaline phosphatase, hypoglycemia (in
vitro artifact of high white blood cell count), hypoal- • Prevention depends on minimizing tick exposure,
buminemia, and hyperglobulinemia. using an effective tick preventative product on dogs
• Radiographically, most dogs infected with H. ameri- in endemic areas, and routinely checking dogs for
canum develop diffuse periosteal bony proliferations, ticks and removing them promptly.
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drug regimens are recommended: RG (ed): The Cat: Diseases and Clinical Management, 2nd ed. New
York: Churchill Livingstone, 1994, p 565.
• Allopurinol (Zyloric, Glaxo): 15 to 20 mg/kg PO Dubey JP, Carpenter JL: Histologically confirmed clinical toxoplas-
q12–24h, initially combined with sodium stiboglu- mosis in cats: 100 cases (1952–1990). J Am Vet Med Assoc 203:1556,
1993.
conate or meglumine antimonite, then continued Dubey JP, Lappin MR: Toxoplasmosis and neosporosis. In Greene CE
alone for several months to maintain remission. (ed): Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis:
• Sodium stibogluconate (Pentostam, Wellcome): 30 to 50 Elsevier, 2006, pp 749–769.
mg/kg IV or SC q24h, combined with allopurinol, for Lappin MR: Protozoal and miscellaneous infections. In Ettinger SJ
(ed): Textbook of Veterinary Internal Medicine, 6th ed. St. Louis:
3 to 4 weeks or until resolution of signs and lab abnor- Elsevier, 2005, pp 638–646.
malities; available in the United States through the Lappin MR, Greene CE, Winston S, et al: Clinical feline toxoplasmo-
CDC at http://www.cdc.gov/ncidod/srp/drugs/drug- sis: Serologic diagnosis and therapeutic management of 15 cases. J
service.html. Vet Intern Med 3:139, 1989.
• Meglumine antimonite (Glucantime, Merial; available
in Europe): 100 mg/kg IV or SC q24h, combined with Neosporosis
allopurinol, for 4 weeks or until resolution of signs Lappin MR: Protozoal and miscellaneous infections. In Ettinger SJ
and lab abnormalities. (ed): Textbook of Veterinary Internal Medicine, 6th ed. St. Louis:
• Amphotericin B lipid complex (ABLC) (Abelcet, Enzon) Elsevier, 2005, pp 638–646.
at 3 mg/kg IV q48h (3 times weekly) for a minimum Lindsay DS, Dubey JP, McAllister M: Neospora caninum and the poten-
of five treatments. ABLC can be used as an alterna- tial for parasite transmission. Compend Contin Educ Pract
21:317–321, 1999.
tive to antimonials in animals with good renal func-
tion. Dilute in 5% dextrose to a concentration of 1
mg/ml and infuse over 1 to 2 hours (see Chapter 20). Leishmaniasis
Liposome-encapsulated amphotericin (AmBisome, Ciaramella P, Corona M: Canine leishmaniasis: Clinical and diagnos-
Gilead Sciences) is a more expensive alternative. tic aspects. Compend Contin Educ Pract 25:358–369, 2003.
Ciaramella P, Corona M: Canine leishmaniasis: Therapeutic aspects.
Compend Contin Educ Pract 25:370–375, 2003.
Prevention and Public Health Rosypal AC, Zajac AM, Lindsay DS: Canine visceral leishmaniasis and
its emergence in the United States. Vet Clin North Am Small Anim
• In endemic regions, avoid sand flies, especially at Pract 33:921–937, 2003.
night when they feed, and use insecticides as premise Schantz PM, Steurer FJ, Duprey, ZH, et al: Autochthonous visceral
sprays and topical applications to dogs. Deltamethrin leishmaniasis in dogs in North America. J Am Vet Med Assoc
collars are highly effective. Permethrin spray is also 226:1316–1322, 2005.
effective.
• Screen potential blood donors to prevent iatrogenic Hepatozoonosis
transmission.
Macintire DK, Vincent-Johnson NA, Kane CW, et al: Treatment of
• Direct contact with infected dogs is unlikely to pose dogs infected with Hepatozoon americanum: 53 cases (1989–1998). J
a risk of human infection; however, dogs serve as a Am Vet Med Assoc 218:77–82, 2001.
reservoir for infection of sand flies that can transmit Vincent-Johnson NA: American canine hepatozoonosis. Vet Clin
infection to people. In highly endemic countries, North Am Small Anim Pract 33:905–920, 2003.
control of canine infections is key to reducing leish-
maniasis in people. Trypanosomiasis (Chagas Disease)
Meurs KM, Anthony MA, Slater M, Miller MW: Chronic Trypanosoma
cruzi infection in dogs: 11 cases (1987–1996). J Am Vet Med Assoc
OTHER PROTOZOAL INFECTIONS 213:497, 1998.
▼
Section
3 Hematology/Oncology
Janet L. Peterson
▼ Chapter
231
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Bone Marrow Aspiration Biopsy Technique • Donors are incompatible if any agglutination or
hemolysis occurs in the major cross-match. The types
1. Use an Illinois sternal disposable needle, 15 to 18 of cross-match are defined as follows:
gauge, 1 to 2 inches long (Cardinal Health, Dublin, • Major: 100 ml donor cells + 100 ml patient serum/
OH). plasma
2. Pass the needle with the stylet through the cut skin • Minor: 100 ml patient cells + 100 ml donor serum/
and subcutaneous tissues and into the bone a few plasma
millimeters until it is firmly embedded. • Donor or patient controls: 100 ml of donor or patient
3. Place a 12-ml syringe containing 0.5 ml of 5% ethyl- cells to 100 ml of donor or patient serum/plasma,
enediaminetetraacetic acid (EDTA) solution onto respectively
the biopsy needle and collect 1 to 2 ml of bloody • Under emergency conditions, donors may be used if
material. mild agglutination occurs in the minor cross-match.
4. Place the marrow material on a plastic Petri dish and
pick up the glistening particles with a glass pipette. Cross-matching Procedure:
5. Gently expel this material out of the pipette onto a
glass slide. Make a squash preparation by laying a • After 15 minutes of incubation, centrifuge tubes at
second slide on the first and sliding them horizon- 280 ¥g for 1 minute.
tally apart. • Note any hemolysis in supernatant and gross aggluti-
nation of resuspended cells.
Bone Marrow Core Biopsy Technique • Place a small drop on glass slide and examine for
microscopic agglutination.
1. Use a Jamshidi aspiration biopsy disposable needle,
11 to 13 gauge, 2 to 4 inches long (Cardinal Health,
Dublin, OH).
Whole Blood Transfusion
2. Pass the needle with the stylet through the cut skin • In dogs, this procedure is best performed using
and subcutaneous tissues. animals negative for the dog erythrocyte antigen
3. Remove the stylet while advancing the needle 0.5 to DEA-1 and DEA-7 blood types.
1.5 cm into the bone, depending on the size of the • Although most cats have type A blood, it is best to
animal. cross-match blood, because as little as 1 ml of mis-
4. Twist the instrument sharply to cut the sample, and matched blood can cause a fatal transfusion reaction
withdraw the needle slowly. in cats.
5. Remove the core sample and roll it onto a glass slide • Estimated dosage is 10 to 20 ml/kg in dogs or cats,
for cytologic examination; then place the sample in with a maximum of 40 ml in an adult cat. A more spe-
10% buffered formalin for histologic fixation. cific guideline for the amount of donor blood in anti-
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Anemia
Coagulation profile
(PT, APTT, FDP, Platelets, Fibrinogen)
ABNORMAL Disseminated
intravascular
coagulopathy
Young dog?
Exercise-induced hemoglobinuria? YES
Certain canine breed?
breeds, erythrocytes are morphologically normal and • A positive Coombs test result may be associated with
enzyme activities are not affected. feline hemoplasmosis, presumably because of ery-
Poodles. Poodles develop an autosomal dominant throcyte membrane alteration.
condition that resembles pyruvate kinase deficiency, • PCR-based assays are available for the diagnosis of
but decreases in this enzyme are not demonstrable. hemoplasma infections in cats.
Affected animals have a persistent macrocytic hypo-
chromic anemia (PCV of 13–31%) with moderate retic- Treatment
ulocytosis. It is clinically evident by 1 year of age and • Consider whole blood transfusion if the anemia is
fatal by 3 years of age. Myelofibrosis, osteosclerosis, and severe.
hemosiderosis are present at death. • Prednisolone (2 mg/kg PO q12h) may be necessary
Beagles. In beagles, the condition presents with initially to suppress the severe immune-mediated
chronic anemia and moderate reticulocytosis. The destruction of erythrocytes.
mode of inheritance is likely autosomal recessive. The • Doxycycline (5 mg/kg PO q12h for 4 weeks) is pre-
disease is less severe in beagles than in poodles, and ferred for dogs and cats.
the disorder can remain subclinical for up to 4 years in • Enrofloxacin (5 mg/kg PO q24h for 14 days) can be
affected dogs. The short erythrocyte life span in beagles used in cats intolerant of doxycycline.
may be caused by an unidentified membrane abnor- • Cats who recover may become latent carriers.
mality.
Babesiosis
Immune-Mediated Hemolytic Anemia
Babesiosis is a tick-borne protozoal disease affecting
See the chapter on systemic immune-mediated diseases erythrocytes of dogs (Babesia canis, B. gibsoni). B. canis is
(Chapter 24). common in kennel conditions and is associated espe-
cially with greyhounds. B. gibsoni has been associated
Infectious Causes of Hemolysis with pit bull and American Staffordshire terriers.
Babesia felis has not been reported in North American
Hemoplasmosis cats but is reported in Africa and southern Asia. Con-
Hemoplasmosis or hemotrophic mycoplasmosis, previ- current infections with other tick-borne agents such as
ously known as hemobartonellosis, is caused by a Ehrlichia canis are common.
mycoplasma organism that infects the erythrocytes of Clinical Signs. Clinical signs in babesiosis range from
dogs (Mycoplasma haemocanis) and cats (M. haemofelis and an acute hemolytic crisis to an unapparent subclinical
“Candidatus M. haemominutum”). It can be transmitted form. Signs of the acute disease include splenomegaly,
by ticks and fleas or by queens to their newborn kittens icterus, anemia, thrombocytopenia, hemoglobinuria,
in the absence of blood-sucking arthropods. Splenec- and fever.
tomy (especially in the dog), immunosuppression Diagnosis. Initial diagnosis is made by examination
caused by glucocorticoid therapy, or stress in cats with of a blood smear.
latent M. haemofelis infection predispose to the devel-
opment of clinical disease in the animal infected by the • A large, clear, teardrop-shaped trophozoite organism
organism. in erythrocytes, sometimes seen in pairs, is represen-
Clinical Signs. Clinical signs include those generally tative of the three subtypes of B. canis.
observed with anemia. Weight loss may occur if the • A much smaller, signet ring–shaped form occurring
anemia develops slowly, whereas acute, severe anemia singularly and more frequently suggests subtypes of
produces sudden depression and icterus. Splenomegaly B. gibsoni or a Californian isolate genetically similar
often is noted. to Theileria species.
Diagnosis. Laboratory findings generally reflect a • An indirect fluorescent antibody (IFA) serum test is
strong regenerative response in the CBC. The absence available but may be negative in early infections or
of marked anisocytosis or polychromasia in confirmed display crossreactivity.
cases of feline hemoplasmosis may suggest peracute • A nested PCR test is most sensitive and can distin-
infections with too little time to respond or concurrent guish among canine babesial subtypes.
infection with feline leukemia virus (FeLV) or feline • A Coombs test is frequently positive in dogs with
immunodeficiency virus (FIV). severe anemia related to a secondary immune-
mediated disease.
• Thin smears, made directly without anticoagulant,
assist in finding the epicellular organisms. Blood Treatment. Treat babesiosis with one of the follow-
films should be well stained without precipitate to ing drugs. The only drug approved in the United States
minimize any confusion in identifying the parasite. is imidocarb. In general, the small Babesia species infec-
• Cats often have coccoid or ring shapes, whereas dogs tions are considered more resistant to treatment and
mostly have linear chain forms. often develop a chronic carrier state.
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Anemia
Minimal or no regeneration
ABNORMAL
Immune-mediated
FeLV-included POSITIVE Serology
nonregenerative
Hypothyroidism amemia erythroid dysplasia
Drug history
Drug-induced LOW
dyserythropoiesis
(folate antagonism)
Figure 22-2. Diagnostic approach to common nonregenerative anemias in dogs and cats when only the erythrocyte line is involved. (FeLV,
feline leukemia virus; MDS, myelodysplastic syndrome; M/E, myeloid-to-erythroid ratio; PCR, polymerase chain reaction; TIBC, total iron-
binding capacity.)
clinical manifestations, diagnosis, and treatment of • In the chronic or late stages of monocytic ehrlichio-
these infections are described in Chapter 17. sis, bone marrow cellularity decreases severely, with
fat replacing hematopoietic elements.
• Intracytoplasmic morulae are found infrequently in
mononuclear cells (E. canis, Ehrlichia chaffeensis) or
granulocytes (Ehrlichia ewingii, Anaplasma phagocy- Leishmaniasis
tophilum), during the acute stage of the disease. Bone Leishmaniasis is an infrequent protozoal disease in dogs
marrow, at this time, is often normocellular to hyper- caused by Leishmania spp. The parasite, transmitted by
cellular with increased numbers of megakaryocytes sand flies, produces visceral or cutaneous manifesta-
and plasma cells. tions. Organisms are present in macrophages of the
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Anemia
Cytauxzoonosis
RBC indices Cytauxzoonosis is a highly fatal protozoal disease of cats
Blood smear evaluation
caused by Cytauxzoon felis. It is a tick-borne infection,
Lack of regeneration? most prevalent in the wooded areas of the southern
United States. The bobcat is the natural reservoir
Cytopenia of >1 cell line? YES Further cytologic evaluation Erythrocyte piroplasms? host.
Tissue schizonts?
Clinical Signs. Initial clinical signs include anorexia,
Bone marrow evaluation
YES
dehydration, and lethargy, with gradual development of
Hypocellular?
fever. This progresses rapidly to icterus, moderate
YES History Antibiotics? Feline cytauxzoonosis anemia, leukopenia, thrombocytopenia, and spleno-
Anti-inflammatory drugs?
Estrogen-like compounds?
megaly. Cats usually die within a week after clinical signs
Antineoplastic agents? are recognized.
Diagnosis. The diagnosis is generally made post-
YES Drug-induced aplastic anemia
mortem by histologic identification of large schizonts in
Irradiation? YES Radiation-induced aplastic anemia
endothelial cells of the lungs, liver, bone marrow, or
Serology
PCR assay
FeLV?
FIV?
spleen. Terminally, blood films may contain small (1 to
Ehrlichia canis?
Canine distemper?
2 mm in diameter) ring or “safety pin” structures within
erythrocytes.
POSITIVE Infection-induced aplastic anemia Treatment. Treatment is usually unsuccessful despite
Surgery/histopathology Ovarian/testicular neoplasia?
the use of antibiotics and supportive care. Most
reported cases have been fatal, except for several sus-
Myelophthisis?
YES Estrogen-induced aplastic anemia pected to be infected with a less virulent strain of the
organism.
YES Fibrosis? YES Myelofibrosis
Necrosis? YES Myelonecrosis
Neoplasia? YES Primary leukemia Nutritional Deficiencies
Metastatic malignancy
Iron Deficiency
Dysplastic and/or hypercellular?
Iron deficiency produces a poorly regenerative anemia
YES Serology
PCR assay
FeLV?
FIV?
caused by deficient hemoglobin synthesis. It occurs with
Ehrlichia canis? increased iron utilization, such as during growth or
RMSF?
pregnancy, from decreased intestinal absorption of
POSITIVE Infection-induced anemia iron, and most commonly, when iron stores are reduced
Serum folate assay
through hemorrhage or blood loss.
Serum cobalamin assay Etiology. Iron deficiency anemia is caused by neo-
plasia with tissue necrosis, trauma, internal or external
LOW Folate deficiency
Vitamin B12 deficiency parasites (hookworms, fleas), coagulopathies, and
Blast cell count various GI diseases that cause hematemesis, melena, or
hematochezia.
<20% ≥20% Diagnosis. Diagnosis is based on history and low
serum iron levels.
MDS AML
CML
• Erythrocytes in blood smears may appear normal in
Figure 22-3. Diagnostic approach to common nonregenerative size but lighter in color, with increased central pallor
anemias in dogs and cats when multiple cytopenias are present. (hypochromasia). Electronic cell counters report an
(AML, acute myeloid leukemia; CML, chronic myeloid leukemia;
FeLV, feline leukemia virus; FIV, feline immunodeficiency virus; MDS,
MCV of less than 60 fl (microcytosis) in dogs.
myelodysplastic syndrome; PCR, polymerase chain reaction; RMSF, • Poikilocytosis may be prominent in the form of schis-
Rocky Mountain spotted fever). tocytes, keratocytes, codocytes, and elliptocytes.
• Thrombocytosis occurs in 50% of canine cases.
bone marrow, lymph nodes, spleen, and liver. The clin- • Iron profiles have normal to increased level of trans-
ferrin (total iron-binding capacity) and decreased
ical signs, diagnosis, and treatment are discussed in
serum iron level (in cats <60 mg/dl, in dogs <8 mg/dl).
Chapter 21.
The percentage of saturation of transferrin in iron-
• Leishmaniasis is endemic in many North American deficient animals is often less than 19% (normal is
foxhound kennels. In other dogs, the history usually about 33%).
indicates travel outside the United States to endemic • Bone marrow examination is necessary to determine
countries such as Greece, Spain, or Italy. iron storage amounts, especially in the dog. It is less
• Hyperglobulinemia and a mild to moderate normo- helpful in the cat, which typically lacks stainable iron
cytic, normochromic anemia may occur. in the bone marrow. Aspirate and core biopsies of the
W0422-Ch022.qxd 11/10/05 4:58 PM Page 241
bone marrow indicate hypercellularity with marked decreased RBC survival. Primary infections and neopla-
erythroid proliferation. sia are most often responsible for chronic inflamma-
tion. The animal may present with prolonged anorexia,
Treatment. Correct the inciting cause and treat with
weight loss, and weakness. Other clinical signs reflect
iron supplementation. Give ferrous sulfate at a dosage
the actual source of chronic inflammation or organ
of 4 to 6 mg of iron per kilogram per day PO in divided
systems affected.
doses. Continue therapy for several weeks to months
until the PCV and MCV return to normal. • Laboratory findings indicate a normocytic, nor-
mochromic anemia, inflammatory leukogram, low
Cobalamin Deficiency serum iron, low total iron-binding capacity, and
increased bone marrow stores of iron.
Cobalamin (vitamin B12) deficiency may occur through
acquired disorders such as small intestinal disease, • The bone marrow is usually hypocellular with a
normal to increased myeloid-to-erythroid ratio.
exocrine pancreatic insufficiency, or bacterial over-
growth in dogs (see Chapter 69). • Treatment depends on the original cause. Iron sup-
plementation does not effectively reverse this form of
• Selective malabsorption of vitamin B12 has been anemia.
described in giant schnauzers having an autosomal
mode of inheritance. Clinical signs include weight Organic Disease
loss, decreased appetite, and failure to thrive at 3
months of age. Kidney Disease
• Laboratory findings involve chronic normocytic, Chronic kidney disease may be associated with nor-
normochromic, nonregenerative anemia with occa- mocytic, normochromic, nonregenerative anemia.
sional erythroid dysplasia in peripheral blood or
bone marrow. • The mechanisms involved include reduced erythro-
poiesis, decreased erythrocyte survival, and blood
• Serum cobalamin levels can be measured to deter-
loss.
mine affected animals (for normal values and addi-
tional information, see Chapter 69). • Diagnosis of renal failure involves the presence of
azotemia and an abnormal urinalysis. For pathogen-
• Resolution of clinical and hematologic effects occurs
esis, diagnosis, and treatment, see Chapter 77.
with parenteral administration of cobalamin (initially
1 mg IM daily).
Liver Disease
Folate Deficiency Chronic liver disease may be associated with nor-
Folate deficiency may produce macrocytic anemia in mocytic, nonregenerative anemia. Blood smears often
animals with neoplasia, intestinal malabsorption, liver reveal poikilocytosis (acanthocytes, budding fragmenta-
disease, dietary imbalance, and severe anorexia or star- tion). Pathogenic mechanisms include concurrent
vation. Drugs such as anticonvulsants (phenobarbital, inflammation with iron sequestration, reduced erythro-
primidone), sulfonamides (sulfasalazine, trimethoprim- poiesis, and decreased erythrocyte survival.
sulfadiazine), and antineoplastic agents (methotrexate) • Blood loss may occur from coagulopathies related to
may act as folate antagonists by impairing its absorption decreased synthesis of clotting factors.
or production. • Portosystemic shunts may develop erythrocyte micro-
cytosis and poikilocytosis, with or without anemia,
• Diagnosis is based on a history of drug exposure or possibly related to a relative decrease in iron
concurrent disease. Serum folate levels can be mea-
sured to confirm the deficiency (for normal values availability.
and additional information, see Chapter 69). • Laboratory findings suggestive of hepatic disease
include elevated serum liver enzymes (ALT, SAP,
• The hemogram may indicate a normochromic
GGT), increased serum bile acid levels, hypoalbu-
anemia with macrocytosis and megaloblastic changes
in erythroid precursors. minemia, and hyperbilirubinemia. Liver disease is
discussed in Chapter 71.
• Treatment is aimed at the inciting cause, along
with oral folate supplementation (5 mg/day in dogs,
2.5 mg/day in cats). Endocrine Disease
Hypothyroidism
Inflammatory Disease Hypothyroidism may present with mild anemia in one-
Anemia of inflammatory disease is a frequent cause of third of cases. Pathogenetic mechanisms include
nonregenerative anemia. The mechanism may involve reduced tissue oxygen demand and depressed erythro-
increased macrophage activity with cytokine release poiesis at the stem cell level. Diagnosis is based on
leading to decreased erythropoiesis, reduced iron avail- history, dermatologic signs, and hormone assay results
ability through sequestration in macrophages, and (see Chapter 31).
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Hyperestrogenism Diagnosis
Hyperestrogenism is associated with endogenous pro-
• The diagnosis of lead toxicity often is based on a
history of exposure to lead in paint or automobile
duction by tumors (e.g., testicular Sertoli cell or ovarian
batteries. Heparinized blood samples are used to
granulosa cell) or exogenous administration of estro-
determine lead levels. Affected animals have levels
genic compounds (see Chapters 51, 86, and 90). The
greater than 0.06 mg/dl.
mechanism of reduced erythropoiesis is thought to
occur at the level of DNA transcription.
• The hemogram strongly suggests lead poisoning
when large numbers of nucleated erythrocytes are
• Moderate to severe anemia may be accompanied by present with a normal or slightly decreased PCV. The
thrombocytopenia and leukopenia. anemia is often normocytic and normochromic but
• Diagnosis of an estrogen-producing tumor may be may be microcytic and hypochromic.
confirmed by surgical removal with subsequent recov- • Basophilic stippling is best seen with Romanowsky-
ery of the cell lines. stained blood films prepared without EDTA antico-
• Supportive care, such as blood transfusion and ana- agulant. Polychromasia generally is rare.
bolic steroids, may be necessary. • Bone marrow aspirates or core biopsies are charac-
terized by maturation arrest at the metarubricyte
Hypoadrenocorticism stage.
Hypoadrenocorticism may be a cause of nonregenera- Treatment. Treat lead toxicity in dogs and cats with
tive anemia in a small percentage of cases. The anemia calcium EDTA (100 mg/kg) diluted to 10 mg/ml in 5%
usually is discovered after fluid replacement for volume dextrose and given SC, in four divided doses, daily for
deficits associated with the disease (see Chapter 33). 5 days.
Myelonecrosis Polycythemia
Myelonecrosis is an uncommon cause of non- Relative Polycythemia
regenerative anemia. It often is associated with neopla-
sia but may be related to infections or toxic agents. The Increase in erythrocytes (erythrocytosis) in relative poly-
mechanism likely involves occlusion of microcirculation cythemia generally is related to fluid depletion (e.g.,
or direct injury to endothelium. dehydration or hemoconcentration). However, excite-
ment or fear may cause splenic contraction and a tran-
• Diagnosis is based on bone marrow examination. sient rise in PCV. Greyhounds normally have a high PCV
Aspirate biopsies may contain peripheral blood, of 60%.
degenerative cells, increased macrophage activity,
and amorphous stringy material representing • Clinical signs include dark red mucous membranes
necrotic bone marrow particles. Focal to diffuse with slow capillary refill time.
regions of necrosis appear on histologic sections of • Diagnosis is based on a history of stress or fluid loss,
bone marrow. elevated PCV, and increased erythrocyte and plasma
protein concentrations. The erythrogram returns to
• Treatment includes removal of the inciting cause,
normal after fluid replacement.
along with supportive care. Prognosis is often poor.
• If splenic contraction is suspected, the PCV should be
retaken after the patient has relaxed.
Osteopetrosis
Osteopetrosis is an uncommon inheritable condition Absolute Polycythemia
affecting the normal development of bone. It causes The erythrocytosis in absolute polycythemia may be
obliteration of the marrow cavities by bone and may be primary or secondary, with a sustained increase in the
associated with refractory anemia, or pancytopenia in circulating erythrocyte mass, based on erythropoietin
immature or young adult dogs. production.
• Clinical signs usually are related to anemia. • Primary erythrocytosis, or polycythemia vera, has low
• Diagnosis is established by the inability to obtain serum erythropoietin that suggests the increased ery-
bone marrow material on aspiration and by distinc- throcyte numbers are derived from an intrinsic stem
tive radiographic findings. Increased bone density is cell defect (see “Leukemic Disorders”).
present and cortices are thickened, leaving a narrow • Secondary erythrocytosis involves overproduction of
medullary region. Histologic examination of medul- erythropoietin. Causes of secondary erythrocytosis
lary bone reveals thickened trabeculae, reduced include hypoxia (e.g., caused by high altitude,
marrow cavities, and an absence of osteoclasts. chronic pulmonary disease, or cardiac disease with
• Despite supportive care, the prognosis is poor. right-to-left shunting), tumors that produce erythro-
poietin (e.g., renal lymphoma, renal carcinoma,
and renal fibrosarcoma), and renal disease (e.g.,
Irradiation pyelonephritis).
Irradiation acts as a local cytotoxic agent for cancer
therapy. It also is used to treat hemolymphatic Diagnosis
malignancies and genetic defects before bone marrow Diagnosis of hypoxia is based on history and evidence
transplantation. High doses produce irreversible pan- of lung disease or right-to-left shunting heart disease.
cytopenia and aplastic bone marrow. Supportive care Renal disease, benign or malignant, can be excluded
(e.g., blood transfusions, antibiotics, and immunosup- by urinalysis, radiography, ultrasonography, or biopsy.
pressive drugs) often is given after transplantation. Serum erythropoietin levels currently are measured by
radioimmunoassay and ELISA methods.
exceed 30%. The patient is often dyspneic, weak, and screening and may be mistaken as a severe left shift.
ataxic. Inflammatory conditions should be ruled out.
• No treatment is necessary.
Diagnosis
The appearance of dark red or chocolate-colored Feline Chédiak-Higashi Syndrome
blood, even after exposure to air, is diagnostic for the This is a rare, inheritable disorder seen in blue-smoke
condition. The color change, from dark to bright red Persian cats with yellow eye color. Pathogenesis involves
in normal blood, is readily visible by a spot test on filter abnormal and enlarged lysosomal granule formation in
paper. The blood of affected animals shows no such granulocytes and monocytes. Affected cats may be pho-
color change if the methemoglobin content exceeds tophobic with cataract formation. There is increased
15%. bleeding time because of platelet granule defects. With
• Severe disease is produced from oxidant drugs and Romanowsky stains, neutrophils contain characteristic
chemicals, similar to those mentioned in the previous large, pink to magenta cytoplasmic inclusions that stain
section on Heinz body formation. Both conditions positive with peroxidase and Sudan black B. These cats
present together, but methemoglobinemia tends to do not exhibit an increased susceptibility to infection
occur before Heinz bodies appear. although neutropenia may occur.
• Several breeds of dog and a domestic shorthaired
cat were reported to have a rare enzyme (NADH- Lysosomal Storage Diseases
methemoglobin reductase) deficiency with a mild to
moderate form of the disease. Mucopolysaccharidosis and Gangliosidosis
• Quantitative measurement of methemoglobin con- These are inheritable lysosomal storage diseases
tent is performed by spectrophotometry at special- reported in cats and dogs caused by an enzyme defi-
ized laboratories. ciency. Mucopolysaccharidosis (MPS) types VI and VII
have been reported in cats and dogs and present with
Treatment skeletal and ocular lesions. In cats with GM2-gangliosi-
Treatment is similar to Heinz body anemia. In addition, dosis, neurologic deficits and corneal opacification are
methylene blue (1 mg/kg IV, as a 1% solution), if care- displayed.
fully administered, has been used to treat the condition • In all these diseases, neutrophils may contain coarse,
caused by oxidant drugs. Caution is necessary to avoid red-purple granules when stained with Wright-
potentiating a hemolytic crisis. Therapy usually is not Giemsa or toluidine blue. Cells must be distinguished
required for animals with the reductase enzyme from toxic neutrophils.
deficiency. • A urine spot test is used to screen for glycosamino-
glycans, whereas a cell enzyme activity test is
▼ Key Point A mild secondary polycythemia may diagnostic.
develop in animals with methemoglobin reductase • Experimentally, bone marrow transplantation has
deficiency. been used to treat some of these disorders. Affected
animals should not be bred.
Abnormal Granulation Syndrome in Birman Cats • Immune-mediated reactions, such as systemic lupus
erythematosus, can result in a left shift with
This is a genetic anomaly recognized in Birman cats neutrophilia.
without associated clinical disease. Diagnosis is based on
the presence of fine, pinkish-purple granules within the
• Granulocytopathy syndrome in Irish setters is a congeni-
tal cause of inflammatory neutrophilia. Neutrophils
cytoplasm of neutrophils. These lysosomal granules appear morphologically normal but have impaired
have normal morphology, and neutrophil function is bactericidal activity related to a deficiency of adhe-
unaffected. sion proteins. Affected dogs have recurrent bacterial
Neutrophilia infections with extreme leukocytosis that can mimic
chronic granulocytic leukemia (see “Leukemic
Neutrophilia is defined as more than 11,500 neu- Disorders”).
trophils per microliter in the dog and more than 12,500
neutrophils per microliter in the cat. Neoplastic neu- Diagnosis
trophilic conditions are discussed in the section on
leukemic disorders. Diagnosis of inflammatory neutrophilia is based on a
careful history and a CBC evaluation. A regenerative left
Physiologic Neutrophilia shift requires a simultaneous neutrophilia.
Epinephrine release as the result of stress, fear, or • A left shift without neutrophilia is considered degen-
strenuous muscular exertion causes demargination of erative, especially if there is neutropenia (see the
leukocytes, producing a rapid rise in neutrophils and next section), or if more non-segmented forms are
lymphocytes. Within 30 minutes, the cell counts return present compared with mature neutrophils.
to normal. The effect is more common and greater in • In addition to a significant shift toward immaturity
cats than in dogs. (bands >1000/ml), neutrophils may exhibit toxicity.
Toxins released from bacteria are mostly responsible
Corticosteroid-Induced Neutrophilia for the focal or diffuse cytoplasmic basophilia
and vacuolation found in mature or immature
Neutrophilia may be related to exogenous administra-
neutrophils.
tion or endogenous release of glucocorticoids. Cells are
released from marginating pools and bone marrow • Antibiotic responsiveness suggests a bacterial cause.
storage pools. The magnitude and duration of the effect • Tests for specific infectious agents and immune-
mediated disorders may be indicated.
depends on the type of corticosteroid given.
• Diagnosis is determined by the history and by the Treatment
presence of concurrent lymphopenia, eosinopenia,
Treatment depends on the inciting cause.
or monocytosis, without a left shift.
• Neutrophil hypersegmentation is common because
of a prolonged life span. ▼ Key Point Animals possessing neutrophil function
defects present with neutrophilia and persistent
Inflammatory Neutrophilia and recurrent infections.
Evidence of inflammation is an increase in non-
segmented forms of neutrophils, termed a left shift. Neutropenia
Etiology Neutropenia is defined as less than 3000 neutrophils
per microliter in the dog and less than 2500 neutrophils
Etiology involves infectious or non-infectious sources. per microliter in the cat.
• Infectious agents include bacteria, systemic fungi, pro-
tozoa, or rickettsiae (see Section 2). Congenital Cyclic Neutropenia
• Non-infectious conditions involve tissue necrosis, such as Cyclic neutropenia or cyclic hematopoiesis is an inher-
necrotizing pancreatitis, neoplasia, thrombosis, and
ited disorder of gray collies. It is characterized by peri-
burns.
odic fluctuations in neutrophils and, to a lesser extent,
• Certain malignancies (e.g., metastatic fibrosarcoma or
in monocytes, platelets, and reticulocytes as a result of
renal tubular carcinoma) are reported to induce a
the intrinsic bone marrow stem cell defect. Neutropenic
leukemoid response, presumably as a paraneoplastic
cycles recur at 12-day intervals.
disorder, rather than come from tissue necrosis
alone. Leukemoid counts range from 50,000 to
100,000 leukocytes per microliter with a left shift back
Clinical Signs
to bands, metamyelocytes, and myelocytes. Clinical signs during neutropenic episodes include
• Severe abscessation (e.g., pyometra) can also cause this lethargy, pyrexia, anorexia, arthritis, keratitis, and res-
extreme degree of leukocytosis. piratory or GI infections.
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• Physical examination discloses sites of hemorrhage, by direct observation of morulae within platelets or
presence of hepatosplenomegaly, and concurrent by serologic and PCR tests (see Chapter 17).
infections or neoplasia.
• Use CBC to screen for hematologic abnormalities Modified Live Virus Vaccination
including the adequacy of the platelet numbers.
Canine distemper virus vaccine may induce thrombo-
• Perform platelet counts on fresh samples (within 1–2
cytopenia within 1 week after vaccination. The effect is
hours). Thrombocytopenia is considered less than
transient but may persist as long as 3 weeks. It is rarely
100,000 platelets per microliter. However, clinical
of clinical significance unless surgery is performed
signs of bleeding are not expected until there are less
during the platelet count nadir.
than 20,000 platelets per microliter.
• Include both aspirate and core biopsies in bone
marrow evaluation to check for adequate megakaryo- Hemorrhage
cyte numbers. Bleeding can consume platelets. Consumption of
• Perform clotting profile, including fibrinogen, PT, platelets may occur through hemorrhage alone or in
and APTT or activated clotting time (ACT), to association with bacterial or viral infections that pro-
help rule out other coagulopathies (as described duce inflammation. Endotoxemia from gram-negative
in Chapter 23). ACT may be slightly prolonged if bacteria leads to endothelial damage and platelet
platelet counts are less than 10,000/ml. activation.
• Perform a von Willebrand factor assay if the breed
and clinical signs suggest a deficiency (see Chapter • Diagnosis is based on history, physical examination,
23). cytology, histopathology, and culture techniques.
• Bleeding time, a platelet function test, may be pro- • Treatment is aimed at the inciting agent. Whole
longed because of low platelet numbers. blood or platelet transfusions may be necessary if
thrombocytopenia is severe.
▼ Key Point Examine the blood smear carefully,
especially at the feathered edge, before making a Disseminated Intravascular Coagulation
diagnosis of thrombocytopenia. This condition leads to increased consumption of
platelets, as well as clotting factors. It is associated most
Treatment often with infections, neoplasia, heartworm disease,
pancreatitis, and shock.
Supportive therapy may include fresh blood transfu-
sions (administered within 8 hours of collection) if both • Clinical signs involve petechial and ecchymotic hem-
platelets and erythrocyte numbers are low. If only orrhages. Organ dysfunction usually reflects the
platelets are needed, administer platelet-rich plasma effects of the primary disease.
(see Chapter 23). • Diagnosis is based on the findings in tests of
coagulation, including hypofibrinogenemia, pro-
Immune-Mediated Platelet Injury longed PT and APTT, increased fibrin degradation
This is one of the most frequent and important causes products, and decreased antithrombin III activity
of thrombocytopenia manifested by clinically significant (see Chapter 23). Microthrombi formation is found
bleeding. The clinical findings, diagnosis, and treat- on histopathology.
ment are discussed in Chapter 24. • Treatment is aimed at the inciting or underlying
cause when possible. Supportive care, including
Increased Platelet Consumption or Utilization fluids, is necessary to prevent shock. Replacement of
platelets and coagulation factors using fresh plasma
Infectious Agents usually is indicated. Heparin rarely is effective, espe-
Thrombocytopenia produced by such agents as E. canis, cially if the hemorrhagic stage already has occurred
E. ewingii, Anaplasma platys, and A. phagocytophilum pre- (see Chapter 23).
sumably is the result of increased consumption and the
presence of antiplatelet antibodies. Platelet Sequestration: Splenomegaly
• Thrombocytopenia is the most frequent hematologic The spleen normally stores approximately one-third of
finding in canine ehrlichiosis. Bone marrow evalua- the body’s platelets. With enlargement of the spleen
tion during the acute course of E. canis infection indi- from any cause, there is an increase in blood volume
cates megakaryocytic hyperplasia. The diagnosis of that sequesters more platelets within endothelial pas-
ehrlichiosis is based on a history of tick exposure and sages, resulting in thrombocytopenia. Physical exami-
serologic and PCR tests (see Chapter 17). nation of an enlarged spleen without evidence of other
• A. platys infection produces a cyclic thrombocytope- conditions that induce thrombocytopenia supports the
nia occurring in 2-week cycles that may be diagnosed diagnosis. It is usually of little clinical significance if
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Neoplastic Thrombocytosis
Drug-Induced Thrombocytopenia
See the section on leukemic disorders.
Causes of drug-induced thrombocytopenia are similar to
those that produce aplastic anemia (see “Nonregenera-
tive Anemia”). Antineoplastic agents such as cisplatin,
cyclophosphamide, chlorambucil, doxorubicin, and
DYSPLASTIC DISORDERS
hydroxyurea produce significant thrombocytopenia.
Congenital Dysplasia
Myelophthisic Thrombocytopenia Inherited Erythrocyte Macrocytosis
See the section on nonregenerative anemia. An inherited disorder of toy and miniature poodles is
associated with abnormal morphology of erythrocytes
▼ Key Point Thrombocytopenia associated with and their precursors.
neoplasia occurs through several mechanisms • Affected animals present with no clinical signs of
including hemorrhage, microangiopathy, dissemi- anemia, and the dysplastic findings are usually inci-
nated intravascular coagulation, myelophthisis, dental.
immune-mediated destruction, and chemothera- • Diagnosis is based on the breed and on findings of a
peutic drugs. normal hematocrit, presence of macrocytosis (MCV
> 80 fl), megaloblastosis in the blood and bone
Thrombocytosis marrow, and absence of polychromasia or reticulocy-
tosis. An asynchrony in maturation between the
Physiologic Thrombocytosis
nucleus and the cytoplasm characterizes the RBC
Increased numbers of platelets are released from the abnormalities. Neutrophil hypersegmentation and
spleen as a result of epinephrine release or during giantism also may occur but are less common.
heavy exercise. Pulmonary stores of platelets also may • The condition persists and is not responsive to folate
be released during exercise. This is transient and of no or cobalamin.
clinical significance.
Inherited Macroplatelets
Reactive Thrombocytosis
Macroplatelets as an inherited disorder have been
Conditions associated with reactive or regenerative reported in Cavalier King Charles spaniels without hem-
thrombocytosis include acute blood loss, iron deficiency orrhages or clinical signs.
anemia, trauma, surgery, inflammation, splenectomy,
hyperadrenocorticism, and neoplasia.
Infectious Causes of Dysplasia
• Tumors that may cause thrombocytosis are mast cell Abnormal morphology of erythroid, granulocytic, and
tumor, hemangiosarcoma, osteosarcoma, lymphoid
megakaryocytic lines occurs in cats infected with either
and myeloid leukemias, and some carcinomas.
FeLV or FIV.
• Vincristine administration produces increased throm-
bopoiesis and cytoplasmic fragmentation of megakary- • Macrocytosis, megaloblastosis, neutrophil giantism,
ocytes because of a reduced maturation time. hypersegmentation, and dwarf megakaryocyte for-
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mation characterize the dysplastic changes found as chronic infections, hepatosplenomegaly, mild lym-
a result of viral effects on nuclear development. phadenopathy, and hemorrhagic tendencies.
• Peripheral cytopenias arise from abnormal matura-
tion of affected cell lines.
Diagnostic Principles
• Clinical signs often include concurrent bacterial or
protozoal infections, neoplasia, and chronic wasting. Myeloid leukemias are suggested by the history (e.g.,
• Definitive diagnosis requires serologic testing. FeLV infection), clinical signs of unexplained or fre-
• Treatment is supportive in nature. The median sur- quent infections, and hematologic abnormalities that
vival is 12 weeks. affect multiple cell lines. Definitive diagnosis is made
from bone marrow aspirate and core examinations.
Drug-Induced Dysplasia • Acute myeloid leukemia has been defined in the past as
Dyserythropoiesis characterized by macrocytosis, mega- subtypes M1 to M7, which have blast cells in the bone
loblastoid changes, nuclear fragmentation, sideroblas- marrow equal to or exceeding 30% of non-erythroid
tosis, and siderocytosis may occur in animals treated cells. However, to follow the current human classifi-
with azathioprine, cyclophosphamide, cytosine arabi- cation, the percentage of myeloblasts may be defined
noside, vincristine, or chloramphenicol. as greater than 20% of non-erythroid cells. In
general, survival involves weeks to months for
• These changes are not associated with folate patients with acute myeloid leukemia.
deficiency. • Chronic myeloid leukemia subtypes have increased
• Diagnosis is based on blood and bone marrow numbers of blast cells, but these cells account for less
samples taken during routine post-treatment hema- than 20% of non-erythroid cells of the bone marrow.
tologic evaluations. A longer survival of months to years is expected for
• Normal morphology of hematopoietic cells returns patients with chronic myeloid leukemia.
several days after cessation of drug therapy. • Cytochemical staining or immunocytochemistry of
blast cells from blood and bone marrow smears may
Nutritional Dysplasia be performed on unfixed slides submitted to special
• Erythroid dysplastic changes and neutrophil hyper- laboratories to determine the cell type primarily
segmentation may occur in giant schnauzers with an involved.
inherited selective malabsorption of vitamin B12 • Alternatively, flow cytometry may be helpful in some
(described in this chapter under “Nonregenerative cases to define the cell type.
Anemia”).
• A macrocytic nonregenerative anemia is found in Treatment Principles
acquired folate deficiencies such as intestinal malab-
sorption, neoplasia, liver disease, dietary imbalance, Treatment generally consists of supportive care (e.g.,
and severe starvation. antibiotics, blood transfusions, and fluids).
• Drugs such as anticonvulsants, antibiotics, and anti- • Antineoplastic agents, including corticosteroids,
neoplastic agents that inhibit folate metabolism cytosine arabinoside, chlorambucil, busulfan, and
produce megaloblastic changes in erythroid precur- hydroxyurea, have been used with limited success.
sors (see under “Nonregenerative Anemia”). • Bone marrow transplantation has been attempted in
the cat but is cost prohibitive for clinical application.
granulocytic myelosis. It is an uncommon condition Hoenig M: Six dogs with features compatible with myelonecrosis and
that results in intramedullary and extramedullary myelofibrosis. J Am Anim Hosp Assoc 25:335, 1989.
Huibregtse BA, Turner JL: Hypereosinophilic syndrome and
hematopoiesis accompanied by a reactive or secondary eosinophilic leukemia: A comparison of 22 hypereosinophilic cats.
marrow fibrosis late in the course of the disease. The J Am Anim Hosp Assoc 30:591, 1994.
hematopoietic precursors most involved are granulo- Macintire DK, Boudreaux MK, West GD, et al: Babesia gibsoni infection
cytic and megakaryocytic forms, which infiltrate the among dogs in the southeastern United States. J Am Vet Med Assoc
220:325, 2002.
spleen and liver. Some cases may be mistaken for acute Maggio-Price L, Emerson CL, Hinds TR, et al: Hereditary nonsphe-
myeloid leukemia of megakaryocytic origin. rocytic hemolytic anemia in beagles. Am J Vet Res 49:1020, 1988.
Marks SL, Mannella C, Schaer M: Coral snake envenomation in the
• The peripheral blood often has concurrent immature dog: Report of four cases and review of the literature. J Am Anim
granulocytes and erythroid cells, termed a leukoery- Hosp Assoc 26:629, 1990.
throblastic reaction. Erythrocytes may display poikilocy- Meinkoth JH, Kocan AA: Feline cytauxzoonosis. Vet Clin North Am
tosis with a teardrop appearance (dacryocytosis). Sm Anim Pract 35:89, 2005.
Meinkoth J, Kocan AA, Whitworth L, et al: Cats surviving natural infec-
• Bone marrow aspiration is often difficult related to
tion with Cytauxzoon felis: 18 cases (1997–1998). J Vet Intern Med
the presence of myelofibrosis, so core biopsy is rec- 14:521, 2000.
ommended to confirm the diagnosis. Messick JB: Hemotrophic mycoplasmas (hemoplasmas): A review and
• Survival varies from months to years depending on new insights into pathogenic potential. Vet Clin Pathol 33:2, 2004.
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ings in small companion animals with lead poisoning: 347 cases
anemia. (1977–1986). J Am Vet Med Assoc 199:93, 1991.
Neer TM: Hypereosinophilic syndrome in cats. Compend Contin
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Blue JT: Myelofibrosis in cats with myelodysplastic syndrome and Randolph JF, Center SA, Kallfelz FA, et al: Familial nonspherocytic
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Anim Pract 33:885, 2003. marrow in dogs with multicentric lymphoma. J Am Vet Med Assoc
Breuer W, Hermanns W, Thiele J: Myelodysplastic syndrome (MDS), 194:1427, 1989.
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▼ Chapter
23 Coagulation Diseases
Marjory B. Brooks
Coagulation disorders comprise a group of bleeding the factors to assume an active conformation and
diatheses caused by dysfunction of the clotting cascade participate in the coagulation cascade.
and subsequent failure of fibrin clot formation. • The most common vitamin K deficiency state in
Included in this discussion of coagulation disorders small animal medicine occurs after ingestion of
are von Willebrand disease and the complex syndrome anticoagulant rodenticides. These poisons prevent
of disseminated intravascular coagulation. Common intrahepatic vitamin K recycling, which depletes
bleeding diatheses that are not coagulation disorders vitamin K from body stores. Potency and duration
include thrombocytopenia and acquired platelet dys- of effect vary for different poisons. Overdose of the
function (platelet disorders are discussed in Chapter anticoagulant drug warfarin causes bleeding via the
22). Initial examination should aim to differentiate same mechanism.
bleeding caused by localized blood vessel injury or • Posthepatic biliary obstruction and infiltrative
vessel disease from bleeding due to a systemic platelet bowel disease also cause vitamin K deficiency by
or coagulation defect. reducing its intestinal absorption.
• Occasionally, bleeding due to vitamin K deficiency
is seen in neonatal puppies. Typically, these
ETIOLOGY puppies are born prematurely or are delivered by
cesarean section.
Categories of bleeding disorders are listed in Table
23-1 and include coagulation factor deficiencies, von Factor Inhibition
Willebrand disease, and disseminated intravascular Heparin
coagulation.
• Heparin inhibits fibrin clot formation by enhancing
Coagulation Factor Deficiencies the activity of the plasma anticoagulant protein,
antithrombin III, several thousand-fold.
Acquired Deficiencies • Bleeding due to iatrogenic factor inactivation results
Acquired deficiencies of functional coagulation factors from overdose of heparin for treatment of throm-
are common disorders and are caused by decreased botic disorders or excessive heparinization of trans-
production of coagulation factors, release of inactive fused blood products.
factors, or inhibition of factor activity. • Release of heparin from mast cell tumor granules
often causes local tissue hemorrhage and edema. In
Production Defect rare cases, massive degranulation of disseminated
tumor causes systemic anticoagulation.
Coagulation factors are proteins synthesized primarily
or exclusively in the liver. Clinically significant reduc- Pathologic Inhibitors
tion in these factors most often accompanies acute ful-
minant necrosis, chronic cirrhosis, and portosystemic • High plasma concentration of fibrin(ogen) degrada-
shunting diseases; each of these causes severe liver tion products can interfere with mature fibrin clot
failure and marked reduction in functional hepatic formation.
mass. • Autoantibodies and alloantibodies directed against
specific coagulation factors have been reported in
Inactive Factors human patients and should be included in the differ-
ential of acquired coagulopathy in animals.
Vitamin K Deficiency
• Antibodies directed against phospholipid-binding
• The prothrombin group of coagulation factors proteins, referred to as “lupus anticoagulants,” cause
(factors II, VII, IX, and X) require vitamin K for post- prolongation of in vitro clotting times but are associ-
translational carboxylation. This modification allows ated with clinical thrombotic syndromes.
256
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tion of von Willebrand factor (vWF), a plasma protein • Coagulation factor deficiencies tend to cause sponta-
critical for normal platelet function in the primary neous bleeding into the chest, abdomen, or muscles,
phase of hemostasis. and subcutaneous hematoma formation.
• The trait is autosomal; both males and females can • vWD is associated most often with spontaneous hem-
orrhage from mucosal surfaces of oral and nasal
transmit and/or express vWD.
cavities or from intestinal and genitourinary tracts.
• Exacerbation of the bleeding tendency of vWD may Excessive or prolonged bleeding occurs after injury
be seen in association with concurrent thrombocy-
or surgery.
topenia, infection, hormonal fluctuation, or endo-
crinopathy (especially thyroid insufficiency). Avoid
• Bleeding in association with DIC is usually severe and
occurs from mucosal surfaces and into body cavities;
giving drugs with antiplatelet effects, such as aspirin
in addition, signs of the underlying disease are
and other nonsteroidal anti-inflammatory drugs,
usually present.
plasma expanders, and heparin, to vWF-deficient
patients.
• Bleeding from venipuncture sites most often accompanies
severe deficiencies of multiple coagulation factors or
• Breeds with high prevalence or severe forms of
fulminant DIC. Absence of this sign does not rule out
vWD include Doberman pinscher, Scottish terrier,
a clinically significant coagulation disorder.
Shetland sheepdog, German wirehair and shorthair
pointer, Pembroke Welsh corgi, Chesapeake retriever,
and Australian shepherd. The vWD trait can occur in
any breed and is occasionally diagnosed in mixed- DIAGNOSIS
breed dogs.
▼ Key Point The first consideration when evaluating
Disseminated Intravascular Coagulation bleeding patients is to differentiate a blood loss
due to injury of a single or local group of blood
Disseminated intravascular coagulation (DIC) is a vessels from a systemic bleeding diathesis. This
dynamic disease process caused by systemic activation of distinction is usually apparent after thorough
the coagulation cascade. The loss of localized clot for- history, physical examination, and evaluation of
mation results in thrombotic occlusion of small and quick assessment tests.
midsize vessels, with compromise to tissue blood sup-
plies and secondary activation of fibrinolytic pathways. History
• Disorders that trigger the DIC process cause wide- The history should include specific questions to
spread damage to vascular tissue, platelet aggregation identify previous episodes of spontaneous bleeding or
and consumption, or intravascular release of tissue excessive hemorrhage after surgery or trauma.
factor.
• DIC most often accompanies severe inflammatory • Gingival bleeding from tooth eruption and bleeding
disease syndromes and diseases causing severe tissue from docking or dewclaw removal are common signs
injury such as sepsis, neoplasia (especially heman- of inherited coagulation factor deficiency and vWD.
giosarcoma, hepatic neoplasia, lymphoma, and pro- Conversely, history of severe trauma or invasive sur-
static and mammary carcinoma), burn or crush gical procedure without excessive hemorrhage rules
wounds, pancreatitis, and intravascular hemolysis. out an inherited hemostatic defect.
• Bleeding may develop in patients with DIC as coagu- • Patients with histories of hepatic disease or disorders
lation factors, platelets, and regulatory hemostat- associated with DIC are at risk for acquired coagula-
icproteins are depleted in the systemic thrombotic tion defects and should be further evaluated before
process. invasive procedures.
Physical Examination
CLINICAL SIGNS Physical examination should define as thoroughly as
possible the nature, severity, and precise anatomic
Coagulation disorders are characterized by sponta-
source of hemorrhage. In patients with a single obvious
neous hemorrhage and/or excessive bleeding after
site of external blood loss, ophthalmoscopy, digital
surgery or trauma. Hemorrhage into the central
anorectal examination, careful auscultation, and joint
nervous system (CNS) may cause acute onset of neuro-
palpation may identify additional sites of hemorrhage
logic dysfunction or sudden death. Thrombocytopenia
that would be suggestive of a systemic hemostatic defect.
(see Chapter 22), rather than coagulation factor defi-
ciency, is by far the most common cause of petechiae
in small animals. Hemorrhagic macules, papules, and
Radiographic Examination
ecchymoses are lesions most characteristic of primary or Radiography of the thorax and abdomen can detect
secondary vasculitic diseases and rarely are caused by fluid densities indicative of bleeding in pleural, peri-
coagulopathy. toneal, or retroperitoneal spaces. Intrapulmonary
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hemorrhage causes an alveolar pattern on thoracic in the vein, remove the first tube, and replace it with
films. Epistaxis, hematuria, and gastrointestinal hemor- a second evacuated tube containing siliceous earth
rhage may be difficult to differentiate as being signs of (Vacutainer, Becton-Dickinson) to withdraw a
local vessel trauma versus signs of systemic coagulation second 2-ml sample.
disorder. Contrast radiography, ultrasonography, and • Warm the evacuated tube to 37°C before sampling.
computed tomography (CT) scan can non-invasively • Immediately after blood collection, gently invert
identify erosive, infiltrative, or mass lesions causing the second tube several times to mix the blood with
vessel damage. CT scan is especially useful for evaluat- the siliceous activator then place it in a heating
ing the nasal cavity to identify focal lesions early in the block calibrated at 37°C.
disease process before they extend into the CNS. • After incubation for 45 seconds, remove the tube
from the block at 5- to 10-second intervals, gently
Quick Assessment Tests tilt it, and evaluate for clot formation.
Quick assessment tests (QATs) are useful for identifying • ACT is the time elapsed from sampling to clot
formation.
hemostatic defects and evaluating hemostatic function
prior to performing invasive procedures. Table 23-2 pre- • Normal range of canine ACT is 60 to 120 seconds;
feline range is 60 to 70 seconds.
sents additional diagnostic ruleouts and procedures,
based on results of QATs, for differentiating coagulation • ACT may be technically difficult to perform in cats
and small dogs.
disorders from other hemostatic defects. Table 23-3 lists
expected results of the following QATs for categories of • Sampling from the jugular vein is not recommended
in patients with severe hemorrhagic disorders
common coagulation disorders.
because iatrogenic hematoma formation and subse-
quent upper respiratory obstruction might occur.
Slide Estimate of Platelet Number
Thrombocytopenia can be ruled out if examination of Bleeding Time Tests
a stained blood film under oil immersion reveals at least
Bleeding time tests are in vivo measures of hemostatic
7 to 10 platelets per field for dogs and 10 to 15 platelets
function performed by making a standard wound and
per field for cats.
timing the interval to cessation of blood flow. These
tests should be performed only on patients with platelet
Activated Clotting Time counts greater than 100,000/ml because significant
Most of the common acquired and inherited coagula- thrombocytopenia prolongs bleeding time.
tion factor deficiencies can be detected by prolongation
of activated clotting time (ACT), a functional test of the Buccal Mucosa Bleeding Time Test
intrinsic clotting system.
• Procedure
• Procedure • Evert the lip, then hold it in place with gauze that
• Collect 2 ml of whole blood directly into a test tube, encircles the muzzle and causes the buccal veins to
maintain the needle (Vacutainer, Becton-Dickinson) engorge slightly.
CBC, complete blood count; QAT, quick assessment test; vWF:Ag, von Willebrand factor antigen.
W0422-Ch023.qxd 11/10/05 4:57 PM Page 260
A, abnormal; ACT, activated clotting time; BMBT, buccal mucosal bleeding time; DIC, disseminated
intravascular coagulation; N, normal; QAT, quick assessment test; TBT, toenail bleeding time; vWD, von
Willebrand disease.
aPTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation; FDP, fibrin or fibrinogen degradation product; PT, prothrombin time;
TCT, thrombin clotting time; vWF : Ag, von Willebrand factor antigen.
Reference ranges author’s laboratory 2004: Canine: aPTT (10–17 sec); PT (14–18 sec); TCT (5–9 sec); fibrinogen (147–479 mg/dl). Feline: aPTT (14–18 sec);
PT (18–22 sec); TCT (5–8 sec); fibrinogen (76–270 mg/dl). Both species: Bleeding time < 4 minutes; vWF : Ag > 50%; antithrombin > 75%; FDP < 5 mg/ml;
D-dimer < 250 ng/ml.
• Prothrombin time (PT) detects deficiencies in extrinsic platelet count do not detect abnormal vWF. Three sub-
and common pathways. types of vWD occur in dogs: Type 1 vWD is a mild to
• Fibrinogen concentration (mg/dl) is a quantitative moderate form characterized by low vWF concentration
measure of plasma fibrinogen. and normal vWF structure. Type 2 vWD causes a severe
• Thrombin clotting time (TCT) detects both deficiency bleeding diathesis, with low vWF concentration and
and dysfunction of fibrinogen. abnormal structure. Type 3 vWD is a severe form caused
• Based on the pattern of abnormalities detected in by a complete lack of vWF.
coagulation screening assays, individual clotting
factor analyses identify specific single or multiple
• Measurement of vWF antigen is a specific measure-
ment of plasma vWF concentration.
coagulation factor deficiencies.
• Patients with vWF below the normal range (estab-
lished at each testing laboratory) are considered at
Specific von Willebrand Factor Assays risk for carrying and/or expressing the vWD trait.
Specific tests must be performed to establish diagnosis • In addition to low or absent plasma vWF, affected
of vWD. Clotting time tests, coagulation assays, and individuals have prolonged in vivo bleeding time.
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*
Transfuse at a rate of 1–2 ml/min for cats and puppies, 3–6 ml/min for adult dogs.
†
Collected in citrate anticoagulant, transfused within 4–6 hours of collection.
‡
Frozen within 4–6 hours of collection, stored below -20∞C.
§
Supernatant remaining after thawing fresh frozen plasma for separation of cryoprecipitate.
¶
1 unit = cryoprecipitate produced from 200 ml of fresh frozen plasma.
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sensitize recipients and can be considered universal • Give transfusions for patients with severe anemia,
donors. pulmonary, or CNS hemorrhage at presentation (see
• Cross-species transfusions of any blood product are Table 23-6).
contraindicated because fatal anaphylaxis can result. • Initiate parenteral vitamin K1 as for warfarin
(2.2 mg/kg SC).
Nursing Care • Administer vitamin K1 at 1.1 mg/kg SC, q12h, until
the hematocrit value stabilizes and active bleeding
Nursing care practices that reduce hemorrhage include subsides.
the following: • Maintain oral vitamin K1 at 1.1 mg/kg PO, q12h, for
• Confinement to limit activity a total of 2 weeks.
• Feeding soft food • Taper the maintenance dose by one-half every 2
• Avoidance of neck leads and intramuscular injections weeks during treatment.
• Use of peripheral veins for sampling or intravenous • To prevent relapse, continue therapy for 4 to 6 weeks.
catheter placement
Do not give platelet inhibitory drugs, including sulfas ▼ Key Point Subcutaneous injection of vitamin K is
and nonsteroidal anti-inflammatory agents. the preferred parenteral route of administration
because intravenous vitamin K can cause anaphy-
laxis, and hematomas may form at intramuscular
Wound Management injection sites. Vitamin K3 (Synkayvite) is not effec-
Good management reduces the need for transfusion in tive for treating rodenticide toxicity because of its
some patients with coagulation disorders and mucosal delayed onset of action.
or cutaneous hemorrhage. The best treatment, for even
small wounds, is usually suture and/or pressure ban- Hormonal Therapy
dages. Application of tissue adhesive (Vetbond, 3M Co.)
to focal areas of bleeding also can limit local blood loss. Endocrine imbalance (hypercortisolism or hypocorti-
solism, hypothyroidism, and hyperestrogenism) can
Drug Therapy impair hemostasis and complicate the management of
acquired or hereditary platelet and coagulation disor-
Vitamin K Therapy ders. Diagnosis and correction of the endocrinopathy
Vitamin K therapy improves hemostasis only in vitamin can prevent or minimize transfusion requirements.
K-deficient patients. It often is initiated pending test
results, but maintenance of vitamin K therapy is not Thyroxin
indicated when diagnosis of inherited factor deficiency, Thyroid insufficiency (see Chapter 31) is common in
non-obstructive liver disease, vWD, or DIC is made. Anti- many breeds with the vWD trait, including Doberman
coagulant rodenticide toxicities are the most common pinscher, Bernese mountain dog, golden retriever, and
cause of vitamin K deficiency in dogs and cats. Vitamin standard poodle.
K reverses the anticoagulant effect of rodenticides over
a period of 24 to 48 hours from initiation of therapy. • Treat hypothyroid dogs with L-thyroxine at a standard
replacement dosage of 0.02 mg/kg PO q12–24h, with
post-pill monitoring to ensure attainment and main-
Treatment for Warfarin Toxicity
tenance of normal T4 values.
Warfarin is a relatively short-acting poison, and treat-
ment for a total of 1 week usually is adequate. Standard Desmopressin Acetate
treatment is as follows: Desmopressin acetate (DDAVP, USV Pharmaceutical), a
• Administer an initial dose of vitamin K1 (AquaMe- vasopressin analogue, has shown efficacy in transiently
phyton, Merck, Sharp, Dohme), 2.2 mg/kg subcuta- improving hemostasis in some dogs affected with type
neously (SC). 1 vWD.
• Follow with a dose of 1.1 mg/kg SC or by mouth
• Its activity probably is the result of release of vWF
(PO), q12h, until active bleeding subsides. from intracellular stores, and its effectiveness
• Continue therapy with an oral preparation (Mephy- depends on the patient’s ability to produce func-
ton) at the same twice-daily dosage for a total of 1 tional vWF protein.
week.
• Duration of action, after a dose of 1 mg/kg SC, is 3 to
4 hours; repeated dosage within 24 hours does not
Treatment for Long-acting Rodenticide Toxicity prolong response time. The onset of action is 15 to
The following steps are taken to treat toxicity from 30 minutes.
second-generation or long-acting rodenticides (dipha- • Desmopressin is often given as preoperative prophy-
cinone, pindone, bromadiolone, and brodifacoum): laxis to dogs with mild to moderate type 1 vWD.
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▼ Chapter
24 Systemic Immune-Mediated Diseases
Michael Stone
265
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Clinical Signs
• Historical findings may include weakness, collapse,
pale gums and/or discolored urine. Diagnosis
• Physical examination may reveal fever, pale or icteric • Perform a CBC with manual differential count,
gums, systolic heart murmur, hepatosplenomegaly platelet count, reticulocyte count, chemistry profile,
(sites of red cell phagocytosis), tachycardia and/or urinalysis, thoracic and abdominal radiographs, coag-
tachypnea. ulation profile, Coombs’ test and abdominal ultra-
sonography. Serology for Babesia canis and B. gibsoni
is indicated in endemic areas. Bone marrow cytology
PCV is indicated if the anemia is nonregenerative or if
infiltration with hemolytic histiocytes is suspected
(hemophagocytic syndrome).
• Cats should be tested for feline leukemia virus (FLV)
and feline immunodeficiency virus (FIV) as well as
PCV, NORMAL PCV, TOTAL PROTEIN hemoplasmosis (microscopic blood examination,
TOTAL PROTEIN polymerase chain reaction).
• Typical CBC findings include anemia, reticulocytosis,
- BLOOD LOSS spherocytosis, and leukocytosis with left shift. Hemol-
- IMHA - OVERHYDRAT ION
- NONREGENERATIVE ysis can cause a severe granulocytic response that
ANEMIA should not be confused with infection.
Figure 24-1. Classification of anemia. PCV, packed cell volume; • Coombs’ (direct antiglobulin) test results are usually,
IMHA, immune-mediated hemolytic anemia. but not invariably, positive, with both false-positive
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and false-negative results possible. Spontaneous ulin (0.5g/kg IV once daily for 3 days), cyclosporine
autoagglutination of red blood cells may occur when (Sandimmune 10 mg/kg IV or PO twice daily; Neoral
blood is placed on a slide, however, rouleaux forma- or Atopica 5 mg/kg PO twice daily), or methylpred-
tion must be excluded. Rouleaux tend to disperse nisolone sodium succinate pulse therapy (11 mg/kg
when one drop of anticoagulated blood is diluted in IV once daily for 3 days).
three to four drops of saline, whereas antibody- • Monitor blood counts daily until stabilization occurs,
mediated autoagglutination remains. then at least weekly until the PCV is >25%. Full doses
of immunosuppressive medications are administered
▼ Key Point Spherocytosis is present in most cases until the hematocrit normalizes, and then they are
of IMHA, and strongly supports the diagnosis of tapered as discussed in the Treatment section. It is
immune-mediated hemolytic anemia. not necessary to normalize the hematocrit to elimi-
nate clinical signs of disease, and in some cases it may
• Biochemistry may reveal increased liver enzymes be preferable to allow a low grade of anemia to persist
(thought to reflect hypoxic damage) and hyper- in order to decrease medications to tolerable levels.
bilirubinemia. The minimum length of treatment is 6 months.
• Coagulation profile results are often abnormal in
patients with severe hemolysis. Thromboembolism
and disseminated intravascular coagulation are Prognosis
recognized as common complications of hemolytic
anemia. ▼ Key Point Mild IMHA may respond well to treat-
• Consider thoracic radiographs to screen for evi- ment, whereas rapidly progressive cases are asso-
dence of neoplasia or pulmonary thromboembolism. ciated with a high rate of mortality.
Abdominal imaging commonly reveals mild hepa-
tosplenomegaly (representing hyperactivity of the The prognosis is guarded to fair for mild cases and very
mononuclear-phagocytic cell system), however, con- guarded for aggressively hemolytic cases. Many patients
sider biopsy for nodular irregularities or lym- are able to taper completely off medications, however,
phadenopathy. relapses occur unpredictably. Relapses may be associ-
ated with immune stimulation due to vaccination, infec-
Concurrent Diseases tion, or stress, and avoidance of these causes may be
prudent. Monitoring for control, recurrence, and infec-
IMHA may coexist with other immune-mediated tion should be performed at least 3 to 4 times per year
disease, the most common of which is immune-medi- for the life of the patient.
ated thrombocytopenia. Interpretation of test results
must be cautious, because low platelets may also indi-
cate systemic thrombosis or disseminated intravascular
coagulation. IMMUNE-MEDIATED THROMBOCYTOPENIA
*Number of cases with clinical finding/number of reported cases (from Stone, 2004).
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▼ Chapter
The spleen can be the site of primary disease, or it can complicated network within the organ. The muscular
be affected by disease elsewhere as an active or passive capsule and trabeculae in the dog and cat spleen
participant. The spleen has hematopoietic, reservoir, permits a several-fold increase in size in the relaxed
filtering, and immunologic functions. The spleen versus contracted state. The smooth muscle com-
may be affected by a variety of neoplastic and non- ponent allows contraction and distension of the
neoplastic disorders. It has an important role in spleen.
responding to a number of infectious diseases through
phagocytosis, antibody production, and modulation of White Pulp
hemoparasitic infections.
Splenic disorders usually are identified by a change • The white pulp consists of diffuse and nodular lym-
phoid and reticuloendothelial cells. Nodules are
in shape, size, and function of the spleen. Splenomegaly
usually less than 1 mm in diameter. White pulp lym-
is defined as a localized or diffuse splenic enlargement.
phocytes and reticuloendothelial cells are associated
Splenomegaly generally can be detected on physical,
with the splenic arterial circulation; forming periar-
radiographic, or ultrasonographic examination.
teriolar lymphatic sheaths (PALS) rich in T lympho-
cytes. B lymphocytes are located in nodules along
these sheaths and represent areas of B lymphocyte
ANATOMY AND HISTOLOGY proliferation and antibody production.
• The spleen is located in the left cranial abdomen, Marginal Zone
attached to the greater curvature of the stomach by
the greater omentum. Anatomically, the spleen con- • The marginal zone separates the white pulp from the
sists of a capsule, trabeculae, and parenchyma that red pulp. Arterial vessels terminate either in the mar-
include the white pulp, marginal zone, and red pulp. ginal zone or in the red pulp. The marginal zone is
The blood vessels of the spleen are the splenic artery, not well developed in the dog and cat. In other
a branch of the celiac artery, and the splenic vein, species, the marginal zone is functionally important
which drains into the gastrosplenic vein. Blood as a major area of circulatory interchange, cell-to-cell
enters the spleen through approximately 25 splenic interaction, and cell sorting. The marginal zone is
branches that enter the capsule through the hilus where the distribution of blood flow between slow
and then enter the trabeculae. The vessels branch and fast transit pathways is controlled. The slow path-
repeatedly, then leave the trabeculae and enter the ways permit prolonged exposure of blood cells and
white and red pulp. Blood from the venous sinuses particles to phagocytic cells.
coalesce into veins of the red pulp and merge to
become the trabecular veins. The canine spleen is Red Pulp
considered to be sinusoidal, while that in the cat is
non-sinusoidal. Blood cells in the canine spleen
• The red pulp consists of the venous sinuses, pulp
cords, and the terminal branches of the arterial
extravasate by moving between adjacent endothelial system. Together, these elements filter the blood. The
cells in order to enter the red pulp sinuses; however, periarterial lymphatic sheath is lost as arteries enter
in the feline spleen large gaps are present between the red pulp and is replaced by the periarteriolar
adjacent endothelial cells, permitting passage into macrophage sheath. Particles, cells, and plasma pass
the sinuses without deformation of cell shape. through gaps between endothelial cells in the termi-
nal arterial capillaries. The red pulp culls abnormal
Capsule and Trabeculae blood cells and processes particulate antigens for
• A capsule rich in elastic and smooth muscle fibers sur- presentation to the white pulp where an immune
rounds the spleen. Fibromuscular trabeculae form a response is mounted.
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• Splenic rupture also can lead to splenosis, the dis- of disorders that may be associated with generalized
seminated development of “daughter” spleens splenomegaly is provided in Table 25-2 (see the
throughout the abdominal cavity. various chapters in this book on infectious diseases for
details concerning these disorders). The various types
Abscess can be classified based on the primary type of cellular
infiltrate (suppurative, necrotizing, eosinophilic,
• Splenic abscesses can form from hematogenous lymphoplasmacytic, granulomatous, or pyogranulo-
spread of microorganisms but are rare in the dog and
matous splenitis). Different etiologic agents are
cat. The most common isolate in the dog is Staphylo-
associated with the different cellular infiltrates.
coccus. Splenic abscess has been associated with
cholangiohepatitis in cats.
Hyperplastic Splenomegaly
Generalized Splenomegaly • The spleen commonly reacts to blood-borne antigens
and red blood cell destruction with hyperplasia of the
Generalized splenomegaly refers to diffuse enlarge-
reticuloendothelial and lymphoid cells.
ment of the spleen. Four major categories of general-
ized splenomegaly exist: inflammatory and infectious,
• Hyperplastic splenomegaly is common in dogs with
immune-mediated disease including immune-
hyperplastic, congestive, and infiltrative.
mediated hemolytic anemia or thrombocytopenia.
Inflammatory and Infectious Disease • It commonly occurs in dogs with subacute bacterial
endocarditis and chronic bacteremic disorders such
• Inflammatory changes within the spleen usually result as discospondylitis or brucellosis.
in diffuse enlargement. A wide range of infectious dis- • It has been seen in association with systemic lupus
eases can result in diffuse splenomegaly. A partial list erythematosus.
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• The same occurs in certain other hemolytic disor- • Hypereosinophilic syndrome of cats can lead to
ders, including hemophagocytic syndrome, drug- infiltration of the spleen with mature eosinophils.
induced hemolysis, pyruvate kinase deficiency This syndrome is characterized by peripheral blood
anemia, phosphofructokinase deficiency anemia, eosinophilia, bone marrow hyperplasia of eosinophil
familial non-spherocytic hemolysis in poodles, Heinz precursors, and multiple organ infiltration by mature
body hemolysis, and Mycoplasma haemofelis infection eosinophils.
(hemobartonellosis). • Splenic amyloidosis can cause splenomegaly but is
rare.
Congestive Splenomegaly
• Splenic enlargement resulting from congestion can Hypersplenism
occur through a number of different mechanisms. Hypersplenism is characterized by the following:
Splenic distension occurs as a result of smooth
muscle relaxation in the splenic capsule and trabec- • Cytopenias
ulae. Phenothiazine tranquilizers and barbiturates • Bone marrow hyperplasia of the affected cell line or
a normocellular bone marrow
increase blood pooling. Pooling of blood in an
enlarged spleen may account for up to 30% of the • Splenomegaly
total blood volume. Consider these changes when • Resolution of the cytopenia in response to
splenectomy
evaluating red blood cell parameters from anes-
thetized or tranquilized patients. Hypersplenism results mainly from the filtering and
• Portal hypertension also can lead to congestive phagocytic functions of the spleen.
splenomegaly; however, splenic congestion secondary
to portal hypertension does not appear to be a • Primary hypersplenism occurs when the splenic dys-
function is idiopathic.
common cause of congestive splenomegaly in dogs
and cats. Right-sided congestive heart failure, caudal
• Secondary hypersplenism occurs as the result of an
underlying disease process that has resulted in
vena cava obstruction (e.g., congenital anomalies,
splenomegaly.
neoplasia, and heartworm disease), and intrahepatic
obstruction may cause splenic congestion. Ultra-
sonography usually reveals markedly distended
Hyposplenism
splenic, portal, and/or hepatic veins. • Hyposplenism, or decreased splenic function, can
• Splenic torsion, either isolated or associated with occur secondary to a wide range of disease processes.
gastric dilatation-volvulus syndrome, commonly A number of hematologic changes are recognized in
results in marked splenomegaly due to congestion. A association with hyposplenism (Table 25-3). These
high percentage of dogs with splenic torsion have changes are also seen in splenectomized animals.
hemoglobinuria. The treatment of choice for dogs
with splenic torsion is splenectomy (see the descrip-
tion in this chapter). CLINICAL SIGNS
• EMH is common in dogs but by itself rarely results in Regenerative anemia Target cells
detectable splenomegaly. EMH can be associated with Neutropenia Acanthocytes
neoplastic infiltrations and also has been observed in Thrombocytopenia Howell-Jolly bodies
Bicytopenias Nucleated red blood cells
dogs with immune-mediated hemolysis, immune- Pancytopenia Reticulocytosis
mediated thrombocytopenia, bone marrow hypopla- Thrombocytosis
sia, pyometra, and infectious diseases.
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Table 25-4. TREATMENT PROTOCOLS ▼ Key Point Generalized splenomegaly often is not a
FOR HEMANGIOSARCOMA surgical disease. Attempt to diagnose and treat
the underlying disorder before performing a
VAC Protocol (21-Day Cycle)
splenectomy.
Doxorubicin*‡: 30 mg/m2 (or 1 mg/kg if <10 kg), IV, day 1
Vincristine‡: 0.75 mg/m2, IV, days 8, 15
Cyclophosphamide: 200–300 mg/m2, day 10 Technique
Sulfa-trimethoprim: 15 mg/kg, q12h
Partial Splenectomy
AC Protocol (21-Day Cycle)
Doxorubicin: 30 mg/m2 (or 1 mg/kg if <10 kg), IV, day 1 1. Prepare the ventral abdomen for aseptic surgery.
Cyclophosphamide†: 200–300 mg/m2, day 10 2. Make a ventral midline abdominal incision from
Sulfa-trimethoprim: 15 mg/kg, q12h
the xiphoid to 2 to 4 cm cranial to the pubis or
Doxorubicin (Monotherapy) more caudally if necessary.
Doxorubicin: 30 mg/m2 (or 1 mg/kg if <10 kg), IV, q21 days
3. Place a Balfour retractor to expose the abdominal
*
viscera.
Doxorubicin is potentially cardiotoxic. Perform cardiac evaluation prior
to treatment and monitor throughout treatment. The recommended
4. Examine the spleen and other abdominal organs
maximum cumulative dose is 180–240 mg/m2 or 6–8 doses, but it must be for evidence of abnormalities.
applied to each patient individually. 5. Gently pull the spleen out of the abdominal cavity.
†
Cyclophosphamide can cause hemorrhagic cystitis. If it occurs, discontinue 6. Doubly ligate the splenic branches of the splenic
cyclophosphamide immediately and usually limit therapy to oral antibiotics
and corticosteroids. Resolution of signs usually occurs within 8 weeks.
artery and vein to the affected area of the spleen
‡
Evaluate a complete blood count before each doxorubicin or vincristine with absorbable suture. Divide the vessels among
treatment to check for bone marrow suppression. Monitor patient progress the ligatures. Alternatively, use the ligate-and-divide
every two cycles (radiographs of thorax, abdominal radiographs or ultra- stapling instrument (LDS).
sound, and echocardiography if indicated). Allow completion of two to 7. Place two non-crushing clamps (e.g., Doyen) on the
three cycles of treatment before making a decision about response to
therapy.
spleen between the healthy and the diseased areas.
AC, Adriamycin (doxorubicin)-cyclophosphamide; VAC, vincristine- 8. Divide between the clamps and remove the splenic
Adriamycin (doxorubicin)-cyclophosphamide. tissue.
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9. Oversew the splenic capsule on the remaining vessels before ligation. Include two or three of the
spleen (3-0 or 4-0 polydioxanone [PDS], simple vessels in each clamp. Divide the vessels between
continuous suture). each pair of clamps and then place the next pair of
10. Alternatively, use the thoraco-abdominal stapler clamps (see Fig. 25-1). After all vessels have been
(TA) (55- or 90-mm cartridge) to staple the splenic clamped and divided, remove the spleen. Ligate all
parenchyma prior to excision. vessels with absorbable sutures.
11. Check vessels and splenic incision for bleeding. 9. Alternatively, use the LDS to ligate and divide the
Close the abdomen routinely. vessels.
10. When splenic torsion is present, do not untwist the
Total Splenectomy spleen because release of tissue breakdown prod-
ucts and bacteria may result. Ligate the entire vas-
1. to 5. These steps are the same as for partial
cular pedicle with two or three absorbable ligatures.
splenectomy.
Consider placing a transfixing ligature in large
6. Doubly ligate all the splenic branches of the splenic
dogs. Place two clamps across the vascular pedicle,
artery and vein with absorbable suture. Ligate the
divide between them, and remove the spleen.
vessels close to the hilus of the spleen. Usually, two
Remove the remaining clamp and check the
or three vessels can be included in each ligature. If
pedicle for hemorrhage.
possible, preserve the left gastroepiploic artery and
11. Check the vessels for hemorrhage. Close the
vein (Fig. 25-1); this may not be possible when
abdomen in a routine fashion.
removing large splenic tumors.
7. Divide each vessel among the ligatures and remove
the spleen.
8. An alternative and more rapid procedure for total Postoperative Care and Complications
splenectomy is to place vascular clamps across the • The gross appearance of the spleen cannot be used
to differentiate hematoma, hemangioma, and
hemangiosarcoma. A histopathologic diagnosis is
crucial for determining postoperative treatment and
prognosis.
Left • Postsplenectomy sepsis is a serious complication in
gastroepiploic humans and can be fatal. Although this is a rare com-
artery and vein plication in dogs and cats, partial splenectomy or
splenic biopsy may be advisable in certain animals.
Partial splenectomy is a viable option for those
animals with localized masses unless malignancy is
suspected.
• Other possible complications of splenectomy include
exacerbation of certain diseases such as hemobar-
tonellosis and babesiosis in animals that are latent
carriers and cytopenia(s) in patients with EMH
secondary to a primary bone marrow disorder.
▼ Chapter
26 Principles of Oncology
Stephen D. Gilson / Rodney L. Page / Rance M. Gamblin
Cancer management in animals has evolved consider- size, consistency, and fixation to adjacent tissues. To
ably over the past 3 decades as the result of several sig- complete the clinical evaluation, a list of differential
nificant factors. Improved health care of animals has diagnoses is made and a diagnostic and staging plan is
increased the age distribution of pets and hence their determined.
likelihood of developing cancer; clients are more aware
of aggressive treatment choices; and there have been Client Counseling
significant improvements in treatment success. There
remains some controversy and confusion over the best A diagnosis of cancer can evoke considerable emotional
course of treatment for many tumor types, and more response from owners. For many clients, the diagnosis
studies are needed to provide the necessary data. implies pain, discomfort, and impending death of their
However, clinicians can use a generic framework for pet. Proper counseling on the part of the veterinarian
evaluation and treatment management of many tumor should include the following:
types. This chapter provides an outline useful for clini- • Listen to the needs of the client and mutually deter-
cal management of an animal with cancer. mine a set of realistic goals for treatment.
• Explain treatment procedures, discussing risks, ben-
efits, toxicity, and costs. It is helpful to provide written
INITIAL CLINICAL PRESENTATION material for home review of information.
• Provide a realistic and unbiased view of all treatment
Signalment options available and the animal’s likely prognosis.
Many neoplasms more commonly affect animals of a • Beware of the tendency for clinicians untrained in
certain age, sex, or breed, and such knowledge often oncology to prematurely recommend euthanasia.
aids diagnosis. Table 26-1 is a partial list of specific • Consider consultation with or referral to a specialist
breeds and characteristics of dogs and cats predisposed when appropriate.
to certain types of neoplasia.
History DIAGNOSIS
The onset and duration of a mass, its growth rate, the Laboratory Evaluation
presence of other masses, signs of paraneoplastic syn-
dromes, and knowledge of prior treatments further Assess general health status to identify concurrent
help narrow diagnostic and treatment options and disease or paraneoplastic syndromes that may adversely
define the behavioral characteristics of a neoplasm. affect prognosis and limit or alter therapy. After a thor-
ough physical examination, perform screening labora-
Physical Examination tory evaluations, including a complete blood count,
serum biochemistry panel, and urinalysis. Perform
Examination is used to define the extent of tumor other special laboratory tests as indicated to aid diag-
burden and identify concurrent diseases that may limit nosis (e.g., feline leukemia virus, feline immunodefi-
treatment or affect survival. Tumor characteristics such ciency virus, bone marrow aspirate, adrenal or thyroid
as size (measure with calipers to determine objectively), function tests, etc.).
location (e.g., oral melanoma is more malignant than
cutaneous melanoma), invasiveness (is mass fixed to
adjacent tissue), and presence of ulceration or necrosis of Diagnostic Imaging
the tumor is important to determine tumor behavior • Obtain survey radiographs to detect metastases (on
and to plan adequately an appropriate biopsy and treat- the thorax, abdomen, or skeleton), to evaluate ortho-
ment regimen. Regional lymph nodes are evaluated for pedic soundness before amputation or limb-sparing
283
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Surgery
Surgery is primarily useful for localized neoplasms. In
select cases, en bloc dissection of regional lymph nodes
and the primary mass is used for treatment of regional
disease, and surgery can be useful for treatment of
metastatic disease that is slow growing or causing clini-
cal morbidity.
Applications
Surgery is the most widely applied modality for control
Figure 26-1. Surgical options for removal of a neoplasm. Wide
of localized cancer. Surgery can also be used for pre- excision or a more radical, compartmental resection is recommended
vention (e.g., ovariohysterectomy before 2.5 years of age for tumors that are not superficial or are infiltrative. Additional
for mammary cancer in dogs), diagnosis (see section on therapy may be indicated from histologic evaluation of tumor speci-
Biopsy), staging (see section on Staging), and treatment men. (Reprinted with permission from Gilson SD, Stone EA:
Compend Contin Educ Pract Vet 12:1047, 1990.)
(cure or palliation). Surgery also is used for treatment
of oncologic emergencies (e.g., obstruction or perfora-
tion) and for complications related to chemotherapy or
radiotherapy (e.g., drug extravasation, radionecrosis).
• Fulgurate or electrocoagulate any exposed tumor
Principles of Surgery surfaces.
A special technique is used to prevent surgical spread • When en bloc resection is performed, maintain ade-
of cancer cells and to ensure complete tumor resection. quate margins and dissect from the most peripheral
affected lymph node toward the primary mass.
▼ Key Point Aggressive initial surgical management • When postoperative radiotherapy is used, all surgi-
of neoplasia may be the most important principle cally exposed tissues plus a margin of normal tissue
for improved cancer control. The best chance for are irradiated. Position tissue grafts, flaps, and drains
complete resection and cure is with the first to minimize treatment fields. Use of hemoclips or
surgery. other metallic markers are helpful in radiographi-
cally establishing the margins of manipulated tissues
• Decide resection margins in advance of the surgery for radiation treatment planning.
based on tumor type, expected behavior, extent of • Submit all resected specimens for histologic analysis
local invasion, and the barrier provided by sur- and evaluation of margins.
rounding tissues (Fig. 26-1). Vascular-poor, collagen-
rich tissue (e.g., cartilage and fascia) are most ▼ Key Point A pseudocapsule made up of com-
impermeable to tumor invasion. Other tissues (e.g., pressed cancer cells surrounds most tumors.
fat and subcutaneous tissue) provide less of a barrier. Although seemingly a convenient plane for dis-
• Resect all neoplastic tissue; if necessary, use skin flaps section, it is not a true capsule and provides no
or grafts to close large defects (see Chapter 57). If barrier to tumor invasion. A properly excised
uncertain about achieving complete resection or tumor is encased completely in an envelope of
wound closure, consider referral to a specialist. normal tissue.
• Protect healthy tissues from tumor cell contamina-
If histopathology of the excised tumor reveals incom-
tion by use of barrier drapes and laparotomy sponges.
Employ glove, instrument, and drape changes as nec- plete excision, promptly plan and perform a re-excision
essary to prevent contamination of normal tissue with if possible.
cancer cells. Copious lavage of surface wounds also
may reduce the likelihood of residual tumor. Sources of Failure
• Minimize tumor manipulation. Handle tumors by Treatment failures result from surgery-related morbid-
placing stay sutures in normal margin tissues. ity and mortality, local or regional tumor recurrence,
• Ligate vascular and lymphatic vessels early, and always and tumor seeding or metastatic disease. Most failures
before severing, to prevent shedding of tumor can be minimized by use of proper surgical technique
emboli. and appropriate patient selection.
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Alkylating Agents
Cyclophosphamide Lymphoproliferative 50 mg/m2 PO q48 hr BM, GI, hemorrhagic cystitis
(Cytoxan; Mead-Johnson) disorders, mast cell tumors, 50 mg/m2 PO q24h for
hemangiosarcoma, 4d weekly
miscellaneous carcinomas 100–300 mg/m2 IV q3wk
Chlorambucil (Leukeran; Lymphoproliferative disease, 2–4 mg/m2 q24–48 h BM
Burroughs-Wellcome) macroglobulinemia
Melphalan (Alkeran; Multiple myeloma 2–4 mg/m2 PO q24–48 h BM
Burroughs-Wellcome)
Lomustine/CCNU Lymphomas, mast cell tumors 60–90 mg/m2 PO q21–28 d BM, GI, Liver
Cisplatin (Platinol; Bristol) Osteosarcoma, transitional cell 50–70 mg/m2 IV q3wk BM, GI, renal; DO NOT
carcinoma, squamous cell (vigorous hydration) USE IN CATS!
carcinoma
Carboplatin (Paraplatin; Similar to cisplatin 250–300 mg/m2 IV q3wk BM, GI
Bristol)
Antimetabolites
Methotrexate (Lederle) Lymphoproliferative disorders 2.5 mg/m2 PO q24–48 h BM, GI, renal
15–20 mg/m2 IV q3wk
5-Fluorouracil (Roche) Gastrointestinal and hepatic 150–200 mg/m2 IV q7d BM, GI, CNS; DO NOT
carcinoma USE IN CATS!
Cytosine Arabinoside Lymphoproliferative disorders, 100 mg/m2 IV or SC for BM, GI
(Cytosar-U; Upjohn) myeloproliferative disorders 4 days q3–4wk
Plant Alkaloids
Vincristine (Oncovin; Eli Lymphoproliferative disorders, 0.5–0.7 mg/m2 IV q7d GI, vesicant
Lilly) sarcomas, carcinomas
Vinblastine (Velban; Eli Mast cell tumors 2 mg/m2 IV q7–14d GI, BM, vesicant
Lilly)
Antibiotics
Doxorubicin (Adriamycin; Lymphoproliferative disorders, 20–25 mg/m2 IV q3wk for BM, GI, cardiac; severe
Adria Labs) soft tissue sarcoma, carcinomas dogs £l0 kg and cats; vesicant; urticaria, alopecia
30 mg/m2 IV q3wk for dogs
>10 kg; maximum cumulative
dose = 180–240 mg/m2
Mitoxantrone (Novantrone; Lymphoproliferative disorders 4–6 mg/m2 IV q3wk BM
Lederle)
Hormones
Prednisone Lymphoproliferative disorders, 20–50 mg/m2 q24–48h Iatrogenic Cushing’s
mast cell tumors, brain tumors syndrome
Miscellaneous
l-Asparaginase (Elspar; Lymphoproliferative disorders 10,000 IU/m2 IM, SC Anaphylaxis
Merck, Sharp & Dohme)
BM, bone marrow; CNS, central nervous system; GI, gastrointestinal; IM, intramuscularly; IP, intraperitoneally; IV, intravenously; m2, body surface area in square
meters (see Table 26-4); PO, per os; SC, subcutaneously;
*Specific values can be calculated using the following formula: Principles of Chemotherapy
(k) ¥ (Wt)2/3
Body surface area (m2) =
104 • Use only drugs with documented activity against the
where (k) = 10.1 for dogs and 10.0 for cats specific tumor type.
• Administer all drugs at maximum tolerated doses and
intervals.
• Some protocols are administered in two phases: an
initial phase of intensive therapy (induction), followed
Table 26-6. PRACTICAL RECOMMENDATIONS by a period of less frequent drug administration
FOR SAFE HANDLING OF CYTOTOXIC (maintenance).
ANTINEOPLASTIC AGENTS • Combination chemotherapy using agents with differ-
ent mechanisms of action and no overlap in toxicity
1. Designate a specific hospital location for drug handling results in enhanced cancer cell destruction, reduced
(reconstitution, preparation, disposal).
2. Use an absorbent, disposable, plastic-backed sheet to cover work
induction of drug resistance, and reduced toxicity.
surface; change it regularly. • Continue chemotherapy past the time of complete
3. Wear latex, non-powdered, non-permeable gloves when handling remission because a microscopic tumor remains after
all cytotoxic agents. the clinically detectable tumor has resolved.
4. Reduce exposed skin surfaces by wearing laboratory coats,
gowns, and other protective wear. Wear particulate respiratory
filtration masks to prevent inhalation of aerosolized drug Sources of Failure
particles.
5. Reconstitute all materials carefully and safely, avoiding potential Treatment failures result from excessive chemotherapy-
contamination of materials or aerosolization. related side effects (e.g., renal, hepatic, or myocardial
6. Clean reconstituted material of any contamination and properly toxicity or sepsis) or from progressive tumor growth
label concentration and date. because of intrinsic or acquired drug resistance. Intrin-
7. Dispose of contaminated materials in leak-proof, puncture-
resistant containers. Proper disposal by health regulatory officials
sic resistance results from molecular or biological adap-
is necessary. tations or mutations within cancer cells that provide
8. Wash hands thoroughly after removing gloves. mechanisms for circumventing drug effects. The larger
the tumor is, the more likely the existence of resistant
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cells. Clinically detectable tumors are likely to have mul- currently are being tested. Early results indicate that
tiple resistant cell lines. photodynamic therapy may be useful for treatment of
localized solid tumors and in palliation of tumor-asso-
Intrinsic Drug Resistance ciated signs (esophageal or urethral obstruction, etc.).
Causes of intrinsic resistance include the following:
• Inherent genetic mechanisms of cell protection Post-Treatment Monitoring
• Sanctuary sites (site where cells are protected, such Patient monitoring after therapy is important to assess
as the CNS) toxicity, adjust subsequent treatment, and monitor
• Tumor cell dormancy, or insensitivity to specific tumor response.
action of a drug
• Insufficient drug delivery • Reevaluate animals at regular intervals
• Tailor follow-up schedule and appropriate diagnostic
Acquired Drug Resistance tests to each patient and the particular stage and
expected behavior of the tumor.
Acquired resistance arises from selection pressure • The goal of follow-up evaluation is to detect tumor
induced by sublethal drug doses. It occurs when cancer recurrence or metastasis at the earliest possible time
cells survive long enough to do the following: and to maximize the response to any additional alter-
• Develop alternate metabolic pathways nate therapies.
• Change drug transport mechanisms
• Initiate cellular repair
• Inhibit drug activation ADJUNCT CLINICAL CONSIDERATIONS
Pleiotropic (Multiple) Drug Resistance Nutritional Management
Resistance can develop to a single drug, a group of
Many animals with cancer have alterations of metabo-
drugs, or many classes of drugs (pleiotropic resistance).
lism that result in malnutrition. When severe, these
Pleiotropic resistance is associated most commonly with
alterations result in the clinical syndrome of cancer
the anthracyclines and vinca alkaloids.
cachexia. Malnutrition impairs the immune system,
inhibits wound healing and normal cell repair, and
Miscellaneous Therapy increases treatment morbidity and mortality.
Hyperthermia • Factors contributing to malnutrition include the
Heat is an effective adjunct therapy because it enhances following:
the cytotoxic effect of radiation and many chemother- • Anorexia
apy agents. Hyperthermia is induced locally by ultra- • Decreased nutrient intake
sound or radio waves or implemented as whole-body • Metabolic or digestive abnormalities that cause
hyperthermia induced by a humidified chamber or inefficient or inappropriate use of nutrients
radiant heat device. • Treatment-related factors such as therapy-induced
nausea and vomiting
Immunotherapy • Proposed mechanisms of cachexia include:
• Tumor-produced anorexigenic substances
Immunotherapy has emerged with renewed potential. • Alterations in brain neurotransmitter and anabolic
Because neoplastic cells may be immunologically dif- hormone function
ferent from healthy cells, selective or nonselective • Treatment is directed toward early elimination of the
induction of the host immune system by various bio- cachexia syndrome (by elimination of neoplasia) and
logic response modifiers (e.g., bacterial agents, inter- supportive care to minimize its effects during the
ferons, monoclonal antibodies, lymphokines, and interim. Nutritional support is provided by enteral or
tumor vaccines) may enhance elimination of tumor parenteral feeding (see Chapter 3), and should be
cells. Immunotherapy appears to have the greatest provided when patients do not eat for more than 5
potential as an adjunct to other therapies to eliminate days or have more than 10% acute loss of body
microscopic residual tumor. weight. Laboratory parameters indicative of malnu-
trition include hypoalbuminemia, lymphopenia, and
Photodynamic Therapy anemia.
Many tumor cells selectively accumulate certain system-
ically administered photoactive chemicals. Tumors then Pain Management
are exposed to light of selected wavelengths (laser Clinical management of pain in cancer patients is an
light), and the photoactive substances become cyto- important aspect of care to reduce morbidity and
toxic. Various photoactive drugs and light sources improve the quality of life.
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• Pain can be: sia is the last humane “treatment” they can give to their
• Acute or chronic pet. Review the details of the euthanasia process in
• Treatment- or tumor-related advance with owners and options for them to remain
• Visceral, somatic, or neurogenic in origin present or not. For clients having difficulty coping,
• Pain can contribute significantly to development of provide assistance to help them find bereavement coun-
inappetence, weight loss, reduced mobility, depres- seling. Condolence cards, telephone calls, or other
sion, and poor interaction with the owner. Presence forms of communication afterward are useful to provide
of pain is determined by changes, often subtle, in closure. A positive experience with the euthanasia
normal behavior patterns (see Chapter 6). process often leaves clients with a positive feeling about
• The severity is determined and a treatment protocol the whole cancer treatment process.
implemented to provide adequate analgesia with
minimal sedation and other side effects. Prevention
or early treatment of pain is more effective than
trying to resolve established significant or chronic SUPPLEMENTAL READING
pain signs. Therapy is by use of local or regional anes-
Chun R, Garrett LD, MacEwen EG: Cancer Chemotherapy. In
thesia, or with systemic treatment using transdermal Withrow SJ, MacEwen EG, eds.: Small Animal Clinical Oncology
delivery of narcotic-based pain medication, or par- 3rd ed. Philadelphia: WB Saunders, 2001, pp 92–118.
enterally administered nonsteroidal anti-inflamma- Gilson SD: Surgical oncology. Vet Clin North Am Small Anim Pract
tory agents, and narcotics (see Chapter 6). Continual 25:1, 1995.
reassessment and modification of therapy is Hogge GS, MacEwen EG: Immunology and Biologic Therapy of
Cancer. In Withrow SJ, MacEwen EG, eds.: Small Animal Clinical
necessary. Oncology 3rd ed. Philadelphia: WB Saunders, 2001, pp 138–
168.
Euthanasia LaRue SM, Gillette EL: Radiation Therapy. In Withrow SJ, MacEwen
EG, eds.: Small Animal Clinical Oncology, 3rd ed. Philadelphia: WB
When treatment options fail and an animal’s disease is Saunders, 2001, pp 119–137.
progressing, consideration of euthanasia is appropriate. Swanson LV: Potential hazards associated with low dose exposure to
Encourage owners in advance to establish limits for antineoplastic agents: Part I. Compend Contin Educ Pract Vet
10:293, 1988.
their pet’s level of deterioration. When the decision for Swanson LV: Potential hazards associated with low dose exposure to
euthanasia is reached by an owner, it should be sup- antineoplastic agents: Part II. Compend Contin Educ Pract Vet
ported by the veterinarian. For many owners, euthana- 10:615, 1988.
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▼ Chapter
27 Lymphoid Neoplasia
David M. Vail
The lymphoproliferative disorders presented here are lymphomas. Conclusive evidence of a viral etiology has
characterized by neoplasia involving cells or cell lines of not been established in the dog.
lymphoid origin, including lymphoma, lymphoid leuke-
mia, multiple myeloma, and plasmacytoma. Because of Genetic
differences in diagnosis, therapy, and prognosis among
A genetic predisposition for the development of certain
these conditions, they are discussed here as separate
forms of lymphoma may exist.
entities.
Carcinogenic Agents
Exposure to chemical, physical, and viral carcinogens
LYMPHOMA may play a role in the development of many tumor
types. Weak associations with herbicide use and expo-
Lymphoma (lymphosarcoma) is defined as a lymphoid sure to high tension wires have been reported.
neoplasm primarily affecting lymph nodes or other
solid visceral organs such as the liver or spleen. It is
the most common of the lymphoproliferative disorders Classification and Clinical Signs
in small animals. Middle-aged to older dogs primarily Traditionally, lymphoma is classified based on anatomic
are affected without sex predilection. Although site. Clinical signs vary with the sites involved. In cats,
lymphoma can occur in any purebred or mixed-breed the frequency of anatomic forms associated with FeLV
dog, it may be more prevalent in golden retrievers, antigenemia (i.e., mediastinal and multicentric forms)
German shepherds, boxers, poodles, bassets, and Saint has declined along with the declining frequency of
Bernards. FeLV-associated lymphomas. Whereas these sites made
No breed predilection exists for cats; however, up the bulk of cases observed in cats before 1985, they
several reports have observed a 1.5:1 male-to-female are now in the minority. Currently, the alimentary form,
ratio. Affected cats that are feline leukemia virus (FeLV) which only rarely is associated with FeLV antigenemia,
antigenemic tend to be younger (median age 3–5 years) makes up the bulk of lymphomas in cats. Other less
than FeLV-negative cats (median age 7–10 years). common forms occurring in cats include renal, hepatic,
and miscellaneous extranodal sites.
Etiology World Health Organization (WHO) clinical staging
of lymphoma also can be used to classify the extent of
Retrovirus the disease (Table 27-1).
A retroviral etiology for certain forms of lymphoma has
been demonstrated in a variety of species, including Multicentric Lymphoma
cats, chickens, and humans. In the cat, evidence exists This is the most common form in the dog. It usually
for direct induction of lymphoma by FeLV and indirect manifests as increased lymph node size with non-
induction by the feline immunodeficiency virus (FIV). specific signs such as inappetence, weight loss, polyuria
Before 1985, most cats with lymphoma (>70%) were or polydipsia, and lethargy. Hepatic and splenic involve-
FeLV antigenemic. Since then, the general availability ment, manifested as diffuse organ enlargement, also is
of FeLV vaccination and testing has increased and FeLV- common in multicentric lymphoma.
positive cats currently make up a minority of lymphoma
cases (<25%). This shift is likely due directly to vacci-
nation and to FeLV antigen testing before vaccination, Alimentary Lymphoma
which allowed separation of potentially infective cats This type of lymphoma often is associated with vomit-
from the susceptible population. In either situation, the ing, diarrhea, and nonspecific signs such as weight loss
result is a reduction in the number of FeLV-associated and lethargy.
292
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• DDx for mediastinal lymphoma includes ectopic thyroid chemotherapy protocols, although often more effec-
tumors, heart base tumors, thymoma, and pulmonary tive, are also more expensive.
lymphomatoid granulomatosis. • Time: Time commitments can be more important to
• DDx for cutaneous lymphoma includes pyoderma, some clients than the cost of the therapy. In general,
immune-mediated and parasitic skin disorders, and the more elaborate the protocol, the more time
other neoplastic dermatopathies. invested in the care of the patient.
• Efficacy: As a general rule, the more complex the
Treatment protocol, the longer the duration of remission and
of survival time. Conversely, single-agent chemother-
▼ Key Point Lymphoma is the most chemores- apy is generally less effective than combination
ponsive malignancy encountered in veterinary chemotherapy.
medicine. • Toxicity: The toxicity of most protocols is designed to
be acceptable to the general public; however, the
Most dogs and cats with lymphoma have multicentric potential risks and benefits of each protocol must be
systemic disease and therefore require systemic discussed with each owner. Complex protocols
chemotherapy to improve quality of life and survival increase the potential for toxicity and increase the
time. Untreated, dogs and cats with malignant lym- importance of client education.
phoma live an average of only 4 to 6 weeks once a • Experience of the attending clinician: The successful
diagnosis has been established. With standard-of-care application of any chemotherapy treatment requires
combination chemotherapy, 75% to 90% of dogs and experience and confidence because the effective
60% to 70% of cats go into remission and survive a dosage is very near the toxic dosage.
median of 7 (cats) to 12 (dogs) months with an excel-
lent quality of life. With most combination protocols,
approximately 25% of patients survive 2 years or more. Induction Chemotherapy Protocols
Cures are still uncommon. Cost is within the financial Several chemotherapy protocols for dogs and cats
reach of many clients, especially with the availability of have been reflecting that cures are still uncommon,
generic brands of cytotoxic drugs. and several investigators are continually attempting to
Many combination chemotherapy protocols have an improve on previous outcomes. Listing dosage and
“induction” period designed to place a dog or cat into timing of all available protocols is beyond the scope of
a remission, followed by a less intensive “maintenance” this chapter; therefore, I have chosen to elaborate on
treatment period intended to sustain a remission. three protocols of varying cost, time commitment,
Current data suggest that intensive “up front” therapy and effectiveness: the University of Wisconsin-Madison
to induce a sound remission is as effective as less intense CHOP-based combination protocol, the single-agent
protocols with continuously administered maintenance doxorubicin protocol, and single-agent prednisone
therapy for most cats and dogs (see below). therapy.
Complete remission is more difficult to achieve in Dosages of chemotherapeutic agents are based on
cats; however, if a remission can be achieved and main- body surface area expressed in square meters (m2).
tained for approximately 6 months, cats are more likely Refer to Chapter 26, Table 26-5, for conversion of body
to experience prolonged survivals compared with dogs. weight to body surface area.
Cats are generally more resistant to the adverse effects
of chemotherapy than dogs. The exception to this rule
University of Wisconsin-Madison Short Protocol
is cats who receive doxorubicin as part of their proto-
col. Most dogs tolerate doxorubicin every 21 days at a Most combination protocols are variations on the so-
dosage of 30 mg/m2; however, cats appear to be more called CHOP-based protocols (C = cyclophosphamide;
sensitive to the drug and therefore are treated at a H = hydroxydaunorubicin [doxorubicin]; O = oncovinR
dosage of 25 mg/m2 (or 1 mg/kg) given every 21 days. [vincristine]; P = prednisone). The University of
Cats with preexisting azotemia should not receive Wisconsin-Madison protocol is one such protocol
doxorubicin. (Table 27-2). This protocol is complex but gratifying
because the majority of dogs and cats achieve remissions
Criteria for Choosing Chemotherapy and survive for medians of 12 and 7 months, respec-
tively. This is a no-maintenance protocol, and dogs
When choosing a chemotherapy protocol, several
and cats are off all medication after 19 weeks. Notice
points must be discussed with the companion animal
the absence of L-asparaginase from this protocol, a
owner.
drug often included in earlier versions. Several
• Cost: Many chemotherapeutic agents are generally studies have shown that the addition of L-asparaginase
affordable. The additional costs of blood work, office does not increase the length of remissions and survivals;
visits, and catheters and the potential cost of treating I reserve the use of this drug for “rescue” situations
toxicity also must be considered. Combination (see below).
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Treatment Week Drug, Dosage, and Route Treatment Week Drug, Dosage, and Route*
Treatment Week Drug, Dosage, and Route Treatment Week Drug, Dosage, and Route
2
1 Vincristine, 0.5–0.7 mg/m , IV
Prednisone, 2.0 mg/kg, PO 11 Vincristine, 0.5–0.7 mg/m2, IV
2 Cyclophosphamide, 200 mg/m2, IV
Prednisone, 2.0 mg/kg, PO 13§ Cyclophosphamide, 200 mg/m2, IV
3 Vincristine, 0.5–0.7 mg/m2, IV
Prednisone, 1.0 mg/kg, PO 15 Vincristine, 0.5–0.7 mg/m2, IV
4 Doxorubicin, 25 mg/m2, IV
Prednisone, 1.0 mg/kg, PO¶ 17 Doxorubicin, 25 mg/m2, IV
6 Vincristine, 0.5–0.7 mg/m2, IV 19 Vincristine, 0.5–0.7 mg/m2, IV
7‡ Cyclophosphamide, 200 mg/m2, IV 21§ Cyclophosphamide, 200 mg/m2, IV
8 Vincristine, 0.5–0.7 mg/m2, IV 23 Vincristine, 0.5–0.7 mg/m2, IV
9 Doxorubicin, 25 mg/m2, IV 25|| Doxorubicin, 25 mg/m2, IV
*Refer to Chapter 26, Table 26-5, for conversion of body weight to body surface area.
†
Cyclophosphamide is always delivered concurrently with 1 mg/kg of furosemide, IV, to decrease the incidence of sterile hemorrhagic cystitis.
‡
If in complete remission at week 19, therapy is discontinued and monthly reevaluations are instituted.
§
If renal lymphoma or CNS lymphoma is present, substitute cytosine arabinoside at 600 mg/m2 divided SC bid over 2 days at these treatments.
¶
Prednisone is continued (1 mg/kg, PO) every other day from this point on.
||
If in complete remission at week 25, therapy is discontinued and cat is rechecked monthly for recurrence.
Reinduction and Rescue Therapy practical. More commonly, surgery is combined with
adjuvant chemotherapy or radiotherapy. Of the
Reinduction therapy is defined as therapy instituted when chemotherapeutic agents commonly used in veterinary
a patient has recrudescence of lymphoma following dis- medicine, only prednisone and cytosine arabinoside
continuation of chemotherapy that had resulted in a consistently cross the blood-brain barrier in therapeutic
successful remission. In those cases, cycle the patient concentrations. Radiotherapy also has been used suc-
back through the same induction protocol as was used cessfully for the treatment of CNS lymphoma.
initially. The length of remission following reinduction
is generally half that of the initial induction; however,
several cases have been known to have equally or more Cutaneous Lymphoma Therapy
durable second remissions. Cutaneous lymphoma, if solitary and confined, can be
Rescue therapy is defined as therapy instituted when treated with local radiotherapy or surgery; however, the
either induction or reinduction fails to achieve a remis- likelihood of ultimate systemic spread is high. General-
sion and other drugs not previously used are initiated. ized, cutaneous lymphoma tends to be less responsive
Several rescue protocols have been published and to chemotherapy than multicentric lymphoma, and
include non-CHOP drugs, including mitoxantrone, L- clinical signs can wax and wane considerably over time.
asparaginase, lomustine (CCNU), and actinomycin D. CCNU (lomustine), cis-retinoic acid therapy, and L-
In general, remissions can be achieved with rescue; asparaginase have all proven effective in approximately
however, they are rarely durable and last approximately 40% to 60% of dogs with cutaneous lymphoma,
1 to 2 months. although long-term survival is uncommon.
Future goals for the treatment of lymphoma in com-
panion animals include increasing the remission time Therapy for Hypercalcemia
while decreasing cost, toxicity, and time involved to
treat the patient. The future role of biologic-based ther- Treatment of hypercalcemia secondary to lymphoma is
apies, including signal transduction modification, accomplished best by attaining tumor remission. If nec-
immunotherapeutics, and staged adjuvant radiother- essary, diuresis with high sodium crystalloids (0.9%
apy, is under investigation. The question of whether cats NaCl) delivered at twice the maintenance rate (see
benefit from long-term maintenance therapy has yet to Chapter 32) is often sufficient along with initiation of
be answered. chemotherapy. If hypercalcemia is severe, calcitonin
therapy can be initiated. The addition of prednisone
also decreases serum calcium levels; initiate only after a
Small Cell Variant Lymphoma histologic or cytologic diagnosis.
This less common form of lymphoma is a “low-grade”
variant. In represents a moderately common form of GI Prognosis
or hepatic lymphoma in cats and a rare multicentric
form in dogs. It tends to be less chemoresponsive than Prognostic Indicators for Dogs with Lymphoma
intermediate or high-grade lymphoma; however, it has • WHO clinical stage V (see Table 27-1) is associated
a more protacted course and patients can survive a long with shorter survival times, especially when the bone
time with their disease. In my practice, small cell lym- marrow involvement results in significant cytopenias.
phoma is initially treated with continuous chlorambucil • WHO substage b (i.e., presenting ill, with significant
(20 mg/m2, by mouth [PO], q14 days) and prednisone clinical signs) is strongly predictive of shorter remis-
therapy. sion and survival times.
• The presence of a T cell origin lymphoma is strongly
Extranodal Lymphoma Therapy predictive of shorter remission and survival times.
Therapy unique to extranodal lymphoma depends on • In some reports, female dogs have significantly
the site of involvement and the extent of disease. Extra- longer remission and survival times than males.
nodal lymphoma that is determined, after thorough • Hypercalcemia and mediastinal involvement have
staging, to be a local disease can be treated locally (e.g., been reported to worsen prognosis; however, this has
excisional surgery or radiotherapy) without the neces- been shown to be due to their T cell association
sity for systemic chemotherapy. Follow diligent reevalu- rather than a direct effect.
ation schedules to identify recurrence or systemic • Anatomic site of involvement can have prognostic
spread of disease. Initiate systemic chemotherapy once significance. Alimentary, disseminated cutaneous,
systemic involvement has been documented. and leukemic forms have a poorer prognosis than
Therapy for CNS lymphoma depends on location, multicentric forms.
the capacity of drugs to cross the blood-brain barrier,
and the presence of disease outside the CNS. Surgical Prognostic Indicators for Cats with Lymphoma
intervention can be used for diagnosis or removal of • A higher clinical stage is associated with lower remis-
accessible CNS tumors, but usually this is not feasible or sion rates and survival times (approximately 90%
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complete remission rate in stage I versus 50% in stage • In some forms, the neoplastic lymphoid cells are very
III or higher) undifferentiated, making special histochemical stains
• FeLV status is strongly predictive of remission and necessary to differentiate them from other forms of
survival times. FeLV-antigenemic cats and the leukemia and myeloproliferative conditions.
anatomic forms of lymphoma associated with them • ALL may be clinically differentiated from late stages
(mediastinal, multicentric) have a poorer prognosis of lymphoma by the following:
than FeLV-negative cats (most often alimentary • More acute progression of ALL
form). • Less likelihood of lymphadenopathy (<50%)
• Leukemia, anemia, neutropenia, and sepsis nega- • Poor response to therapy
tively affect response to therapy and survival times. • Shorter survival times
• Response to therapy is strongly predictive of
outcome. Cats that achieve a complete remission Treatment and Prognosis
early in their treatment often go on to have a pro-
longed and durable remission. This indicator cannot • Most published reports utilize CHOP-based protocols
be assessed before therapy, however, and therefore is (see earlier discussion in this chapter). Strict atten-
not clinically useful at initial diagnosis. tion to treatment of secondary infection and symp-
tomatic care are mandatory.
• A poor prognosis resulting from a meager short-lived
response to therapy generally is the rule. Exceptions
LYMPHOID LEUKEMIA do exist.
Leukemia is defined as the proliferation of neoplastic
cells in the bone marrow; such cells may or may not be
Chronic Lymphocytic Leukemia
circulating in the peripheral blood. There are two major Chronic lymphocytic leukemia (CLL) is defined as an
categories of lymphoid leukemia: acute lymphoblastic abnormal proliferation of morphologically mature lym-
leukemia and chronic lymphocytic leukemia. Both phocytes in the bone marrow or peripheral blood. It
forms are relatively rare in dogs; however, they may con- occurs primarily in older dogs and cats.
stitute up to one-third of feline lymphoid neoplasms.
Clinical Signs
Acute Lymphoblastic Leukemia • Presenting complaints for the most part are non-
Acute lymphoblastic leukemia (ALL) is defined as an specific and include lethargy, inappetence, polyuria
abnormal proliferation of morphologically immature or polydipsia, bleeding diathesis, intermittent lame-
lymphoblasts in the bone marrow or peripheral blood. ness, and episodes of collapse.
This form of leukemia is rapidly progressive and • Two-thirds of dogs have lymphadenopathy and
responds poorly to therapy. splenomegaly; pale mucous membranes and fever are
common.
Epidemiology and Clinical Signs
Hematologic Abnormalities
• No sex, breed, or weight predilection exists. Most
affected dogs are of late middle age; the mean age in • Most animals are anemic (normocytic, normochromic,
cats with ALL tends to be younger, owing to an asso- and nonregenerative), and approximately half are
ciation with FeLV. thrombocytopenic.
• Clinical signs can include fever, generalized or • One-third of dogs are hyperproteinemic, and half
abdominal pain, anorexia, splenomegaly, and pale have monoclonal gammopathies on serum elec-
mucous membranes. trophoresis, often with Bence Jones proteins in the
• Anemia occurs in nearly half of ALL patients, and urine, indicative of a B cell origin; however, recent
one-fourth are thrombocytopenic. evidence suggests the majority of CLL in dogs is of T
• Most cats with ALL are FeLV-positive. cell origin.
• All reported cases in cats are FeLV-negative.
Diagnosis
Treatment and Prognosis
• Diagnosis depends on documentation of abnormal
lymphocytes in the bone marrow or peripheral blood. • Therapy for CLL is recommended only if the patient
• The presence of 30% or more abnormal cells in the is symptomatic, if significant cytopenias exist (e.g.,
bone marrow is diagnostic. anemia, thrombocytopenia, and neutropenia), or if
• Most patients have absolute leukocytosis with circu- splenomegaly or lymphadenopathy is present.
lating abnormal lymphocytes; 10% are classified as • Prednisone and chlorambucil are the drugs most
having aleukemic leukemia (bone marrow involve- commonly used, and nearly 75% of animals respond,
ment without peripheral blood involvement). with median survivals of nearly 1 year.
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• Chlorambucil (Leukeran), 20 mg/m2 PO given every Approximately 50% of dogs with MM have radi-
1 to 2 weeks or 6 mg/m2 daily, has provided excellent ographic evidence of bone lesions, whereas skeletal
results. lesions are rare in cats with MM.
• The prognosis for CLL is much better than that for • Serum or urine myeloma proteins, as revealed by
ALL. Most dogs respond well to therapy, and quality immunoelectrophoresis.
of life is good.
Histological confirmation may be necessary for those
cases that do not meet all three criteria.
▼ Chapter
28 Soft Tissue Sarcomas and Mast
Cell Tumors
Joanne C. Graham
301
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Hemangiosarcoma Lymphangiosarcoma
Tumor of blood vessel endothelium Tumor of lymphatic endothelial vessels
• Common in dogs (German shepherds at risk); rare • Rare in dogs and cats
in cats • May be invasive
• Very invasive and rapid growing • Metastasis is rare
• Spleen, heart, and skin are common primary sites • Draining tracts on skin or edema are possible pre-
• Metastasis is common senting signs
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Malignant Fibrous Histiocytoma logic evaluation of the tumor. Histologic grade is useful
in predicting tumor behavior and prognosis for dogs
Tumor containing a mixture of fibroblast-like cells and with soft tissue sarcomas.
histiocyte-like cells
• Uncommon in dogs and cats History
• Invasive (may cause bone lysis) The history helps determine how long the mass has
• Usually found in subcutaneous tissue been present and the rate of growth. Also important is
• Metastasis is uncommon information regarding exposure to carcinogens, recent
vaccination, and past traumatic incidents. Concurrent
Feline Injection-Site Sarcomas systemic disorders may be present if metastatic disease
Most are fibrosarcomas, but the category also includes or paraneoplastic syndromes have developed.
rhabdomyosarcomas, leiomyosarcomas, chondrosarco-
mas, osteosarcomas, malignant fibrous histiocytomas, Physical Examination
and undifferentiated sarcomas Perform a thorough examination to determine the
• The number of giant cells in the histopathology number of masses and their physical characteristics.
sample may correlate with the grade (higher number • In general, benign neoplasms are well delineated,
of cells = higher grade) slow growing, and freely moveable. They seldom are
• Aggressive, highly invasive tumors ulcerated or inflamed.
• Cervical or interscapular area and hind limbs are the • Malignant tumors are often rapid-growing, fixed
most common sites masses with ill-defined borders. However, some low-
• Metastasis is possible (20–30% of cases) grade sarcomas are slow growing and appear well
demarcated. The appearance of these masses can be
Clinical Signs misleading and should not preclude biopsy.
Clinical signs depend on the location, size, and degree
• Search for evidence of metastasis. Palpate the regional
lymph nodes for size and mobility. Look for hepa-
of invasiveness of the tumor as well as on the presence
tomegaly, splenomegaly, and increased respiratory
and degree of metastatic disease.
sounds or dyspnea as signs of systemic involvement.
• Soft tissue sarcomas are more common in older
animals (mean age 9 years). Clinical Pathology
• Because of the widespread distribution of mesoder- Evaluate a complete blood count (CBC), platelet count,
mal tissues in the body, soft tissue sarcomas may occur serum biochemical profile, and urinalysis in animals
in almost any anatomic location, including the with soft tissue sarcomas. Although results are often
abdomen. unremarkable, in some cases these may suggest the pres-
• Tumors may become quite large before any clinical ence of metastatic disease, paraneoplastic syndromes,
signs are apparent. They often are noticed first by the or other concurrent disease. The values obtained also
owner, either by observation or by handling the provide a baseline for future therapy. Abnormalities
animal. may include the following:
• Certain types of sarcoma may invade bone, causing
lameness, or may obstruct lymphatics, causing edema. • Anemia of chronic inflammatory disease
• GI leiomyosarcomas may cause signs of GI obstruc- • Leukocytosis
tion (vomiting) or melena. • Thrombocytopenia (may be associated with dissemi-
• Smooth muscle sarcomas of the bladder may cause nated intravascular coagulation)
hematuria, pollakiuria, or dysuria. • Hypoglycemia
• Hemangiosarcomas may cause a variety of clinical • Increased serum concentrations of alanine trans-
signs, including collapse due to tumor rupture and ferase (ALT), alkaline phosphatase (ALP), and
hemorrhage. gamma-glutamyl transpeptidase (GGT)
• Injection-site sarcomas arise in injections sites.
Diagnostic Imaging
Diagnosis Radiography
The goals of diagnosis are to identify the histologic type • Radiograph the mass to aid in determining the extent
and grade of the primary tumor, to delineate the extent of the sarcoma and assess for underlying bone
of the tumor, and to determine whether metastatic invasion.
disease is present. Although history, physical examina- • Radiograph the thorax and abdomen to help identify
tion, laboratory evaluation, and diagnostic imaging metastatic disease.
provide valuable information, the only way to obtain a • Dystrophic calcification caused by some anaplastic
definitive diagnosis is through biopsy and histopatho- sarcomas may be seen on radiographs.
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Table 28-1. WORLD HEALTH ORGANIZATION CLINICAL STAGING SYSTEM FOR CANINE SOFT
TISSUE SARCOMAS
T = Primary Tumor N = Regional Lymph Node M = Distant Metastasis
Stage
I T1N0M0, T2N0M0
II T1N1M0, T2N1M0
III T1N2,3M0, T2N2,3M0, T3N0–3M0, T4N0–3M0, any Nb
IV any M1
From Owen LN: Classification of tumours in domestic animals. Geneva, Switzerland: World Health Organization, 1980.
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malignant tumors, surgical resection can be curative. In • A 91% response rate has been reported in dogs with
animals with non-resectable malignant tumors, attempt hemangiopericytoma treated using orthovoltage irra-
to prolong survival time and provide good quality of diation in combination with hyperthermia.
life. • Unfortunately, hyperthermia requires training and
equipment found in few hospitals and thus is of
Surgery limited accessibility.
Surgical excision remains the mainstay of therapy for Chemotherapy
soft tissue sarcomas (see Chapter 26 for principles of
oncologic surgery). However, many of these tumors Chemotherapy has been used with some success to treat
recur because of inadequate resection. A well-planned, patients with soft tissue sarcomas.
aggressive initial surgery has the greatest likelihood of • Agents most often used are vincristine, doxorubicin,
success. cyclophosphamide, mitoxantrone, dacarbazine, car-
boplatin, and lomustine. Response rates range from
▼ Key Point Excise soft tissue sarcomas with 3-cm 15% to 50%. Commonly used protocols are outlined
margins in all planes. Remove one fascial plane in Table 28-2.
deep to the tumor if 3-cm margins are not possible. • Chemotherapy is not likely to be efficacious in treat-
ing patients with large tumor burdens. Rather, it is
best used to treat patients with microscopic disease
• Remove overlying subcutaneous tissues and skin as following incomplete excision, metastatic disease,
well as underlying tissues to which the mass is fixed.
micrometastatic disease, or patients with grade 3
In some cases, limb amputation is indicated.
sarcomas.
• Include all previous biopsy sites in the excision.
• Remove the tumor intact to prevent seeding of
normal tissues with malignant cells.
• Have the specimen margins histologically evaluated
MAST CELL TUMORS
for completeness of excision and grade.
Mast cell tumors (MCTs) comprise approximately 7%
• Do not remove regional lymph nodes unless they are
to 20% of cutaneous neoplasms in the dog and 20% in
involved.
the cat. MCTs may develop in almost any location but
are found most commonly in the skin and subcutaneous
Radiation Therapy tissues of the dog, and in the skin, spleen, liver, and
Soft tissue sarcomas are variably responsive to radiation intestines of the cat. Mast cells are a normal component
therapy depending upon the histologic type and grade of the immune system and are important in the inflam-
of the tumor. matory response to tissue trauma as well as in allergic
reactions. Cytoplasmic granules found in mast cells
• Radiation therapy is used most frequently to irradiate contain biologically active substances such as heparin,
incompletely excised tumor fields or reduce tumor histamine, platelet-activating factor, prostaglandins,
volume preoperatively. Tumor control rates of 95% at cytokines, and leukotrienes. The quantity and type of
1 year and 91% at 2 years post-radiation therapy have granules in MCTs depends on the degree of differenti-
been reported for patients with incompletely excised, ation. Well-differentiated tumors contain more heparin
well-differentiated sarcomas. than undifferentiated tumors, which have a higher his-
• High-dose (8 Gy) weekly radiation has been reported tamine content.
to be successful for palliative control of soft tissue sar-
comas in dogs. Etiology
• Repeat irradiation of previously irradiated tumors is
possible. A 38% local control rate after 1-year repeat The cause of MCTs is unknown; however, breed predis-
irradiation has been reported. Unfortunately, if the position, chronic inflammation, and viruses may play a
regrowth of tumors is within 4 to 5 months of the first role.
treatment, the chance of complications from addi-
tional radiation is much higher. Breed Predisposition
Boxers, Boston terriers, English bulldogs, English bull
Hyperthermia terriers, Sharpeis, and Labrador and golden retrievers
are at risk. However, MCTs in boxers are more likely to
Hyperthermia involves electromagnetic radiation or
be well differentiated and may have a more favorable
ultrasound to heat tissues.
prognosis. Siamese cats younger than 4 years of age
• Hyperthermia is cytotoxic when used alone; however, have been reported to have a higher incidence of cuta-
the best results are seen when it is used as a combined neous histiocytic-like MCTs that may spontaneously
modality with radiation or chemotherapy. regress.
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*Caution: The use of chemotherapeutics requires careful handling and knowledge of potential toxicities.
**See Chapter 26 (Table 26-5) for conversion of body weight to body surface area in square meters (m2).
enlarged organs (especially the spleen) can be helpful • Excise the mass with 3-cm margins on all sides and
in confirming metastatic MCT. Thoracic radiographs one fascial plane deep to the tumor.
are seldom helpful. • Remove regional lymph nodes if enlarged or if metas-
tasis is detected.
Fine-Needle Aspiration • Have the specimen margins histologically evaluated
for completeness of excision and grade. If the tumor
MCTs exfoliate well and usually can be diagnosed by
extends to the margins, plan a second wider excision
FNA. Aspirates generally contain numerous discrete
(if possible).
round cells with abundant basophilic granules (mast
cells). Occasionally, the granules may not stain well with • If tumors are excised incompletely or are non-
resectable, proceed with radiation therapy and/or
Diff-Quik stains.
chemotherapy.
Histopathology • Wound complications, such as excessive inflamma-
tion, edema, and dehiscence, can occur after MCT
Histopathology is important to evaluate completeness excision.
of excision and histologic grade. Special stains (tolui-
dine blue, Giemsa) are sometimes needed to identify Radiation Therapy
undifferentiated MCTs. Other stains or immunohisto-
Radiation therapy alone or in combination with other
chemical assays that can be performed on histopathol-
treatment modalities may be used to treat incompletely
ogy samples and may aid with prognosis are agyrophilic
excised or non-resectable MCTs.
nucleolar staining organizing regions (AGNORs), pro-
liferating cell nuclear antigen (PCNA), and Ki-67 stain- • Patients with grade 1 and 2 tumors respond better
ing. The higher the counts, the poorer the prognosis. than those with grade 3. In one study, tumor-free
survival rates of 94% at 1 year and 86% at 5 years
Grading of Tumors post-radiation therapy were reported in dogs with
The most reliable predictor of MCT behavior and prog- incompletely excised grade 1 and 2 MCT.
nosis in dogs is tumor grade. The most widely used • Radiation is most effective against microscopic
grading system (Patnaik) assigns grades I, II, and III to disease.
well, moderately, and poorly differentiated tumors, • Irradiate involved regional lymph nodes, if necessary.
respectively (based on histologic appearance).
Chemotherapy
• Low-grade tumors are less likely to recur or metasta- Chemotherapy is indicated for patients with systemic
size, and dogs with low-grade tumors have increased
mastocytosis, grade 3 tumors, non-resectable tumors, or
survival times.
incompletely excised tumors when a second surgery or
• The Patnaik grading system has not been found
radiation therapy is not possible.
useful in determining prognosis in cats.
• Glucocorticoids (prednisone and prednisolone) are
Treatment of Canine Cutaneous Mast Cell commonly used but are effective in less than 25% of
Tumors dogs when used alone.
• Vinblastine, cyclophosphamide, and lomustine are
Treatment of MCTs may include surgery, radiation chemotherapy drugs reported to have efficacy against
therapy, chemotherapy, or some combination of the MCTs (Table 28-4 shows dosages). Combination
three. The type of treatment instituted depends pri- therapy is thought to be superior to single-agent use.
marily on the histologic grade of the tumor and the
clinical stage of the patient.
Ancillary Drug Therapy
Surgery Patients with grade 3 tumors, systemic mastocytosis, or
gastrointestinal hemorrhage should receive ancillary
Wide surgical excision is the treatment of choice for
drug therapy.
canine MCTs.
• Use H2-antagonists to reduce gastric acid secretion
▼ Key Point Although they appear to be discrete and help decrease the incidence and severity of gas-
masses, MCTs may extend deep into surrounding trointestinal ulcers in MCT patients. Administer one
tissues, making wide surgical excision imperative of the following H2-blockers:
(especially for grade 3 tumors) • Cimetidine (Tagamet), 5 to 10 mg/kg PO q8h
• Ranitidine (Zantac), 1 to 2 mg/kg PO q12h
• Administer an antihistamine (e.g., diphenhydramine; • Famotidine (Pepcid), 0.5 to 1 mg/kg PO q24h
2 mg/kg IM or IV) just before surgical excision of large • When an active gastrointestinal ulcer is suspected in
tumors to decrease the effects of histamine release an animal with MCT, also administer the following:
from the tumor. • Sucralfate (Carafate), 250 to 1000 mg PO q6–8h
W0422-Ch028.qxd 11/10/05 5:02 PM Page 309
CVP
Cyclophosphamide (Cytoxan) 250–300 mg/m2 divided PO 8–11
Vinblastine (Velban) 2 mg/m2 IV 1
Prednisone 1 mg/kg PO q24h
Repeat cycle every 21 days
VLP (Dogs)
Vinblastine (Velban) As above IV 1
Lomustine (CeeNU) 60–70 mg/m2 PO 14
Prednisone 2 mg/kg PO q24h
Gradually taper to 0.5 mg/kg
Repeat cycle every 28 days
Lomustine (CeeNU) 50–70 mg/m2 PO 1
Repeat cycle every 21 days
Prednisone 1 mg/kg PO q24h
*See Chapter 26 (Table 26-5) for conversion of body weight to body surface area in square meters (m2).
• Use an H1-antagonist (diphenhydramine) as needed Buerger RG, Scott DW: Cutaneous mast cell neoplasia in cats: 14 cases
(1975–1985). J Am Vet Med Assoc 190:1440, 1987.
to reduce inflammation and pruritis associated with Chastain CB, Turk MAM, O’Brien D: Benign cutaneous mastocytomas
histamine release. is two litters of Siamese kittens. J Am Vet Med Assoc 193:959, 1988.
Couto SS, Griffey SM, Naydan DK, et al (personal communication):
Feline vaccine associated sarcomas: A morphological study and
Treatment of Feline Mast Cell Tumors immune phenotyping of intratumoral and peritumoral leukocyte
population. Proc 19th Vet Cancer Soc 34, 1999.
Cutaneous Dorn CR, Taylor DO, Schneider R, et al: Survey of animal neoplasms
• Wide surgical excision is the treatment of choice. in Alameda and Contra Costa Counties, California. II. Cancer mor-
bidity in dogs and cats from Alameda County. J Natl Cancer Inst
• Chemotherapy and radiation therapy have not been 40:307, 1968.
well evaluated but may be helpful in recurrent or Elmsie R: Combination chemotherapy with and without surgery for
metastatic tumors. One study found a 57% response dogs with high-grade mast cell tumors with regional lymph node
rate to lomustine in cats with MCTs. metastasis. Vet Cancer Society Newsletter 6, 1997.
Feinmehl R, Matus R, Mauldin GN, et al (personal communication):
Splenic mast cell tumors in 43 cats (1975–1992). Proc 12th Vet
Visceral Cancer Soc 50, 1992.
• Splenectomy may ameliorate clinical signs and Hauck M: Feline injection site sarcomas. Vet Clin North Am 33:553,
2003.
prolong survival in cats with splenic MCT even when Holzinger EA: Feline cutaneous mastocytomas. Cornell Vet 63:87,
other organs are involved. Median survival times 1973.
following splenectomy was 19 months in one study of Howard EB, Sawa TR, Nielson SW, et al: Mastocytoma and gastro-
43 cats. duodenal ulceration. Vet Pathol 6:146, 1969.
Johnson TO, Schulman FY, Lipscomb TP, et al: Histopathology and
• Treat intestinal MCTs by wide surgical excision (5- to biologic behavior of pleomorphic cutaneous mast cell tumors of
10-cm margins). However, the prognosis for cats with fifteen cats. Vet Pathol 39:452, 2002.
intestinal disease is poor. Kuntz C, Dernell W, Powers B, et al: Prognostic factors for surgical
• Chemotherapy has not been critically evaluated. treatment of soft tissue sarcomas in dogs: 75 cases (1986–1996). J
Am Vet Med Assoc 21:1147, 1997.
Lombard LS, Moloney JB: Experimental transmission of mast cell
sarcoma in dogs. Fed Proc 18:490, 1959.
London CA, Seguin B: Mast cell tumors in the dog. Vet Clin North
SUPPLEMENTAL READING Am 33:473, 2003.
MacEwen EG, Powers BE, Macy D et al: Soft tissue sarcomas. In
Al-Sarraf R, Mauldin GN, Patnaik AK, et al: A prospective study of radi- Withrow SJ, MacEwen EG (eds): Small Animal Clinical Oncology,
ation therapy for the treatment of grade 2 mast cell tumors in 32 3rd ed. Philadelphia: WB Saunders, 2001.
dogs. J Vet Intern Med 10:376, 1996. Madewell BR, eds: Veterinary Cancer Medicine, 2nd ed. Philadelphia:
Baez JL, Richardson C, Sorenmo KU (personal communication): Lea & Febiger, 1987.
Liposarcomas in dogs: 19 cases (1989–2000). Proc 20th Vet Cancer McCaw DL, Miller MA, Ogilvie GK, et al: Response of canine mast cell
Soc 30, 2000. tumors to treatment with oral prednisone. J Vet Intern Med 8:406,
Bostock DE: Neoplasms of the skin and subcutaneous tissues in dogs 1994.
and cats. Br Vet J 142:1, 1986. McKnight J, Mauldin G, McEntee M, et al: Radiation therapy for
Bostock DE: The prognosis following surgical removal of mastocy- incompletely resected soft tissue sarcomas in dogs. J Am Vet Med
tomas in dogs. J Small Anim Pract 14:27, 1973. Assoc 217:205, 2000.
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McManus PM: Frequency and severity of mastocytemia in dogs with Rassnick KM, Moore AS, Williams LE, et al: Treatment of canine mast
and without mast cell tumors: 120 cases (1995–1997). J Am Vet Med cell tumors with CCNU (lomustine). J Vet Intern Med 13:601,
Assoc 215:355, 1999. 1999.
Miller MA, Nelson SL, Turk JR, et al: Cutaneous neoplasia in 340 cats. Rebar AH, Boon GD, DeNicola DB: A cytologic comparison of
Vet Pathol 28:389, 1991. Romanowsky stains and Papanicolaou type stains. II. Cytology
Molander-McCrary H, Henry CJ, Potter K, et al: Cutaneous mast cell of inflammatory and neoplastic lesions. Vet Clin Pathol 11:16,
tumors in cats: 32 cases (1991–1994). J Am Anim Hosp Assoc 1982.
34:281, 1998. Simoes JP, Schoning P, Butine M: Prognosis of canine mast cell
Ogilvie GK, Obradovich JE, Elmslie RE, et al: Efficacy of mitoxantrone tumors: A comparison of three methods. Vet Pathol 31:637, 1994.
against various neoplasms in dogs. J Am Vet Med Assoc 198:1618, Stevenson S, Hohn RB, Pohler OEM, et al: Fracture-associated
1991. sarcoma in the dog. J Am Vet Med Assoc 180:1189, 1982.
Ogilvie GK, Reynolds HA, Richardson RC, et al: Phase II evaluation Thamm DH, Vail DM: Mast cell tumors. In Withrow SJ, MacEwen EG
of doxorubicin for treatment of various canine neoplasms. J Am (eds): Small Animal Clinical Oncology, 3rd ed. Philadelphia: WB
Vet Med Assoc 195:1580, 1989. Saunders, 2001.
O’Keefe DA, Couto CG, Burke-Schwartz C, et al: Systemic mastocyto- Thrall DE, Goldschmidt MH, Biery DN: Malignant tumor formation
sis in 16 dogs. J Vet Intern Med 1:75, 1987. at the site of previously irradiated acanthomatous epulides in four
Patnaik AK, Ehler WJ, MacEwen EG: Canine cutaneous mast cell dogs. J Am Vet Med Assoc 178:127, 1981.
tumor: Morphologic grading and survival time in 83 dogs. Vet Turrel JM, Kitchell BE, Miller LM, et al: Prognostic factors for radia-
Pathol 21:469, 1984. tion treatment of mast cell tumor in 85 dogs. J Am Vet Med Assoc
Peterson SL: Scar-associated canine mast cell tumor. Canine Pract 193:936, 1988.
12:23, 1985. Turrel JM, Theon AP: Re-irradiation of tumors in cats and dogs. J Am
Priester WA, McKay FA: The occurrence of tumors in domestic Vet Med Assoc 193:465, 1988.
animals. National Cancer Institute Monograph 54, Bethesda, 1980, White AS: Clinical diagnosis and management of soft tissue sarcomas.
U.S. Dept. of Health and Human Services. In Gorman ND (ed): Oncology: Contemporary Issues in Small
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(1997–2003). Vet Parasitol 119:209, 2004. feline cutaneous mastocytomas. Vet Pathol 23:320, 1986.
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▼ Chapter
29 Mammary Gland Neoplasia
Kechia M. Davis / Elizabeth A. Stone
The mammary gland tumor (MGT) is the most • Anorexia and weight loss may be noted in cats with
common tumor in the female dog and the third most inflammatory mammary carcinoma (IMC).
common neoplasm in the female cat. MGTs have been • MGTs can be seen concurrent with uterine neoplasms
reported in the male dog and cat but are rare. in cats.
311
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• Survival may be decreased in cats with multiple Dorn CR, Taylor DO, Schneider R, et al: Survey of animal neoplasms
tumors and tumors >8 cm3. in Alameda and Contra Costa Counties, California. II. Cancer mor-
bidity in dogs and cats from Alameda County. J Natl Cancer Inst
• Vascular endothelial growth factor expression is an 40:307–318, 1968.
important prognostic indicator in cats. Gilbertson SR, Kurzman ID, Zachrau RE, et al: Canine mammary
epithelial neoplasms: Biologic implications of morphologic char-
acteristics assessed in 232 dogs. Vet Pathol 20:127, 1983.
Hellman E, Bergström R, Holmberg L, et al: Prognostic factors in
PREVENTION canine mammary tumors: A multivariate study of 202 consecutive
cases. Vet Pathol 30:20, 1993.
▼ Key Point The risk of MGT is less than 0.5% in dogs Kurzman ID, Gilbertson SR: Prognostic factors in canine mammary
that are spayed before their first estrus and less tumors. Semin Vet Med Surg 1:25, 1986.
than 8% in those spayed before their second MacEwen EG, Hayes AA, Harvey HJ, et al: Prognostic factors for feline
mammary tumors. J Am Vet Med Assoc 185:201, 1984.
estrus. Morris JS, Dobson JM, Bostock DE, et al: Effect of ovariohysterectomy
in bitches with mammary neoplasms. Vet Rec 142:656, 1998.
• After 2.5 years, OHE has no protective effect on MGT Moulton JE: Tumors of the mammary gland. In Moulton JE (ed):
development. In dogs spayed at any age, risk of MGT Tumors in Domestic Animals. Berkeley: University of California
Press, 1990, p 518.
is reduced if dogs were thin at 9 to 12 months of age. Perez-Allena MD, Tabanera E, Pena L: Inflammatory mammary car-
• Spayed cats have a 0.6% risk for developing cinoma in dogs: 33 cases (1995–1999). J Am Vet Med Assoc
mammary carcinoma compared with intact cats. 219:1110, 2001.
Sonnenschein EG, Glickman LT, Goldschmidt MH, et al: Body con-
formation, diet, and risk of breast cancer in pet dogs: A case-control
study. Am J Epidemiol 133:694, 1991.
SUPPLEMENTAL READING Sorenmo KU, Shofer FS, Goldshmidt MH: Effect of spaying and
timing of spaying on survival of dogs with mammary carcinoma.
Allen SW, Mahaffey EA: Canine mammary neoplasia: Prognostic indi- J Vet Intern Med 14:266, 2000.
cators and response to surgical therapy. J Am Anim Hosp Assoc Viste JR, Myers SL, Singh B, et al: Feline mammary adenocarcinoma:
25:540, 1989. Tumor size as a prognostic indicator. Can Vet J 43:33, 2002.
Cooley DM, Waters DJ: Skeletal metastasis as the initial clinical man- Weijer K, Hart AAM: Prognostic factors in feline mammary carci-
ifestation of metastatic carcinoma in 19 dogs. J Vet Intern Med noma. J Nat Cancer Inst 70:709, 1983.
12:288, 1998.
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▼ Chapter
316
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Table 30-1. MOST COMMON SKIN AND Table 30-4. CLASSIFICATION OF SKIN
SUBCUTANEOUS TUMORS TUMORS BY ANATOMIC LOCATION
Young Dogs Head and neck Trunk
Histiocytoma Basal cell tumor Mast cell tumor
Transmissible venereal tumors Squamous cell carcinoma Lipoma
Viral papillomas Sebaceous adenoma Sebaceous gland adenoma
Papilloma Fibrosarcoma
Canine
Histiocytoma Nerve sheath tumor
Lipomas
Mast cell tumor (primarily in cats) Hemangiosarcoma
Mast cell tumors
Ceruminous gland adenoma/ Perineum/genitals
Histiocytomas
adenocarcinoma Mast cell tumor
Sebaceous gland adenomas
Hemangiosarcoma Perianal adenoma
Feline
Extremities Transmissible venereal tumor
Basal cell tumors
Mast cell tumor Perianal adenocarcinoma
Squamous cell carcinomas
Hemangiopericytoma Anal sac (apocrine gland)
Fibrosarcomas
Squamous cell carcinoma (nail bed) adenocarcinoma
Mast cell tumors
Malignant melanoma (nail bed)
Nerve sheath tumor
Synovial cell sarcoma
Hemangiosarcoma
They can occur as a single tumor (usually non-viral eti- and cocker spaniels. When metastases from sebaceous
ology) or as multiple tumors (usually viral etiology) in gland adenocarcinomas occur, they generally spread
the skin, mucous membranes, or mucocutaneous to the regional lymph nodes and subsequently to the
regions. lungs.
are similar to adenomas; however, they are frequently Epidemiology and Biologic Behavior
invasive.
These tumors occur more frequently in cats, especially
in white cats or in those with hypopigmented areas that
Cytology are more likely to be exposed to sunlight, especially ear
Cytologic examination reveals mature or immature tips and nose. Dogs have an increased frequency of
(ceruminous gland adenocarcinoma) secretory cells these tumors in the ventral abdomen (especially),
with epithelial characteristics. trunk, scrotum, and lips. They are locally invasive with
late metastases to the local lymph nodes and lungs.
Epidemiology and Biologic Behavior
Treatment
This is the most common external ear tumor in older
dogs and cats but appears to be more common in cats. Perform complete surgical excision for squamous cell
carcinomas if they are in an easily accessible location.
Perform complete pinna resection for tumors of the ear
Treatment (see Chapter 60) and digital amputation for squamous
Total ear canal ablation may be necessary to completely cell carcinoma of the digit (see Chapter 114). Consider
excise these tumors (see Chapter 60). Surgical removal radiation therapy and photodynamic therapy for dogs
may be sufficient in animals with ceruminous gland ade- and cats with non-resectable or incompletely excised
nomas; however, external beam irradiation is highly rec- squamous cell carcinomas. Retinoids may be considered
ommended for dogs and cats with ceruminous gland for those animals with preneoplastic lesions. Consider
adenocarcinomas with incomplete resection after an chemotherapy for non-resectable or metastatic tumors,
aggressive ear canal ablation and for recurrent or non- using cisplatin, carboplatin, bleomycin, mitoxantrone,
excisable adenomas. Chemotherapy also may be con- and doxorubicin (see Chapter 26, Table 30-7 for
sidered for patients with incomplete tumor resection dosages).
or metastases using protocols that contain cisplatin,
carboplatin, mitoxantrone, and doxorubicin (see Table Anal Sac or Apocrine Gland Adenocarcinoma
30-7 for dosages).
Origin and Etiology
Squamous Cell Carcinoma Apocrine gland adenocarcinomas are derived from the
Origin and Etiology apocrine glands that secrete into the anal sac.
Treat all liposarcomas with complete surgical excision with giant cells in cats appear to be more responsive to
and radiation therapy if incomplete margins are chemotherapy. Chemotherapy could include doxoru-
obtained. bicin or mitoxantrone (see Table 30-7 for dosages).
Other treatment options include radiation therapy and
Fibrosarcoma hyperthermia.
Origin and Etiology
These tumors typically originate in the subcutaneous Nerve Sheath Tumors
fibrous connective tissue from fibrocytes or fibroblasts. Neurofibromas, neurofibrosarcomas, schwannomas,
In cats, fibrosarcomas can occur in association with and neurilemomas are discussed in Chapter 129.
feline sarcoma virus or feline leukemia virus, as vaccine-
associated sarcomas (see also Chapter 28), and as
sporadic non-retrovirus-induced tumors. Retrovirus- Hemangiosarcomas
induced fibrosarcomas occur in young cats, are rare, Origin and Etiology
and do not respond to any form of treatment (see
Chapter 6). Fibrosarcomas generally occur on the These tumors (also known as malignant hemangioen-
head, trunk, or limbs. There is a strong association be- dotheliomas and angiosarcomas) originate from the
tween the administration of inactivated vaccines (e.g., vascular endothelium.
feline leukemia virus, rabies, and certain herpes-calici-
panleukopenia [FVRCP] vaccines) and subsequent Description
development of soft tissue sarcomas (primarily fibrosar- Hemangiosarcomas generally are solitary masses found
comas) at the vaccination site. on the limbs, flank, or neck. They can occur in the
skin and/or subcutaneous tissue. Those in the sub-
Description cutaneous tissue also may infiltrate the underlying
muscle. Hemangiosarcoma must be differentiated from
Fibrosarcomas can occur as solitary or multiple masses.
hemangioma.
They are frequently firm, lobulated, and infiltrative into
underlying tissues.
Cytology
Cytology Cytology reveals spindle-shaped or polygonal cells with
large nuclei and a lacy chromatin pattern; one or more
Cytology reveals typical spindle or mesenchymal cells, nucleoli; and a bluish, usually vacuolated cytoplasm.
although cells from these tumors tend not to exfoliate Hemangiosarcomas also can exfoliate cells in sheets
well. similar to those of epithelial cells.
Histiocytoma Description
Origin and Etiology Transmissible venereal tumors tend to occur on the
external genitalia and the face and frequently appear as
The origin of canine cutaneous histiocytomas is the
ulcerated, friable, cauliflower-like masses that can be
monocyte-macrophage cells in the skin.
solitary or multiple.
Description
Cytology
These are dermoepidermal tumors frequently located
Cytology reveals round to ovoid cells with round nuclei
on the head and neck and less commonly on the
and numerous mitotic figures. The cytoplasm is blue or
extremities. They are round, alopecic, and sometimes
transparent, contains distinct clear vacuoles, and is sur-
pink or erythematous, and they occasionally ulcerate.
rounded by a distinct cell membrane.
Because of their gross appearance, they also are
referred to as “button tumors.”
Epidemiology and Biologic Behavior
Cytology This tumor is transmitted by mucocutaneous trans-
plantation of tumor cells through coitus, licking, biting,
Cytology reveals a round cell tumor with a moderate
and scratching. It occurs more frequently in areas where
amount of cytoplasm and, possibly, an eccentrically
dogs are free roaming. No breed or sex predilections
located nucleus. Histiocytomas also tend to be highly
have been observed. These tumors have a low metasta-
pleomorphic and moderately vacuolated. Lymphocytes
tic potential.
are abundant. These tumors can appear inflammatory.
Treatment
Epidemiology and Biologic Behavior
Transmissible venereal tumors can be cured with single-
These tumors generally exhibit benign behavior and are
agent vincristine chemotherapy, surgery, and/or radia-
found mostly in young dogs (approximately 1 to 3
tion therapy (see Table 30-7).
years). Histiocytomas usually regress spontaneously
within 4 to 8 weeks of diagnosis. This tumor does not
occur in cats. Malignant Fibrous Histiocytoma (Extraskeletal
Giant Cell Tumors)
Treatment
See Chapter 28.
Observation alone may be appropriate for most histio-
cytomas because the majority regress with age. Perform
surgical excision if this tumor does not regress in a rea- Melanocytic Tumors (Melanomas)
sonable period; in older dogs, for cosmetic reasons; and Origin and Etiology
finally, to avoid an erroneous diagnosis and further
growth of the tumor. Melanomas originate from melanocytes (melanin-
producing cells) or melanoblasts, which are cells of
Mast Cell Tumor neuroectodermal origin.
Treatment
Local recurrence and distant metastases are very SUPPLEMENTAL READING
common. Surgery is the treatment of choice. Results
Holzworth J: Diseases of the Cat. Philadelphia: WB Saunders, 1987.
of chemotherapy have been unrewarding; however, Ogilvie GH, Moore AS: Managing the Veterinary Cancer Patient.
DTIC, carboplatin, and cisplatin may be the drugs Trenton: Veterinary Learning Systems, 1995.
of choice (see Table 30-7 for dosages). Palliative radia- Theilen GH, Madewell BR: Veterinary Cancer Medicine. Philadel-
tion therapy may be another option in some cases. phia: Lea & Febiger, 1987.
Withrow SJ, MacEwen EG: Clinical Veterinary Oncology, 3rd edition.
Philadelphia: WB Saunders, 2001.
W0422-Ch031.qxd 11/10/05 5:00 PM Page 327
▼
Section
• Unknown cause
HYPOTHYROIDISM IN DOGS • Not associated with antithyroglobulin antibodies
Hypothyroidism is a common, multisystemic disease in Other Causes
dogs. Thyroid hormone deficiency affects virtually all
body systems, resulting in a wide array of clinical signs. • Uncommon causes of primary hypothyroidism
include congenital types (e.g., dyshormonogenesis
It occurs predominantly in middle-aged, pure-breed
and thyroid dysgenesis), replacement of thyroid
dogs, including the golden retriever, Doberman pin-
gland parenchyma by nonfunctional neoplastic
scher, Irish setter, boxer, miniature schnauzer, dachs-
tissue, surgical thyroidectomy, and radioiodine
hund, and cocker spaniel. There is no strong sex
treatment.
predilection.
327
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• Antithyroglobulin antibodies can be present in euthy- • A serum T4 concentration collected 4 to 6 hours after
roid dogs, and they do not indicate hypothyroidism. pill administration should be near the upper limit or
• This assay may be useful to identify dogs affected with slightly above the reference range; T3 concentration
autoimmune thyroid disease prior to development of may be low despite normal or high T4.
hypothyroidism to help plan breeding, but it is not • If signs of hyperthyroidism occur, such as polyuria,
clear if the antibodies predict hypothyroidism in the polydipsia, tachycardia, weight loss, diarrhea, or
future. tachycardia, measure serum T4 and T3, stop treatment
for 1 to 2 days, and reduce the dosage based on this
Thyroid Hormone Autoantibodies evaluation.
• Treatment for myxedema stupor and coma consists
• Antibodies occasionally form against T3 and T4 that of IV administration of L-T4 (0.66 mg/kg), passive
interfere with radioimmunoassay of these hormones. warming, judicious fluid therapy, glucocorticoid sup-
• These antibodies cause a false increase in T3 or T4 in plementation, and mechanical ventilation if neces-
most assays, with apparent elevation of the hormone sary. The prognosis is guarded.
into the normal or hyperthyroid range.
• Dogs with thyroid hormone autoantibodies may or
may not have signs of hypothyroidism.
• Measurement of free T4 by equilibrium dialysis is not HYPOTHYROIDISM IN CATS
affected by T4 autoantibodies.
▼ Key Point Spontaneous hypothyroidism is ex-
▼ Key Point The most reliable method of confirming tremely uncommon in cats.
a diagnosis of hypothyroidism in a dog with com-
patible clinical signs is the demonstration of Most clinical cases of feline hypothyroidism occur as
decreased serum total T4 or free T4 by equilibrium a rare complication of treatment for hyperthyroidism.
dialysis combined with elevated serum endoge- Non-iatrogenic feline hypothyroidism has been
nous TSH. reported primarily in kittens with dwarfism. Cretinism
is the most common cause of endocrine congenital
dwarfism in cats (growth hormone deficiency has not
Treatment been reported in cats). Adult onset spontaneous
Treat dogs with hypothyroidism with daily administra- hypothyroidism has been proven in only one cat.
tion of thyroid hormone. Response to treatment is
usually noted within 1 to 2 weeks with an increase in Etiology
activity and improvement in attitude. Weight loss and
neurologic abnormalities usually begin to resolve within • Congenital hypothyroidism is associated with thyroid
1 to 4 weeks of initiating treatment, whereas dermato- gland atrophy or defective thyroid hormone biosyn-
logic changes may require 4 to 6 weeks to improve and thesis. In many kittens, this may go undetected and
months to completely resolve. Failure to respond within may result in early death.
6 to 8 weeks of initiating treatment should prompt • Primary iatrogenic hypothyroidism results from surgical
reevaluation of the diagnosis and reasons for possible removal of thyroid glands or their destruction
therapeutic failure. by radioactive iodine in the treatment of feline
hyperthyroidism.
Synthetic L-Thyroxine
Clinical Signs
Synthetic L-thyroxine (levothyroxine) is the treatment
of choice in all cases of hypothyroidism. Synthetic L-tri- Congenital Hypothyroidism
iodothyronine (L-T3), combinations of synthetic L-T4 • Disproportionate dwarfism (stunted growth of long
and L-T3, and desiccated thyroid gland preparations or bones, enlarged head).
extracts are not indicated in the treatment of canine • Lethargy and mental dullness.
hypothyroidism. • Hypothermia.
• The initial dosage of L-T4 is 0.022 mg/kg q12h PO. • Bradycardia.
Once-daily treatment at the same dose is usually ade- • Bilaterally symmetric alopecia does not occur.
quate for resolution of clinical signs and can be used
initially or after twice-daily treatment has resulted in Primary Iatrogenic Hypothyroidism
a good clinical response. • History of treatment for hyperthyroidism.
• Decrease the dosage slightly in dogs over 30 kg. • Lethargy.
• Reevaluate after 6 to 8 weeks of treatment by exam- • Seborrhea sicca and dry haircoat.
ining for resolution of clinical signs and measuring • Obesity is common.
serum T4. • Bilaterally symmetric alopecia does not occur.
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thumb and forefinger, gently palpate the tissues on increased tissue metabolism and oxygen require-
either side of the trachea, starting at the larynx and ments. The cardiac compensatory mechanisms are
moving caudally to the thoracic inlet (see Fig. 1-3 in dilation (in response to volume overload) and hyper-
Chapter 1). trophy (in response to dilation). There also appears
• A small percentage of cats have intrathoracic thyroid to be a direct myopathic effect of thyroid hormones
nodules that evade palpation. on cardiac muscle.
Basal Total Thyroid Hormone ▼ Key Point In most cats with hyperthyroidism, the
Concentration (T4 and T3) diagnosis can be confirmed by a high serum total
The diagnosis of hyperthyroidism is confirmed by T4 concentration alone.
demonstrating increased production of the thyroid hor-
mones. In cats, T4 is the main secretory product of the Free T4 Concentration
thyroid gland. T3 is 3 to 5 times more potent than T4,
but approximately 60% of circulating T3 is produced by
• Determination of the serum concentration of free T4
by dialysis (Free T4 kit, Nichols Institute) is useful in
extrathyroidal 5’-deiodination of T4. Over 99% of cir- the diagnosis of hyperthyroidism in cats, especially in
culating T4 is protein-bound, while approximately 0.1% those cats with clinical signs of the disease and a pal-
is free and metabolically active. Overall control of pable thyroid nodule in which the basal total T4 value
thyroid hormone production is provided by a negative is normal or only slightly elevated.
feedback mechanism of circulating T4 and T3 on TRH
from the hypothalamus and TSH from the anterior pitu-
• Serum free and total T4 concentrations are highly
correlated in hyperthyroidism. However, serum free
itary. In hyperthyroid cats, there is autonomous and T4 concentrations, as measured by equilibrium dialy-
excessive secretion of thyroid hormones from the sis, are more consistently (over 98% of cases) elevated
abnormally functioning thyroid gland. in hyperthyroid cats. More significantly, serum free T4
concentrations are high in 95% of hyperthyroid cats
▼ Key Point High resting serum concentrations of with total T4 values in the normal reference range as
total T4 and, less reliably, T3 are the biochemical a result of mild disease and hormone fluctuation or
hallmarks of hyperthyroidism in the majority of of the suppressive effect of concurrent non-thyroidal
cats with the disease. illness.
• Euthyroid cats with non-thyroidal disease usually
• Over 30% of cats with hyperthyroidism maintain maintain normal free T4 concentrations; however, a
normal serum T3 concentration despite elevation in false-positive elevation of free T4 concentration also
T4. These cats generally have milder disease; serum occurs in approximately 10% of these sick cats
T3 concentration in these cats is expected to increase without hyperthyroidism. Based on reported clinical
eventually. studies, the following recommendations can be made
• Most hyperthyroid cats exhibit a clearly high circu- regarding the use of free T4 as a diagnostic test to
lating total T4 concentration. However, a proportion identify cats with hyperthyroidism:
of hyperthyroid cats (approximately 10% of all cases • In all hyperthyroid cats with a high serum total T4
and 40% of cases with mild hyperthyroidism) have concentration, free T4 concentration is concur-
serum total T4 concentration within the reference rently high and its measurement adds no further
range. Such values are usually within the middle to diagnostic information. Given the expense of free
high end of the reference range. Thus hyperthy- T4 measurement coupled with the necessity for
roidism cannot always be excluded in cats by demon- interpretation with a total T4 estimation, and the
stration of a single total T4 concentration within the high prevalence of high total T4 values in hyper-
normal reference range. thyroid cats, it is more cost effective to initially
• Thyroid hormone concentrations in some cats are measure total T4 concentration alone. If a diagno-
subject to a degree of fluctuation. In cats with mild sis is not confirmed, consideration can be given
disease, serum T4 concentrations have been shown to to measurement of the corresponding free T4
fluctuate in and out of the normal range. The finding concentration.
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• Always measure free T4 in conjunction with a total • Collect a blood sample for T4 and T3 measurements.
T4 determination. In cats with occult hyperthy- • Administer oral T3 (liothyronine: Cytomel,
roidism, the total T4 concentration is expected to SmithKline Beecham) starting the next morning at a
be in the middle to high end of the reference range dosage of 25 mg/cat q8h for 2 days.
limits (i.e., 2.5–4.0 mg/dl; 25–50 nmol/L). • On the morning of the third day, give the cat a final
• Never use free T4 as the sole screening test for 25-mg dose of T3 before returning to the veterinarian
hyperthyroidism because high free T4 concentra- for blood sampling.
tions also occasionally are found in cats with • Measure serum T4 and T3 in the same assay run on
non-thyroidal diseases that do not have hyperthy- both basal and post-exogenous T3 blood samples.
roidism. The reason for high free T4 concentra- • In cats with hyperthyroidism, minimal, if any,
tions in these cats with non-thyroidal disease is suppression of serum T4 occurs. A rise in serum T3
unclear, but almost all of these cats have serum concentration confirms owner compliance in admin-
total T4 concentrations that are below or at the low istering the drug to the cat.
end of the reference range.
• Free T4 by dialysis is a useful diagnostic test for Thyrotropin-Releasing Hormone Stimulation Test
hyperthyroidism and eliminates the need for
provocative testing (T3 suppression test or TRH Administration of TRH stimulates pituitary TSH secre-
stimulation test; see the following section) in most tion and produces a subsequent rise in thyroidal T4
cases. However, in order to interpret the test result, secretion in the normal cat. In cats with autonomously
the cat must have clinical signs (i.e., weight loss hyperfunctioning thyroid adenomas, TSH secretion has
despite a good appetite) and physical exam find- been chronically suppressed and exogenous TRH
ings (i.e., a palpable thyroid nodule) that are con- administration does not appreciably affect the pituitary-
sistent with hyperthyroidism. thyroid axis. The protocol for the TRH stimulation test
• If a high free T4 concentration is found in a cat is as follows:
without classic clinical signs of hyperthyroidism, • Collect a blood sample for serum T4 measurement.
and especially if a thyroid nodule cannot be pal- • Administer TRH at a dosage of 0.1 mg/kg IV.
pated, repeat the tests (total and free T4 determi- • Collect another blood sample for serum T4 measure-
nations) in 2 to 4 weeks. Alternatively, use one of ment 4 hours later.
the provocative tests (T3 suppression or TRH stim- • Although the effects are transient, TRH administra-
ulation; see the following section) to confirm tion causes hypersalivation, tachypnea, and vomiting
hyperthyroidism. in most cats. However, this test is less time consum-
ing than the T3 suppression test and does not rely on
Provocative Thyroid Tests owner compliance.
• Interpretation:
In the majority of hyperthyroid cats with reference- • Administration of TRH to normal cats and cats with
range total T4 concentration, identification of concur- non-thyroidal disease causes a twofold or greater
rent disease, repeat total T4 analysis, or simultaneous increase in serum T4 concentrations at 4 hours.
measurement of free T4 allows confirmation of the diag- • In contrast, serum T4 concentration in cats with
nosis. Further diagnostic tests are rarely required. mild hyperthyroidism generally increases little, if at
However, dynamic thyroid function tests have been rec- all, after administration of TRH.
ommended in the past as helpful in confirming a diag-
nosis of hyperthyroidism. Currently, the T3 suppression
or TRH stimulation tests should only considered in cats
Thyroid Radionuclide Uptake and Imaging
with clinical signs suggestive of hyperthyroidism when • Increased thyroidal uptake of radioiodine after the
repeated total T4 concentration remains within the administration of a small tracer dose of radionuclide
reference range or free T4 analysis is unavailable or is a characteristic finding in cats with hyperthy-
inconclusive. roidism. However, the relative lack of nuclear medi-
cine facilities available to small animal practitioners
limits the usefulness of this diagnostic modality to
Triiodothyronine Suppression Test referral hospitals.
Administration of exogenous T3 causes suppression of • Thyroid imaging (scanning) can be performed using
pituitary TSH secretion and a subsequent drop in thy- either radioiodine or pertechnetate and is useful in
roidal T4 secretion in the normal cat. In cats with delineating hyperfunctioning thyroid tissue. This
autonomously hyperfunctioning thyroid adenomas, technique is a helpful adjunct in the diagnosis of
TSH secretion has been chronically suppressed and hyperthyroidism in cats and provides valuable pre-
exogenous T3 administration does not appreciably operative information. The disadvantages are that
affect the pituitary-thyroid axis. The protocol for the T3 nuclear medicine facilities are required and that the
suppression test is as follows: cat generally needs to be sedated for the procedure.
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the median survival time was 24 months and 89%, Distant metastasis, especially to the lungs, occurs in 60%
72%, 52%, and 34% of cats were alive at 1, 2, 3, and to 80% of cases. The prognosis associated with most of
4 years after treatment, respectively. these tumors is poor. However, early detection and sur-
gical removal of small, non-invasive thyroid carcinomas
Effect of Treatment on Renal Function can result in good survival rates (up to 3 years).
• Hyperthyroidism is known to increase glomerular fil- Clinical Signs
tration rate (GFR), decrease circulating creatinine
concentration, and mask underlying renal disease. See Table 31-3.
All treatments for hyperthyroidism have been associ-
ated with a decrease in GFR capable of unmasking Non-thyrotoxic Thyroid Tumors
latent renal disease. Therefore renal dysfunction Clinical signs are related to structural damage to the
should always be considered a potential adverse reac- cervical area and metastatic disease.
tion of treatment and assessed if clinical signs
develop. • A palpable cervical mass (goiter) is often firm,
• Predicting those cats in which renal failure is likely to attached to surrounding soft tissues, and irregular in
develop is difficult. In the absence of methods for shape.
accurately measuring GFR in practice, serum urea • Respiratory distress and cough.
and creatinine concentrations and urine specific • Vomiting.
gravity should be carefully evaluated in individual • Dysphagia.
cases. If any parameter is considered abnormal, then • Anorexia.
renal failure may develop upon treatment of the • Weight loss.
hyperthyroidism.
• Antithyroid medication offers the optimum treat- Hyperfunctional Thyroid Tumors
ment when there is evidence of pre-existing renal See “Hyperthyroidism in Cats” for an explanation of the
disease. If there is no discernible deterioration of pathophysiology of similar signs.
renal function once euthyroidism has been achieved
medically, other more permanent treatment options • A palpable cervical mass (goiter) is often firm,
(surgery, radioactive iodine) may be considered. If attached to surrounding soft tissues, and irregular in
renal function deteriorates, the effects of the drug shape.
will dissipate within 48 hours of withdrawal. • Polydipsia and polyuria are common.
• The decision whether to continue treatment for • Weight loss.
hyperthyroidism depends on which of the two dis- • Polyphagia.
eases is more severe. Maintenance of a mildly hyper- • Heat and stress intolerance.
thyroid state may be beneficial in some cases. • Nervousness and hyperexcitability.
However, preliminary studies suggest that although
there may be an initial effect of treatment on GFR,
this is not a progressive problem in the long term.
However, avoidance of hypothyroidism is important Table 31-3. INCIDENCE OF CLINICAL SIGNS
because it may have its own detrimental effect on IN DOGS WITH THYROID TUMOR
GFR.
Sign Percentage of Cases
Surgery
See under “Thyroidectomy.”
• Thyroidectomy can be a difficult procedure.
• Complete excision of a thyroid carcinoma is un- Cranial thyroid
common unless the tumor is small and not locally artery
invasive (moveable on palpation).
Parathyroid gland
Chemotherapy
Thyroid gland
• Doxorubicin 30 mg/m2 body surface area (for a con-
version table, see Chapter 26), IV, every 3 weeks for
five treatments.
• A potentially limiting long-term side effect of Carotid artery
doxorubicin is congestive cardiomyopathy.
• Combination treatment with doxorubicin and
cyclophosphamide has been used with varying
degrees of success and with less cardiac toxicity. Figure 31-1. Gross appearance of bilateral thyroid tumors in a cat.
W0422-Ch031.qxd 11/10/05 5:00 PM Page 339
A B C
Esophagus
Recurrent
Recurrent laryngeal
laryngeal nerve
nerve
Thyroid
tumor
Esophageal tube Figure 31-5. Remove canine thyroid tumors with a combination
of blunt and sharp dissection. Finger dissection of the tumor and sur-
rounding structures may be necessary for large invasive tumors. Be
Carotid careful when handling the recurrent laryngeal nerve to avoid the
arteries possibility of postoperative laryngeal paralysis.
a. These tumors are very vascular, and dissection is with simple continuous, absorbable suture; and
difficult. the skin with simple interrupted, non-absorbable
b. Avoid injury to the esophagus, carotid artery, suture.
jugular vein, vagosympathetic trunk, and recur-
rent laryngeal nerve (Fig. 31-4). Postoperative Care and Complications
c. A stomach tube or small endotracheal tube in the
esophagus helps identify this structure. Short-Term
d. Ligate or cauterize the extensive vascular network • Closely monitor for hemorrhage or seroma
and carefully dissect out the tumor (Fig. 31-5). formation.
Begin dissection at the caudal aspect of the tumor • Check serum calcium concentrations at least 2 to 4
and gradually work cranially. days postoperatively if a bilateral thyroidectomy was
e. Identify and preserve the parathyroid glands if performed. Monitor the calcium concentrations
bilateral thyroidectomy is performed. With large longer if decreasing. Treat hypoparathyroidism if
malignant tumors, this may be impossible. necessary, according to the guidelines in Chapter 32.
f. If complete removal is impossible, debulk the • Check serum T3 and T4 levels if bilateral thyroidec-
mass, leaving the portion closest to the larynx tomy is performed. Treat hypothyroidism if present
intact to preserve the parathyroid glands. Bleed- (see previous discussion of hypothyroidism).
ing from the remaining thyroid tissue may be
difficult to control.
3. Closure
Long-Term
a. Place Penrose drains or a closed suction drain if • Reevaluate the dog frequently (every 3 months) for
significant dead space results from tumor recurrence of the primary tumor and metastasis.
removal. Have the drains exit through separate • Consider postoperative chemotherapy or radiother-
stab incisions. apy if the tumor was malignant (see previous discus-
b. Close the muscle routinely with simple continu- sion on treatment of thyroid tumors and Chapter 26
ous, absorbable suture; the subcutaneous tissue on chemotherapy).
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▼ Chapter
32 Diseases of the Parathyroid Gland
and Calcium Metabolism
Patricia A. Schenck / Dennis J. Chew
▼ Key Point Ionized calcium is the biologically active ▼ Key Point The net effects of PTH are to increase
fraction of serum total calcium. serum ionized calcium and to decrease serum
phosphorus concentrations.
• Ionized calcium: This is the biologically active fraction
of calcium and accounts for approximately 55% of Calcitonin
the total serum calcium concentration in dogs.
• Complexed calcium: Complexed calcium accounts for Calcitonin is synthesized by C cells in the thyroid gland
approximately 10% of the total serum calcium con- and is secreted in response to hypercalcemia and to a
centration in dogs but may be elevated in chronic calcium-rich meal. The effects of calcitonin on normal
renal failure (CRF). Complexed calcium may be calcium homeostasis are considered minor. The major
bound to anions such as lactate, phosphate, bicar- target site for calcitonin is bone, where it inhibits
bonate, sulfate, citrate, and oxalate. resorption of calcium and phosphorus.
• Protein-bound calcium: Protein-bound calcium
accounts for approximately 35% of the total serum Vitamin D Metabolites
calcium concentration. Albumin is the primary
The cholecalciferol (vitamin D3 of animal origin)
protein bound to calcium. Protein binding is affected
metabolites 25-hydroxyvitamin D3 (calcidiol) and 1,25-
by changes in pH, with increased binding as pH
dihydroxyvitamin D3 (calcitriol) are the most important
increases and decreased binding as pH decreases.
vitamin D metabolites. These metabolites may also be
derived from ergocalciferol (vitamin D2 of plant origin),
Regulation of Calcium and are equally bioactive. Dogs and cats inefficiently
Regulation of serum calcium concentration is complex photosynthesize vitamin D in their skin and conse-
and requires the integrated actions of parathyroid quently are dependent on vitamin D in their diet.
hormone (PTH), vitamin D metabolites, and calcitonin. Hydroxylation of vitamin D occurs in the liver to
The intestine, kidney, and bone are the major target produce 25-hydroxyvitamin D. This 25-hydroxyvitamin
343
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D is further hydroxylated in the proximal tubule of the tration does not parallel total calcium concentration,
kidney to form calcitriol. and thus ionized calcium concentration must be mea-
sured for an accurate assessment of calcium status. Total
Calcitriol calcium is usually measured using a colorimetric
Calcitriol is the only active metabolite of vitamin D. Cal- method and may be spuriously elevated if hyperlipemia
citriol increases serum calcium and phosphorus con- or hemolysis is present.
centrations and acts on the intestine, kidney, and bone.
Adjusted Total Calcium Values
• Bone: Calcitriol stimulates osteoclastic calcium mobi-
lization and resorption of bone. Formulas to adjust serum total calcium to albumin or
• Intestine: Calcitriol increases calcium, phosphorus, total protein concentration have been published for
and magnesium absorption. dogs. Due to a high level of diagnostic discordance
• Kidney: Calcitriol increases renal tubular resorption between adjusted total calcium and ionized calcium
of calcium and phosphorus. concentrations, the use of these formulas is
discouraged.
▼ Key Point The net effect of calcitriol is to increase
both serum ionized calcium and serum phospho- Ionized Calcium Concentration
rus concentrations.
• Ion-selective methods are available in some laborato-
ries. Special handling of serum or heparinized
DIAGNOSTIC TESTS OF CALCIUM plasma is necessary to prevent lowering of ionized
calcium due to pH increases. Serum samples
METABOLISM appear to be stable for 72 hours at 4∞C if handled
anaerobically. Some laboratories have developed
Measurement of total calcium, ionized calcium, and species-specific pH adjustment formulas to allow
hormones of calcium metabolism aid in the diagnosis measurement of aerobically handled samples.
of calcium disorders (see Tables 32-1 and 32-2).
• A handheld analyzer is also available for cage-side
analyses. Heparinized whole blood is used for
Total Serum Calcium measurement; for best results, a standard quantity
Total serum calcium is part of most routine serum of dry heparin and blood should be utilized for
profile evaluations. However, ionized calcium concen- each assay.
1,25(OH)2-D, 1,25-dihydroxyvitamin D3; 25(OH)-D, 25-hydroxyvitamin D3; alb, albumin; Corr tCa, corrected total calcium; iCa, ionized calcium; N, normal;
Pi, phosphorus; PTG, parathyroid glands; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; tCa, total calcium; US, ultrasound.
W0422-Ch032.qxd 11/10/05 5:09 PM Page 345
Primary Ø Ø N Ø ≠N ØN N N NØ MultipleØ
hypoparathyroidism
Pseudohypoparathyroidism Ø NØ N Ø ≠N ≠ N N N≠ N≠
Sepsis/critical care ØN Ø N ØN N≠ ≠N N N N N
Ethylene glycol toxicity Ø Ø N Ø ≠N ≠ N N ØN N
Paraneoplastic Ø Ø N Ø Ø ≠N N N N N≠
Phosphate enema Ø Ø N Ø ≠ ≠ N N NØ≠ N
Eclampsia Ø Ø N Ø Ø Mild≠, N N N NØ N
Hypoalbuminemia Ø ØN Ø N N N≠ N N N≠ N≠
1,25(OH)2, 1,25-dihydroxyvitamin D3; 25(OH)-D, 25-hydroxyvitamin D3; alb, albumin; Corr tCa, corrected total calcium; iCa, ionized calcium; N, normat;
Pi, phosphorus; PTG, parathyroid glands; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; tCa, total calcium; US, ultrasound.
Parathyroid Hormone
HYPERCALCEMIA
The PTH molecule is composed of three portions:
amino-terminus, mid-molecule, and carboxy-terminus. Defining Criteria
The amino-terminus is the biologically active portion of
the molecule. An intact PTH assay (a two-site assay) pro- • Serum total calcium concentration
vides accurate determination of PTH concentration. • Dogs: >12.0 mg/dl (3.0 mmol/L)
PTH fragments are excreted by the kidneys. In animals • Cats: >11.0 mg/dl (2.75 mmol/L)
with renal failure, concentration of inactive fragments • Serum ionized calcium concentration
may increase. Only an intact PTH assay should be used • Dogs: >5.8 mg/dl (1.45 mmol/L)
in patients with renal disease or failure. Serum or sepa- • Cats: >5.6 mg/dl (1.40 mmol/L)
rated plasma samples can be assayed but should be kept • Young dogs may have a mild hypercalcemia (usually
refrigerated or frozen prior to assay. <13.0 mg/dl total serum calcium concentration)
related to skeletal growth.
Parathyroid Hormone-Related Protein • Hyperlipemia and/or hemolysis of the sample may
result in spurious elevations of calcium.
The parathyroid hormone-related protein (PTHrP) is a
hormone secreted by some malignant neoplasms in
animals with hypercalcemia. This hormone can bind to ▼ Key Point Severe clinical signs are associated with
PTH receptors in the kidneys and bone and result in a serum total calcium concentration >18 mg/dl.
humoral hypercalcemia of malignancy (HHM). Sepa-
rated plasma samples can be assayed but should be kept Etiology
refrigerated or frozen prior to assay.
Hypercalcemia may be parathyroid-dependent (pri-
Vitamin D Metabolites mary hyperparathyroidism) or parathyroid-independent
(normal functioning of the parathyroid gland).
• 25-hydroxyvitamin D3 (calcidiol)
• Metabolites of vitamin D3 are chemically identical • In parathyroid-independent hypercalcemia, elevated
in all species. Calcidiol concentration is a good ionized calcium concentration causes suppression of
indicator of vitamin D3 ingestion and can be used PTH production. On analysis, ionized calcium con-
to diagnose hypovitaminosis or hypervitaminosis D. centration is elevated, and PTH concentration is in
Serum or separated plasma can be assayed, but the lower part of or below the reference range.
samples should be protected from degradation due PTHrP concentration may be elevated if there is a
to exposure to light. tumor producing PTHrP. Concentration of 25-
• 1,25-dihydroxyvitamin D3 (calcitriol) hydroxyvitamin D3 may be elevated in cases of vitamin
• Calcitriol is the most active vitamin D metabolite, D toxicity.
and it circulates in low concentrations. Assays have • Parathyroid-dependent hypercalcemia (primary hy-
been developed for calcitriol but are not readily perparathyroidism) is characterized by elevated
available due to cost. ionized calcium concentration without the appropri-
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ate suppression of PTH production due to a PTH- • Anorexia, vomiting, and constipation can result from
secreting tumor of the parathyroid gland. decreased excitability of gastrointestinal smooth
muscle.
See Table 32-3 for a list of hypercalcemia-related
conditions.
• Generalized weakness may develop from decreased
muscle excitability.
Clinical Signs • Depression, muscle twitching, and seizures can occur
as neurologic manifestations.
Clinical signs in hypercalcemia depend on the magni- • Cardiac arrhythmias can develop from direct
tude of the calcium elevation, how quickly the hyper- effects on the myocardium or secondary to cardiac
calcemia developed, and the duration of the mineralization.
hypercalcemia. Serum total calcium concentrations of
<15 mg/dl (<3.75 mmol/L) may not be associated with ▼ Key Point Polydipsia and polyuria are the most
systemic signs; however, serum total calcium concentra- common clinical signs of hypercalcemia.
tions of >18 mg/dl (>4.5 mmol/L) are often associated
with severe life-threatening signs. Soft tissue mineral- Diagnosis
ization may occur with prolonged hypercalcemia when
Abnormalities depend on the underlying cause, sever-
the product of total calcium (mg/dl) times serum phos-
ity, and duration of hypercalcemia (see later under
phorus (mg/dl) equals 70 or greater.
“Conditions Associated with Hypercalcemia”).
• Polydipsia and polyuria are the most common signs
of hypercalcemia in dogs due to direct stimulation of History and Physical Examination
the thirst center and a decreased ability of the kidneys
to concentrate urine.
• A complete history and thorough physical examina-
tion are essential for diagnosing the cause of hyper-
calcemia. Obtain dietary history to assess the possibility
of over-supplementation or under-supplementation
with vitamin D.
Table 32-3. CONDITIONS ASSOCIATED
WITH HYPERCALCEMIA Laboratory Tests
Nonpathologic Conditions • Perform a complete blood count (CBC) and serum
Hyperlipemia chemistry profile, and consider tests such as serum
Non-fasted serum samples ionized calcium, PTH, 25-hydroxyvitamin D, and
Young growing dogs
Laboratory error or improper handling of sample PTHrP concentrations. Collect samples for diagnos-
tic testing prior to treatment.
Transient Conditions
Hemoconcentration
Hyperproteinemia Radiography and Ultrasound
Pathologic Conditions • Soft tissue mineralization of the kidneys, heart, lungs
Parathyroid-dependent hypercalcemia stomach, and other tissues may be detected.
Primary hyperparathyroidism
Parathyroid-independent hypercalcemia • Abdominal masses, mediastinal masses, pulmonary
Malignancy-associated hypercalcemia lesions suggestive of metastasis, or lymph node
Lymphoma enlargement especially in the tracheobronchial
Adenocarcinoma of the apocrine glands of the anal sac region may be visualized.
Multiple myeloma
Metastatic bone tumors
Miscellaneous tumors (lymphocytic leukemia, mammary Electrocardiography
carcinoma, fibrosarcoma, pancreatic adenocarcinoma,
testicular interstitial cell tumor, lung carcinoma, squamous • Prolongation of the PR interval, shortening of the QT
cell carcinoma, thyroid adenocarcinoma, osteosarcoma) interval, and cardiac arrhythmias (ventricular fibril-
Hypoadrenocorticism lation) may develop with severe hypercalcemia.
Renal failure
Hypervitaminosis D Principles of Treating Hypercalcemia
Cholecalciferol (rodenticide) toxicity
Dovonex ingestion
Iatrogenic due to dietary supplementation ▼ Key Point The definitive treatment for hypercal-
Houseplants (Cestrum diurnum, Solanum malacoxylon, Trisetum cemia is to remove the underlying cause.
flavescens)
Granulomatous disease (blastomycosis, schistosomiasis) Unfortunately, the etiology may not be apparent, and
Grape toxicity
Bone lesions (sepsis, disuse osteoporosis)
supportive measures must be taken to decrease the
Severe hypothermia serum calcium concentration (see Table 32-4 for spe-
Idiopathic hypercalcemia in cats cific drugs and dosage recommendations). Supportive
measures may include the following.
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Volume Expansion
SQ saline (0.9%) 75–100 ml/kg/day Mild hypercalcemia Contraindicated if peripheral
edema is present
IV saline (0.9%) 100–125 ml/kg/day Moderate to severe Contraindicated in congestive
hypercalcemia heart failure and hypertension
Diuretics
Furosemide 2–4 mg/kg q8–12h IV, SC, PO Moderate to severe Volume expansion is necessary
hypercalcemia prior to use of this drug
Glucocorticoids
Prednisone 1–2.2 mg/kg q12h PO, SC, IV Moderate to severe Use of these drugs prior to
Dexamethasone 0.1–0.22 mg/kg q12h IV, SC hypercalcemia identification of etiology may
make definitive diagnosis
difficult
Inhibition of Bone Resorption
Calcitonin 4–6 IU/kg q8–12h SC Hypervitaminosis D toxicity Response may be short lived;
vomiting may occur
Bisphosphonates
Etidronate (EHDP) 5–15 mg/kg daily to q12h Moderate to severe Expensive; use in dogs limited
hypercalcemia
Clodronate 20–25 mg/kg in 4-hr IV infusion Approved in Europe; availability
in U.S. limited
Pamidronate 1.3 to 2.0 mg/kg in 150-ml 0.9%
saline in 2-hr IV infusion; can
repeat in 1–3 wks
EHDP, ethane-1-hydroxy-1,1-diphosphonate.
Hypoadrenocorticism Treatment
• Approximately 30% of dogs with hypoadrenocorti- • Feed a low-calcium diet (most renal diets) and restrict
cism (Addison’s disease) have mild to moderate hyper- intake of dairy products.
calcemia (total calcium concentration <15 mg/dl). • Give phosphate binders that do not contain calcium
Ionized calcium concentration may be normal or (e.g., aluminum hydroxide, Amphojel, Wyeth-Ayerst;
slightly elevated. 10–30 mg/kg q8h PO with meals), to decrease the
• Multiple factors resulting in hypercalcemia include calcium X phosphorus product.
increased calcium citrate (complexed calcium), • In severe cases of hypercalcemia, aggressive treat-
hemoconcentration (relative increase), increase in ment with IV fluids, furosemide, prednisone, and/or
renal resorption of calcium, and increased binding of calcitonin may be necessary for several weeks.
calcium to serum proteins. • Recent reports show that intermittent IV
• Hypercalcemia usually resolves quickly with therapy pamidronate is effective treatment in dogs and is
for hypoadrenocorticism. superior to calcitonin as ancillary treatment for long-
term effects.
• Because of the prolonged half-life of 25-hydroxyvita-
Hypervitaminosis D min D3, monitor serum calcium, phosphorus, and
creatinine weekly for 4 to 6 weeks. If aggressive
With hypervitaminosis D, ionized calcium concentra-
therapy is maintained for several weeks, complete
tion is elevated with suppression of PTH production.
recovery can be achieved, depending upon the extent
Elevation of 25-hydroxyvitamin D3 may be observed
of the initial renal injury.
depending on the vitamin D metabolites present.
Dovonex Ingestion
▼ Key Point In vitamin D toxicosis, hyperphos-
phatemia often accompanies hypercalcemia.
• Dovonex is a calcipotriene-containing cream used to
treat human psoriasis. This cream contains 50 mg of
calcipotriene per gram of cream, and the oral LD50
in dogs is reportedly 100 to 150 mg/kg of body weight.
Rodenticides Containing Cholecalciferol
• Calcipotriene has a shorter duration of action than
Cholecalciferol-based rodenticides have gained popu- cholecalciferol, so the duration of effect is shorter.
larity over anticoagulant rodenticides because, unlike • Measured concentration of 25-hydroxyvitamin D3 is
anticoagulant rodenticides, there is no rodenticide usually normal since calcipotriene is not detected by
resistance, and there is no secondary toxicity to species this assay.
that ingest poisoned rodents. Although one manufac-
turer (Bell Labs) reports the median lethal dose (LD50)
Iatrogenic Vitamin D Intoxication
to be 88 mg/kg of body weight, toxicity in dogs and cats
has been seen with much lower doses (<10 mg/kg). The • Iatrogenic vitamin D intoxication may occur follow-
effect may last for weeks. ing the administration of vitamin D products and
dietary supplements. Use of ergocalciferol (vitamin
Clinical Manifestations D2) may cause hypercalcemia because its slow onset
of action and prolonged duration of action make it
• Clinical signs are vague and related to hypercalcemia difficult to dose correctly.
(see “Clinical Signs” under “Hypercalcemia”). • Treatment is directed at discontinuing the supple-
• Hypercalcemia is often severe (serum total calcium ment or decreasing the dose of vitamin D.
of 15–20 mg/dl; ionized calcium concentration of
1.9–2.5 mmol/L) and accompanied by hyperphos-
phatemia at initial presentation. Concentration of
Houseplant Ingestion
25-hydroxyvitamin D3 is typically elevated. Houseplants such as Cestrum diurnum (day-blooming
• Azotemia may occur several days after ingestion sec- jessamine), Solanum malacoxylon, and Trisetum flavescens
ondary to renal damage from hypercalcemia. contain a substance similar to calcitriol that may cause
hypercalcemia when ingested.
Goals of Treatment
• Decrease cholecalciferol absorption in the gastroin- Granulomatous Diseases
testinal tract. Granulomatous disorders such as systemic fungal dis-
• Correct the fluid and electrolyte imbalances. eases and tuberculosis are rare causes of hypercalcemia
• Reduce hypercalcemia. in dogs possibly due to increased vitamin D metabolites.
• Treat miscellaneous complications such as seizures Serum calcium concentrations return to normal with
and cardiac arrhythmias. treatment (e.g., antifungal drugs or surgical removal).
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or an ionized calcium concentration <5.0 mg/dl • Behavior changes (restlessness, aggression, panting,
(1.25 mmol/L) in dogs or <4.0 mg/dl (1.00 mmol/L) hypersensitivity to stimuli, and disorientation) are
in cats. Normal serum total calcium may be slightly frequent.
lower in older animals than in middle-aged animals. • Bradycardia, hyperthermia, polyuria, polydipsia, and
vomiting are sometimes seen.
Etiology
Causes of hypocalcemia are listed in Table 32-5. Hypoal- Diagnostic Evaluation
buminemia is the most common cause of a low serum
History and Physical Examination
total calcium concentration; however, it is of no clinical
consequence because only the protein-bound fraction • A complete history (including dietary history) and a
is affected. A mildly decreased serum calcium without thorough physical examination can aid in the diag-
signs of hypocalcemia can be seen in various systemic nosis of the underlying cause of the hypocalcemia.
conditions such as renal failure, pancreatitis, and
intestinal malabsorption. Conditions associated with Routine Laboratory Tests
symptomatic hypocalcemia are discussed. • Evaluation of CBC and serum chemistry profile may
aid in the diagnosis of hypocalcemia. Both serum
Clinical Signs total calcium and ionized calcium concentrations
The severity of clinical signs may not always be may be decreased; however, in patients with renal
commensurate with the degree of hypocalcemia. failure or hypoproteinemia, ionized calcium may not
Concurrent acid-base disorders, other electrolyte parallel changes in total calcium. Measurement of
imbalances, and ionized calcium concentration play a serum ionized magnesium concentration may reveal
role in the development of clinical signs that are often a decreased concentration. Changes in serum phos-
episodic. phorus may support a specific diagnosis.
• Tremors, twitching, tetany, muscle spasms, facial Endocrine Testing
rubbing, and gait changes (stiffness and ataxia) result
from increased neuromuscular excitability. Occa- • Measurement of PTH concentration is helpful in
sionally, generalized seizure activity is seen. diagnosing hypoparathyroidism. Determination of
serum 25-hydroxyvitamin D3 concentration may also
be of benefit to exclude other causes.
Electrocardiography
• Hypocalcemia may cause prolongation of QT inter-
Table 32-5. CONDITIONS ASSOCIATED val and ventricular premature contractions on an
WITH HYPOCALCEMIA electrocardiogram (ECG).
Causes of Severe Symptomatic Hypocalcemia
Puerperal tetany/eclampsia Principles of Treating Hypocalcemia
Hypoparathyroidism
Spontaneous (lymphocytic parathyroiditis) The definitive treatment for hypocalcemia is to elimi-
Iatrogenic secondary to bilateral thyroidectomy nate the underlying cause. Specific treatment options
Postoperative secondary to removal of parathyroid adenoma/ for hypocalcemia are listed in Table 32-6.
carcinoma
Phosphate enemas (acute hyperphosphatemia causes reciprocal
calcium decrease) Parenteral Calcium
Causes of Mild Asymptomatic Hypocalcemia Parenteral calcium may be necessary in patients with
Hypoalbuminemia (most frequent cause of hypocalcemia) active tetany, hyperthermia, and seizures.
Primary renal disease
Chronic renal failure • Calcium gluconate and calcium chloride usually are
Acute renal failure (e.g., urethral obstruction, ethylene glycol given by slow IV administration.
toxicity)
Pancreatitis
• Signs of toxicity from injection of excess calcium too
Intestinal malabsorption syndromes quickly include bradycardia and shortening of the
Chelating agents that bind calcium (EDTA, citrates, oxalates, QT interval.
phosphates) • Calcium can also be diluted in saline and given as a
Rhabdomyolysis due to soft tissue trauma continuous IV drip to maintain normal serum
Nutritional secondary hyperparathyroidism
Dilutional with infusion of calcium-free fluids calcium concentrations.
Laboratory error/artifact • Calcium gluconate (even if diluted with saline)
Idiopathic (unexplained) should not be given subcutaneously due to the occur-
rence of dermal necrosis and severe granulomatous
EDTA, ethylenediaminetetraacetic acid. inflammation.
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Parenteral Calcium*
Calcium gluconate 10% solution 9.3 mg of a. Slow IV to effect Stop if bradycardia or shortened
Ca/ml (0.5–1.5 ml/kg IV) QT interval occurs
Infusion to maintain normal calcium
b. 5–15 mg/kg/hr IV SQ calcium salts are not
recommended; they can cause
severe skin necrosis/mineralization
Calcium chloride 10% solution 27.2 mg of 5–15 mg/kg/hr IV Only given IV as extremely caustic
Ca/ml perivascularly
Oral Calcium†
Calcium carbonate Many sizes 40% tablet 25–50 mg/kg/day Most common calcium supplement
Calcium lactate 325-, 650-mg tabs 13% tablet 25–50 mg/kg/day
Calcium chloride Powder 27.2% 25–50 mg/kg/day May cause gastric irritation
Calcium gluconate Many sizes 10% 25–50 mg/kg/day
Vitamin D Time for Maximal Time for Toxicity
Effect to Occur: Effect to Resolve:
Vitamin D2 Initial: 4000–6000 U/kg/day 5–21 days 1–18 wks
(ergocalciferol) Maintenance: 1000–2000 U/kg
once daily to once weekly
Dihydrotachysterol Initial: 20–30 ng/kg/day 1–7 days 1–3 wks
Maintenance: 10–20 ng/kg
q24–48h
1,25-(OH)2D3 (calcitriol) Initial: 20–30 ng/kg/day for 1–4 days 2–14 days
3–4 days
Maintenance: 5–15 ng/kg/day
*Do not mix calcium solution with bicarbonate-containing fluids as precipitation may occur.
†
Calculate dose based on elemental calcium content.
further elevation of serum calcium levels to prevent 32-3) to reduce risks of anesthesia and surgery if
calcium-induced renal damage from the resulting possible.
hypercalciuria. • To reduce the possibility of postoperative hypercal-
• If hypocalcemic tetany or seizures are present, imme- cemia, treat with calcitriol (see Table 32-6) for 1 to 2
diately administer calcium IV. weeks prior to parathyroidectomy.
• For maintenance of normocalcemia, supplement oral
calcium and vitamin D compounds (see Table 32-6). Surgical Procedure
If serum magnesium concentration is also low,
magnesium supplementation may be required Objectives
for adequate maintenance of ionized calcium • Explore the thyroid and parathyroid region.
concentration. • Remove the parathyroid adenoma.
• Hypercalcemia is a common complication of vitamin • Maintain meticulous hemostasis.
D therapy, and onset may be delayed and duration
may be prolonged depending on the type of vitamin
D supplementation used. When starting vitamin D Equipment
therapy, monitor serum calcium concentrations • Standard general surgical pack and suture
weekly at first then monthly when serum calcium has • Self-retaining retractors (e.g., Gelpi)
stabilized at the desired level. If hypercalcemia does • Magnifying loop (optional)
occur as a complication of treatment, manage as dis-
cussed previously under “Hypercalcemia.” Discon-
tinue calcium supplementation and use vitamin D Technique
alone at a lower dosage for maintenance or switch to 1. Place the dog in dorsal recumbency with the fore-
a more manageable vitamin D metabolite such as limbs tied caudally and the neck hyperextended with
calcitriol. a rolled towel.
2. Prepare the ventral cervical region from caudal
Treatment for Iatrogenic Hypoparathyroidism mandible to manubrium for aseptic surgery.
3. Incise the skin on the ventral midline from larynx to
• Supplement calcium and vitamin D compounds post- manubrium.
operatively (see Table 32-6). If serum calcium con-
4. Separate the paired sternohyoideus and sternothy-
centrations remain normal, discontinue calcium
roideus muscles.
supplementation and then gradually decrease and
5. Exploration.
finally discontinue vitamin D supplementation. Eval-
a. Identify all four parathyroid glands if possible.
uate serum calcium concentrations weekly for 1
The non-adenomatous glands are often atrophied
month. If hypocalcemia returns, reinstitute vitamin D
and difficult to identify.
and calcium supplementation. Occasionally, perma-
b. Parathyroid adenomas are firm, whitish, solid
nent supplementation is necessary.
structures 4 to 20 mm in diameter. They are
sometimes more hyperemic than the normal
parathyroids.
PARATHYROIDECTOMY c. If an enlarged parathyroid gland is cystic, it is
probably not a neoplasm but an incidental con-
Parathyroidectomy is the treatment of choice for genital cyst.
primary hyperparathyroidism caused by benign d. If a readily identifiable mass is not found in the
functional adenomas of the parathyroid gland in thyroid area, explore the accessible region along
dogs. Functional adenocarcinomas are very rare. the trachea to the base of the neck and cranial
Parathyroidectomy is an infrequent procedure because
mediastinum.
primary hyperparathyroidism is uncommon in dogs and
e. Avoid injury to the carotid sheath structures and
extremely rare in cats.
recurrent laryngeal nerves.
Familiarity with normal thyroid and parathyroid
6. Dissection of the mass.
anatomy is essential before surgery.
a. Perform complete excision of the mass, using
appropriate blunt and sharp dissection. Remove
Preoperative Considerations the associated thyroid lobe if necessary to achieve
• Always submit all excised parathyroid gland tissue for complete resection of the tumor (see Chapter 31).
histopathology to confirm the diagnosis. b. Carefully examine the surgical field for evidence
• Ectopic parathyroid gland adenomas are uncommon of residual hemorrhage prior to closure.
but may be present in the cranial mediastinum or 7. Routinely close the muscle (simple continuous
near the base of the heart. absorbable suture), subcutaneous tissue (simple con-
• If the animal is hypercalcemic, attempt preopera- tinuous absorbable suture), and skin (simple inter-
tively to decrease serum calcium levels (see Table rupted non-absorbable monofilament suture).
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▼ Chapter
33 Diseases of the Adrenal Gland
Peter P. Kintzer / Mark E. Peterson
Signalment
HYPOADRENOCORTICISM IN DOGS AND CATS
• Age: Most dogs and cats are young to middle-aged, but
Hypoadrenocorticism is an endocrinopathy character- can range in age from 6 months to over 10 years.
ized by a deficiency of glucocorticoid and/or miner- • Breed: In dogs, any breed can be affected, but Great
alocorticoid secretion from the adrenal cortex. Danes, Portuguese water dogs, rottweilers, standard
Spontaneous hypoadrenocorticism is uncommon in poodles, West Highland white terriers, and Wheaton
dogs and is rare in cats. terriers appear to be at an increased risk of develop-
ing naturally occurring primary hypoadrenocorti-
cism. No breed predilection has been reported in
Etiology cats.
Primary Adrenocortical Insufficiency • Sex: Female dogs are at an increased risk of develop-
ing naturally occurring primary hypoadrenocorticism
Primary adrenocortical insufficiency (Addison disease) (71% females in one study). No sex predilection has
is the result of atrophy or destruction of all layers of the been reported in cats.
adrenal cortex, usually resulting in glucocorticoid and
mineralocorticoid deficiency. Potential causes include Clinical Signs
the following:
No historical or clinical finding or set of clinical signs
• Idiopathic (probably immune mediated). is pathognomonic for hypoadrenocorticism, and most
• Iatrogenic, which can result from mitotane therapy clinical signs occur frequently in various other more
of hyperadrenocorticism in dogs. Mineralocorticoid common disorders. The severity and duration of clini-
concentrations remain normal in most dogs, and the cal signs vary greatly among patients. A high index
glucocorticoid deficiency is usually transient (weeks of suspicion is needed to recognize some cases of
to months). However, permanent iatrogenic Addison hypoadrenocorticism.
disease can occur.
• Granulomatous (fungal) adrenalitis, neoplasia, hem- Acute Hypoadrenocorticism
orrhage (very rare). • History consistent with chronic hypoadrenocorticism
preceding the acute addisonian crisis
Secondary Hypoadrenocorticism • Weakness and depression progressing to collapse
Secondary hypoadrenocorticism is due to deficient pitu-
• Slow capillary refill time, weak pulses progressing to
hypovolemic shock
itary adrenocorticotropic hormone (ACTH) secretion
resulting in inadequate glucocorticoid production,
• Bradycardia and hypothermia
while mineralocorticoid secretion is preserved. Poten-
• Cardiac arrhythmias (secondary to electrolyte abnor-
malities, acidosis, azotemia, and poor perfusion)
tial causes include the following:
Chronic Hypoadrenocorticism
• Abrupt withdrawal of long-term and/or high-dose
glucocorticoid administration • Anorexia, vomiting, and diarrhea.
• Megestrol acetate (Ovaban, Schering Plough) • Muscle weakness, lethargy, and depression.
therapy in cats • Weight loss, dehydration, shaking, polydipsia,
• Lesions of the hypothalamus or pituitary gland (e.g., polyuria, melena, abdominal pain, and hair loss may
tumors) be present.
• Idiopathic ACTH deficiency (rare) • Waxing and waning course.
357
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available from various compounding pharmacies. hydrocortisone is being administered, these are discon-
The bioavailability and reproducibility of these tinued and the glucocorticoid supplementation is
various formulations have not been stringently evalu- changed to dexamethasone for at least 24 hours before
ated. Therefore, it may be prudent to assess the activ- the ACTH stimulation test is done.
ity of each new vial by performing an ACTH
stimulation test on a normal dog. Acute Hypoadrenocorticism
• In cats, obtain a plasma or serum sample for cortisol This is a medical emergency requiring immediate
determination before and 1 and 2 hours after IM intervention.
injection of 2.2 U/kg of ACTH gel.
• Correct hypotension and hypovolemia.
Interpretation • Improve vascular integrity.
• Provide an immediate source of rapid-acting
• Dogs and cats with hypoadrenocorticism show a glucocorticoid.
blunted or absent cortisol response to ACTH • Correct electrolyte imbalance and acidosis.
administration. • Following stabilization of the acute addisonian crisis,
• Primary hypoadrenocorticism: Basal and post-ACTH institute long-term mineralocorticoid and glucocorti-
cortisol concentrations are usually <1 mg/dl coid replacement therapy as described for treatment
(30 nmol/L). of chronic hypoadrenocorticism.
• Secondary hypoadrenocorticism: The serum cortisol
response to exogenous ACTH is blunted; however, Hypovolemia and Hyponatremia
post-ACTH concentrations of cortisol may be as high
as 3.0 mg/dl (85 nmol/L) in some cases. • Infuse 0.9% NaCl solution at a dosage of 60 to
• False elevations of cortisol concentrations may occur 80 ml/kg/hr IV over the first 1 to 2 hours, then grad-
after administration of prednisone, prednisolone, ually reduce the rate to the maintenance require-
cortisone, or fludrocortisone because these cross- ment, depending on patient response. Monitor urine
react on the cortisol radioimmunoassay. Discontinue output. Administer a colloid if necessary to address
these drugs 24 to 48 hours prior to the test. the hypovolemia and hypotension (uncommon).
• Dexamethasone and desoxycorticosterone pivalate • Administer dexamethasone sodium phosphate, 2 to
(DOCP) do not interfere with the cortisol assay (see 4 mg/kg IV, or prednisolone sodium succinate, 15 to
“Treatment”); however, dexamethasone is a potent 20 mg/kg IV. Repeat in 2 to 6 hours as needed. Glu-
steroid and suppresses the pituitary-adrenal axis. cocorticoid supplementation is gradually tapered to
a maintenance dose of prednisone (0.2 mg/kg/day)
Plasma Concentration of ACTH over the following 3 to 5 days as the patient’s condi-
tion improves.
Plasma concentration of ACTH is high (>500 pg/ml) in
dogs and cats with primary hypoadrenocorticism and Hyperkalemia
very low or undetectable with secondary hypoadreno-
corticism. This assay is available at several diagnostic • Hyperkalemia associated with hypoadrenocorticism
laboratories. Contact the appropriate laboratory for can often be successfully treated with parenteral fluid
collection, shipping, and handling instructions (e.g., therapy (0.9% NaCl solution) only.
see www.ahdl.msu.edu for the Diagnostic Laboratory of • For severe hyperkalemia causing life-threatening
Michigan State University). bradyarrhythmias and sinoatrial standstill, more
aggressive therapy is indicated. Administer short-
acting insulin (e.g., regular insulin) and dextrose IV
Treatment (first choice), sodium bicarbonate, or calcium salts.
▼ Key Point Collect proper blood and urine samples • A rapid-acting parenteral mineralocorticoid formula-
tion is no longer available. However, begin oral sup-
and perform necessary diagnostic testing before
plementation with fludrocortisone (Florinef, Squibb)
instituting therapy.
immediately if the animal is not vomiting.
The ACTH stimulation test (preferably using syn-
thetic ACTH administered IV) can be performed simul- Acidosis
taneously with initial therapy if dexamethasone is used • Correct mild to moderate acidosis with parenteral
for glucocorticoid replacement because it does not fluid therapy (0.9% NaCl solution).
interfere with the cortisol assay. ACTH stimulation • Treat severe acidosis (pH < 7.1) with serum bicar-
testing using ACTH gel should not be performed on bonate. Give 25% of the calculated bicarbonate
dehydrated, hypovolemic, or hypotensive patients, since deficit over the first 6 to 8 hours of therapy if the
impaired absorption of the gel may result in erroneous serum bicarbonate concentration is <12 mEq/L. It is
results. Alternatively, testing can be performed after unusual for additional bicarbonate administration to
initial stabilization. If prednisone, prednisolone, or be needed.
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• Correction of acidosis also drives extracellular potas- • Adjust dose by 0.05 to 0.1 mg/day based on serum
sium into cells, thereby reducing hyperkalemia. electrolyte concentrations.
• Average dose to control the disease is 0.02 to
Other Supportive Care as Needed 0.03 mg/kg/day; very few animals can be
controlled on less than 0.01 mg/kg/day.
• Correct hypothermia. • Side effects include polyuria, polydipsia, polypha-
• Treat symptomatic hypoglycemia with a slow IV bolus gia, and weight gain.
of 1.5 ml/kg of 50% dextrose and 2.5% to 5% dex- • Development of side effects, relative resistance to
trose added to the IV fluids if needed. the drug, or financial considerations may necessi-
tate a change to DOCP.
Chronic Hypoadrenocorticism
Animals with chronic disease generally do not require Glucocorticoid Supplementation
aggressive therapy; however, parenteral fluid therapy Many patients require glucocorticoid supplementation
and parenteral glucocorticoid supplementation may ini- in addition to mineralocorticoid therapy to prevent
tially be indicated in some cases. Dogs and cats with signs of glucocorticoid deficiency or to control persis-
primary hypoadrenocorticism require lifelong gluco- tent mild azotemia. Use one of the following:
corticoid and mineralocorticoid replacement therapy
and sometimes the addition of salt to the diet. Animals • Prednisone or prednisolone, 0.2 mg/kg/day PO.
with documented secondary hypoadrenocorticism • Cortisone acetate, 1 mg/kg/day PO.
require glucocorticoid replacement only. • Give 2- to 10-fold higher glucocorticoid doses for
brief periods of stress, surgery, or illness.
Hypovolemia
Sodium Chloride Therapy
• Give 0.9% NaCl solution, 60 to 80 ml/kg/day IV, for • NaCl, 1 to 5 g daily, may be beneficial in some
initial correction of hypovolemia.
patients to help normalize serum sodium concentra-
• Decrease fluid volume over 48 to 96 hours based on
tion.
return of clinical and laboratory parameters to
normal. • NaCl supplementation may have a sparing effect on
the required fludrocortisone dose needed occasion-
ally in dogs.
Mineralocorticoid Supplementation
Use one of the following treatment protocols:
• DOCP (Percorten-V, Novartis) HYPERADRENOCORTICISM IN DOGS
• DOCP is a long-acting injectable mineralocorti-
coid; give it initially at 2.2 mg/kg IM or SQ, every Spontaneous hyperadrenocorticism (Cushing’s syn-
4 weeks. A dosage interval of 3 to 4 weeks is effec- drome) is a collection of clinical and biochemical
tive in most cases. abnormalities caused by chronic overproduction of cor-
• Percorten-V is approved by the Food and Drug tisol by the adrenal cortices.
Administration (FDA) for treatment of primary
hypoadrenocorticism in dogs. Etiology
• Monitor serum electrolytes, blood urea nitrogen Hyperadrenocorticism can be pituitary dependent, sec-
(BUN), and creatinine every 1 to 2 weeks until sta- ondary to cortisol-secreting adrenocortical neoplasia, or
bilized in the normal range to ensure an appro- iatrogenic.
priate dose and duration of action; reevaluate every
3 to 6 months during long-term therapy. Pituitary-Dependent Hyperadrenocorticism
• Less than 10% of dogs require a dose greater
than 2.2 mg/kg. Dose less than 2.2 mg/kg may be This is the most common cause of naturally occurring
sufficient in some cases. If financial constraints hyperadrenocorticism in dogs, accounting for 85% to
are present, gradually reduce to the lowest 90% of cases. The excessive secretion of ACTH from
effective dose while monitoring serum electrolyte pituitary corticotroph hyperplasia, microadenoma,
concentrations. macroadenoma, or (very rarely) adenocarcinoma
• Side effects are rare. results in bilateral adrenocortical hyperplasia.
• Fludrocortisone acetate (Florinef, Squibb)
Cortisol-Secreting Adrenocortical Tumors
• Give an initial dosage of 0.01 to 0.02 mg/kg/day
PO. These tumors are responsible for approximately 10% to
• Monitor serum electrolytes, BUN, and creatinine 15% of dogs with spontaneous Cushing’s syndrome.
every 1 to 2 weeks until stabilized in the normal About half of adrenocortical tumors are benign and
range, then reevaluate every 3 to 4 months. half are malignant.
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Physical Examination • In dogs with adrenal neoplasia, evaluate the liver for
Perform a careful examination to determine the clini- metastasis and the caudal vena cava for tumor
cal signs listed on the previous page. thrombus.
▼ Key Point The most important diagnostic proce- Computed Tomography and Magnetic
dures for hyperadrenocorticism are a careful and Resonance Imaging
complete history and physical examination. • Pituitary tumors >1 cm in diameter (macroadenomas
or macroadenocarcinomas) are relatively easy to
Routine Laboratory Testing define with these imaging techniques.
• The hemogram may reveal a stress leukogram and • Pituitary microadenomas may be identified if they are
mild erythrocytosis. ideally positioned or approach 1 cm in diameter.
• Up to 80% of dogs with hyperadrenocorticism have magnetic resonance imaging (MRI) is more sensitive
high serum alkaline phosphatase activity, composed than computed tomography (CT) for imaging pitu-
primarily of the steroid-induced isoenzyme. itary microadenomas.
• Elevated serum cholesterol concentration is • CT and MRI are the most accurate and reliable
common. methods for imaging the adrenal glands, followed by
• Increased serum alanine aminotransferase (ALT) ultrasonography and then radiography. With CT or
and aspartate aminotransferase (AST) concentra- MRI, the location of the adrenal tumor and evidence
tions are common. of metastasis can be identified in most dogs.
• Mild hyperglycemia is common. Overt diabetes mel-
litus (glucose >250 mg/dl) occurs in up to 10% of Pituitary-Adrenal Function Tests
dogs with untreated hyperadrenocorticism. Basal Serum Cortisol Concentration
• Urinalysis often reveals a low specific gravity (<1.020).
• Proteinuria is occasionally seen. A urine protein-to- Basal serum (or plasma) cortisol concentrations cannot
creatinine ratio >3.0 is usually due to glomerular be used to diagnose hyperadrenocorticism because
disease or urinary tract infection. of significant overlap among dogs with hyperadreno-
corticism, dogs with non-adrenal illness, and normal
Radiography dogs.
be greater after administration of the 1.0 mg/kg • Common side effects during the induction phase of
dose. therapy (the loading period) include lethargy, vom-
• Interpretation iting, anorexia, weakness, and diarrhea. If adverse
• Dogs with adrenal tumors do not show feedback effects occur during initial therapy, discontinue
suppression of cortisol after administration of a mitotane and give glucocorticoids until the dog can
high dose of dexamethasone, with serum cortisol be evaluated. Monitor the dog’s appetite closely
concentrations remaining >1.5 mg/dl (>40 nmol/ during the induction period, and if decreased
L) during the testing period. Suppression of serum appetite develops, discontinue mitotane and evaluate
cortisol concentration to <1.5 mg/dl excludes an by an ACTH stimulation test.
adrenal tumor. • Monitor therapy with the ACTH stimulation test.
• In dogs with pituitary-dependent hyperadrenocor- Perform this test at the end of the 10-day induction
ticism, approximately 80% demonstrate suppres- phase or sooner if adverse effects develop.
sion of cortisol (<1.5 mg/dl or <40 nmol/L) after
administration of a high dose of dexamethasone. ▼ Key Point The goal of therapy is to achieve sub-
• The remaining 20% of dogs with pituitary- clinical hypoadrenocorticism, whereby both basal
dependent hyperadrenocorticism fail to demon- and post-ACTH cortisol concentrations are within
strate adequate cortisol suppression (i.e., all the normal basal (or resting) cortisol range (1 to
cortisol values remain >1.5 mg/dl or >40 nmol/L). 5 mg/dl or 30 to 150 nmol/L for most laboratories).
Additional testing is necessary to distinguish these
dogs from those with an adrenal tumor. Many dogs • If basal and post-ACTH concentrations fall below the
with non-suppressible pituitary-dependent hyper- normal basal range (<1 mg/dl or <30 nmol/L), tem-
adrenocorticism have large pituitary tumors. porarily suspend mitotane administration and sup-
• The use of percentage of suppression to differen- plement glucocorticoids as needed until circulating
tiate between pituitary- and adrenal-dependent cortisol concentrations normalize. Cortisol concen-
hyperadrenocorticism can be misleading in some trations generally return to the normal range within
cases. We prefer the use of a cutoff value. 2 to 4 weeks but occasionally take several weeks to
months.
Treatment of Pituitary-Dependent • If basal or post-ACTH cortisol concentrations are
Hyperadrenocorticism above the normal resting range, continue daily
mitotane treatment and repeat ACTH stimulation
Mitotane Therapy tests at 5- to 10-day intervals until serum cortisol con-
Mitotane (o,p¢-DDD; Lysodren, Bristol-Myers Squibb) centrations fall within the normal resting range.
is the drug most frequently used in the treatment of
hyperadrenocorticism in dogs. Mitotane causes selective Maintenance Phase
necrosis of the zona fasciculata and zone reticularis of
the adrenal cortex. The administration protocol for • When desired cortisol concentrations are docu-
mitotane involves an initial induction phase that uses a mented by ACTH stimulation testing, continue
daily dosage for induction of remission (loading dosage), mitotane at a maintenance dosage of 40 to 50 mg/kg
followed by a maintenance phase that uses a dosage given weekly in two to three divided doses. Lifelong main-
once or twice weekly (maintenance dosage). tenance therapy is needed to maintain remission of
the disease.
Induction Phase
• If adverse side effects occur during maintenance
therapy, discontinue mitotane and supplement glu-
• The initial loading dosage of mitotane is 30 to cocorticoids until the dog can be evaluated by serum
50 mg/kg/day, given once daily or divided q12h PO, electrolyte determinations and an ACTH stimulation
for 7 to 10 days. Mitotane absorption is enhanced by test. In most dogs with iatrogenic hypoadrenocorti-
food (especially fat) and, therefore, should be given cism (but normal serum electrolytes), maintenance
with a meal. mitotane can be resumed 2 to 6 weeks later, when
• Concurrent glucocorticoid supplementation with oral pred- serum cortisol concentrations have returned into the
nisone or prednisolone (0.15–0.25 mg/kg/day, up to normal resting range. About 20% to 25% of dogs
a maximum daily dose of 5 mg/day/dog) can be used experience side effects, usually mild, at some point
to mitigate the adverse effects associated with serum during induction or maintenance mitotane therapy.
cortisol concentrations falling rapidly into the • Up to 5% of dogs develop iatrogenic hypoadreno-
normal or subnormal range during this initial treat- corticism with associated hyponatremia and hyper-
ment. The major disadvantage of providing gluco- kalemia. These dogs generally require lifelong
corticoid is that it may not be possible to know if supplementation with mineralocorticoids, that is, flu-
overdosage has occurred, since clinical signs of glu- drocortisone acetate or DOCP (see “Hypoadreno-
cocorticoid deficiency may not develop. corticism in Dogs and Cats”).
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• Nearly 50% of dogs with hyperadrenocorticism have hours and then start again at a lower dose. Perform
a relapse of disease within the first 12 months of an ACTH stimulation test in 7 to 10 days.
maintenance therapy. These cases require reinduc- • If signs of hypoadrenocorticism occur, discontinue
tion with daily doses of mitotane for 7 to 10 days, trilostane until the dog can be evaluated and ACTH
followed by a higher maintenance dosage (weekly stimulation testing and a chemistry profile (including
dosage usually increased 50%). electrolytes) can be performed. Administer gluco-
• To ensure continued control and prevent serious corticoid if necessary.
relapse during mitotane treatment, repeat ACTH
stimulation testing after 3 and 6 months of mainte-
nance treatment and every 6 months thereafter. Adverse Effects
Relapse of hyperadrenocorticism can thereby usually • Trilostane is usually well tolerated. Mild, self-limited
be detected before recurrence of clinical signs is adverse effects including lethargy, vomiting, and diar-
evident. rhea were reported in 63% of dogs in one study.
• Side effects required withdrawal of trilostane in
Trilostane Therapy approximately 3% to 4% of dogs.
• Acute death was reported in two dogs a few days after
Trilostane is a synthetic steroid analogue. It competi- starting trilostane therapy. Other anecdotal reports of
tively inhibits the 3-beta hydroxysteroid dehydrogenase acute death have been noted. The exact relationship
enzyme; thereby blocking cortisol, aldosterone, and sex of trilostane to these deaths is not completely clear at
hormone production. Trilostane is available in the this time.
United Kingdom (Vetoryl, Arnolds Veterinary Prod- • One report describes bilateral adrenal necrosis seen
ucts). Until an approved product is available in the on histopathology in two dogs on trilostane.
United States, the manufacturer recommends contact- • Acute hypoadrenocorticism has been reported in two
ing the FDA for permission to import a 90-day supply dogs. One of these cases died despite discontinuation
for a given patient. of trilostane and appropriate medical intervention.
Trilostane is effective in controlling the clinical signs • Occasional instances of prolonged (up to several
in most dogs with pituitary-dependent hyperadreno- months) adrenocortical suppression can be seen in
corticism. Reported efficacy is less than or equal to that dogs receiving trilostane. It is not clear how an
of mitotane. enzyme inhibitor can cause prolonged adrenocorti-
cal suppression or acute hypoadrenocorticism.
Initial Dose • Hyperkalemia and/or hyponatremia can be seen in
a significant number of dogs at variable times after
• Give 2 to 12 mg/kg PO with food (the mean starting starting trilostane. These changes are not typically
dose is approximately 6 mg/kg/day). associated with clinical signs of hypoadrenocorticism
• Do not use trilostane in animals with renal failure or or altered aldosterone levels.
primary liver disease, lactating animals, or those
intended for breeding.
Ketoconazole Therapy
Follow-up Treatment and Monitoring Ketoconazole (Nizoral, Janssen) reversibly inhibits
adrenal steroidogenesis through enzymatic blockade.
• Evaluate response to treatment based on resolution The major problems of ketoconazole compared with
of clinical signs of hyperadrenocorticism and results
mitotane include its high cost, the necessity for lifelong
of ACTH stimulation tests.
twice-daily administration, and reported lack of efficacy
• Examine the patient and perform an ACTH stimula-
in some cases (up to 50% in some reports).
tion test at 10 days, 1 month, 3 months, and every 3 to
6 months thereafter. Evaluate complete blood counts • The initial dosage of ketoconazole is 10 mg/kg q12h
and serum chemistry profiles on a regular basis. PO.
• Perform ACTH stimulation testing 4 to 6 hours after • Assess adrenal reserve with an ACTH stimulation test
trilostane is administered. after 7 to 10 days of therapy. The goal of therapy is
• Increase or decrease the trilostane dosage to achieve to achieve subclinical hypoadrenocorticism, whereby
pre-ACTH and post-ACTH cortisol concentrations both basal and post-ACTH cortisol concentrations
between 1 and 5 mg/dl. During the first 6 months of are within the normal basal cortisol range (1–5 mg/dl
therapy, at least 50% of dogs can be expected to or 25 to 150 nmol/L for most laboratories).
require a change of dosage (usually an increase). • The dosage of ketoconazole can be increased (up to
• Some dogs may need twice-daily administration of 20 mg/kg q12h) if necessary.
trilostane to adequately control clinical signs. • Once adequate control is achieved, lifelong twice-
• If the post-ACTH serum cortisol concentration is daily therapy is required to maintain remission of the
below 1 mg/dl, discontinue trilostane for 48 to 72 hyperadrenocorticism.
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• Adverse effects include anorexia, vomiting, diarrhea, • Deliver the total dose of radiation in fractions over a
lethargy, and idiosyncratic hepatopathy. period of 4 to 6 weeks. Complications appear to be
minimal in most cases.
• The primary prognostic factor is the severity of neu-
L-Deprenyl Therapy rologic signs. Dogs with a pituitary macroadenoma
L-deprenyl (selegiline HCl; Anipryl, Pfizer) is a selec- and severe neurologic signs have a grave prognosis.
tive, monoamine oxidase type B inhibitor that decreases • The disadvantages of radiation therapy include its
pituitary ACTH secretion by increasing dopaminergic high cost, limited availability, and the need for mul-
tone to the hypothalamic-pituitary axis, with a resultant tiple anesthetic episodes.
fall in serum cortisol concentrations. Drawbacks of L- • Plasma ACTH and serum cortisol concentrations may
deprenyl therapy include low reported efficacy rates, take weeks to months to normalize. In the interim,
the need for lifelong daily administration, and the medical management of the hyperadrenocorticism
expense of the medication. may be necessary.
• Initiate L-deprenyl therapy at a dosage of 1 mg/kg ▼ Key Point Advances in diagnostic imaging (CT and
PO daily. If an inadequate response is seen after MRI) have enabled the antemortem diagnosis of
2 months of therapy, increase the dosage to pituitary macroadenomas. Treatment of pituitary
2 mg/kg/day. Should this dose also prove ineffective, tumors may be attempted with radiotherapy, espe-
use alternative therapy. If effective, continue daily cially if a diagnosis of macroadenoma can be made
therapy for the remainder of the dog’s life. before the onset of profound neurologic signs.
• The drug is indicated for the treatment of uncom-
plicated cases of pituitary-dependent hyperadreno- Surgical Management of Pituitary-Dependent
corticism. L-deprenyl is not recommended for Hyperadrenocorticism
treatment in dogs with concurrent diabetes mellitus,
pancreatitis, heart failure, renal disease, or other Hypophysectomy has recently been described in a large
severe illness, and it is not effective for the treatment series of dogs and has been shown to be a viable
of cortisol-secreting adrenocortical neoplasia. and effective treatment for pituitary-dependent
• The manufacturer’s multicenter trial reported that hyperadrenocorticism.
75% to 80% of dogs had a good response to therapy • At this writing, the procedure has limited availability
as assessed by resolution of clinical signs and monthly in the United States.
low-dose dexamethasone suppression testing. Inde- • Preoperative advanced imaging studies (preferably
pendent studies have reported efficacy rates of 20% MRI) are needed.
or less. • The experience of the surgeon and the provision of
• The current label recommendation is to evaluate the intensive 24-hour postoperative care are of vital
efficacy of L-deprenyl therapy based solely on resolu- importance for the success of this procedure.
tion of clinical signs of hyperadrenocorticism. It
seems prudent, however, to monitor low-dose dexa- Adrenocortical Tumors
methasone suppression tests every 4 to 6 weeks to
evaluate for normalization (or improvement) of the Surgical Management
pituitary-adrenal axis in dogs receiving the drug. The See the section on “Adrenalectomy.”
ACTH stimulation test is not indicated for assessing
the response to treatment with L-deprenyl. Mitotane Therapy
• Adverse effects such as anorexia, lethargy, vomiting,
and diarrhea are uncommon (<5% of dogs) and • Mitotane is an effective and relatively safe treatment
usually mild. alternative for most dogs with adrenal tumors.
• Do not administer L-deprenyl concurrently with Mitotane therapy has been successful for over 24
other monoamine oxidase inhibitors, opioids, or tri- months in some dogs with adrenocortical adenomas
cyclic antidepressants (e.g., fluoxetine), as significant and carcinomas. In general, higher dosages of
adverse drug interactions have been reported in mitotane are required than for treatment of dogs
humans. with pituitary-dependent hyperadrenocorticism.
Only 15% to 20% of dogs with adrenal tumors
respond to the standard treatment protocol used in
Radiation Therapy for Pituitary-Dependent dogs with pituitary-dependent hyperadrenocorticism.
Hyperadrenocorticism ▼ Key Point In dogs with adrenal tumors, mitotane is
Radiation therapy may be useful in dogs with hyper- used as a true chemotherapeutic agent with the
adrenocorticism caused by a pituitary macroadenoma goal of destroying all functional, neoplastic
or macrocarcinoma. adrenocortical tissue. Therefore, both the serum
W0422-Ch033.qxd 11/10/05 5:08 PM Page 367
basal and the post-ACTH cortisol concentrations opment of hypoadrenocorticism, but in approxi-
should be low to undetectable (<1 mg/dl or mately 50% of dogs the side effects appear to result
<30 nmol/L). The induction of overt hypoadreno- from direct drug toxicity. If adverse reactions occur,
corticism may improve the long-term prognosis, stop the drug and evaluate the dog as soon as possi-
but mitotane toxicity (from the high doses of ble to exclude glucocorticoid and mineralocorticoid
mitotane needed) prevents this approach in many deficiency. If direct drug toxicity is occurring, start
dogs. mitotane again later at a 25% to 50% lower dosage.
Reinstitution of the higher maintenance dosage can
Indications for Mitotane Therapy of Adrenal Tumors be attempted later but usually results in recurrence
of adverse effects. Complete glucocorticoid and min-
• Gross metastatic disease evident prior to surgery eralocorticoid deficiency (Addison disease) has been
• Unresectable or incompletely resectable tumor reported in a few cases.
• Residual disease after adrenalectomy as detected by
ACTH stimulation testing
Patient Monitoring
• Unacceptable anesthetic or surgical risks to the
patient • Mitotane overdosage and underdosage can compli-
• Refusal of surgery by the client cate therapy; long-term monitoring is therefore nec-
essary. Instruct owners to observe for recurrence of
Procedure symptoms, especially polyuria and polydipsia.
Perform an ACTH stimulation test every 3 to 6
• Initiate mitotane therapy at dosage of 50 to months to assess adrenal reserve and to guide
75 mg/kg/day and repeat ACTH stimulation testing mitotane dosage adjustments.
every 10 to 14 days to evaluate adrenal reserve.
Administer a glucocorticoid (e.g., prednisone or
prednisolone, 0.2 mg/kg/day PO) throughout the Trilostane Therapy
period of mitotane administration to help prevent
Trilostane has been used to treat a small number of dogs
adverse effects secondary to hypoadrenocorticism.
with adrenal-dependent hyperadrenocorticism with
• Continue daily mitotane at this dosage or increase it
good response in most cases.
(based on ACTH stimulation test results) until
desired cortisol levels are reached or drug intoler- • Being an enzyme inhibitor, trilostane provides
ance develops. Dogs with adrenal tumors often control of serum cortisol levels but should not affect
require a cumulative mitotane induction dose up to the underlying neoplastic process. However, there
10 times higher than dogs with pituitary-dependent are a few reports of acute hypoadrenocorticism
hyperadrenocorticism (due to a longer period of as well as bilateral adrenal necrosis in dogs with
daily mitotane administration). pituitary-dependent hyperadrenocorticism receiving
• Once serum cortisol concentrations are undetectable trilostane.
to low, start maintenance therapy at 75 to 100 mg/kg • Trilostane is not cytotoxic. Therefore mitotane may
weekly in divided doses. Continue daily glucocorti- be preferable for treatment of malignant adrenocor-
coid supplementation. Perform an ACTH stimula- tical tumors.
tion test in 1 month to ensure continued suppression • Trilostane may be useful for the preoperative control
of serum cortisol concentrations. of serum cortisol concentrations and clinical signs in
• Dogs with adrenal tumors typically require higher dogs undergoing adrenalectomy.
maintenance dosages of mitotane than dogs with
pituitary-dependent hyperadrenocorticism; about
25% need a maintenance dosage >150 mg/kg weekly. Prognosis
Relapses are not uncommon. The prognosis for hyperadrenocorticism is always
• Although not correlated with tumor response in all guarded because of the many complications associated
dogs, cortisol determinations are a practical and rel- with the disease. Dogs that succumb to such complica-
atively reliable means of monitoring therapy. They tions usually do so within the first 3 to 6 months after
should be performed 1 month after any change in diagnosis. Dogs that survive this period typically die of
mitotane dosage and every 3 to 6 months during other geriatric disorders unrelated to hyperadrenocor-
long-term therapy. Periodic ultrasonographic evalua- ticism. The average life span after diagnosis is 2 years.
tion is also useful for evaluating tumor response. Complications include the following:
Adverse Effects
• Thromboembolism
• Infection
• Common side effects include anorexia, weakness, • Hypertension
vomiting, diarrhea, and lethargy and are seen in up • Congestive heart failure
to 60% of cases. Adverse effects may be due to devel- • Recurrence of clinical signs
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• Progression of CNS signs (expanding pituitary corticism. Dogs with non-adrenal illness can have
tumor) elevated 17-hydroxyprogesterone levels after ACTH
• Glomerulopathy stimulation.
• Pancreatitis
Imaging Studies
ATYPICAL HYPERADRENOCORTICISM • As in cases of “typical” hyperadrenocorticism, radi-
IN DOGS ography, ultrasound, CT, and/or MRI may be helpful
in evaluating dogs with atypical hyperadrenocorti-
These dogs have the typical historical, physical exami- cism and in differentiating pituitary-dependent from
nation and routine laboratory findings associated with adrenal-dependent cases.
hyperadrenocorticism but have normal cortisol values
after ACTH stimulation and low-dose dexamethasone Treatment
suppression testing. The adrenal steroid indicator in • Dogs with pituitary-dependent atypical hyper-
serum for this disease is 17-hydroxyprogesterone rather adrenocorticism can be treated with mitotane or
than cortisol. Atypical hyperadrenocorticism can be due trilostane (see the corresponding sections above).
to pituitary-dependent disease or adrenal tumor. Hypophysectomy is a viable treatment option if
available.
Diagnosis • When using mitotane, pre-ACTH and post-ACTH 17-
Adrenocorticotropic Hormone Stimulation Test hydroxyprogesterone levels can be used to monitor
therapy. Because of the shorter turnaround time, we
This is an adrenal function test that measures the rela-
typically use pre-ACTH and post-ACTH cortisol levels
tive “thickness” of the adrenal cortex.
to monitor mitotane therapy. The treatment protocol
and desired cortisol levels during therapy are similar
Intravenous Procedure to those for dogs with “typical” hyperadrenocorticism
• Obtain a serum sample for 17-hydroxyprogesterone (see the previous sections).
determination before and 1 hour after IV injection • If trilostane is used, 17-hydroxyprogesterone levels
of 5 mg/kg of the synthetic ACTH, cosyntropin cannot usually be used to monitor therapy. Serum
(Cortrosyn, Amstar). Once reconstituted, the solu- concentrations of 17-hydroxyprogesterone appear to
tion appears to be stable for at least 4 weeks if refrig- be greatly elevated, likely a result of crossreactivity
erated. Alternatively, the remaining solution can be with the assay by 17-hydroxypregnenolone, which is
aliquoted and frozen. This method is recommended. increased by trilostane inhibition of the 3-beta
Availability and backorder issues, however, may pre- hydroxysteroid enzyme.
clude use of this product. • Atypical hyperadrenocorticism caused by an adrenal
tumor can be managed with surgical adrenalectomy,
Intramuscular Procedure mitotane, or trilostane as in cases of “typical” hyper-
adrenocorticism (see other sections).
• Obtain a serum sample for 17-hydroxyprogesterone
analysis before and 2 hours after IM injection of
2.2 U/kg ACTH gel. Acthar Gel (80 U/ml, Questcor
Pharmaceuticals) is available but is very expensive. HYPERADRENOCORTICISM IN CATS
ACTH gel (usually 40 U/ml) is available from various
compounding pharmacies. The bioavailability and Etiology
reproducibility of these various formulations has not Hyperadrenocorticism in cats can be due to pituitary-
been stringently evaluated. Therefore, it may be dependent disease, adrenocortical neoplasia, or iatro-
prudent to assess the activity of each new vial by per- genic disease. Hyperadrenocorticism is uncommon in
forming an ACTH stimulation test on a normal dog. cats.
17-Hydroxyprogesterone Assay • Pituitary-dependent hyperadrenocorticism is the most
common cause of the naturally occurring disorder in
• This adrenal function assay is available at the Uni- cats, accounting for 80% of the cases.
versity of Tennessee’s College of Veterinary Medicine
Endocrine Diagnostic Lab at www.vet.utk.edu/
• Cortisol-secreting adrenocortical neoplasia is present in
approximately 20% of cats with spontaneous hyper-
diagnostic/endocrinology. adrenocorticism. About one-third of adrenal tumors
in cats are malignant.
Interpretation
• Iatrogenic hyperadrenocorticism can occur in cats, despite
• A post-ACTH 17-hydroxyprogesterone concentration the relative resistance of cats to the effects of gluco-
>6.5 nmol/L is consistent with atypical hyperadreno- corticoids when compared with dogs.
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• Chemotherapy and radiation therapy have been • Adrenal size is breed dependent. In dogs, the average
employed in humans with pheochromocytoma, but size is 22 mm long, 10 mm wide, and 4 mm thick.
the efficacy of these modalities has not been estab- • The adrenal glands are well vascularized by branches
lished in dogs or cats. of the renal, accessory renal, phrenic, cranial abdom-
inal, phrenicoabdominal, and lumbar arteries.
• Venous drainage is through the left and right adrenal
ADRENALECTOMY and the phrenicoabdominal veins.
• The phrenicoabdominal artery crosses the dorsal
Adrenalectomy usually is performed for treatment of surface of the adrenal glands; the phrenicoabdomi-
adrenal tumors and hyperadrenocorticism in the dog nal vein courses across the ventral surface. These
and cat. Unilateral adrenalectomy is done primarily for paired vessels are the largest supplying the adrenal
removal of adrenal neoplasia (adenoma, adenocarci- glands.
noma, or pheochromocytoma). Bilateral adrenalec-
tomy is less commonly used for bilateral adrenocortical Preoperative Considerations
hyperplasia. The anatomy and surgical and medical
management for adrenalectomy is the same in the dog • Obtain a minimum database consisting of complete
blood count, serum chemistry profile, and thoracic
and cat. Adrenalectomy is performed infrequently in
radiographs.
cats owing to the low incidence of hyperadrenocorti-
cism and adrenal neoplasia. • Abdominal radiographs may help localize a unilateral
adrenal mass, especially if the tumor is mineralized.
Surgical Anatomy of the Adrenal Gland • Ultrasonography and CT scan are also very helpful in
identifying a mass and determining if invasion of the
• The adrenal glands are paired, flattened, bilobed vena cava has occurred.
glands located retroperitoneally and craniomedial to • Correct any fluid and electrolyte abnormalities.
the kidneys (Fig. 33-1). • Treat arrhythmias and hypertension that may accom-
• The right adrenal gland lies near the level of the last pany pheochromocytoma (see the next section).
thoracic to the first lumbar vertebrae. • Surgical removal of large adrenal tumors can be tech-
• The capsule of the right adrenal gland may be con- nically challenging, and postoperative intensive care
tiguous with the tunica externa of the caudal vena may be necessary. Consider referral to a surgical
cava. specialist.
• The left adrenal gland is slightly caudal to the right
and is separated from the caudal vena cava by a layer Anesthesia and Perioperative Care
of fat.
For Hyperadrenocorticism
• Induce and maintain anesthesia following standard
Caudal
procedures.
vena cava • Sevoflurane and isoflurane are preferred over
Diaphragm Adrenal glands halothane, as there is less sensitization of the
myocardium to catecholamines.
• Administer a broad-spectrum bactericidal antibiotic
Phrenicoabdominal by IV bolus 30 minutes before surgery. Administer
Kidney vein isotonic fluids an appropriate rate during and after
surgery.
• Supplement corticosteroids in the form of dexa-
methasone (0.1–0.2 mg/kg IV) immediately before
Testicular or
the onset of surgery, at the completion of the surgi-
ovarian veins
cal procedure, and then every 6 to 8 hours during the
immediate postoperative period (24–48 hours).
For Pheochromocytoma
Testicular or • Avoid premedication with atropine because of the
ovarian arteries potential for severe tachycardia.
Renal artery
and vein
▼ Key Point Dogs with pheochromocytoma produce
high circulating concentrations of the cate-
Ureter cholamines epinephrine and norepinephrine,
Figure 33-1. Anatomy of the adrenal glands from the ventral which may cause severe hypertension or profound
midline abdominal approach. cardiac arrhythmias.
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Surgical Procedure
Objectives Figure 33-2. Incision for the ventral midline approach may be
extended paracostally for better exposure of the adrenal gland.
• Handle tissue gently, especially tumor tissue.
▼ Key Point Surgical handling of a pheochromocy-
toma may precipitate catecholamine release and Phrenicoabdominal
hypertension. Profound hypotension may rapidly Renal vein
Renal vein
occur following tumor removal.
artery Right adrenal
Vena
• Use meticulous hemostasis to minimize blood loss. cava gland
• Avoid trauma to the caudal vena cava.
• Close the linea alba with a non-absorbable suture
material.
Equipment
• Standard general surgical pack and suture Figure 33-3. Surgical anatomy of the right adrenal gland and its
• Balfour retractors associated vascular structures as viewed from the retroperitoneal
• Malleable retractors approach.
• Bipolar cautery
• Sterile cotton-tipped applicator sticks
2. Expose the affected gland(s) and isolate with moist-
• Hemostatic clips
ened laparotomy sponges.
• Gelfoam
3. Perform gentle dissection with cotton-tipped appli-
cator sticks, especially when separating the gland
Technique from the vena cava.
1. Make a ventral midline abdominal incision, extend- 4. Ligate the phrenicoabdominal artery and vein and
ing from the xiphoid to about 2 cm caudal to the any other vascular structures serving the adrenal
umbilicus. This may be combined with a paracostal gland. Hemostatic vascular clips are very helpful for
incision if necessary (Fig. 33-2). this.
a. Alternatively, use a retroperitoneal approach (Fig.
33-3). This provides good exposure of the ipsilat- ▼ Key Point Identify and preserve the renal artery
eral gland but must be performed bilaterally if and vein, which may lie close to the adrenal
bilateral adrenalectomy is required. glands.
W0422-Ch033.qxd 11/10/05 5:08 PM Page 374
(ed): Principles and Practice of Veterinary Anesthesiology. dependent hyperadrenocorticism treated with trilostane. Am J Vet
Philadelphia: Williams & Wilkins, 1987, p 251. Res 63:506, 2002.
Peterson ME, Greco DS, Orth DN: Primary hypoadrenocorticism in Syme HM, Scott-Moncrieff JC, Treadwell NG et al: Hyperadrenocor-
ten cats. J Vet Intern Med 3:55, 1989. ticism associated with excessive sex hormone production by an
Peterson ME, Kintzer PP: Pretreatment clinical and laboratory find- adrenocortical tumor in two dogs. J Am Vet Med Assoc 219:1725,
ings in dogs with hypoadrenocorticism: 225 cases (1979–1993). 2001.
J Am Vet Med Assoc 208:85, 1996. van Sluijs FJ, Sjollema BE, Voorhout G, et al: Results of adrenalectomy
Peterson ME, Kintzer PP: Medical treatment of pituitary-dependent in 36 dogs with hyperadrenocorticism caused by adreno-cortical
hyperadrenocorticism: Mitotane. Vet Clin North Am Small Anim tumour. Vet Q 17:113, 1995.
Pract 27:255, 1997. Widmer WR, Guptill L: Imaging techniques for facilitating diagnosis
Ristic JM, Ramsey IK, Heath EM, et al: The use of 17-hydroxyproges- of hyperadrenocorticism in dogs and cats. J Am Vet Med Assoc
terone in the diagnosis of canine hyperadrenocorticism. J Vet 206:1857, 1995.
Intern Med 16:433, 2002.
Ruckstuhl NS, Nett CS, Reusch CE: Results of clinical examinations,
laboratory tests, and ultrasonography in dogs with pituitary-
W0422-Ch034.qxd 11/10/05 5:08 PM Page 376
▼ Chapter
34 Diabetes Mellitus
Deborah S. Greco
376
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Figure 34-1. Summary of the pathophysiologic factors contributing to hyperglycemia in non–insulin-dependent (type 2) diabetes mellitus.
(From Lutz TA, Rand JS: Pathogenesis of feline diabetes mellitus. Vet Clin North Am Small Anim Pract 25:544, 1995; with permission.)
fatty acids are converted to acetyl coenzyme A • Stress hormones such as cortisol and epineph-
(acetyl-CoA) rather than being incorporated into rine contribute to the hyperglycemia in a vicious
triglycerides. cycle.
• Acetyl-CoA accumulates in the liver and is converted • Eventually, severe dehydration may result in hyper-
into acetoacetyl-CoA and then ultimately to ace- viscosity, thromboembolism, severe metabolic acido-
toacetic acid. Finally, the liver starts to generate sis, renal failure, and finally death.
ketones including acetoacetic acid, beta-hydroxybu-
tyrate, and acetone.
• As insulin deficiency culminates in DKA, accumula-
CLINICAL SIGNS
tion of ketones and lactic acid in the blood and loss
of electrolytes and water in the urine results in pro-
found dehydration, hypovolemia, metabolic acidosis,
Uncomplicated Diabetes Mellitus
and shock. • Most diabetic animals have the classic clinical signs of
• Ketonuria and osmotic diuresis caused by glyco- polyuria and polydipsia.
suria result in sodium and potassium loss in • Weight loss is more common in dogs than in cats.
the urine and exacerbation of hypovolemia and • Acute onset of blindness caused by bilateral cataract
dehydration. formation is a common presenting complaint of
• Nausea, anorexia, and vomiting, caused by stimu- diabetes mellitus in dogs.
lation of the chemoreceptor trigger zone via • Cats may present with chronic complications of dia-
ketonemia and hyperglycemia, contribute to the betes, such as diabetic neuropathy leading to gait
dehydration caused by osmotic diuresis. abnormalities, plantigrade stance, difficulty jumping,
• Dehydration and shock lead to prerenal azotemia and inappropriate elimination. Chronic gastroin-
and a decline in the glomerular filtration rate. This testinal signs such as vomiting, diarrhea, and
declining rate leads to further accumulation of anorexia may also result from concurrent pancreati-
glucose and ketones in the blood. tis or from autonomic neuropathy.
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Intravenous (regular only), mixed in 250 ml of 0.9% NaCl; discard 50 ml through IV tubing.
Blood Glucose (mg/dl) Rate Route Dose (u/kg) Monitor Frequency
Potassium (mEq/L)
3.6–5.0 20 26
2.6–3.5 40 12
2.1–2.5 60 9
<2.0 80 7
Phosphorus (mg/dl)
1–2 0.03 mmol phosphate/kg/hr Monitor serum phosphorus q6h
<1.0 0.1 mmol phosphate/kg/hr Monitor serum phosphorus q6h
Magnesium (mg/dl)
<1.2 0.75–1 mEq/kg/day constant rate infusion; Use 5% dextrose: magnesium is incompatible
use MgCl or MgSO4 with calcium-containing and NaHCO3 solutions
Step Four: Acid-Base Balance
<7.1 <12 mEq/L IV = 0.1 ¥ body weight (kg) ¥ (4 - HCO3 [mEq/L]) Over 2 hr
CVP, central venous pressure; IM, intramuscular; IV, intravenous; PCV, packed cell volume; SC, subcutaneous; TS, total solids.
From Greco DS: Endocrine pancreatic emergencies. Comp Cont Educ Pract 19:23, 1997; with permission.
W0422-Ch034.qxd 11/10/05 5:08 PM Page 380
Phosphorus
• Lente preparations control absorption by regulating
the size of the insulin crystals.
• Serum and tissue phosphorus may also be depleted • Semilente is composed of small zinc-insulin crystals,
during a ketoacidotic crisis; thus, supplement one- and Ultralente is composed of large zinc-insulin crys-
third of the potassium dose as potassium phosphate tals that are more slowly absorbed.
(see Table 34-1), particularly in small dogs and cats • Lente insulin is a mixture of 30% prompt zinc-insulin
that are most susceptible to hemolysis caused by suspension (Semilente) and 70% extended zinc-
hypophosphatemia. insulin (Ultralente).
• Use caution, as oversupplementation of phos- • Lente insulin, because of the small zinc-insulin crystal
phorus can result in metastatic calcification and component, may be used to attenuate postprandial
hypocalcemia. hyperglycemia.
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Table 34-2. INITIAL INSULIN REGIMENS FOR DIABETIC DOGS AND CATS
Frequency Feeding Insulin Frequency of
Insulin Type Initial Dose of Dosing Schedule Adjustment Adjustment
Dogs
Lente 0.5 U/kg q12h q12h 0.5–3 U/dog q5–7d
Humulin-L (Lilly),
Novolin-L (Novo Nordisk)
NPH 0.5 U/kg q12h q12h 0.5–3 U/dog q5–7d
Humulin-N (Lilly),
Novolin-N (Novo Nordisk)
2
Ultralente 0.7 U/kg q24h /3 morning; 1–4 U/dog q5–7d
1
Humulin-U (Lilly) /3 evening
Cats
NPH 0.2–0.5 U/kg q12h Throughout day 0.5 U/cat q5–7d
NPH (Novo Nordisk)
Lente 0.2–0.5 U/kg q12h Throughout day 0.5–1 U/cat q5–7d
Humulin-L (Lilly),
Novolin-L (Novo Nordisk)
Ultralente 1–3 U/cat q12–24h Throughout day 0.5 U/cat q5–7d
Humulin-U (Lilly)
Protamine zinc insulin 1–3 U/cat q24h Throughout day 0.5 U/cat q5–7d
Protamine analine zinc (Anthony)
Modified from Greco DS, Broussard JD, Peterson ME: Insulin therapy. Vet Clin North Am Small Anim Pract 25:684, 1995; with permission.
W0422-Ch034.qxd 11/10/05 5:08 PM Page 382
Food Digestible
Diet Form Protein Fat Carbohydrate Fiber
dipsia, polyuria, and urine glucose and ketone 5. Assess the owner’s injection technique.
concentrations. 6. Collect serial blood samples at 2-hour intervals for 12
• Initially monitor urine glucose and ketones daily hours.
(morning). Urine glucose should decrease to trace or
1+ with appropriate therapy. Decrease urine moni- Ideal Blood Glucose Curve
toring to once weekly or biweekly in well-regulated The ideal blood glucose curve is characterized by three
diabetic animals. features (Fig. 34-2): the glucose nadir, the timing of the
• Consistently high urine glucose readings coupled nadir, and the glucose differential.
with uncontrolled clinical signs, such as polyuria or
polydipsia, indicate that the insulin dose may be • The ideal blood glucose curve has a glucose nadir
inadequate. (lowest blood glucose concentration on the curve)
• Consistently negative readings on urine glucose may between 100 and 120 mg/dl.
indicate that insulin dosages are either adequate or • The time of the glucose nadir indicates peak insulin
excessive. action. The nadir should occur approximately
• In dogs, collect urine with a long-handled cup halfway through the dosing interval. For example, if
holding device (males) or a flat pie tin (females). insulin is being given every 12 hours, the nadir should
Collect cat urine by placing a small amount of litter occur 5 to 6 hours after the dose.
in the pan, by placing plastic wrap over litter, or by • The glucose differential is the difference between the
using a non-absorbent litter substitute (e.g., aquar- glucose nadir and the blood glucose concentration
ium gravel). prior to the next insulin dose.
• Aim for a glucose differential of <100 mg/dl in
Blood Glucose Curves dogs without cataracts and <150 mg/dl in dogs
with cataracts.
Evaluate insulin therapy once weekly for the first month
• Cats generally have a higher glucose differential;
and as needed thereafter by serial blood glucose curves
however, aim for <200 to 250 mg/dl.
(blood glucose, 100–250 mg/dl), assessment of body
weight, and resolution of clinical signs.
• The duration of insulin action is related to both the
time of the glucose nadir and the absolute concen-
tration of the glucose nadir. Insulin duration cannot
Procedure for Blood Glucose Curve
be determined unless the target glucose nadir con-
1. Collect initial blood sample. centration (80–120 mg/dl) has been achieved. If the
2. Feed usual amount and type of food. glucose nadir occurs approximately halfway through
3. Feed and give insulin at the usual time. the dosing interval, the duration of action of insulin
4. Watch the owner administer the insulin. should be adequate.
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Problems Identified on the Blood Glucose Curve corticism, acromegaly, estrus, drug therapy, and infec-
tions. The approach to insulin resistance is outlined
It is rare to obtain a perfect glucose curve. Several
in Tables 34-4 for cats and 34-5 for dogs.
possible outcomes of blood glucose monitoring are
illustrated in Figure 34-3. Generally, blood glucose
• If the animal is receiving <2.2 U/kg of insulin per
dose, the blood glucose curve may indicate one of the
curve problems can be differentiated by the character-
following (see Fig. 34-3):
istics of the curve and the insulin dosage (per dosing
• Insufficient dosage of insulin. Corrective action—
interval).
Increase the insulin dose.
• If the patient is receiving >2.2 U/kg of insulin per • Short duration of action of insulin. Corrective
dose, evaluate for causes of insulin resistance or action—Change to a longer-acting insulin or twice-
antagonism, such as hyperthyroidism, hyperadreno- daily insulin regimen.
Figure 34-3. Algorithm for the unregulated diabetic dog or cat. (From Miller E: Long-term monitoring of the diabetic dog and cat: Clini-
cal signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin North Am Small Anim Pract 25:582, 1995;
with permission.)
W0422-Ch034.qxd 11/10/05 5:08 PM Page 384
Table 34-4. STEPS FOR THE DIAGNOSIS AND TREATMENT OF INSULIN RESISTANCE IN CATS
Causes of Insulin
Steps Resistance Procedure or Test Treatment
ACTH, adrenocorticotropic hormone; CBC, complete blood count; CT, computed tomography; IM, intramuscularly; IV, intravenously; T4, thyroxine.
From Peterson ME: Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 25:705, 1995.
Table 34-5. STEPS FOR THE DIAGNOSIS AND TREATMENT OF INSULIN RESISTANCE IN DOGS
Causes of Insulin
Steps Resistance Procedure or Test Treatment
ACTH, adrenocorticotropic hormone; CBC, complete blood count; CT, computed tomography; cTSH, canine thyroid-stimulating hormone; IM, intramuscu-
larly; IV, intravenously; T4, thyroxine; TRH, thyroid-releasing hormone; TSH, thyroid-stimulating hormone.
From Peterson ME: Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 25:706, 1995.
W0422-Ch034.qxd 11/10/05 5:08 PM Page 385
• Insulin-induced hypoglycemic hyperglycemia (Somo- limits indicate good to excellent diabetic control,
gyi effect). Corrective action—Reduce insulin dose whereas slightly increased levels indicate fair to good
by 25%. control and very high levels indicate poor glycemic
• Insulin overlap. Corrective action—Change to a control. Relative changes in serum concentrations
shorter-duration insulin. may be more helpful than absolute values in some
• Prolonged insulin action. Corrective action— cases.
Change to an insulin mixture of 30% regular and
70% NPH. Hypoglycemia
• Causes of hyperglycemia and hypoglycemia in dia-
betic dogs and cats are listed in Table 34-6. • Clinical signs of hypoglycemia in diabetic animals are
associated with epinephrine excess, which is released
Fructosamine and Glycosylated Hemoglobin to counter the hypoglycemia. Nervousness, anxiety,
vocalization, muscle tremors, ataxia, and pupillary
Monitor long-term insulin therapy by serum fruc- dilatation should alert the owner to the possibility of
tosamine or glycosylated hemoglobin concentrations. hypoglycemia. Have the owner offer food to the
These glycosylated blood proteins are indicative of animal then bring it in for reevaluation.
mean glucose concentrations in serum over an • Late in the course of hypoglycemic shock the animal
extended period of time. may become recumbent or comatose, or the animal
• Glycosylated blood proteins are particularly useful may have a seizure.
for monitoring diabetic cats that may be stressed by • If access to a vein is not readily available or if the
hospitalization and venipunctures for serial blood owner is administering therapy, 50% dextrose solu-
glucose curves. tion, Karo syrup, or pancake syrup may be applied to
• As plasma glucose concentrations increase, hemo- the mucous membranes of the mouth using a large
globin glycosylation increases proportionately. Simi- syringe. Caution the owner to pour the syrup on the
larly, serum fructosamine is formed by glycosylation gums from a reasonable distance from the animal’s
of serum protein such as albumin; thus, serum con- teeth to prevent accidental injury from biting. Have
centration of fructosamine is also directly related to the owner transport the animal to a veterinarian as
blood glucose concentration. soon as possible.
• Because of the shorter life span of albumin compared • In a veterinary facility, treat hypoglycemia by slow IV
with hemoglobin, fructosamine concentrations bolus of 50% dextrose (0.5 g/kg diluted 1:4) followed
reflect more recent (1–3 weeks) changes in serum by continuous infusion of 5% dextrose until the
glucose concentrations. animal can be fed.
• In general, fructosamine and glycosylated hemoglo- • Many animals that experience insulin overdose suffer
bin concentrations that lie within reference range cerebral edema and temporary blindness or behavior
changes; often these signs are temporary and resolve
after several weeks or months.
Table 34-7. ORAL HYPOGLYCEMIC DRUGS USED IN THE TREATMENT OF TYPE 2 DIABETES
(NIDDM) IN HUMANS AND CATS
Drug (Trade Name) Dose Frequency Side Effects Mechanism of Action
FR < 400 FR > 400 FR > 400 FR > 400 FR > 400
BG < 180 BG < 180 BG < 60 BG > 180 BG > 180
• Normal fructosamine concentrations are consistent Gougeon R, Jones JHP, Styhler K, et al: Effects of oral hypoglycemic
agents and diet on protein metabolism in type 2 diabetes. Diabet
with moderate to good long-term control of hyper- Care 23:1–8, 2000.
glycemia. Relative improvement of serum fruc- Greco DS, Peterson ME (eds): Diabetes mellitus. Vet Clin North Am
tosamine may be more important than absolute Small Anim Pract 25, 1995.
fructosamine values. Jackson RA, Hawa MI, Jaspan JB, et al: Mechanism of metformin
action in non–insulin-dependent diabetes. Diabetes 36:632, 1987.
Kettlehut IC, Foss MC, Migliorini RH: Glucose homeostasis in a car-
nivorous animal (cat) and in rats fed a high-protein diet. Amer J
PREVENTION Physiol 239:R115–R121, 1978.
Kitamura T, Yasuda J, Hashimoto A: Acute insulin response to intra-
venous arginine in nonobese healthy cats. J Vet Intern Med
• In humans, and presumably in cats, obesity manage- 13(6):549–556, 1999.
ment may be helpful in preventing development of Martin GJW, Rand JS: Lack of correlation between food ingestion and
type 2 diabetes mellitus. blood glucose in diabetic cats. Proc 15th Ann Amer Coll Vet Int
• In dogs and cats, prevention of secondary forms of Med 670, 1997.
Mazzaferro EM, Greco DS, Turner AS: Treatment of feline diabetes
diabetes is possible by limiting the use of diabeto- mellitus with a high-protein diet and acarbose. J Feline Med Surg
genic drugs such as glucocorticoids, progestational 5(3):183–189, 2003.
compounds, and somatotropin. Nelson RW: Diabetes mellitus. In Ettinger SJ, Feldman EC (eds): Text-
• Similarly, prevention and treatment of underlying book of Veterinary Internal Medicine, 4th ed. Philadelphia: WB
disease is the mainstay of prevention of secondary Saunders, 1995, p 1510.
O’Brien TD, Butler PC, Westermark P, Johnson KH: Islet amyloid
diabetes resulting from hyperthyroidism, hyper- polypeptide: A review of its biology and potential roles in the patho-
adrenocorticism, or acromegaly. genesis of diabetes mellitus. Vet Pathol 30:317, 1993.
Rand JS: Management of feline diabetes. Aust Vet Practit 27:68–75,
1997.
Saltiel AR, Olefsky JM: Thiazolidinediones in the treatment of insulin
SUPPLEMENTAL READING resistance and type II diabetes. Diabetes 45:1661, 1996.
Shechter Y, Shisheva A: Vanadium salts and the future treatment of
Ballard FJ: Glucose utilization in mammalian liver. Comp Biochem diabetes. Endeavour 17:27, 1993.
and Physiol 14:437–443, 1965. Unger RH, Foster DW: Diabetes mellitus. In Wilson and Foster (eds):
Bennett N, Greco DS, Peterson ME: Comparison of a high-fiber vs. Williams Textbook of Endocrinology. Philadelphia: WB Saunders.
low-carbohydrate diet for the treatment of diabetes mellitus in cats. 1998, pp 973–1060.
J Fel Med Surg (in press). Wallace MS, Peterson ME, Nichols CE: Absorption kinetics of regular,
Frank G, Anderson W, Pazak H, et al: Use of a high-protein diet in isophane, and protamine zinc insulin in normal cats. Domest Anim
the management of feline diabetes mellitus. Vet Therapeut Endocrinol 7:509, 1990.
2(3):238–246, 2001.
Genuth S: Classification and diagnosis of diabetes mellitus. Med Clin
North Am 66:1191, 1982.
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▼ Chapter
Signalment
Signalment is not always useful in differentiating insuli-
ETIOLOGY noma from other common causes of hypoglycemia
(Table 35-2).
• Insulin-secreting tumors are almost always malignant.
• Metastatic sites include the lymphatics and lymph • Insulin-secreting tumors typically occur in the middle-
nodes (duodenal, mesenteric, hepatic, splenic), liver, aged or older dog, with an age range of 6 to 14 years.
mesentery, and omentum. • There is no apparent sex or breed predilection,
• The hyperinsulinemia caused by beta cell tumors although the Labrador retriever, German shepherd,
interferes with glucose homeostasis by decreasing the Irish setter, golden retriever, collie, fox terrier,
rate of glucose release from the liver and by increas- and standard poodle are commonly affected in our
ing the uptake of glucose by insulin-sensitive tissues. hospital.
• The net effect is hypoglycemia and secretion of • Islet cell neoplasia is rare in cats.
the counter-regulatory hormones (most notably
glucagons, epinephrine, cortisol and growth Physical Examination
hormone). The physical examination of dogs with insulin-secreting
• The brain is dependent on a constant supply of tumors is surprisingly unremarkable.
glucose for energy and has very limited storage capac-
ity. Hypoglycemia results in decreased delivery of • Weight gain is evident in some dogs and is probably
glucose to the brain (neuroglycopenia). a result of the potent anabolic effects of insulin.
• Peripheral neuropathies have been reported in dogs
with insulin-secreting tumors and may be manifested
as proprioception deficits, depressed reflexes, and
CLINICAL SIGNS muscle atrophy.
390
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• In the hospital, administer 50% dextrose solution presence of cerebral edema or rarely the presence of a
(1 ml/kg) slowly IV until clinical signs are controlled. permanent cerebral lesion (i.e., necrosis). If intractable
• If the dog is home, instruct the owner to rub a sugar- seizures due to hypoglycemia develop, take the follow-
containing solution (e.g., Karo syrup) on the buccal ing actions:
mucosa until clinical signs are controlled.
• Discontinue bolus injections of dextrose.
• Dogs and cats with hypoglycemia should respond to
• Begin continuous IV infusion of 2.5% to 5.0% dex-
the administration of glucose in 30 to 120 seconds. trose solution that is 11/2 to 2 times the maintenance
rate (90–120 ml/kg/day).
▼ Key Point Avoid overstimulation of the tumor • Consider mannitol (0.5 g/kg IV) if signs of cerebral
when administering dextrose IV. Overzealous edema are present (i.e., anisocoria).
administration of dextrose can stimulate the tumor
to release excessive amounts of insulin into the cir-
• Consider the addition of rapid acting glucocorticoids
(i.e., dexamethasone sodium phosphate).
culation and cause severe rebound hypoglycemia.
A vicious cycle that is difficult to break may ulti-
• Administer the somatostatin analog SMS 201-995
(octreotide; Sandostatin, Sandoz), 10 to 40 mg
mately result in persistent seizures and eventually q8–12h SC, to decrease insulin secretion by the
death. tumor.
• Anti-convulsants may be needed if seizures persist
• The goal of therapy is to control the clinical signs, not (i.e., phenobarbital; see Chapter 127).
correct hypoglycemia, through the judicious admin-
istration of dextrose.
• Administer small amounts of dextrose slowly rather
SURGICAL TREATMENT
than large boluses rapidly to minimize stimulation of
the tumor.
• IV dextrose supplementation should be replaced by Surgical Anatomy
frequent feedings as soon as possible. The pancreas consists of the right lobe, left lobe, and
• Constant rate infusion of glucagon has been used the body.
to successfully manage acute hyperinsulinemic-
hypoglycemic crisis in a dog with insulinoma. Right Lobe
The right lobe is located in the mesoduodenum adja-
Seizures cent to the descending duodenum. The proximal
Occasionally, seizures will persist despite normalization portion of the right lobe is intimately associated with
of blood glucose concentration. This may indicate the the duodenum (Fig. 35-1). The proximal half of the
Stomach
Common hepatic
artery
Right
gastroepiploic
artery
Left
gastroepiploic
Gastroduodenal artery
artery
Left lobe
Body of pancreas of pancreas
Caudal
pancreaticoduodenal
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Technique (Using Visual Examination and Palpation) Technique (Using Intraoperative Ultrasound)
1. Approach the abdomen via a ventral midline incision The following technique is commonly used in human
from the xiphoid to the pubis. patients with 90% diagnostic accuracy. It is not yet
2. Examine the entire pancreas visually and by careful widely used in veterinary medicine but offers a safer
palpation. alternative to methylene blue IV infusion.
a. Islet cell tumors are usually firmer than the sur- 1. Use a 7.5- or 10-MHz probe in a sterile sleeve.
rounding tissue. 2. Apply a thin layer of saline to the tissues to improve
b. Islet cell tumors may be small and sandwiched contact.
between pancreatic lobules so that they are not 3. Scan for primary tumors in the pancreas and metas-
readily visible. tasis in the liver.
4. Direct intraoperative ultrasonography decreases the
effect of gas in the surrounding gastrointestinal (GI)
Technique (Using Methylene tract, which allows better identification of the masses.
Blue Intravenous Infusion)
The following technique to facilitate tumor identifica- Technique (Removal of Neoplastic Tissue)
tion utilizes IV infusion of methylene blue. It should 1. Handle the pancreas and masses gently to avoid pan-
be considered only if a mass cannot be identified at creatitis and potential insulin release.
surgery. 2. Check the blood glucose frequently during surgery.
1. Surgically expose the pancreas as described 3. Remove abnormal pancreatic masses by partial pan-
previously. createctomy or by local excision. Make a wide exci-
2. Administer methylene blue as an IV infusion in sion if possible.
normal isotonic saline solution to a total dose of 4. Remove tumors located in the left lobe or the distal
3 mg/kg of body weight. Begin the infusion 30 portion of the right lobe by partial pancreatectomy
minutes before the pancreas is exposed. (Fig. 35-3).
3. Methylene blue is concentrated by the endocrine a. Isolate the affected pancreas with moistened
pancreas and intensely stains hyperfunctional abdominal sponges.
areas. b. Divide the mesentery surrounding the affected
a. Normal pancreatic endocrine tissue is stained a lobe and ligate and divide the appropriate vessels
dusky slate blue. (see Fig. 35-3A).
b. Hyperfunctional tissue is stained more intensely c. Incise the mesentery covering both surfaces of the
(often a reddish blue). pancreas at the level of transection of the lobe.
4. Potential complications include hemolytic anemia d. Remove the lobe at least 1 to 2 cm proximal to
and acute renal failure postoperatively. the tumor.
A C
W0422-Ch035.qxd 11/10/05 5:07 PM Page 395
e. Bluntly separate the lobules using a mosquito • Monitor blood glucose concentration at least twice
hemostat, dissecting alternately from each side of daily.
the gland (see Fig. 35-3B). • Discontinue the dextrose infusion if hyperglycemia
f. Isolate the main duct, ligate with a monofilament (>150 mg/dl) develops.
absorbable synthetic suture material, and transect • If vomiting does not occur, offer small amounts of
it (see Fig. 35-3C). water after 48 hours and then small amounts of a
g. Alternatively, simply ligate the pancreatic tissue in bland, easily digestible diet.
guillotine style to occlude the vessels and ducts • If the dog tolerates a bland diet well, resume the
(3-0 or 4-0 polydioxanone suture). normal diet in 5 to 7 days.
5. When the tumor is located in the proximal portion
of the right lobe or the body, local excision of the Complications
tumor, including at least 1- to 2-cm margins of
normal-appearing pancreatic tissue, is the preferred • Hyperglycemia may occur following surgery due to
technique because of the vascular and ductal inadequate insulin secretion by atrophied non-neo-
anatomy of the area. plastic beta cells. This often resolves within a few days.
a. Gently separate the pancreatic lobules by blunt • If hyperglycemia and glycosuria persist for several
dissection with a mosquito hemostat. Cauterize days following surgery, initiate insulin therapy (see
small vessels and ligate and divide larger vessels. Chapter 34).
b. Preserve the pancreaticoduodenal vessels supply- • Diabetes mellitus is usually transient and resolves
ing the duodenum. Avoid damaging the pancre- within a few weeks to several months.
atic ducts and the common bile duct. • Periodically, discontinue insulin therapy on a trial
6. Explore the entire abdomen for evidence of metasta- basis to determine if endogenous insulin production
tic disease. The most common sites of metastasis are is resuming.
the liver and regional lymph nodes (duodenal, • If hypoglycemia does not resolve postoperatively or if
hepatic, splenic, greater mesenteric). it recurs following resection of an islet cell tumor,
assume metastatic disease to be present and institute
▼ Key Point Metastatic disease is common; approxi- medical therapy for chronic hypoglycemia, as
mately 30% to 50% of cases have identifiable described in the following section.
metastasis to the liver or regional lymph nodes at • Other potential postoperative complications include
the time of surgery. pancreatitis (see Chapter 73 for treatment), duode-
nal necrosis (from vascular compromise), ventricular
a. Resect all enlarged lymph nodes and suspicious arrhythmias, and central nervous system dysfunction
hepatic lesions if possible and submit them for secondary to prolonged hypoglycemia.
histopathologic examination.
b. A recent study (Tobin et al., 1999) showed a poor
correlation between gross inspection during
MEDICAL TREATMENT FOR
surgery and histopathologic examination of CHRONIC HYPOGLYCEMIA
biopsy specimens for potential metastatic lesions.
Only 57% of the lesions biopsied as metastatic Institute palliative medical management for chronic
disease were confirmed metastatic beta cell neo- hypoglycemia in preparation for exploratory laparo-
plasia by histopathologic examination. tomy, for patients with persistent postoperative hypo-
c. Biopsy lesions that cannot be completely excised. glycemia, when exploratory surgery is refused by the
owner or when an inoperable tumor or metastases
▼ Key Point Many dogs with metastases of islet cell result in recurrence of clinical signs.
neoplasms can be managed medically for longer
than a year. Goals of Chronic Palliative Therapy
• To reduce the frequency and severity of clinical signs.
7. Close the abdomen routinely. This is typically achieved initially via dietary therapy.
If dietary therapy is inadequate, other medical ther-
Postoperative Care and Complications apies are added.
• To prevent an acute hypoglycemic crisis through
Postoperative Care dietary management and nonspecific anti-hormonal
• Give nothing by mouth for 48 hours. therapy.
• Administer a balanced electrolyte solution IV con- Diet and Exercise Recommendations
taining 5% dextrose that is 11/2 to 2 times the daily
maintenance requirements (90–120 ml/kg/day). • Feed frequent small meals to provide a constant
Maintain adequate blood pressure and perfusion to source of calories, which may prevent or reduce the
prevent pancreatitis. number of hypoglycemic episodes.
W0422-Ch035.qxd 11/10/05 5:07 PM Page 396
▼ Chapter
398
W0422-Ch036.qxd 11/10/05 5:12 PM Page 399
(hypersomatotropism) occurs after closure of the epi- • Sex: Most acromegalic cats are male, whereas acrome-
physes, acromegaly develops. In acromegaly, only the galic dogs are female
membranous bones (e.g., nose, mandible, and portions
of the vertebrae) increase in length, because the long General Appearance
bones cannot grow longitudinally once the epiphyses
close. ▼ Key Point The clinical features of acromegaly
GH exerts both direct and indirect effects on the develop so insidiously that they are frequently
body. The indirect actions of GH, mediated by insulin- overlooked.
like growth factor I (IGF-I), are anabolic and include
increased protein synthesis and soft tissue and skeletal • Large paws
growth. In contrast, the direct effects of GH are • Soft tissue swelling of the head and neck with promi-
predominantly catabolic (e.g., lipolysis and restricted nent skin folds
cellular glucose transport). • Prognathism due to mandibular enlargement
• Widened interdental spaces
Etiology • Macroglossia
• Increase in body size and weight; weight loss in some
• In cats: The major cause of acromegaly is a GH- cases
secreting tumor of the pituitary gland. • Pot-bellied appearance
• In dogs: Endogenous (diestrus) or exogenous • Long, thick, or coarse haircoat
progestogens may cause acromegaly by inducing GH • Rapid growth of toenails
production from the hyperplastic ductular epithe-
lium of the mammary glands. Respiratory System
▼ Key Point Acromegaly in dogs is caused by • In cats: Dyspnea as a result of pulmonary edema or
progestogens. Feline acromegaly develops from a pleural effusion from GH-induced cardiac failure.
GH-secreting pituitary tumor. • In dogs: Excessive panting, exercise intolerance,
and inspiratory stridor develop because oropharyn-
Clinical Signs geal soft tissue proliferation compresses the upper
airway.
Signalment
Cardiovascular System
• Age: Middle to old age
• Breed: No breed predilection In cats, cardiac involvement includes the following:
W0422-Ch036.qxd 11/10/05 5:12 PM Page 400
• Diabetes mellitus and its accompanying clinical Basis for a Presumptive Diagnosis
signs of polyuria, polydipsia, and polyphagia develop of Canine Acromegaly
because GH restricts cellular glucose transport. • Characteristic clinical and laboratory findings
Insulin resistance results and large dosages of insulin • Exposure to a progestogen source and improvement
(>2.2 U/kg/day) are frequently needed to control in clinical signs following removal of that progesto-
the hyperglycemia. gen source
• In acromegalic cats, the growth-promoting effects • No evidence of spontaneous hyperadrenocorticism
of GH lead to enlargement of endocrine glands on adrenal testing
(thyroid, parathyroid, adrenal), but the function of
these glands remains normal.
• In contrast, dogs in which acromegaly is caused by ▼ Key Point Suspect acromegaly in female dogs
chronic administration of progestogens have subnor- receiving progestogens and in intact female dogs
mal basal cortisol concentrations. The glucocorticoid- that develop diabetes mellitus or laryngeal stridor
like activity of these progestogens probably suppresses due to soft tissue overgrowth. Suspect acromegaly
adrenocorticotropic hormone (ACTH) secretion and in cats with insulin-resistant diabetes mellitus.
causes secondary hypoadrenocorticism.
Central DI (also called neurogenic DI) is an uncommon • Hematologic and serum biochemical results are
usually normal or consistent with mild dehydration
condition that results from disorders that disrupt
(mild increases in packed cell volume and serum con-
the ADH-producing hypothalamic neurohypophyseal
centrations of total protein and sodium).
neurons.
• Idiopathic ▼ Key Point Urine dipstick and sediment evaluations
• Central nervous system (CNS) trauma are normal, but USG is typically in the range of
• CNS neoplasia 1.000 to 1.007.
• CNS inflammation
• Congenital anomalies • Animals with partial deficiencies in ADH may
produce more concentrated urine (USG 1.008–
1.020).
Clinical Signs • Urine culture is negative.
Signalment
• Age is variable, depending on the cause. Radiography
• Idiopathic and trauma-induced DI has no specific Findings usually are normal.
age predilection.
• Animals with suspected congenital DI are <1 year
Other Diagnostic Imaging
of age.
• Animals with DI caused by CNS neoplasia are MRI and CT can aid in identifying a pituitary or hypo-
usually middle-aged to older. thalamic lesion.
• Breed: No predilection
• Sex: No predisposition Water Deprivation Test
This test is designed to determine whether endogenous
Polyuria and Polydipsia
ADH is released in response to dehydration and
• ADH acts on the distal tubules and collecting whether the kidneys can respond to ADH. Minimal
ducts of the kidneys to allow increased water increases in plasma osmolality should stimulate the
reabsorption. release of ADH.
• Lack of ADH or interference with the ability of ADH
to bind to its receptors results in water diuresis. ▼ Key Point Water deprivation tests are contraindi-
• This primary polyuria results in volume contraction cated in animals that are already dehydrated (since
and subsequent compensatory polydipsia. the stimulus for ADH release already exists) or in
the presence of other laboratory abnormalities
Diagnosis such as azotemia or hypercalcemia.
The diagnosis of DI requires its differentiation
from other more common causes of polyuria and Because water deprivation causes dehydration, this
polydipsia, such as renal insufficiency, diabetes test is potentially dangerous and can result in acute
mellitus, hypercalcemia, pyometra, feline hyperthy- renal failure, neurologic complications, and death. For
roidism, and canine hyperadrenocorticism. this reason, perform comprehensive diagnostic testing,
W0422-Ch036.qxd 11/10/05 5:12 PM Page 405
Procedure
Table 36-2. PROCEDURE FOR WATER
DEPRIVATION TEST • See Table 36-2. Initial gradual reduction in water in-
take in patients with renal medullary washout (which
• Quantitate daily unrestricted water consumption. often accompanies polyuric disorders) allows them to
• Measure urine specific gravity (USG) and weigh the reestablish the medullary concentration gradient.
animal.
• Gradually restrict water intake over 3 to 5 days to Interpretation
100 ml/kg/day. Monitor body weight and USG daily.
Use the criteria below as end points.
• When deprived of water, normal animals can con-
centrate the USG to 1.075 in cats and 1.045 in dogs.
• To continue the test, empty the urinary bladder and Nevertheless, a USG of 1.030 is generally considered
measure USG (and urine osmolality if possible). an adequate response to water deprivation. Failure to
• Withhold all food and water. concentrate to this degree in the absence of renal
• Every 2 hours, reweigh the animal, empty the urinary disease or other laboratory abnormalities indicates
bladder, and measure USG (and urine osmolality if that the animal has central or nephrogenic DI (Fig.
possible). Use the criteria below as end points. 36-3).
• Stop the test when any of the following occur:
• The animal loses 5% of its body weight. Antidiuretic Hormone Response Test
• The animal is clinically dehydrated or ill.
• USG ≥ 1.030. If the animal fails to concentrate urine adequately fol-
lowing water deprivation, perform an ADH response
test. The test evaluates the ability of the renal tubule to
including complete blood count, serum biochemical respond to exogenous ADH and concentrate urine in
profile with electrolyte determinations, complete uri- the face of dehydration.
nalysis, urine culture, and imaging of body cavities, to
Procedure
rule out disorders that may decompensate following
dehydration (e.g., pyometra, pyelonephritis, renal • Immediately following the water deprivation test,
insufficiency, and hypercalcemia). Tests of renal func- administer aqueous vasopressin (Pitressin, Parke-
tion (e.g., iohexol or 99m technetium-diethylenetri- Davis) at 0.5 U/kg (maximum dose is 5 units) IM.
aminepentaacetic acid clearance), adrenal function • Withhold all water and food during the test.
(e.g., low-dose dexamethasone test, ACTH stimulation • Empty the urinary bladder and measure USG (and
test, or urine cortisol-to-creatinine ratio), and thyroid osmolality if possible) at 30, 60, 90, and 120 minutes
function (total thyroxine determination in cats) also after vasopressin injection.
may be indicated before initiating water deprivation. • The animal may drink after the test is completed.
• Calculate the animal’s water deficit based on the Crawford MA, Kittleson MD, Fink GD: Hypernatremia and adipsia in
serum sodium concentration or osmolality and a a dog. J Am Vet Med Assoc 184:818, 1984.
Eigenmann JE: Pituitary-hypothalamic diseases. In Ettinger SJ
normal total body weight of water of 60%: (ed): Textbook of Veterinary Internal Medicine. Philadelphia: WB
Saunders, 1989, p 1579.
Water deficit (liters) @ 0.6 ¥ Body weight (kg) Feldman EC, Nelson RW: Canine and Feline Endocrinology and
Normal sodium (mEq L) ˆ Reproduction: Philadelphia: WB Saunders, 2004.
Ê
¥ Á1 - ˜ Goossens MMC, Feldman EC, Nelson RW, et al: Cobalt 60 irradiation
Ë Patient sodium (mEq L) ¯ of pituitary gland tumors in three cats with acromegaly. J Am Vet
Med Assoc 213:374, 1998.
• Replace the water deficit to lower serum sodium Kooistra HS, Voorhout G, Selman PJ, et al: Progestin-induced growth
concentration £ 0.5 mEq/L/hr. Generally, this rule hormone (GH) production in the treatment of dogs with congen-
ital GH deficiency. Dom Anim Endocrinol 15:93, 1998.
translates to replacing the calculated water deficit Lewitt MS, Hazel SJ, Church DB, et al: Regulation of insulin-like
during a period of 3 days. growth factor-binding protein-3 ternary complex in feline diabetes
• Add maintenance fluid requirement (60 ml/kg/day) mellitus. J Endocrinol 166:21, 2000.
with isotonic polyionic solution to the daily infusion. Nichols R, Hohenhaus AE: Use of the vasopressin analogue desmo-
• Monitor serum electrolytes frequently and adjust pressin for polyuria and bleeding disorders. J Am Vet Med Assoc
205:168, 1994.
fluid type and rate as needed to ensure that serum Peterson ME, Randolph JF, Mooney CT: Endocrine diseases. In
sodium concentration is not lowered too rapidly. Sherding RG (ed): The Cat: Diseases and Clinical Management.
New York: Churchill Livingstone, 1994, p 1403.
Maintenance Therapy Peterson ME, Taylor RS, Greco DS, et al: Acromegaly in 14 cats. J Vet
Intern Med 4:192, 1990.
For chronic management once the animal is eating, mix Randolph JF, Miller CL, Cummings JF, et al: Delayed growth in two
maintenance daily water intake (50–60 ml/kg/day) with German shepherd dog littermates with normal serum concentra-
tions of growth hormone, thyroxine, and cortisol. J Am Vet Med
food. Assoc 196:77, 1990.
Rijnberk AD: Acromegaly. In Ettinger SJ, Feldman EC (eds): Textbook
of Veterinary Internal Medicine: Philadelphia: WB Saunders, 2000,
SUPPLEMENTAL READING p 1307.
Selman PJ, Mol JA, Rutteman GR, et al: Progestin-induced growth
hormone excess in the dog originates in the mammary gland.
Abraham LA, Helmond SE, Mitten RW, et al: Treatment of an acrome-
Endocrinol 134:287, 1994.
galic cat with the dopamine agonist L-deprenyl. Aust Vet J 80:479,
Sullivan SA, Harmon BG, Purinton PT, et al: Lobar holoprosen-
2002.
cephaly in a miniature schnauzer with hypodipsic hypernatremia.
Abrams-Ogg ACG, Holmberg DL, Stewart WA, et al: Acromegaly in a
J Am Vet Med Assoc 223:1783, 2003.
cat: Diagnosis by magnetic resonance imaging and treatment by
cryohypophysectomy. Can Vet J 34:682, 1993.
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▼
Section
The use of a variety of cytologic diagnostic tools and house skin cytology in the diagnosis and management
skin biopsy may greatly facilitate the treatment and ulti- of many dermatoses has become more apparent over
mate outcome for the dermatologic patient. Interpre- the past decade. The use of in-house skin cytology is no
tation of the results is as important as the correct longer restricted to the patient with nodules or drain-
collection of the sample. ing tracts but has been expanded to most patients
Skin cytology is a tool that can be used on almost with inflammatory skin disease (and some with non-
every patient presenting with an inflammatory der- inflammatory dermatitis).
matitis or otitis externa. It often provides therapeu-
tically relevant information, particularly regarding ▼ Key Point Surface cytology is indicated at the initial
the selection of antimicrobial therapy. Individual presentation of many, if not all, dermatology
preference and the actual clinical presentation will patients.
dictate which of the different sampling techniques is
selected. The first part of this chapter elaborates on the One of the major reasons for the increased usage of
various cytology techniques, their special indications, this diagnostic method is the recognition of the preva-
and their interpretation. The second part reviews skin lence and significance of staphylococcal pyoderma (see
biopsies. Chapter 38) and yeast dermatitis caused by Malassezia
There are specific indications for performing a skin pachydermatis (see Chapter 41). Furthermore, the wide-
biopsy that, along with interpretation tips, will be dis- spread availability of “user friendly” diagnostic aids such
cussed. The aim is to take steps required to obtain the as in-house rapid cell-staining kits and good quality,
most diagnostic sample and to give the pathologist the price competitive microscopes has facilitated the use of
best chance of reaching a diagnosis. Special reference these techniques by general practitioners.
is made to the biopsy techniques used for sampling the
inner pinnae and claws.
Sampling Techniques
The most common sampling techniques include Scotch
SKIN CYTOLOGY tape impression, adhesive glass slide impression, direct
glass slide impression, skin-scrape and smear (using a
Skin cytology techniques range from those that sample spatula or scalpel blade), cotton bud (Q-tip) “sample
the surface to those that sample deep inside a cuta- and smear,” and aspiration. In-house processing typi-
neous nodule. To the practitioner, the importance of in- cally uses one of the rapid-stain products; these stains
409
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are generally not used by cytologists, who prefer the tra- • This technique is most practical for areas that are
ditional Wright stain because of a superior appearance moist or exudative.
of cellular morphology with these stains. Thus air-dry • Take care to obtain a thin enough smear.
but do not stain samples that will be submitted to a cytol- • The sample collected may need to be separated onto
ogist. Obtain a smear of one cell thickness to clearly another slide and thinly smeared. Some anatomic
observe cellular morphology, irrespective of the stain. sites are not well suited to this technique, such as the
ventral interdigital fold and periocular area. Pressure
Scotch Tape Impression must often be applied to have the material adhere to
the slide; beware of breaking the slide with too much
This is particularly advantageous for scanning the pressure.
surface for yeast and/or significant numbers of bacte- • A variation of this technique may yield significantly
ria (both rods and cocci). It gives poor cellular defini- higher numbers of organisms. The glass slide is not
tion, although inflammatory cells can be identified. Two simply pressed downward but also pushed a little
techniques with different staining have been described, along the surface at a 45-degree angle so that the skin
but the collection method is identical. The use of is smeared along the glass surface. This technique
Scotch tape that is not the “invisible” type avoids the requires a little more pressure, which is directed at
problem of numerous small artifactual circles. In my the leading edge of the slide. Take care that this
hands, the cheapest brands of clear Scotch tape are leading edge does not cut the skin.
often the best.
Cotton Bud (Q-Tip) Sample and Smear type, scan carefully for any evidence of intracellular
organisms. Conversely, and importantly, superficial
Technique pyodermas are often not associated with bacteria on
• Because the Q-tip can be inserted into a small cytologic examination. Acantholytic keratinocytes,
opening, this sampling technique is most useful for which are referred to as “fried eggs” because of their
external ear canals, draining tracts, or interdigital large, rounded shape with a large, round central
folds. nucleus, may be used as supportive evidence for a diag-
• Gently roll the collected material onto the glass nosis of pemphigus foliaceus; however, these rounded
slide; a thin layer of material is best for cytologic keratinocytes may also be seen in superficial pyodermas.
interpretation. Regard acantholytic keratinocytes as suggestive or sup-
• Rolling with too much pressure or “rubbing” the tip portive of a diagnosis of pemphigus foliaceus but not
to and fro may disrupt the cells, affecting interpreta- as sufficient evidence to confirm a diagnosis. Never
tion (see below). institute immunosuppressive therapy on the basis of
• Organisms found on the surface of the sample should those findings alone.
correlate to those “deepest” in the exudate; consider
evaluation of two smears to distinguish organisms on “Aspiration Cytology” Sampling
the surface from those that are deeper.
• In cases of otitis externa, in which there is a consid- This type of sampling is used predominantly for
erable amount of exudate within the ear canal, a nodules. Cytologic evaluation is useful in the initial
third smear may even be added—taken after most of investigation because it may allow an early differentia-
the exudate has been gently removed. Multiple tion between neoplasia and infection.
organisms will often be identified in these situations,
and some may be missed if only one “level” of the Technique
exudate is sampled. A recent bacterial culture study, • Firmly fix the nodule with one hand, insert the
using samples taken sequentially from the same needle to the center of the nodule, and obtain cells
anatomic site of ears with otitis externa, revealed dif- for subsequent cytologic staining.
ferent organisms on sequential samples. • The first method uses a needle without an attached
syringe. Insert the needle several times at multiple
Tzanck Preparation or Smear angles without withdrawing it through the skin. Aim
the tip of the needle at the center of the nodule. By
As originally described, this technique is an aspirate of
this movement, the cells will be driven into the body
the contents of a pustule; however, it is technically diffi-
of the needle. This technique is favored by oncolo-
cult unless there is a large pustule and is therefore rarely
gists because they believe there is the least chance of
performed this way. Such large pustules are typically
“seeding” tumor cells into the surrounding tissue.
seen on the ventral abdomen and with cases of “puppy
impetigo” and pemphigus foliaceus.
• The alternative technique uses a needle with an
attached syringe. Once the needle is inserted into
the center of the nodule, apply negative pressure.
Technique Release this negative pressure before the needle is
• Gently insert the tip of the needle into the pustule, removed from the skin to avoid sucking the cells into
bevel side upward, and with a lifting motion to use the body of the syringe.
the sharp edge of the bevel to cut through the “roof” With either technique, once the needle is removed
or surface of the pustule. from the tissue, attach an air-filled syringe and blow the
• Transfer the contents of the pustule to a glass slide by cells out onto the surface of the glass slide. Hold the
gentle impression. needle bevel side down to collect as many cells as possi-
• Rupturing the roof of the pustule changes the possi- ble. Smear thinly using a blood smear technique or
ble interpretation and negates the possibility of a squash prep technique as appropriate, air-dry, and stain.
“sterile” culture. However, this modified technique is The absence of cellular material using this technique is
adequate to look for cytologic clues about the etiol- interpreted by some as indicating a densely cellular
ogy of the pustule, which is the major reason to mass such as a fibrous cell tumor.
perform this technique.
Assessment for inflammatory cells, bacteria, and the “Touch” Preparation
presence or absence of acantholytic keratinocytes may
help prioritize the differential diagnosis list. The pres- Use this with a surgical biopsy specimen.
ence of eosinophils should alert you to the possibility of
ectoparasites, in particular scabies or fleas. Neutrophils Technique
are most commonly associated with a bacterial infec- • Gently touch the undersurface or base of the tissue
tion; when they are intact and the predominant cell to the glass slide.
W0422-Ch037.qxd 11/10/05 5:11 PM Page 412
• This technique is also useful for cytologic evaluation impression smear is not suitable for those cases in
of crusts: Gently touch the undersurface of the crust which cell morphology is important.
or the exposed surface of the skin once a crust has • Heat fixing is contraindicated if cellular morphology
been removed with the glass slide. is of interest. This procedure is most relevant for
• Air-dry and stain as usual. Submit the tissue from a exudates with a large wax content, such as an otitis
surgical excision for histopathology. I routinely save externa sample, but even in those cases cellular detail
four additional air-dried, unstained slides. These may may be important to assess. Air-drying is the preferred
be used by the laboratory for adjunctive tests. technique; in practice, the use of a cold air–low heat
• In rare instances, organisms have been identified on hair dryer may help reduce the time required for
the touch prep but not on histopathology. drying.
• With some atypical neoplasms, cytology may give • Although clinician preference varies, I typically view
clues about the cell of origin, which even “special these samples using 400¥ microscopic magnification.
stains” may fail to differentiate on histopathology.
• Immunohistochemical staining may be possible
with cytology samples that have been deep-frozen. Interpretation
With some select types of immunohistochemical Surface Cytology
staining, formalin-fixed tissue cannot be used
Regardless of the collection technique, I use surface
because of the degeneration of antigens. In those
cytology to look for organisms and perhaps for inflam-
instances, a cytology slide that has been air-dried and
matory cells. Microbes identified by the regular cytology
deep-frozen can be used immediately, eliminating
stains can be classified by shape, size, and quantity.
the expense, discomfort, and delays created by a
Perform a culture to determine the species. The sub-
repeated surgical procedure. Transport these slides
classification of gram positive or negative is not possible
to the laboratory so that the formalin fumes that may
using the regular cytology stains. Therefore, surface
emit from the tissue specimen do not contact the cells
cytology screening looks for the presence of yeast,
on the slide. Shipping in separate packages may be
cocci, and rods; hyphae may be seen as ghosts (they do
required.
not typically take up the stain) by more experienced
cytologists.
Processing You should not be able to see significant numbers of
As mentioned previously, there are some important microbes on the surface cytology of normal skin.
principles with regard to the processing of cytology Surface cytology sampling yields a significant amount of
samples. debris, associated with the dirt, environmental mold
spores, surface lipids, and free keratin, which all sit on
• Handle the sample gently, whether the material is the outer surface of the stratum corneum. Practice on
rolled onto the glass slide or “squashed and pulled”
non-lesional skin of normal dogs to become familiar
between two slides as in a squash prep. The cells are
with normal versus abnormal surface cytology.
friable and may rupture if handled roughly. Breakage
On the skin, the cocci will be predominantly the
of the cells not only affects the cytologic evaluation
Staphylococcus species, the yeast predominantly the
but also may interfere with interpretation. For
Malassezia species, and the rods generally contaminants.
example, the presence of ruptured neutrophils in a
carefully handled sample may be used as an indica- • Yeast organisms are found in the more humid areas
tion of neutrophil toxicity. of the skin, such as the ventral neck, perianal, inter-
• Always make a duplicate slide, which remains digital, and perioral areas. Geographic variation may
unstained and ready for submission to a cytology be possible so that the “normal” number of yeast is
laboratory should there be a need for more expert higher in warm and humid areas. In one report, the
interpretation based on the in-house test results. presence of one or two organisms per high power
Laboratory cytologists do not regard the “instant stain- field (HPF) was defined as within normal limits.
ing” methods available in general practice as ade- However, in a temperate climate, this number of yeast
quate. This may be particularly useful for clinicians is high, and an animal with clinical signs of infection
with less experience in cytology but who are trying to and one or two yeast per HPF (400¥) is regarded as
improve their skills in this area; compare the results having an active infection and will receive topical
reported by the laboratory cytologist with those therapy. Systemic therapy is based not simply on
obtained in-house. numbers of organisms but also on severity of clinical
• Process the sample carefully if cellular morphology is symptoms and total area of the body affected. Sys-
important, following the exact instructions for the temic antifungals are expensive, and some have the
staining technique. Examples would be impression potential for severe toxicity.
smears from inflammatory dermatoses or aspirates • Cocci may be seen attached to the surface of ke-
from nodules. Under- or over-staining may affect the ratinocytes. This may be interpreted as active colo-
color of the contents of the cell. The Scotch tape nization, indicating a more pathogenic strain. More
W0422-Ch037.qxd 11/10/05 5:11 PM Page 413
often, cocci are seen scattered throughout the • Bacteria form part of the normal otic skin flora.
sample, often in small groups either with or between However it is unusual to identify bacteria with surface
keratinocytes. This is abnormal and typically consis- cytology of the external ear canals; therefore, con-
tent with a superficial pyoderma. Intracellular cocci sider any notable numbers as suspicious of an infec-
are regarded as a sign of increased severity of infec- tion. The presence of small, round organisms that are
tion. Prescribe systemic antibiotics in these animals. not well defined or large enough to be staphylococci
or streptococci probably represent the Bacteroides
▼ Key Point The absence of cocci on cytology does species, which is a ubiquitous organism whose patho-
not rule out the possibility of staphylococcal genicity is controversial. A significant number of
pyoderma. these organisms on surface cytology at least repre-
sents an aberrant surface population and possibly
• The presence of significant numbers of rod-shaped suggests overgrowth.
bacteria is not normal on the skin surface and may • Rod-shaped bacteria on surface cytology of the exter-
be interpreted as representing an abnormal surface nal ear canal suggests the need for a bacterial culture
environment, with overgrowth of a nonpathogen, or and susceptibility testing, especially if initial empiric
colonization. Perform culture if there are abundant therapy has been attempted and was not successful.
rod-shaped organisms, the area of affected skin is • Record the number of bacteria of each type (cocci
large, or a deep pyoderma is clinically determined. and rods), for example, as none, few, many, or abun-
Many cases with surface rod overgrowth but mild clin- dant or on a semiquantitative scale from 0 to 3 (0 =
ical signs will respond to topical shampoo therapy, none, 1 = easily countable, 2 = not easy to count, 3 =
often with specific therapy aimed at the underlying impossible to count). This is useful in monitoring
disease, such as hypothyroidism or severe chronic response to therapy at recheck visits.
allergies. If systemic therapy is necessary, never select
an antibiotic empirically. Perform culture and sus- Fine-Needle Aspiration
ceptibility testing in these cases because rod-shaped
bacteria (e.g., Pseudomonas spp.) are often resistant to Interpretation of fine-needle aspiration (FNA) is
multiple antibiotics. helpful to differentiate an infectious or cystic process
and may or may not identify neoplastic cells (also see
Chapters 26 and 30). Performing in-house cell cytology
Ear Cytology allows the development of a prioritized differential diag-
nosis list. Evaluate cytologic aspirates with some specific
Compared with skin surface cytology (as described pre-
criteria (see below). Send to an experienced cytologist
viously), interpretations of ear cytology vary significantly
those samples that require more expert interpretation.
with otitis externa because the ear canal provides a
Palpate the lesion before obtaining an aspiration
unique surface environment. The narrow, long canal is
sample. Determine if the nodule is within the epidermis,
associated with an increased local humidity and tem-
dermis, or subcutaneous tissue. The epidermis contains
perature compared with the skin surface in general.
four major cell groups, which may become neoplastic.
Variation with season, humidity, degree of hair growth,
These are the squamous (epidermal) cells, melanocytes,
and anatomy (pendulous versus erect pinna types) is
a pluripotential follicular cell (which produces basal cell
important. Finally, the surface of the canal is not readily
carcinoma), and cells that comprise the hair follicle and
visible, so observation of increased exudate or redness
adnexae. Most inflammatory nodules are localized in the
by the owners is not possible until it extends to the
dermis. The dermis contains nerve cells and vascular and
entrance of the canal and on to the pinna or sur-
connective tissue. In addition, the dermis is often the
rounding skin.
host site for neoplastic cells derived from bone marrow.
• Yeast are a normal inhabitant of the external ear Lymphocytes, mast cells, and macrophages may form
canal. Small numbers are regarded as “normal” cutaneous accumulations of neoplastic cells. The sub-
because they may be cultured from most normal cutaneous tissue contains predominantly fat.
canine ears. Nevertheless, on surface cytology this
number has yet to be clearly quantified. For an exter-
• From a clinical viewpoint, neoplasms arising in the
subcutaneous tissue initially do not affect the hair fol-
nal ear canal with significant numbers of yeast on
licles and adnexae; thus the overlying skin and hair
cytology, consider the clinical signs.
remain normal in appearance.
▼ Key Point If there are up to five yeast/HPF and no
• More superficially located neoplasms (such as those
in the epidermis and superficial dermis) commonly
evidence for clinical otitis, then yeast are regarded
affect adnexal structures, resulting in alopecia.
as an overgrowth and an ear cleaner is recom-
mended. If there is clinical evidence of inflam- Palpation can also reveal whether the lesion is min-
mation, then as few as two yeast/HPF will be eralized, painful, cystic, or cellular. Fluctuant tumors
interpreted as supportive of a yeast otitis. must be differentiated from an inflammatory lesion
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Skin Biopsy Sampling Methods In all of these cases, a punch from the center of
the lesion may provide a rapid, relatively non-invasive
There are two major types of biopsy technique—the diagnosis.
punch and the wedge or ellipse. The most common Punch biopsy is quick, relatively atraumatic, and
sampling techniques include punch biopsy and inci- usually employed with suspected infectious, inflamma-
sional and excisional wedge or elliptical biopsies. Two tory, and endocrine dermatoses. Disposable biopsy
less common and more site-specific techniques include punches are readily available in 4-, 6-, and 8-mm diam-
“shave” biopsy and “onychobiopsy without onychec- eter sizes. They can be autoclaved and reused at least
tomy” claw biopsy. The biopsy for deep tissue culture once without greatly affecting their sharpness. Rou-
has specific modifications to that sampled primarily for tinely use 8-mm punches; however, in very small dogs
histopathologic evaluation. and cats, use 6-mm punches. Reserve 4-mm punches for
Punch biopsy refers to the use of the biopsy punch biopsies of foot pads, nasal planum, or eyelids.
instrument, which for veterinary purposes is used in
4-, 6-, and 8-mm diameters. Punch biopsies are fast and
easy to use, and they yield a circular plug of tissue with
Punch Biopsy for Deep Tissue Culture
clean, surgical, non-traumatized edges. Wedge biopsy If cytology revealed a mixed population of cells or his-
refers to the elliptically shaped surgical biopsy, which tiocytic cells, and therefore infection etiologies are pos-
takes a deeper section (or wedge) of tissue. Each sible, consider two options for sampling for culture:
method is used for specific indications, but in general
the choice for smaller samples is one of personal
• Insert a culture swab into the defect left by the exci-
sional biopsy, taking care not to contaminate this with
preference.
surface organisms and remembering that for histopathol-
ogy purposes the surface has not been aseptically prepared.
Principles of Tissue Sampling • Alternatively (and preferably), section the tissue
Regardless of the technique to be chosen, there are sample, once excised and using sterile blades, and
some basic principles when sampling skin for histo- place a piece of that tissue into culture transport
pathology submission that are contrary to routine media. If this was a punch biopsy, then section it lon-
surgery. The first of these is that no skin antisepsis is gitudinally in half, with one half submitted for
practiced. This is to minimize any changes to the epi- histopathology and the other half reserved for tissue
dermal surface. Surgical cleaning may remove layers of culture. Make the longitudinal cut with the blade
stratum corneum, which contain clues through their starting at the deeper tissue area and finishing at
thickness, associated pathology, or the presence of the skin surface so that surface organisms are not
organisms. Indeed, even the use of the surgical clip is dragged through the tissue. Remove with a new
avoided because it may alter the epidermis. The second sterile scalpel blade and make a single cut to remove
principle is that the tissue must be handled gently to the upper half of the punched out tissue. Submit this
avoid crushing. Tissue crush artifact alters the tissue upper part for histopathology as a shave specimen.
architecture and obscures the cell type.
Incisional Biopsy
Incisional sampling is used when evaluation of the
Punch Biopsy
lesional margin is considered important. Examples
When selected for non-nodular dermatoses, punch include the edge of a depigmented lesion and the edge
biopsy is useful to sample multiple small areas that may of an ulcer. Consider incisional samples for areas in
represent various stages of the disease process. Nodules which there is a transition from one stage or age of the
are typically removed with an excision biopsy method. lesion to another. This may reveal important abnor-
However punch biopsy is indicated when sampling malities. Choosing to perform an incisional biopsy may
nodules for several reasons: decrease the potential for laboratory error during
processing (Figure 37-1).
• A large nodule is present in an area for which
complete excision would be difficult, and a
smaller sample from the core may provide the Excisional Biopsy
diagnosis without the concurrent excisional surgical Excisional sampling is useful to avoid the rupture of a
treatment. large pustule or vesicle. Also use excision when a lesion
• An animal with a high anesthetic risk, an animal for involving the deeper tissues, especially the panniculus,
which extensive surgery or adjunctive oncologic must be sampled or when a solitary lesion, which could
therapy will not be elected by the owners, or when a be cured by excision, is present. For a solitary nodule,
cytology aspirate from the nodule suggested an perform wide surgical excision, because this technique
inflammatory and possibly an infectious etiology may provides the entire specimen for histologic examination
be further reasons for using a punch biopsy on and allows margins to be examined if the lesion is a
nodular disease. tumor. Excise a 2- to 3-cm margin of tissue if a neoplasm
W0422-Ch037.qxd 11/10/05 5:11 PM Page 416
technician will routinely section the elliptical biopsy submit some air-dried, unstained slides separately to
along the “long axis” of the sample. When the long the laboratory for storage.
axis does not correspond to the direction in which
the hair follicles grow, the follicles may be cut in Processing and Submitting
“cross section.” A differential diagnosis list is essential with dermatologic
4. For the punch biopsy: cases. This list is important for the clinician to ensure
a. Hold the punch at right angles to the surface of that he or she has considered the options and obtained
the skin and gently place it over the selected from both pet and owner as much information as pos-
lesion. Hold the surrounding skin with the other sible and as necessary before taking the biopsy, and it is
hand. important to alert the pathologist to the possible patho-
b. Apply firm continuous pressure and rotate the logic processes. If the list of clinical differentials fails to
punch in one direction until a sufficient depth has correlate with the histopathology, review the sections. If
been reached to free the dermis from its under- the biopsy submission form clearly states that a deep
lying attachment. This is evident when the skin infectious process is suspected, perform special stains to
no longer tries to “turn” with the rotation of the rule out infectious organisms. If an immune-mediated
punch and by a gentle easing of pressure required dermatosis is suspected and convincing supportive evi-
for the turning. For thin-skinned areas such as the dence is not seen on the first section, order recuts of
ventral abdomen, or with cats and small dogs, this the biopsy sample. Many dermatoses are diagnosed
may not be noted and some visual note of the using a combination of the signalment (age, breed,
depth is warranted. sex), clinical presentation (distribution, type of primary
c. Remove the punch, lift the section of tissue, grasp lesions if present), history (in particular previous
at the base (which should be the panniculus), and response to therapy), and supportive histopathology.
sever the subcutaneous attachments using fine Identification of each sample is important. This may
blunt/blunt iris scissors and iris forceps. be achieved by placing each sample in a separate con-
tainer or inking the samples. Inking the margins may
▼ Key Point During skin biopsy, do not grasp the identify a particular sample (e.g., the one sample of
dermis or epidermis with forceps because this
“clinically normal skin”) or help the technician with
leads to crush artifact.
orientation (e.g., inking the haired skin surface of an
onychectomy sample). Various commercial dyes are
Crushed tissue may be misinterpreted as scarring at best
available, or simple India ink can be used. However it
and may render the sample worthless.
is most important that the ink dries on the surface of the
5. For wedge or elliptical biopsy:
tissue before it is placed in the formalin.
a. Make an elliptical incision, taking care not to
crush or tear the edges.
b. Attempt to orient the central axis of the ellipse
along several different stages of lesion develop- SUPPLEMENTAL READING
ment to allow the pathologist to interpret the
development of the pathology. General
6. Roll the tissue on gauze to gently blot the blood Moriello KA, Rosenthal RC: Clinical approach to tumors of the skin
from its surface. and subcutaneous tissues. Vet Clin North Am Small Anim Pract
7. Place large, thin pieces of tissue panniculus side 20(4):1163–1190, 1990.
Mueller RS: Dermatology for the Small Animal Practitioner. Jackson,
down onto a rigid piece of cardboard or a wooden Wy: Teton NewMedia, 2000.
tongue depressor. This prevents the tissue from Scott DW, Miller WH Jr, Griffin CE: Muller & Kirk’s Small Animal
curling when placed in the formalin, optimizing the Dermatology, 6th ed. Philadelphia: WB Saunders, 2001.
interpretation by the pathologist.
8. Place the tissue and cardboard or tongue depressor Cytology
into 10% formalin (tissue side down) and allow it
to fix for at least 8 hours before sectioning. The Angus JC: Otic cytology in health and disease. Vet Clin North Am
Small Anim Pract 34(2):411–424, 2004.
volume of formalin required is approximately 10 Cohen M, Bohling MW, Wright JC, et al: Evaluation of sensitivity and
times the volume of the sample. specificity of cytologic examination: 269 cases (1999–2000). J Am
9. Section nodules into 1-cm-thick pieces to allow ade- Vet Med Assoc 222(7):964–967, 2003.
quate penetration of the formalin into the center Cole LK, Kwochka KW, et al: Microbial flora and antimicrobial sus-
of the lesion. ceptibility patterns of isolated pathogens from the horizontal ear
canal and middle ear in dogs with otitis media. J Am Vet Med Assoc
10. A valuable adjunctive test is to perform cytology 212(4):534–538, 1998.
from the impression of such a freshly excised Daigle JC, Kerwin S, et al: Draining tracts and nodules in dogs and
surface of a nodule. Make multiple slides and cats. Clin Tech Small Anim Pract 16(4):214–218, 2001.
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Eich CS, Whitehair JG, et al: The accuracy of intraoperative cytopatho- Linder KE: Skin biopsy site selection in small animal dermatology with
logical diagnosis compared with conventional histopathological an introduction to histologic pattern-analysis of inflammatory skin
diagnosis. J Am Anim Hosp Assoc 36(1):16–18, 2000. lesions. Clin Tech Small Anim Pract 16(4):207–213, 2001.
Michels GM, Knapp DW, et al: Prognosis following surgical excision
of canine cutaneous mast cell tumors with histopathologically
Dermatopathology tumor-free versus nontumor-free margins: A retrospective study of
31 cases. J Am Anim Hosp Assoc 38(5):458–466, 2002.
Bettenay SV, Hargis AM: Practical Veterinary Dermatopathology for
the Small Animal Clinician. Jackson, Wy: Teton NewMedia, 2004.
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▼ Chapter
38 Pyoderma
Edmund J. Rosser Jr.
Pyoderma refers to any pyogenic infection of the skin Acute Moist Dermatitis (Hot Spot)
and is most commonly used in reference to bacterial (Pyotraumatic Dermatitis)
skin infections. However, fungal organisms (especially
yeast) have also been recognized as potentially signifi- Etiology
cant opportunists in the development of surface pyo- Self-trauma to the skin, due to an underlying pruritic or
derma in the dog (see Chapter 41). Pyoderma is a painful process, can result in a focal surface pyoderma
common problem in clinical practice. referred to as acute moist dermatitis. Underlying con-
• Primary pyoderma refers to a skin infection that ditions that may be associated with the development of
does not recur after the appropriate treatment. These acute moist dermatitis are listed in Table 38-1.
infections are most likely the result of a transient and
non-recurrent insult to the skin. Clinical Signs
• Secondary pyodermas are far more common and are • Acute moist dermatitis is usually a single alopecic
associated with a persistent or recurrent underlying lesion that is circumscribed, erythematous, thick-
problem that alters the skin’s resistance to infection. ened, and erosive. An exudative film occurs over the
Until the underlying problem is identified and cor- surface, and peripheral hairs are matted onto the
rected, the infection usually responds only tem- lesion. The lesion develops subsequent to the dog’s
porarily to therapy and subsequently recurs. chewing and licking at a focal area of pruritus or
• Pyodermas are caused by bacterial colonization or pain, and it develops within a matter of hours. The
invasion of the skin by coagulase-positive staphylo- lesion is usually painful.
cocci, usually Staphylococcus intermedius. In chronic, • Thick-coated, longhaired breeds are most commonly
recurrent, or deep pyodermas, secondary bacterial affected.
invaders may also be present, especially Pseudomonas • Lesions that appear clinically similar to an acute
spp., Proteus spp., and Escherichia coli. When deep pyo- moist dermatitis (pyotraumatic dermatitis), but
derma occurs, anaerobic bacteria such as Bacteroides develop in the absence of a history of self-trauma, are
spp., Peptostreptococcus spp., Fusobacterium spp., Porphy- often associated with a deeper bacterial folliculitis
romonas spp., and Clostridium spp. may be further and/or furunculosis and are most commonly
opportunistic pathogens. Recently, two additional observed on the side of the face, or cheek region
staphylococci have been isolated from cases of recur- (also referred to as pyotraumatic folliculitis). The
rent pyodermas, namely Staphylococcus schleiferi subsp breeds more commonly affected by this deeper form
schleiferi and Staphylococcus schleiferi subsp coagulans, of an acute moist dermatitis are golden retrievers,
both of which are frequently methicillin-resistant Saint Bernards, Bouviers, and Newfoundlands. In
staphylococci. these cases, satellite popular lesions can usually be
detected surrounding the area of acute moist der-
matitis once the area has been clipped.
SURFACE PYODERMAS
Diagnosis
Surface pyoderma is a bacterial colonization of the
surface of the epidermis only, without invasion into the ▼ Key Point Diagnose acute moist dermatitis by the
stratum corneum or hair follicles. Two types of surface history of self-trauma to the skin, acute onset,
pyoderma are recognized: acute moist dermatitis (“hot rapid development of the lesion (within hours), and
spot” or pyotraumatic dermatitis) and skin fold the typical appearance of the lesion on physical
pyoderma. exam.
420
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Impetigo is most often observed in young dogs before Erythromycin 11 mg/kg q8h
puberty. The condition may be more likely in the pres- Cephalexin 22 mg/kg q8h or 33 mg/kg q12h
Cefadroxil 22 mg/kg q8–12h
ence of contributing factors such as poor nutrition, Trimethoprim/sulfadiazine 30 mg/kg q12h
dirty environment, and ectoparasite or endoparasite Ormetroprim/sulfadimethoxine 55 mg/kg on day 1, then
infection. However, well–cared-for individual puppies 27.5 mg/kg q24h
or litters of puppies may also develop this condition. Amoxicillin/clavulanate 14 mg/kg q12h
Clindamycin 5 mg/kg q12h or 11 mg/kg q24h
Clinical Signs
• Impetigo occurs as pustules in the inguinal and
ventral abdominal regions. Occasionally, pustules are
noted in the axillary region. When the pustules
rupture, a yellow to brownish crust forms.
Topical Therapy
• The pustules are not oriented around hair follicles Once any predisposing factors have been eliminated,
(i.e., no hair shafts protrude through the center of topical therapy is usually all that is required for this
the pustule). Minimal erythema is noted, and the superficial staphylococcal infection. Bathe the dog
patient is usually non-pruritic. with a benzoyl peroxide shampoo (OxyDex Shampoo,
• Impetigo may be an incidental finding during the DVM Pharmaceuticals; Pyoben Shampoo, Allerderm/
physical examination of a recently acquired puppy. Virbac; Benzoyl-Plus, EVSCO Pharmaceuticals) or
chlorhexidine shampoo (Hexadene, Allerderm/Virbac;
Diagnosis ChlorhexiDerm, DVM Pharmaceuticals) 2 to 3 times
weekly for 2 to 3 weeks.
▼ Key Point Impetigo is usually diagnosed in young
dogs before puberty by observing non-follicular Antibiotics
pustules in the inguinal and ventral abdominal
Systemic antibiotic therapy is rarely necessary in
regions with minimal erythema and absence of
impetigo. However, when topical therapy fails to resolve
pruritus.
the pyoderma, add a systemic antibiotic to the topical
• History: Ask the owner about the animal’s previous therapy protocol (Table 38-3).
and current nutrition and housing environment.
• Physical examination: See the related “Clinical Signs” Superficial Folliculitis
section. Etiology
• Cytologic examination: Stained contents of an intact • Superficial folliculitis induced by coagulase-positive
pustule most often reveal neutrophils and cocci.
staphylococci occurs occasionally as a primary
• Skin scrapings: Examine routine skin scrapings for
problem. These infections are most likely the result
ectoparasites such as Demodex canis, Sarcoptes scabiei,
of a transient and non-recurrent insult to the skin.
and Cheyletiella spp.
• Bacterial culture: This is rarely necessary, but if per- • Secondary superficial folliculitis is far more common
and is associated with a persistent or recurrent under-
formed, S. intermedius is usually isolated.
lying problem that alters the skin’s resistance to infec-
• Skin biopsy: This is rarely necessary to establish the
tion. Until the underlying problem is identified,
diagnosis of impetigo. Histopathology indicates sub-
the infection usually responds only temporarily to
corneal pustules containing neutrophils and cocci.
therapy and subsequently recurs (see the discus-
• Fecal flotation: Evaluate the puppy for intestinal
sion under “Recurrent Superficial and Deep
parasites.
Pyodermas”).
Treatment
Clinical Signs
▼ Key Point Objectives include identifying contribut- • Superficial folliculitis initially appears similar to
ing factors and correcting these as an adjunct to impetigo, with papules and pustules in the inguinal
specific treatment. Improve the nutritional status and ventral abdominal regions. However, pustules
and the housing environment and treat any often extend to the axillary region and the ventro-
endoparasite or ectoparasite infections. lateral thorax.
W0422-Ch038.qxd 11/10/05 5:11 PM Page 424
• The papules and pustules are oriented around the 38-3) and that the duration of therapy has been
hair follicle (i.e., hair shafts protrude through adequate. The treatment required for folliculitis is
the center of the pustule). The base of the pustule generally more vigorous than that required for
is often erythematous, and the patient is usually impetigo. In recurrent cases, define the underlying
pruritic. disease process and initiate a systematic approach
• Other lesions may include papules, crusts, and epi- to the disease. See the discussion under “Recur-
dermal collarettes. rent Superficial and Deep Pyodermas.”
• When the truncal skin is affected, the haircoat often
takes on a “moth-eaten” appearance. Topical Therapy
• Rarely, multifocal areas of alopecia are seen without Use twice-weekly bathing with a benzoyl peroxide
erythema or other lesions. shampoo (OxyDex Shampoo, DVM Pharmaceuticals;
Pyoben Shampoo, Allerderm/Virbac; Benzoyl-Plus,
Diagnosis EVSCO Pharmaceuticals) or a chlorhexidine shampoo
(ChlorhexiDerm, DVM Pharmaceuticals; Hexadene,
▼ Key Point Superficial folliculitis is usually diag- Virbac; SebaHex, EVSCO Pharmaceuticals) for 3 weeks.
nosed by observing papules and pustules oriented
around hair follicles in the inguinal, ventral abdom-
Antibiotics
inal, and axillary regions. The base of the pustule
is erythematous and the patient is usually pruritic. Systemic antibiotic therapy can be initially selected
on an empirical basis, choosing an antibiotic effective
• History: Superficial folliculitis is often secondary to an against coagulase-positive staphylococci (see Table 38-
underlying disease problem. Question the owner 3). Treat for a minimum of 21 consecutive days and for
about the effect of antibiotic therapy alone on the at least 7 days beyond apparent clinical cure.
disease problem. This is a very important diagnostic
tool in the systematic approach to a patient with a
recurrent pyoderma. See also the discussion under DEEP PYODERMAS (DEEP FOLLICULITIS
“Recurrent Superficial and Deep Pyodermas.”
• Physical examination: See the related “Clinical Signs”
AND FURUNCULOSIS)
section.
A deep pyoderma is a bacterial skin infection that
• Cytologic examination: The contents of an intact
extends beyond the epidermis, into the dermis, and
pustule usually reveal neutrophils and cocci.
occasionally into the subcutaneous tissues. Although
• Skin scrapings: These are routinely examined for the
there are many possible forms of deep pyoderma, this
presence of ectoparasites, such as D. canis, S. scabiei,
discussion is limited to the most common form, deep
and Cheyletiella spp.
folliculitis and furunculosis.
• Bacterial culture and susceptibility tests: Consider these
in cases of recurrent superficial folliculitis that have • The disease begins as a superficial folliculitis then
not responded to appropriate empirical antibiotic extends deeper into the hair follicle, causing a deep
therapy and are designed to evaluate for resistant folliculitis.
bacteria. Cultures usually reveal S. intermedius. Use • This inflammatory process often results in furuncu-
the sensitivity results as a guideline for antibiotic losis, which is the destruction of the hair follicle wall
selection. and the release of the bacteria, hair shaft material,
• Fungal culture: Submit a sample of the hairs from fol- and follicular keratins into the surrounding dermis
licular pustules for a fungal culture in cases that are and occasionally the subcutaneous tissues.
non-responsive to appropriate anti-bacterial therapy. • Subsequently, the bacteria can produce septicemia
In some instances, a folliculitis due to a dermatophyte and/or bacteremia, and the released hair shafts and
infection can appear clinically indistinguishable from follicular keratins induce a foreign body and pyo-
a folliculitis caused by bacteria. granulomatous inflammatory reaction in the dermis.
• Skin biopsy: Typical findings include folliculitis or per-
ifolliculitis, with coccoid bacteria within the hair
follicle. Folliculitis due to a dermatophyte infection
Etiology
would reveal the presence of spores or hyphae within • Coagulase-positive staphylococci are the most
the hair follicle. Usually, biopsy is not necessary in the common pathogens initially involved in deep pyo-
diagnosis of superficial pyoderma. derma. S. intermedius is the most frequently isolated.
• In contrast to a superficial pyoderma, secondary inva-
Treatment sion with other aerobic bacteria often occurs with
Pseudomonas spp., Proteus spp., and E. coli. Anaerobic
▼ Key Point Be certain that an appropriate antibiotic bacteria may also become opportunistic pathogens,
for staphylococci has been selected (see Table especially Bacteroides spp., Peptostreptococcus spp.,
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Fusobacterium spp., Porphyromonas spp., and Clostridium • Bacterial culture: Perform both aerobic and anaerobic
spp. bacterial culture and susceptibility tests in all cases of
• Deep pyoderma is rarely a primary disease process deep pyoderma. This form of pyoderma is capable of
and is invariably related to some other underlying causing bacteremia and/or septicemia, resulting in a
problem. life-threatening situation. Usually, biopsy is not nec-
essary in the diagnosis of superficial pyoderma.
Clinical Signs • Fungal culture: Do this in cases of deep pyodermas that
are refractory to antibiotic therapy. Fungi are another
• Deep folliculitis and furunculosis initially begin as possible cause of a deep folliculitis and furunculosis.
superficial folliculitis. See the discussion of clinical Fungal diseases to consider include sporotrichosis,
signs under “Superficial Pyodermas,” and see “Super- blastomycosis, coccidioidomycosis, aspergillosis,
ficial Folliculitis.” histoplasmosis, and cryptococcosis.
• When deep folliculitis and furunculosis develop, the • Skin biopsy: This usually reveals deep folliculitis,
papules and pustules become larger and nodular on perifolliculitis, and furunculosis. Bacterial or fungal
palpation. Exudation and crust formation follow. organisms may or may not be identified on special
Ulcers and draining tracts may develop. Hemor- staining.
rhagic bullae may also be noted. • Blood culture: Perform these cultures when bacterial
• In addition to the inguinal, ventral abdominal, and sepsis is suspected in patients with a fever and evi-
axillary regions, the pressure and wear areas of the dence of systemic illness.
body can also be affected. The disease may become
generalized.
• The lesions are painful and/or pruritic. Treatment
• Peripheral lymphadenopathy is a common finding.
Signs of systemic illness may be present (anorexia, ▼ Key Point Be certain that an appropriate antibiotic
depression, weight loss). The patient may also has been selected to eliminate the organism
be febrile, an indication of bacteremia and/or causing the deep pyoderma. Choose the antibiotic
septicemia. based on the results of bacterial culture and sensi-
• A specific form of deep pyoderma can occur in tivity tests. In general, treatment is more vigorous
German shepherds (so-called German shepherd dog than that for superficial folliculitis. In recurrent
pyoderma), which is often related to multiple under- cases, define the underlying disease process
lying problems in the affected patient. and initiate a systematic approach. See the dis-
cussion under “Recurrent Superficial and Deep
Pyodermas.”
Diagnosis
▼ Key Point Deep folliculitis and furunculosis are Topical Therapy
usually diagnosed by observing papules and pus- • Clip the hair around the affected areas. In cases of
tules that become nodular on palpation, with exu- generalized deep pyoderma in long-coated breeds of
dation, crust formation, ulcers, draining tracts, and dogs, clip the entire body.
hemorrhagic bullae. • Initially bathe the patient twice daily (preferably in
a whirlpool bath) using a povidone-iodine prepara-
History and Physical Examination tion (Betadine Whirlpool Concentrate, Purdue-
Deep folliculitis and furunculosis are invariably sec- Frederick) or chlorhexidine solution for the first 1 to
ondary to an underlying disease process. Question 2 weeks of treatment. As the patient responds to treat-
the owner about the effect of antibiotics alone on the ment and the lesions have dried and begun to
disease, as this is a very important diagnostic tool in the heal, change the treatment to once- to twice-weekly
systematic approach to a patient with recurrent pyo- bathing with a benzoyl peroxide shampoo (OxyDex
derma. See the discussion under “Recurrent Superficial Shampoo, DVM Pharmaceuticals; Pyoben Shampoo,
and Deep Pyodermas.” Physical exam findings were Allerderm/Virbac; Benzoyl-Plus, EVSCO Pharmaceu-
described earlier under “Superficial Pyodermas” and ticals) for the next 4 to 8 weeks.
“Superficial Folliculitis.”
Systemic Antibiotics
Laboratory Tests • Always base systemic antibiotic selection on the
• Cytologic examination: Pustules, exudates, and draining results of a bacterial culture and sensitivity tests in
tracts usually reveal neutrophils, macrophages, cocci, cases of deep pyoderma. Use the appropriate dosage
and sometimes rods. (see Table 38-3). Treat for approximately 6 to 8 con-
• Skin scrapings: Evaluate for D. canis mites, a common secutive weeks. Severe cases of deep pyoderma may
underlying cause of deep pyoderma. require a longer treatment regimen. Treat for at least
W0422-Ch038.qxd 11/10/05 5:11 PM Page 426
2 weeks beyond the complete clinical remission of the “Diagnosis” section. Therefore, the observations
infection. being made are those that are noted after the
• In instances when a Pseudomonas spp. is the primary pyoderma has been symptomatically put into
isolate, a fluoroquinolone antibiotic is often most remission.
appropriate. Base the dosing of fluoroquinolones on
the minimal inhibitory concentration (MIC) of the Allergic Skin Disease
isolated organism, using the flexible labeled dosing
schedule provided by the manufacturer, to obtain • Flea allergy dermatitis: Patients with flea allergy der-
a serum maximum concentration (Cmax) that is 8 to matitis have pruritus that persists after resolution of
10 times the MIC for that organism. Commonly the pyoderma and that primarily affects the caudal
used fluoroquinolones for these Pseudomonas spp. third of the body. Most patients initially have the
infections include marbofloxacin at a dosage from problem in warmer weather only. For further discus-
2.75 to 5.5 mg/kg PO q24h (Zeniquin, Pfizer), and sion, see Chapter 45.
ciprofloxacin at a dosage from 10 to 22 mg/kg PO • Atopic dermatitis: Patients with atopic dermatitis have
q24h (Cipro, Bayer). pruritus that persists after resolution of the pyoderma
and that affects various combinations of the follow-
ing areas of the body: face, ears, axillae, inguinal
region, proximal cranial foreleg region, and feet.
RECURRENT SUPERFICIAL AND Most patients initially have the problem in warmer
DEEP PYODERMAS weather only. For further discussion, see Chapter 46.
• Cutaneous adverse food reactions (food allergy): Patients
Antibiotic-responsive but recurrent pyoderma is often with food allergy have pruritus that persists after
a very frustrating problem in clinical practice. This resolution of the pyoderma and that affects various
section stresses the need to evaluate the patient with this combinations of the following areas of the body:
problem for some of the more common, underlying dis- face, ears, axillae, inguinal region, proximal cranial
eases associated with recurrent pyoderma. foreleg region, and feet. All patients have a non-
seasonal (i.e., year-round) problem from the onset.
Etiology For further discussion, see Chapter 47.
ial infections, either in the skin or elsewhere in the culture reveals methicillin resistance (equivalent to, and
body. reported as, oxacillin resistance). Antibiotic selection is
• There are several protocols, but my preference is use based on susceptibility results. Be aware that regardless
of the antibiotic on a continuous basis at a subopti- of the apparent in vitro susceptibility of methicillin-
mal dose. As an example, if the initial appropriate resistant strains of staphylococci, they should be
dose of the antibiotic is 500 mg q8h, give the antibi- regarded as resistant to all B-lactam and cephalosporin
otic at that dosage until clinical remission of the antibiotics.
pyoderma has been reestablished. Then gradually
decrease the dosage over several weeks to 500 mg
q12h and finally to 250 to 500 mg q24–48h. SUPPLEMENTAL READING
• Bactericidal antibiotics with a low potential for devel-
opment of resistance and minimal side effects have DeBoer DJ: Strategies for management of recurrent pyoderma in
been most effective, such as cephalexin. In cases of a dogs. Vet Clin North Am 20:1509, 1990.
Frank LA, Kania SA, Hnilica KA, et al: Isolation of Staphylococcus
relapse of the pyoderma, perform bacterial culture schleiferi from dogs with pyoderma. J Am Vet Med Assoc 222:451,
and sensitivity to examine for possible bacterial resist- 2003.
ance to the antibiotic. Gortel K, Campbell KL, Kakoma I, et al: Methicillin resistance among
staphylococci isolated from dogs. Am J Vet Res 60:1526, 1999.
Hill PB, Moriello KA: Canine pyoderma. J Am Vet Med Assoc 204:334,
1994.
METHICILLIN-RESISTANT Kwochka KW: Recurrent pyoderma. In Griffin CE, MacDonald JM,
Kwochka KW (eds): Current Veterinary Dermatology. St Louis: CV
STAPHYLOCOCCAL SKIN INFECTIONS Mosby, 1993, pp 3–21.
Rosser EJ: German shepherd dog pyoderma: A prospective study of
Recently, methicillin-resistant staphylococci have been 12 dogs. J Am Anim Hosp Assoc 33:355, 1997.
isolated from the skin of dogs with pyoderma. Typically, Rosser EJ: Pustules and papules. In Ettinger SJ, Feldman EC (eds):
Textbook of Veterinary Internal Medicine, 5th ed. Philadelphia:
dogs have had recurrent skin infections and have been WB Saunders, 2000, pp 43–47.
treated repeatedly with antibiotics. Response to empir- Scott DW, Miller WH, Griffin CE: Muller and Kirk’s Small Animal Der-
ical antibiotic therapy is poor or only partial. Bacterial matology, 6th ed. Philadelphia: WB Saunders, 2001, pp 274–308.
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▼ Chapter
39 Mycobacteriosis
Andrew Hillier / Alan C. Mundell
Mycobacteria are gram-positive organisms that cause Feline leprosy refers to mycobacterial disease in
sporadic disease in human beings and in animals. All which single or multiple skin granulomas are present.
mycobacterial organisms contain a lipid-rich cell wall The granulomas contain large numbers of organisms
that inhibits host defense mechanisms and imparts that cannot be cultured using standard techniques.
a characteristic staining property in the laboratory. Until recently, all cases of feline leprosy were thought
This staining property involves the retention of to be caused by M. lepraemurium and to occur in young
carbolfuchsin after acid and alcohol decolorization. cats. Recent studies have identified different syndromes
Thus mycobacteria are classified as acid-fast staining of feline leprosy.
organisms.
Recently, a new conceptual framework for classifica-
tion of mycobacterial infections of dogs and cats was
Feline Leprosy Caused by
proposed. This classification takes into account the Mycobacterium Lepraemurium
mammalian host, the infecting bacteria, and the envi- Etiology
ronment. Consideration of mycobacterial infections
within this framework provides the clinician with impor- • Caused by M. lepraemurium, the rat leprosy organism.
tant information for diagnosis, treatment, and preven- Although the rat leprosy organism had been sus-
tion. The categories of mycobacterial diseases as they pected for many years, it was only in the 1980s that
relate to skin disease specifically are as follows: sophisticated culture techniques and biochemical
analysis could identify M. lepraemurium as the etio-
1. Diseases caused by obligate mycobacterial organisms logic agent.
(e.g., feline leprosy syndromes) • The mode of transmission is unknown, although cats
2. Localized disease caused by saprophytic mycobacte- are thought to become infected following bite
ria in immunocompetent hosts injuries from infected rats.
a. Where the infection is self-limiting and the • In experimental infections, the incubation period is
immune response eventually eliminates the 2 to 18 months.
organisms (e.g., canine leproid granuloma
syndrome)
b. Where the infection remains localized but Clinical Signs
requires intervention for cure (e.g., panniculitis • Young adult cats are affected, predominantly males
syndromes, caused by rapidly growing mycobac- living in either suburban or rural environments.
teria, and Mycobacterium avium complex infec- • Lesions are painless, raised, fleshy, freely movable
tions) nodules of a few millimeters up to 4 cm in diameter.
3. Disseminated disease caused by mycobacteria in They may develop rapidly, and some ulcerate when
immunodeficient hosts large.
• Nodules are usually multiple (but may be single),
tend to initially concentrate in one body region, and
FELINE LEPROSY SYNDROMES may spread to adjacent areas and regional lymph
nodes.
Feline leprosy is a mycobacterial disease of cats that was • Nodules may occur anywhere on the body, but the
first recognized in Australia during the early 1960s. The head and limbs are more frequently affected. Addi-
condition has since been identified in New Zealand, tionally, lesions may occur on the lips, oral mucosa,
Great Britain, France, the Netherlands, and the west tongue, and nasal mucosa. The condition dissemi-
coast of the United States and Canada. The disease is nates rarely to the spleen, bone marrow, liver, kidney,
usually confined to cats living in coastal areas. lung, or adjacent muscle. Cats with disseminated
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disease usually show signs of systemic illness, which mas that are interspersed with neutrophils and sur-
are not seen in cats with localized infection. rounded by a zone of lymphocytes with low numbers
• Lesions tend to recur following surgical excision. of organisms. The lepromatous form is composed of
sheets of large foamy macrophages that contain large
Diagnosis numbers of acid-fast bacilli. The tuberculoid form is
associated with a more competent host immune
• The diagnosis is achieved primarily through histo- response.
logic evaluation of biopsy samples in conjunction
with compatible history, physical examination, Polymerase Chain Reaction
cytology, culture, and laboratory animal inoculation
findings. • Polymerase chain reaction (PCR) amplification of
• The differential diagnoses for feline leprosy include gene fragments from tissue samples provides a rapid
atypical mycobacteriosis, tuberculosis, foreign body and accurate diagnosis and identification of the
dermatitis, deep mycotic infections, mycetomas, causative organisms. Fresh (frozen) tissue or freeze-
dermatophyte pseudomycetomas, chronic bacterial dried tissue is best, although PCR can also be
infections, eosinophilic granuloma complex, and performed on formalin-fixed, paraffin-embedded
neoplastic diseases. samples. (PCR for mycobacterial organisms is per-
formed at the School of Veterinary Medicine, Uni-
History versity of California, Davis, CA.)
• History must be compatible with feline leprosy. The Laboratory Animal Inoculation
cat will typically be young, allowed to roam, and living
in a cool, moist, coastal climate. • Laboratory animal inoculation is used primarily
in research to propagate and investigate the feline
Cytology leprosy organism. This procedure is of greatest value
for differentiating feline leprosy from tuberculosis.
• Cytology of needle aspirates or lesional impression Only tuberculosis-producing mycobacteria routinely
smears reveals mixed inflammatory cells with
kill guinea pigs within 6 to 8 weeks after inoculation.
macrophages and histiocytes containing variable
numbers (often many) of acid-fast bacilli (long
slender rods). In Diff-Quik–stained preparations, Treatment
negative-staining organisms are seen within Treatment may not be necessary when lesions are small,
macrophages. Ziehl-Neelsen stain and a modified unobtrusive, and likely to be self-limiting. However, this
Fite’s stain are the acid-fast stains most commonly strategy is seldom effective and is recommended only
used. for lesions that appear to be resolving spontaneously at
the time of diagnosis.
Culture
▼ Key Point Surgical excision is the treatment of
▼ Key Point Culture of the feline leprosy mycobac- choice when lesions are limited in number and
terium is difficult because the organism fails to wide surgical margins can be obtained. However,
grow on blood agar and standard mycobacterial disease recurrence is common and may require
media (Löwenstein-Jensen and Stonebrink). additional surgical intervention and/or medical
management. Even then, adjunct antimicrobial
• A 1% Ogawa egg yolk medium can be used to grow therapy starting a few days prior to surgery is
the organism when incubated under precise temper- recommended.
ature and CO2 conditions. Most commercial labora-
tories do not perform Ogawa egg yolk medium Clofazimine is an iminophenazine dye with antimy-
cultures. cobacterial properties that is suspended in olive oil
and packaged in 50- and 100-mg capsules. Although
Biopsy the pharmacokinetics of clofazimine in the cat are
unknown, a dosage of 10 mg/kg once daily PO (25–
• Biopsy specimens of lesions are fixed in 10% buffered 50 mg every 1–2 days), for 6 to 12 weeks past complete
formalin and evaluated histologically, using both
clinical resolution appears to be very effective. Wear
hematoxylin-eosin and acid-fast stains (Ziehl-Neelsen
latex gloves to prevent staining of hands. Clofazimine is
and modified Fite’s stains). (See Chapter 37 for skin
not approved by the U.S. Food and Drug Administra-
biopsy technique.)
tion (FDA) for animal use.
• Histologically, two forms are seen: tuberculoid and
lepromatous forms. The tuberculoid form (most • Clofazimine may cause a reversible hepatopathy, and
common in the United States and Canada) consists regular biochemical monitoring of cats is mandatory.
primarily of non-encapsulated epithelioid granulo- Vomiting and inappetence are strong indications to
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• In the case of chronic, non-resolving, and disfiguring sustain penetrating wounds and have concurrent
lesions, combination antimicrobial therapy is effec- exposure to mycobacterial organisms from the
tive. The following drug combinations have been environment.
used with success:
• Rifampicin (10–15 mg/kg PO once daily) and clar- Cats
ithromycin (15–25 mg/kg total daily dose divided
and given 2–3 times daily)
• The inguinal region (fat pad) is most commonly
affected; the axilla, flanks and dorsum are less com-
• Rifampicin (10–15 mg/kg PO once daily) and monly affected. Lesions may spread to the lateral and
doxycycline (5–10 mg/kg PO twice daily) ventral abdominal wall. Lesions resemble cat-fight
abscesses initially (but without the fetid odor and
Prevention turbid pus). A nodular to plaque-like lesion is visible,
• Prevent insects from biting dogs by keeping the dog and the skin and subcutis become thickened and
indoors at the time of day of peak insect activity or firm. Punctate ulcers and fistulas with a watery to
use fly and insect repellants. purulent discharge appear in the affected area.
If surgery is performed, wound breakdown and
chronic, non-healing wounds persist. Cats may
become systemically ill: depression, fever, inappe-
MYCOBACTERIAL PANNICULITIS tence, weight loss, pain, and hypercalcemia of gran-
ulomatous disease are occasionally noted.
Non-tuberculous, non-lepromatous mycobacteria are
classified as atypical or opportunistic. These mycobac-
teria have been placed by Runyon into four groups, Dogs
depending on laboratory culture properties. Almost all • Typically, mycobacterial panniculitis is suspected in
dog and cat atypical mycobacterial skin infections dogs with chronic, non-healing wounds that have
belong to the rapid-growing group IV. These sapro- failed to respond to empirical treatment. Lesions
phytic, facultative pathogens are ubiquitous in nature consist of firm to fluctuant nodules that ulcerate,
and are typically isolated from water and moist soil. drain, and spread to affect large areas of the pan-
Atypical mycobacteriosis is more prevalent in cats niculus. A few animals may have fever, pain, and
than in dogs, with no apparent age, breed, or sex discomfort.
predilection.
Diagnosis
Etiology • Perform bacterial culture and histologic evaluation of
• M. fortuitum, M. chelonei, M. smegmatis, M. thermore- lesions. The differential diagnosis for cutaneous atyp-
sistible, and M. xenopi have produced skin lesions ical mycobacteriosis is extensive and includes feline
in dogs and cats. In the United States, M. fortuitum leprosy (in cats only), tuberculosis, foreign body
and M. chelonae are responsible for most atypical dermatitis, deep mycotic infections, mycetomas, der-
mycobacterial infections. matophyte pseudomycetomas, chronic bacterial infec-
• Typically, these organisms have low virulence for tions, generalized demodicosis (in dogs primarily),
mammals and, unless there is a breakdown of defense sterile nodular panniculitis, pansteatitis, eosinophilic
mechanisms, infections remain localized. The in- granuloma complex, and neoplasia.
fected patient usually mounts a vigorous immune
response that may not be sufficient to resolve the ▼ Key Point Atypical mycobacterial organisms are
infection but usually prevents hematogenous or lym- difficult to isolate. In all suspected cases, perform
phatic spread of the infection. Widely disseminated cultures, biopsies for histopathology, and cytologic
disease is only seen in severely immunocompromised examination of lesional exudates.
patients.
• The organisms have a preference for fat tissue. History
• Skin infection follows contamination of traumatized
• History must be compatible with cutaneous atypical
skin, especially bite wounds and deep scratches. Cats
mycobacteriosis. A history of trauma to the involved
are more commonly infected with rapidly growing
skin site weeks to months before the onset of lesions
mycobacteria than dogs are.
is not uncommon.
Chapter 37 for cytology and biopsy technique.) Cyto- Laboratory Animal Inoculation
logic evaluation frequently fails to confirm acid-fast
organisms. Ziehl-Neelsen stain and modified Fite’s • Laboratory animal inoculation is seldom performed.
stain are the acid-fast stains most commonly used. If cultures fail to identify the mycobacterial organism
An exhaustive search is sometimes necessary to and the possibility of tuberculosis exists, perform
find organisms. Sometimes, organisms may show guinea pig inoculation.
“beading” or appear as ghosts if they are poorly
stained. Treatment
Most reports of successful disease management are
Culture anecdotal or involve low numbers of cases. Because the
• Culture consists of growing the organism on standard condition naturally waxes and wanes with occasional
mycobacterial media (Löwenstein-Jensen and Stone- prolonged periods of remission, carefully assess the
brink) as well as on blood agar. success of all treatment options. Clinical remission may
• Use sterile swab and biopsy techniques to obtain cul- be more easily achieved in the dog than in the cat.
tures. Notify the laboratory that atypical mycobacte- • An approach of no therapy may be taken if the
riosis is suspected so that appropriate cultures are disease involves a reasonably small area and the con-
performed. Runyon group IV mycobacteria are called dition does not bother the animal or owner. This is
rapid growers because colonies appear within 7 days rarely the case. When owners are unwilling to commit
after media inoculation (often there is significant to a prolonged course of therapy, allowing the disease
growth after 2–3 days). In contrast, most other to naturally undergo its cycle may be a viable alter-
mycobacteria are either difficult to culture or require native. In time, the skin lesions may become more
weeks to months to grow. Species identification of the extensive; however, the disease rarely becomes
organisms is very important as this may have a signif- systemic.
icant impact on antimicrobial drug strategies. • Surgical excision is most successful for small, easily
The MIC (minimum inhibitory concentration) for excised lesions. Obtain wide surgical margins. Unfor-
selected antibiotics should be determined to aid in tunately, surgical site dehiscence is common. Surgical
the selection of antibiotics—this can be performed excision without concurrent antimicrobial therapy is
with the Etest or broth microdilution. not recommended.
Biopsy ▼ Key Point Surgically debulking the lesions while
• Handle biopsy samples of lesions similar to those in treating the animal with a prolonged course of an
feline leprosy except that special techniques, such appropriate antibiotic can be very helpful in pro-
as snap (instant) freezing the formalin-fixed tissue viding a cure for mycobacterial panniculitis. Surgi-
before staining or rapid Ziehl-Neelsen staining, may cal excision may be more effective when managing
be necessary to reveal the organisms. Characteristi- canine lesions. Recent reports indicate increased
cally, fewer acid-fast bacilli are observed in atypical success when presurgical antimicrobial therapy is
mycobacteriosis than in feline leprosy. Nodular pyo- administered for 2 to 3 weeks, followed by surgi-
granulomatous dermatitis along with panniculitis is cal debulking and then continued antimicrobial
the common histologic pattern. If organisms are therapy until resolution.
found, they are usually located within extracellular
lipid vacuoles that are ringed by neutrophils. Besides • Medical management has been attempted using a
the paucity of organisms, atypical mycobacteriosis variety of drugs. Table 39-1 provides the dosages of
also differs from feline leprosy by the extracellular the most effective agents. Most of these drugs are not
location of the organisms. approved by the FDA for use in dogs or cats. In vitro
▼ Chapter
40 Deep Fungal Infections
Amy M. Grooters
Deep “mycotic” infections are caused by a heteroge- (e.g., cutaneous lymphoma, cutaneous histiocytosis,
neous group of fungal and pseudofungal pathogens. and disseminated histiocytic sarcoma), foreign body
Cutaneous and subcutaneous lesions may result from reaction, and sterile nodular dermatoses (e.g., sterile
direct inoculation of an opportunistic fungal pathogen pyogranuloma syndrome and idiopathic panniculitis).
via trauma or may represent dermatologic manifesta- Phaeohyphomycosis and melanoma should be sus-
tions of a systemic mycosis. Because the organisms that pected when lesions are visibly pigmented. The pres-
cause systemic mycoses typically exhibit unique mor- ence of granules or grains in exudate is suggestive of
phologic features in tissue, the diagnosis of diseases actinomycosis, nocardiosis, actinobacillosis, and eumy-
such as blastomycosis, histoplasmosis, cryptococcosis, cotic mycetoma.
and coccidioidomycosis can often be made by histologic
or cytologic identification of the pathogen in biopsy Cytology
specimens or exudates (see Chapter 20). In contrast, Cytologic examination is often the quickest and least
specific identification of the less familiar opportunistic expensive tool for either making a definitive diagnosis
fungal pathogens that typically cause infection via or categorizing diseases that cause nodules and drain-
wound contamination is not usually possible without ing tracts. Fine-needle aspirates of cutaneous nodules
culture. Despite this fact, opportunistic fungal or enlarged lymph nodes, direct smears of exudate, or
pathogens can often be placed in a general category impression smears of ulcerated lesions often contain
based on their morphologic features in tissue (such as infectious organisms in animals with blastomycosis,
pigmentation, hyphal diameter, and septation) and the cryptococcosis, histoplasmosis, or rhinosporidiosis and
inflammatory response that they induce. These cate- in cats with sporotrichosis. In other types of deep fungal
gories include the following: infections, organisms are variably present in cytologic
• Phaeohyphomycosis (pigmented hyphal forms) specimens.
• Hyalohyphomycosis (unpigmented hyphal forms)
• Eumycotic mycetoma (fibrosing granuloma with Biopsy
tissue grains containing pigmented or unpigmented Lesion biopsy for histopathology and culture should be
fungal elements) pursued when a definitive diagnosis cannot be estab-
• Pythiosis, lagenidiosis, or zygomycosis (pyogranulo- lished cytologically. When possible, obtain multiple
matous and eosinophilic inflammation associated biopsies of representative lesions (including both drain-
with wide, infrequently septate, unpigmented ing and intact nodules) and include normal tissue at the
hyphae) margin of the biopsy sample.
A list of the pathogens discussed in this chapter and
their categorization is found in Table 40-1. ▼ Key Point Wedge biopsies are preferred to punch
biopsies for the diagnosis of deep fungal
infections.
DIAGNOSTIC APPROACH FOR DEEP MYCOSES
In most cases, tissue biopsies should be submitted for
Dogs and cats with deep fungal infections are typically bacterial (aerobic and anaerobic), mycobacterial, and
presented with dermal or subcutaneous nodules (with fungal cultures and should be shipped at ambient tem-
or without ulceration) and/or draining tracts. In addi- perature to arrive at the laboratory within 24 hours of
tion to fungal infection, differential diagnoses for such collection. When unusual pathogens are suspected, it is
lesions include bacterial infections (e.g., actinomycosis, helpful to contact the laboratory prior to collecting and
nocardiosis, mycobacteriosis, and furunculosis), proto- shipping the samples. For additional information on
zoal infections (e.g., leishmaniasis), neoplastic lesions diagnostic skin biopsy techniques, see Chapter 37.
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• In the United States, pythiosis is most common in the • Clinical signs associated with GI pythiosis include
Gulf Coast states but has been recognized in animals weight loss, vomiting, diarrhea, and/or hema-
living in New Jersey, Virginia, Kentucky, Tennessee, tochezia. Physical examination often reveals thin
southern Illinois, southern Indiana, Oklahoma, Mis- body condition and a palpable abdominal mass. Signs
souri, and Kansas. Recently, a number of cases of of systemic illness are usually absent unless intestinal
GI pythiosis have been confirmed in dogs living in obstruction or infarction occurs.
Arizona and northern California.
• Pythiosis occurs most often in young, large-breed,
Diagnosis
male dogs (especially outdoor working breeds such
as Labrador retrievers). Affected dogs are most Histopathology and Cytology
frequently presented to the veterinarian between Pythiosis causes pyogranulomatous and eosinophilic
October and March and often have a history of recur- inflammation associated with broad (mean, 4 m; range,
rent exposure to lakes or ponds. 2–7 m), infrequently septate hyphae that are not well
• In cats, specific breed and sex predilections have visualized on H&E-stained sections but are readily
not been observed in the few cases that have been detected with a Gomori methenamine silver (GMS)
reported to date. However, of 13 cats with cutaneous stain. Because these same general features are associ-
pythiosis diagnosed through my laboratory since ated with lagenidiosis and zygomycosis, a histologic
1999, 8 were less than 10 months old, with an age diagnosis of pythiosis should be confirmed with culture,
range of 4 months to 9 years. serology, polymerase chain reaction (PCR), or immuno-
histochemical staining of tissue sections with polyclonal
Clinical Signs antibodies specific for P. insidiosum.
The two forms of pythiosis are cutaneous and GI,
depending on the route of infection. Both forms are • In animals with suspected cutaneous pythiosis, obtain
rarely found concurrently in the same patient. wedge biopsies rather than punch biopsies to ade-
quately reach infected tissues.
• Similarly, because inflammation in GI pythiosis
Cutaneous Pythiosis centers on the submucosal and muscular layers rather
Cutaneous pythiosis causes non-healing wounds and than the mucosa and lamina propria, surgical biop-
invasive masses that contain ulcerated nodules and sies are more likely to detect hyphae than are endo-
draining tracts. scopic biopsies. Therefore, consider pythiosis when
endoscopic biopsies reveal eosinophilic or pyogranu-
• Infected dogs often have solitary or multiple cuta- lomatous inflammation without identification of an
neous or subcutaneous lesions involving the extre- etiologic agent.
mities, tail-head, ventral neck, perineum, or lateral • Cytologic examination of exudate associated with
thorax. cutaneous pythiosis often reveals pyogranulomatous
• In cats, lesions include subcutaneous masses in the and eosinophilic inflammation but rarely reveals
inguinal, tail-head, or periorbital regions, draining hyphae.
nodular lesions or ulcerated lesions on the extremi-
ties, and nasopharyngeal lesions associated with
retrobulbar masses. Culture
For best results, ship unrefrigerated tissue samples
wrapped in a sterile, saline-moistened gauze sponge
Gastrointestinal Pythiosis overnight at ambient temperature to a laboratory
GI pythiosis in dogs is characterized by severe segmen- that has experience with the isolation of pathogenic
tal thickening of the stomach, small intestine, colon, oomycetes. Because P. insidiosum isolates rarely produce
rectum, or, rarely, esophagus or pharyngeal region (see sexual reproductive structures in the laboratory,
Chapter 69). The gastric outflow area, duodenum, and identification should be based on specific PCR amplifi-
ileocolic junction are the most frequently affected por- cation or ribosomal RNA gene sequencing whenever
tions of the GI tract, and it is not uncommon to find possible.
two or more segmental lesions in the same patient.
• Mesenteric lymphadenomegaly due to reactive hyper- Serology
plasia is common.
• Involvement of the mesenteric root may form a single ▼ Key Point Detection of anti–P. insidiosum antibod-
large, firm mass in the midabdomen. ies in canine serum using either enzyme-linked
• Extension of disease into mesenteric vessels may immunosorbent assay (ELISA) or immunoblot
result in bowel ischemia, infarction, perforation, or techniques has high sensitivity and specificity for
acute hemoabdomen. the diagnosis of pythiosis.
W0422-Ch040.qxd 11/10/05 5:10 PM Page 438
• Although these techniques have only been evaluated • A vaccine derived from P. insidiosum antigens has
in a small number of cats, they appear to have high been utilized with good success in the treatment of
diagnostic accuracy for feline pythiosis. pythiosis causing cutaneous granulomas in horses
• In addition to providing a means for early, non- and vasculitis in humans but has not been docu-
invasive diagnosis, the ELISA is also useful for moni- mented to have efficacy in small animals and, in my
toring response to therapy in affected patients. experience, is rarely associated with any clinical
Recheck P. insidiosum serology 2 months after surgi- improvement in dogs or cats.
cal resection of infected tissues or every 3 months in
animals receiving medical therapy for non-resectable
lesions.
LAGENIDIOSIS
• Veterinarians interested in submitting diagnostic
samples for serology or culture from animals with sus-
Until recently, P. insidiosum was considered the only
pected pythiosis, lagenidiosis, or zygomycosis should
mammalian pathogen in the class oomycetes. However,
contact Dr. Grooters at 225-578-9600.
in 1999, a pathogenic oomycete in the genus Lagenid-
ium was identified as a cause of severe multifocal cuta-
Treatment neous lesions and regional lymphadenomegaly in a dog.
Since that time, more than 40 dogs with serologic, his-
▼ Key Point Complete surgical resection of infected tologic, and/or culture evidence of Lagenidium species
tissues provides the best opportunity for cure of infection have been identified.
pythiosis.
poorly septate hyphae) are similar to those associated appeared to be limited to cutaneous and subcutaneous
with pythiosis and lagenidiosis. Hyphal diameter tends tissues. In addition, there is recent evidence that
to be significantly larger for Basidiobolus spp. (mean hematogenous dissemination of sporotrichosis may
9 m; range, 5–20 m) and Conidiobolus spp. (mean 8 m; occur in as many as a third of infected cats.
range, 5–13 m) than for P. insidiosum. Because serologic
and immunohistochemical techniques are not currently
Canine Sporotrichosis
available for the diagnosis of conidiobolomycosis and
basidiobolomycosis, definitive diagnosis must be based Dogs with the cutaneous form of sporotrichosis are typ-
on isolation of the pathogen from infected tissues. ically presented with multiple firm dermal or subcuta-
neous nodules on the head or trunk. These nodules
Treatment may ulcerate, drain a purulent exudate, and become
crusted. The cutaneolymphatic form is characterized in
• For focal cutaneous lesions, perform aggressive sur- dogs by the formation of nodules on a distal limb,
gical resection and follow with 2 to 3 months of followed by proximal ascension of infection through
itraconazole administered orally at a dosage from 5 lymphatic vessels with subsequent development of
to 10 mg/kg q24hr (see Chapter 20 for more infor- secondary nodules, draining tracts, and regional
mation on this drug). lymphadenopathy.
• For non-resectable lesions, treat with either itracona-
zole for 3 to 6 months or amphotericin B lipid
complex (see Chapter 20). Monitor closely for signs Feline Sporotrichosis
of recurrence after discontinuation of medical Infected cats may initially be presented with abscesses,
therapy. cellulitis, or draining puncture wounds that resemble
• For focal cutaneous lesions that can be completely routine bacterial fight wound infections but fail to
resected, the long-term prognosis is good. respond to antibiotic therapy. Cutaneous lesions are
• For non-resectable lesions and those involving most often found on the head (especially nose and
regional lymph nodes, the prognosis is guarded. face), distal limbs, or tail-head region. They generally
appear as subcutaneous nodules that ulcerate to form
draining tracts and crusted nodules and may progress
to form large, coalescing exudative ulcers and crusting
SPOROTRICHOSIS lesions. Extensive areas of necrosis may develop, expos-
ing underlying muscle and bone. Regional lym-
Etiology phadenopathy may be present.
Sporotrichosis is caused by the dimorphic fungus
Sporothrix schenckii, which exists as a yeast in tissue ▼ Key Point Because of the high numbers of Sporothrix
(37∞C) but as mold in the environment and in the lab- organisms typically present in exudates from cat
oratory from 25∞C to 30∞C. The organism is a sapro- lesions, people handling infected cats are at risk
phyte typically found in organically rich soils, decaying for acquiring sporotrichosis. Always wear gloves
vegetation, or other organic materials such as sphag- when handling cats with ulcerative cutaneous
num moss and hay. Infection occurs by direct inocula- lesions or draining nodules, and take precautions
tion of the fungus into tissues, often through puncture when handling cytology and culture specimens.
wounds associated with thorns or splinters in dogs or
through claw wounds in cats. Diagnosis
Although sporadic outbreaks involving significant
numbers of animals have been reported, in general, Suspect sporotrichosis in cats with presumed fight
sporotrichosis is uncommon in cats and rare in dogs. wound abscesses that do not respond to appropriate
It is most often diagnosed in outdoor, roaming male antibacterial therapy.
cats and hunting dogs, presumably because of their
increased risk for puncture wounds. Cytology
Cytologic examination of exudates will often demon-
Clinical Signs strate S. schenckii in lesions from infected cats but will
Sporotrichosis in dogs and cats is manifested as cuta- demonstrate it only infrequently from infected dogs, in
neous, cutaneolymphatic, or disseminated disease. which lesions typically contain low numbers of organ-
The cutaneous and cutaneolymphatic forms are most isms. The use of a fungal stain such as GMS or PAS
common and may be present concurrently. The dis- (periodic acid-Schiff) may assist in identification of
seminated form is extremely rare in dogs, but infected the organisms, which appear as round, oval, or cigar-
cats often have evidence of internal organ or lymphatic shaped yeast forms, 5 to 9 m long, found either within
infection at necropsy, even when lesions clinically macrophages or extracellularly.
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Treatment Etiology
Treatment of localized candidiasis consists of removing The term hyalohyphomycosis refers to infections caused
risk factors (if possible), clipping and drying affected by non-pigmented fungi, or those that in tissue form
areas of skin, and performing topical antifungal therapy hyphal elements that have hyaline (clear or trans-
(nystatin, miconazole, or clotrimazole). parent) walls. By convention, this term is not applied
to infections caused by hyaline fungi in the genera
Aspergillus or Penicillium or in the class zygomycetes.
Genera that have been described as causing hyalohy-
PHAEOHYPHOMYCOSIS phomycosis in veterinary patients include Acremonium,
Fusarium, Geotrichum, Paecilomyces, Pseudallescheria, and
Etiology Scedosporium, among others. In general, hyalohyphomy-
The term phaeohyphomycosis refers to cutaneous, sub- cosis is less frequently encountered in small animal
cutaneous, cerebral, or disseminated infections caused patients than is phaeohyphomycosis.
by dematiaceous (pigmented) filamentous fungi that
contain melanin in their cell walls. Infection is thought Clinical Signs
to be the result of traumatic implantation of fungal Infected animals present with lesions ranging from local
elements, which leads to chronic granulomatous disease confined to the skin, nasal mucosa, or cornea to
inflammation. disseminated disease in the lungs, bone marrow, lymph
Fungal genera that have been identified as agents nodes, central nervous system, kidneys, liver, spleen,
of phaeohyphomycosis in veterinary patients include and bones.
Alternaria, Bipolaris, Cladophialophora (previously Xylohy-
pha or Cladosporium), Curvularia, Exophiala, Fonsecaea, Treatment
Moniliella, Phialophora, Ramichloridium, and Scolecobasid-
ium, among others. Surgical removal of the lesion (if feasible) is the treat-
ment of choice for localized hyalohyphomycosis, but
warn owners that recurrence or dissemination is likely
Clinical Signs and recommend postoperative medical therapy with
itraconazole or amphotericin B (see Chapter 20).
▼ Key Point Cutaneous or nasal lesions in cats are
the most common clinical presentations for phaeo-
hyphomycosis in small animals.
MYCETOMA
Patients are presented with ulcerated cutaneous Etiology and Clinical Signs
nodules, upper respiratory signs, and/or a visible nasal
mass. Infected tissues may appear grossly pigmented. The term mycetoma refers to localized, mass-like, mycotic
or actinomycotic infections of the skin, subcutaneous
tissue, muscle, or bone that are characterized by the
Diagnosis presence of colonies or aggregates of organisms that
In H&E-stained tissue sections, fungi that cause phaeo- form “grains” in tissue. Actinomycotic mycetomas are
hyphomycosis appear as dark-walled, irregularly septate caused by bacteria such as Actinomyces spp. and Nocardia
hyphae or as yeast-like cells, solitary or in small groups spp., whereas eumycotic mycetomas are caused by
or chains. The presence of melanin in the walls of fungi. Lesions result from traumatic implantation of soil
lightly pigmented hyphae can be confirmed by the organisms into tissue, resulting in chronic pyogranulo-
examination of unstained sections or the use of a matous inflammation and abscessation.
Masson-Fontana stain for melanin. The grains or granules associated with eumycotic
mycetomas are characteristically pigmented (black-
grain mycetoma, caused by dematiaceous fungi) or
Treatment hyaline (white-grain mycetoma, caused by non-
Because response of phaeohyphomycosis to medical dematiaceous fungi), depending on the type of fungal
therapy is variable, aggressive surgical removal of the pathogen involved.
lesion is the treatment of choice. Clinical response Black-grain mycetomas are most often caused by
to either itraconazole or amphotericin B has been Curvularia spp., and typically result in the development
reported in cats with cutaneous phaeohyphomycosis, of chronic non-healing wounds and cutaneous nodules
but relapse is common following either surgical or on the extremities. Lesions often develop weeks to
medical therapy. months after a traumatic incident in the same area.
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Draining sinus tracts are often present, and black grains Cryptococcosis
may be observed in the exudate. Extension of disease
through muscle or fascial planes into underlying bone Cutaneous lesions are common in cats with cryptococ-
may occur. cosis and have been described in nearly half of reported
White-grain mycetomas, usually caused by Pseudall- cases. Dermal lesions (which are often multifocal)
escheria boydii or Acremonium spp., are most often mani- include small, firm papules or nodules that may enlarge
fested as body wall and/or intra-abdominal granulomas and ulcerate, producing a serous or mucoid exudate.
that develop subsequent to contamination following The head (especially around the nares) is a common
surgical wound dehiscence. Affected dogs may be pre- location for dermal lesions, and a firm, subcutaneous
sented with a draining mass on the body wall or may swelling over the bridge of the nose is often present.
develop clinical signs of peritonitis. In dogs with cryptococcosis, cutaneous lesions are
usually characterized by ulcerations involving the nose,
oral cavity, palate, tongue, lips, or nail beds or by dermal
Treatment masses involving the face.
The treatment of choice for eumycotic mycetoma is
aggressive surgical excision of infected tissues, includ- Histoplasmosis
ing amputation if clinically indicated. Response to Cutaneous lesions are uncommon in animals with histo-
medical therapy is routinely poor. Dissemination of plasmosis. Those that have been described include
eumycotic mycetoma beyond local tissues is rare. dermal and subcutaneous nodules, ulcerated lesions,
and fistulous tracts.
DERMATOLOGIC LESIONS IN Coccidioidomycosis
SYSTEMIC MYCOSES In dogs with coccidioidomycosis, cutaneous lesions are
often found over sites of infected bone and include
Refer to Chapter 20 for information regarding the eti-
ulcerated nodules, draining tracts, and subcutaneous
ology, systemic manifestations, diagnosis, and treatment
abscesses. Infected cats develop similar lesions, but
of systemic mycoses.
underlying bone involvement is less common.
Primary cutaneous coccidioidomycosis secondary to
Blastomycosis direct inoculation is rare but has been described, and is
Because direct inoculation of Blastomyces organisms into usually associated with regional lymphadenopathy.
the skin is rare (and only well documented in situations
such as necropsy or laboratory accidents), cutaneous Aspergillosis
lesions in animals with blastomycosis should be consid- Dermatologic lesions caused by aspergillosis (including
ered signs of disseminated disease, even when obvious cutaneous nodules, abscesses, and draining tracts) have
pulmonary lesions are absent. been associated with disseminated disease in dogs
(usually German shepherds). Mucocutaneous lesions
Clinical Signs (including ulceration and crusting of the external
Cutaneous lesions are present in 20% to 40% of nares) may be associated with nasal aspergillosis in
infected dogs and, although they can be present on any dogs.
part of the body, are most often found on the face, nasal
planum, and nail beds. Skin lesions are often prolifera-
tive and ulcerated, draining a serosanguineous or puru- SUPPLEMENTAL READING
lent exudate. However, discreet subcutaneous abscesses
may also occur. Abramo F, Bastelli F, Nardoni S, et al: Feline cutaneous phaeohy-
Cutaneous lesions appear to be common in cats with phomycosis due to Cladophyalophora bantiana. J Feline Med Surg
blastomycosis, and localized cutaneous infection may 4:157–163, 2002.
occur more often in this species. Bauer RW, LeMarie SL, Roy AF: Oral conidiobolomycosis in a dog.
Vet Dermatol 8:115–120, 1997.
Beale KM, Pinson D: Phaeohyphomycosis caused by two different
Diagnosis species of Curvularia in two animals from the same household.
J Am Anim Hosp Assoc 26:67–70, 1990.
The diagnosis of blastomycosis is most often made by Foil CSO, Short BG, Fadok VA, et al: A report of subcutaneous pythio-
identification of the organism on cytologic examination sis in five dogs and a review of the etiologic agent Pythium spp.
of draining exudates or tissue aspirates or on histologic J Am Anim Hosp Assoc 20:959–966, 1984.
examination. In more than half of infected dogs, Fondati A, Gallo MG, Romano E, et al: A case of feline phaeohy-
phomycosis due to Fonsecaea pedrosoi. Vet Dermatol 12:297–301,
organisms can be identified in cytologic specimens 2001.
obtained from either cutaneous lesions or enlarged Grooters AM: Pythiosis, lagenidiosis, and zygomycosis in small
lymph nodes. animals. Vet Clin North Am Sm Anim Pract 33:695–720, 2003.
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Grooters AM, Foil CS: Miscellaneous fungal infections. In Greene CE McKay JS, Cox CL, Foster AP: Cutaneous alternariosis in a cat. J Small
(ed): Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis: Anim Pract 42:75–78, 2001.
Elsevier, 2006, pp 634–647. Reppas GP, Snoeck TD: Cutaneous geotrichosis in a dog. Aust Vet J
Grooters AM, Hodgin EC, Bauer RW, et al: Clinicopathologic findings 77:567–569, 1999.
associated with Lagenidium sp. infection in six dogs: Initial descrip- Schubach TM, Schubach A, Okamoto T, et al: Evaluation of an epi-
tion of an emerging oomycosis. J Vet Intern Med 17:637–646, 2003. demic of sporotrichosis in cats: 347 cases (1998–2001). J Am Vet
Grooters AM, Leise BS, Lopez MK, et al: Development and evaluation Med Assoc 224:1623–1629, 2004.
of an enzyme-linked immunosorbent assay for the serodiagnosis of Welsh RD: Sporotrichosis. J Am Vet Med Assoc 223:1123–1126, 2003.
pythiosis in dogs. J Vet Intern Med 16:142–146, 2002.
Hillier A, Kunkle GA, Ginn PE, et al: Canine subcutaneous zygomy-
cosis caused by Conidiobolus sp.: A case report and review of Conid-
iobolus infections in other species. Vet Dermatol 5:205–213, 1994.
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▼ Chapter
41 Malassezia Dermatitis
Daniel O. Morris
Malassezia dermatitis (MD) is a superficial fungal (yeast) ers only. Other species isolated from normal canine and
infection occurring on and within the stratum corneum feline skin include M. sympodialis and M. obtusa.
of the epidermis of many mammalian species. There are
several different species of Malassezia yeast recognized,
and various animals may serve as the natural hosts for PATHOGENESIS
specific species of the yeast. For example, most domes-
tic carnivores harbor Malassezia pachydermatis as part of In dogs, cats, and human beings, Malassezia yeast
their natural cutaneous microflora, while human beings contribute to the pathogenesis of several disease states,
primarily harbor Malassezia furfur. As commensal including seborrheic dermatitis, AD, endocrine or
organisms, Malassezia yeast colonize the skin in very metabolic diseases, paraneoplastic diseases, and disor-
low numbers. Overt infection is defined by increased ders of cornification.
numbers of the yeast on the skin surface in conjunction
with inflammation. In dogs with atopic dermatitis (AD), Canine Malassezia Dermatitis
M. pachydermatis may be recognized by the immune
M. pachydermatis colonizes sparsely haired areas and
system as an allergen, in which case a highly inflam-
moist areas of the skin and mucosa of normal dogs in
matory and pruritic response can be mounted to
higher numbers than in more densely haired and dry
relatively low numbers of yeast organisms, blurring
areas.
the line between “colonization” and “infection.” The
role of M. pachydermatis in feline dermatitis is less well • In a diseased state, alterations of the skin’s surface
defined, although it is a known commensal of feline microclimate contribute to increased susceptibility to
skin as well. yeast infection. Primary diseases that cause increased
moisture, altered surface lipids, and/or disruption
of stratum corneum barrier function encourage sec-
ETIOLOGY ondary overgrowth of the organism.
• Pruritic inflammatory diseases (allergic and parasitic)
The genus Malassezia is now described to consist of nine cause microclimate changes due to scratching (dis-
species: M. furfur, M. sympodialis, M. globosa, M. obtusa, ruption of barrier function), licking (added mois-
M. restricta, M. sloofiae, M. equi, M. japonica, and M. pachy- ture), and increased production of sebum.
dermatis. Malassezia yeasts are characterized by a thick, • Endocrinopathies (especially hyperadrenocorticism)
multilayered cell wall and the production of blasto- directly cause alterations in sebum characteristics and
conidia by budding. With M. pachydermatis, the budding stratum corneum function.
process imparts the appearance of unshelled peanuts • Metabolic diseases that result in parakeratotic
when examined microscopically. hyperkeratosis (such as zinc-responsive dermatosis,
In dogs and cats, Malassezia yeast colonize the skin generic dog food dermatosis, and hepatocutaneous
during the immediate perinatal period. Although M. syndrome or superficial necrolytic dermatitis) also
pachydermatis is the species most commonly isolated appear to be risk factors.
from normal and inflamed skin of dogs and cats, other • Secondary MD is also associated with primary (idio-
species are occasionally identified. M. globosa, which has pathic) seborrhea of dogs, especially in basset
a more spherical shape with tiny budding “heads,” is hounds, cocker spaniels, dachshunds, and West High-
sometimes associated with feline ceruminous otitis, land white terriers. Several other skin disorders can
but rarely so in dogs. M. furfur, which is a commensal also be associated with MD (Table 41-1).
of human skin, has been isolated from normal and • A correlation between the onset of MD (or otitis) and
inflamed canine skin, although its role in true “infec- the recent use of antibiotics has been documented.
tion” is unknown; dogs may serve as mechanical carri- However, the opposite has also been noted where MD
445
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Table 41-1. COMMON DIFFERENTIAL DIAGNOSES FOR SKIN DISORDERS THAT MAY BE
ASSOCIATED WITH SECONDARY MALASSEZIA DERMATITIS
Reaction Pattern DDx for Primary Causes Species
Localized, regional, or Allergic diseases (atopy, adverse food reaction, flea bite allergy, contact allergy) D &C
generalized pruritus Parasitism scabies, cheyletiellosis D &C
Demodex gatoi C
Infectious diseases (bacterial pyoderma, dermatophytosis) D & C
Seborrhea oleosa Most causes of pruritus (as above) D & C
Endocrinopathies D & C
Iatrogenic hyperglucocorticoidism D & C
Idiopathic (primary) seborrhea D
Vitamin A–responsive dermatosis D
Seborrhea sicca Same as for seborrhea oleosa
Sebaceous adenitis D
Hyperkeratosis or crusting
(face, foot pads, pressure Zinc-responsive dermatosis, generic dog food dermatosis, superficial necrolytic dermatitis D
points)
(facial only) Idiopathic facial dermatosis of the Persian C
(regional or generalized) Pemphigus foliaceus D&C
Thymoma-associated dermatosis C
Acquired symmetrical alopecia Causes of pruritus (as above) C>D
Endocrinopathies (including iatrogenic) D>C
Paraneoplastic alopecia C
Facial acne Bacterial folliculitis, demodicosis, dermatophytosis, adverse food reaction C
Otitis externa +/- otitis media Conformational/anatomic (hirsute canals, congenital infantile stenosis, etc.) D
Microclimate changes (heat and humidity retention) D>C
Allergic diseases D&C
Parasitic diseases (ear mites, demodicosis) D&C
Endocrinopathies D>C
Erosive diseases (drug eruption, pemphigus) D&C
Space-occupying masses D&C
Immunosuppression (including iatrogenic) D&C
Contact irritants D&C
able environment for yeast growth, and the lipid-rich interdigital Malassezia pododermatitis will be pre-
cerumen is also supportive. sented for the complaint of paw licking or chewing.
• I have noted a higher incidence of primary Malassezia • Paronychia (inflammation of the claw beds) may also
otitis and pododermatitis (in otherwise normal dogs) occur as the sole presenting sign of MD and often
living in a humid coastal climate than in dogs living causes claw biting (also see Chapter 63). Physical
in more arid and temperate climates. examination will usually reveal a reddish-brown stain-
ing of the proximal claw or a waxy exudate in the claw
Canine Malassezia Mucositis fold, with inflammation of the surrounding soft
While rare, it has been reported that M. pachydermatis tissue.
can promote oral pathology (stomatitis, pharyngitis, • MD can occur in any breed (or mixed breeds) but
tonsillitis). West Highland white terriers, English setters, Shih
Tzus, basset hounds, and American cocker spaniels
Feline Malassezia Dermatitis and Otitis are at increased risk. This increased risk may in turn
reflect the propensity for these breeds to develop
• While a definitive (immunologic) relationship allergic dermatitis as a predisposing factor.
between Malassezia yeast and AD has not been • In any dog with a known endocrine or metabolic
described in cats, it does appear to be associated with disease, rule out MD (by surface cytology) if pruritus,
pruritic or inflammatory dermatoses such as AD, cutaneous inflammation, or non-inflammatory seb-
adverse food reaction, and ectoparasitism. orrhea are present.
• Cats with increased numbers of Malassezia spp. in the • Cases of non-pruritic MD are rare, and most will be
external canals often exhibit a highly pruritic ceru- associated with hyperadrenocorticism, hepato-
minous otitis. cutaneous syndrome, zinc-responsive dermatosis,
• In addition to primary pruritic diseases, feline MD or iatrogenic immunosuppression from cancer
appears to occur in conjunction with paraneoplastic chemotherapy.
skin diseases; in a review of 550 feline skin biopsies,
Malassezia spp. were most commonly associated with ▼ Key Point The most common presenting complaint
feline paraneoplastic alopecia and thymoma-associated associated with non-pruritic MD is seborrhea
dermatosis or erythema multiforme. All cats with oleosa accompanied by a foul odor.
histology consistent with these underlying systemic
diseases died within 8 weeks of skin biopsy sampling. Canine Malassezia Otitis
• M. pachydermatis plays an important role in cases of
CLINICAL SIGNS ceruminous otitis externa, in which it is often highly
inflammatory (see Chapter 59). However it is a
Canine Malassezia Dermatitis normal inhabitant of 15% to 49% of healthy canine
ear canals, depending upon the study reported.
• Although MD is usually intensely pruritic, the only
primary lesion produced is erythema. • M. furfur and M. obtusa have also been isolated from
dogs with otitis externa.
• Secondary lesions including excoriations, seborrheic
plaques, lichenification, maceration, and intertrigo • As with the skin, there is no reliable smell or charac-
teristic of otic exudate that routinely indicates an
are common and cannot be reliably distinguished
infection is associated with yeast rather than bacteria
from staphylococcal pyoderma without cytologic
(contrary to anecdotal claims), so cytologic evalua-
examination.
tion is essential (see “Diagnosis”).
• In rare cases, M. pachydermatis can cause a folliculitis
that mimics staphylococcal folliculitis, dermatophy- • Otitis media may also occur in which Malassezia is the
sole infectious organism isolated (see Chapter 61).
tosis, and demodicosis.
These cases result from extension of the infection
• The clinical appearance of the skin in cases of MD is
through a ruptured tympanum, which may some-
highly variable. It may either be dry and flaky (seb-
times heal and therefore seal the infection within the
orrhea sicca) or tacky and greasy (seborrhea oleosa).
bulla. Undiagnosed otitis media is a common under-
• The distribution pattern of canine MD is variable but
lying cause of chronic or relapsing otitis externa and
most commonly affects some combination of the face
must be identified and treated in order for perma-
(especially periocular and perioral skin), feet (inter-
nent resolution of the case to occur.
digital spaces and claw folds), intertriginous areas
(axillae, groin or inguinum, facial folds, and vulvar
and mammary folds), and perineum.
Feline Malassezia Dermatitis and Otitis
• Generalized cases of MD may occur in chronic cases • Feline MD is rare compared with canine MD.
of allergic dermatitis. • It may be associated with any primary pruritic disease
• Malassezia pododermatitis may occur with or without and often causes a diffuse erythematous, scaly to waxy
more widespread MD. The feet are the most common dermatitis. However, not all cases of MD in cats are
single body area affected in allergic dogs. Patients with pruritic.
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viduals will suffer a pathologic effect from what cases of generalized and regional MD (e.g., podo-
would otherwise be considered a “normal” popu- dermatitis) systemically. Otitis media also requires
lation of yeast colonizing the skin or ear canals. systemic therapy to reliably achieve therapeutic
drug levels within the tympanic cavity. Oral keto-
Culture conazole, itraconazole, or fluconazole is most com-
monly recommended. Griseofulvin is ineffective
Culture for Malassezia organisms is generally unneces-
against Malassezia spp.
sary and rarely performed.
Histopathology Ketoconazole
This should not be necessary to make the diagnosis of • Ketoconazole (Nizoral, Janssen, and generics) is an imi-
MD if routine cytology is performed. While Malassezia dazole antifungal with proven efficacy for canine MD.
spp. are often found on biopsies submitted for evalua- It undergoes extensive metabolism by the liver, and
tion of pruritic dermatitis, histopathology cannot be its use in patients with hepatic disease is contraindi-
relied upon to make the diagnosis of MD; loss of cated. It is also a known teratogen in dogs. Adverse
stratum corneum during tissue processing may yield a effects include gastrointestinal upset (anorexia, vom-
false-negative result. iting, diarrhea), thrombocytopenia (rare), and hepa-
totoxicity, although none of these side effects are at
Polymerase Chain Reaction all common. Hepatotoxicity is a moderate risk in
cats, however, and its use in feline MD is not
This technique is capable of identifying the Malassezia
recommended. In aged or debilitated dogs, evaluate
species with an extremely high degree of accuracy but
hepatic enzymes prior to use of ketoconazole. I do
is primarily used for research purposes or to monitor
not routinely perform screening tests in young or
for point sources in epizootic outbreaks.
healthy dogs. For long-term or repeated use, monitor
hepatic function on a case-by-case basis as dictated
by clinical signs (some dermatologists recommend
TREATMENT monthly monitoring). Always administer this drug
along with food for maximum absorption.
Chose therapy based upon the distribution of the infec-
tion, the general health status of the patient, and the
expectations of the pet owner in regards to time and Itraconazole
effort commitment (relevant to topical therapy) and • Itraconazole (Sporanox, Ortho Biotech) and flucona-
side effects (most relevant to systemic therapy). Diag- zole (Diflucan, Roerig) are triazole antifungals
nose and eliminate (or control) underlying diseases to with less risk for hepatotoxicity than ketoconazole.
prevent of recurrence. Since M. pachydermatis is part of Itraconazole is metabolized by the liver, while
the normal cutaneous microflora, complete elimination fluconazole is excreted via the kidneys. Due to cost,
of the organism is likely to be impossible. fluconazole is rarely chosen as a first-line treatment.
Itraconazole is the treatment of choice in cats unless
Systemic Therapy (Table 41-2) preexisting hepatopathy is known, in which case
fluconazole should be used. Always administer itra-
▼ Key Point Unless there is a specific contraindica- conazole with food; feeding does not influence the
tion to using an oral antifungal drug, treat most absorption of fluconazole.
▼ Chapter
42 Dermatophytosis
Karin Muth Beale
451
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c. Gently remove the clipped hairs from the follicles; of the dermatophyte species causing the infection
hemostats are ideal for this purpose. (Table 42-3). The easiest and most practical method of
2. Place hairs on the media (not deeply embedded). observing microscopic morphology is the “acetate tape”
3. In cases of onychomycosis, clip the proximal nail into method:
small pieces for culture. 1. Gently touch a 2-cm strip of clear acetate tape to the
4. Place the sample (hairs or nail particles) in a dark surface of a mature culture colony (>5 days old). A
environment, protected from ultraviolet light and colony on plain Sabouraud’s agar is preferable, if
desiccation. Maintain the cultures at a temperature available.
between 24∞C and 27∞C (75∞F and 81∞F). Do not 2. Then place the tape over a glass slide with a drop of
close the container tightly. lactophenol cotton blue or new methylene blue stain.
5. Observe the sample daily for colony growth and for 3. Observe the slide microscopically for identification
a color change in the media. of the dermatophyte species by conidia formation
6. As a general rule, dermatophytes turn DTM red (Fig. 42-2).
simultaneously with colony growth, whereas sapro-
phytes generally do not turn the media red until after
a week or so after fungal growth commences. There- Biopsy and Histopathology
fore, inspect the culture daily. Generally, it is not necessary to biopsy skin for iden-
7. Fungal colonies that are darkly pigmented (blue, tification of a dermatophyte infection. However,
green, black, or a combination) are not dermato- dermatophytes may be visible in hematoxylin-eosin
phytes. (H&E)-stained sections and are readily detected with
periodic acid-Schiff (PAS) and Gomori methenamine
▼ Key Point Some species of fungi other than der- silver (GMS) stains. In cases of suspected dermatophyte
matophytes may turn the DTM media red within onychomycosis, the nail itself may be submitted in 10%
the first 7 to 10 days; therefore, microscopic exam- formalin for histopathologic evaluation.
ination of the mycelia is necessary to identify the
fungus definitively as a dermatophyte.
Microsporum canis The surface is cottony to woolly and Abundant spindle-shaped macroconidia with thick, spiny walls and
white. The reverse side is yellow- a terminal knob are present. Six or more cells are found in the
orange. macroconidia. One-celled microconidia are uncommon.
Microsporum gypseum The surface is flat, granular, and light tan Abundant spindle-shaped macroconidia with no terminal knobs are
to cinnamon in color with white mycelia. present. Macroconidia contain up to six cells. Microconidia are
The reverse side is pale yellow to tan. uncommon.
Trichophyton The surface usually is cream-colored and Some strains produce spiral hyphae. Microconidia are numerous
mentagrophytes powdery. The reverse side is tan to brown, and often are arranged in grape-like clusters along the hyphae.
or red. Macroconidia are uncommon; if present, they are slender and
cigar-shaped with smooth thin walls.
Procedure
• Topical shampoos and dips may decrease the dura-
tion of systemic therapy and ultimately the cost of
treatment.
• Few topical therapies have demonstrated antifungal
activity in vivo or in vitro. Useful treatments include
lime sulfur (1:16) (LymDyp, DVM Pharmaceuticals),
enilconazole (10%), and miconazole shampoo. Enil-
conazole is not approved for use in dogs and cats in
the United States. Miconazole shampoo is useful as
an adjunct to systemic therapy.
• Because shampooing may spread the lesions through
mechanical trauma, it would appear that the most
effective topical whole-body therapy approved for use
in the United States is lime sulfur. Apply the lime
sulfur as a rinse, and gently sponge or pat (not rub)
Figure 42-2. Identification of dermatophyte species from onto the animal. Lime sulfur dips should be applied
mature fungal colonies is possible by microscopically examining the
conidia morphology: A, Microsporum gypseum. B, Microsporum canis. C,
once to twice weekly.
Trichophyton mentagrophytes. • If lime sulfur is used on a cat, place an Elizabethan
collar after dipping to prevent ingestion of the sub-
stance. Warn owners that the dip may discolor the
pet’s haircoat, may dry the skin and coat, and in some
cases may be irritating with repeated use.
• Cats are usually clinically asymptomatic prior to a
mycologic cure—that is, the dermatophytes are still Local Topical Therapy
present after the animal is free of lesions. Thus two
consecutive negative fungal cultures at 2-week inter- • Localized topical therapy with creams and ointments
vals are necessary before the animal can be said to be containing miconazole, clotrimazole, or terbinafine
cured. seems to have limited value. Restrict use to localized
lesions in dogs. This form of therapy may not speed
▼ Key Point Always treat cats with dermatophytosis resolution of the lesion, but it may help prevent dis-
with systemic antifungal therapy. Dogs with local- semination of infective materials.
ized lesions of dermatophytosis may be treated • Do not use creams and ointments in cats with der-
with topical therapy only; however, always use sys- matophytosis.
temic antifungal therapy in dogs with onychomy-
cosis, multiple lesions, or generalized lesions.
Systemic Therapy
• Systemic antifungal therapy (Table 42-4) is indicated
Topical Therapy in the treatment of all cats with dermatophytosis,
dogs with generalized or multifocal dermatophytosis,
Topical Shampoo and Dip Therapy
and dogs and cats with onychomycosis.
Indications
• Topical therapy with whole-body shampoos or dips is Griseofulvin
most useful for decreasing the spread of disease, and
this helps decrease the probability of the pet becom- ▼ Key Point Griseofulvin, a fungistatic antimicrobial,
is a commonly used drug in the treatment of der-
ing re-infected from re-exposure to dermatophyte
matophytosis in dogs and cats.
spores (particularly M. canis).
• Use topical therapy in every cat with dermatophyto-
• Absorption of the drug is enhanced when it is given
sis and in dogs with multifocal or generalized disease.
with a fatty meal. Griseofulvin is available in micro-
size and ultramicrosize formulations in polyethylene
Clipping the Haircoat glycol to enhance absorption so that lower doses can
• Clipping the haircoat is optimal, especially in cats be used (see Table 42-4).
with dermatophytosis. This helps decrease the release • Never administer griseofulvin, which is a teratogen,
of infected hairs and spores into the environment. to pregnant animals.
W0422-Ch042.qxd 11/12/05 10:37 AM Page 457
Griseofulvin-microsize Fulvicin U/F (Shering) 25–50 mg/kg q24h Not for use in cats Idiosyncratic myelotoxicity,
Grifulvin V (Ortho) Tablets, suspension infected with FIV nausea, vomiting, ataxia,
teratogenic
Griseofulvin-ultramicrosize Gris-PEG (Dorsay) 5–10 mg/kg q24h Not for use in cats Idiosyncratic myelotoxicity,
Tablets infected with FIV nausea, vomiting, ataxia,
teratogenic
Ketoconazole Nizoral (Janssen) 10 mg/kg q24h Not for use in cats, Gastric irritation, anorexia,
Generic ketoconazole Tablets some strains of nausea, idiosyncratic
M. canis may be hepatoxicity, lightening
resistant of haircoat, teratogenic
Itraconazole Sporanox (Janssen) 10 mg/kg q24h Combined/continuous Teratogenic, nausea,
Capsules, suspension pulse therapy: vomiting
10 mg/kg daily for
28 days, then on
alternate weeks
Short-term cycle therapy:
10 mg/kg once daily
for 15 days, followed
by fungal culture.
Cycle repeated until
culture negative
Terbinafine Lamisil (Novartis) 30–40 mg/kg once May be used at this dose Vomiting, nausea
daily in combined/continuous
Tablets pulse therapy or
short-term cycle therapy
as described above
fungal cell wall, and preliminary studies suggested that • Remove and clean all furnace and air conditioning
it may be useful in the treatment of dermatophytosis filters. Catteries or multiple cat households should
in dogs and cats. However, recent, controlled studies consider having air ducts cleaned.
suggest that lufenuron will not prevent infection in • Thoroughly vacuum floors, carpeting, and furniture
exposed cats, nor will it alter the course of infection. I to remove infected hairs. Do this at least 3 to 4 times
do not recommend the use of lufenuron for the treat- weekly. Dust surfaces with an electrostatic dust-
ment of dermatophytosis. trapping cloth on a daily basis. Dispose of vacuum
bags after each use.
Antifungal Vaccine • Clean surfaces that will not be damaged by the solu-
There is a commercially available, killed vaccine for M. tion with a 1:10 dilution of bleach (sodium hypochlo-
canis (Fel-O-Vax MC-K, Fort Dodge). The product insert rite) on a weekly basis.
claims its use is as an “aid in the prevention and treat- • Dispose of all grooming equipment.
ment of clinical signs of disease caused by Microsporum • Wash hands thoroughly after handling infected
canis.” The vaccine is intended as an adjunct to tradi- animals.
tional therapy, not a replacement. The insert also states
that “vaccination has not been demonstrated to elimi- Identification of the Source of Exposure
nate M. canis organisms from infected cats.” Studies by • Examine other animals in the household.
the manufacturer indicate that there is a decrease in • Specific dermatophyte species that are cultured can
clinical signs in affected vaccinated cats compared with provide helpful clues. For example, if T. mentagro-
unvaccinated cats. However, there is no data to suggest phytes is isolated from a dog that spends most of the
that a cure is obtained faster when using this product time indoors and there is a pet rodent in the house-
or that this vaccine helps prevent infection in chal- hold, brush culture the rodent for the presence of
lenged animals. dermatophytes.
• Treat all infected animals in the household.
Monitoring Therapy
Animals treated for dermatophytosis may appear Preventive Measures in a Cattery
clinically normal long before they are actually cured • Identify all infected animals. For best results, use the
or culture negative. Reassess animals frequently to toothbrush culture technique described previously.
monitor response to therapy and to assess the need for • Separate infected from culture-negative animals.
modifications in therapy. • Treat infected cats until tests are culture negative
• Check animals on treatment at least every 3 to 4 before reintroducing them into the general cat
weeks. Monitor for medication side effects. population.
• After 4 to 5 weeks of systemic therapy, check fungal • Disinfect cages on a regular basis and vacuum and dis-
cultures every 2 to 4 weeks depending upon clinical infect air vents.
signs. • Never use the same grooming equipment on both
• Do not discontinue therapy until two negative cul- infected and culture-negative cats.
tures have been obtained. • Place all new animals brought into a cattery in
isolation until culture-negative results have been
obtained.
PREVENTION
When planning and carrying out preventive measures, SUPPLEMENTAL READING
consider that dermatophyte spores can remain viable in
the environment for many years. Chen C: The use of terbinafine for the treatment of dermatophyto-
sis. Vet Dermatol 12(suppl.1):41, 2000.
Current Recommendations for Disinfection Colombo S: Efficacy of itraconazole as combined continuous/pulse
therapy in feline dermatophytosis: Preliminary results in 9 cases.
The purpose of environmental disinfection is to prevent Vet Dermatol 12:347–350, 2001.
reinfection of the pet and to prevent infection of other Foil CS: Dermatophytosis. In Foil C, Foster A, eds.: BSAVA Manual of
Small Animal Dermatology, 2nd ed. Gloucester: British Small
household members. Unfortunately, many of the disin- Animal Veterinary Association, 2003, pp 169–174.
fectants that are in use today are not effective for killing Moriello KA: Symposium on feline dermatophytosis. Vet Med
dermatophyte spores. Evaluation of several different 98:844–890, 2003.
disinfectants found that only concentrated bleach and Moriello KA, DeBoer DJ: Environmental decontamination of
Microsporum canis: In vitro studies using isolated infected cat hair.
1% formalin were 100% effective in killing spores. In Kwochka KW, Willemse T, von Tscharner C, eds: Advances in
These products are not acceptable for routine environ- Veterinary Dermatology, vol. 3. Oxford: Butterworth Heinemann,
mental disinfection. 1998, pp 309–318.
Moriello KA, DeBoer DJ: Feline dermatophytosis: Recent advances
• Discard animal bedding, collars, brushes, and toys. and recommendations for therapy. Vet Clin North Am
• Clean all draperies and bedding material. 25(4):901–921, 1995.
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▼ Chapter
43 Canine and Feline Demodicosis
Sarah Colombini Osborn
459
W0422-Ch043.qxd 11/10/05 5:17 PM Page 460
day, once daily every other week, or the first week of Diagnosis
every month.
• Immunostimulants such as levamisole, thiabenda- • Multiple superficial skin scrapings are the diagnostic
zole, and vitamin E have shown no effect on the tools of choice.
resolution of canine demodicosis and are not
recommended. ▼ Key Point Feline Demodex mites can be very
difficult to find on skin scrapings (much like
canine scabies), and treatment is recommended
whenever feline demodicosis is suspected.
FELINE DEMODICOSIS
Etiology • Due to the small size and translucency of D. gatoi, use
• Feline demodicosis is caused by either Demodex cati the 10¥ objective when searching microscopically for
(long-tailed mite) or Demodex gatoi (short-tailed the mite. Reduce the intensity of the light to increase
mite). the contrast.
• A third possible Demodex mite has also been reported. • The number of mites present in the skin appears to
• D. cati is found in hair follicles and has a similar be dramatically reduced in those cats that are pru-
appearance to D. canis in the dog. The feline mites, ritic, likely due to over-grooming.
however, have a slimmer, elongated body compared • If D. cati is found on skin scrapings, search for an
with the canine mites. underlying disease. Perform complete blood count,
• D. gatoi is a superficial mite found in the stratum serum chemistry panel, urinalysis, and tests for feline
corneum, with a short, broad, blunted abdomen. leukemia and feline immunodeficiency virus.
• Generalized demodicosis with D. cati is rare, and
an underlying immunosuppressive disease (diabetes, Treatment
feline leukemia or feline immunodeficiency virus,
hyperadrenocorticism, respiratory infection, etc.) • The treatment of choice for both species of feline
should always be suspected in affected cats. Demodex mites is lime sulfur dips (LymDyp, DVM
Pharmaceuticals) every 5 to 7 days for six treatments.
• If a cat has demodicosis or lime sulfur dips are being
▼ Key Point D. gatoi is contagious among cats and administered as a therapeutic trial, improvement
generalized infection with this mite is not typically should be evident following three to four dips.
associated with underlying disease. • The superficial location of the mites in the skin of
cats compared with that of dogs likely accounts for
the good response to lime sulfur dips.
Clinical Signs • If D. gatoi is present or the mite cannot be found on
• The clinical signs of feline demodicosis are quite skin scrapings, treat all contact cats simultaneously as
variable and some cats may serve as asymptomatic some cats may serve as asymptomatic carriers of the
carriers. mite.
• Localized demodicosis may present as a single area of • Treatment of localized demodicosis confined to the
alopecia and scaling, primarily affecting the periocu- ear canals includes lime sulfur, ear mite preparations,
lar, head, and neck regions. and amitraz in mineral oil (1:9) applied to the ear
• Occasionally, the mites may be confined to the exter- canal.
nal ear canals, with ceruminous otitis externa being • Do not use amitraz dips for the treatment of feline
the only clinical sign. Large numbers of mites have demodicosis due to the effectiveness of more benign
also been found on skin scrapings from the ear canals therapy and the significant potential for side effects.
of asymptomatic cats. • Recent findings suggest that clinical signs of demod-
• Clinical signs of generalized demodicosis include icosis may resolve with weekly application of
multifocal to generalized alopecia, scaling, erythema, selamectin (Revolution, Pfizer) but that mites are still
and hyperpigmentation. present on skin scrapings. When application of
• Bilaterally symmetrical alopecia can be a common selamectin is decreased or discontinued, the clinical
clinical finding with generalized demodicosis, signs of demodicosis recur.
making differentiation from allergic dermatitis and • Ivermectin has not been shown to be reliably effec-
psychogenic dermatosis difficult. tive unless administered on a daily basis. Further
• Pruritus with D. cati is variable and usually minimal. clinical studies are needed to determine the most
Pruritus with D. gatoi is typically much more pro- effective dosing regimen of ivermectin before this
nounced, with excessive grooming and subsequent medication can be recommended as an appropriate
alopecia being the primary presenting complaints. treatment for feline demodicosis.
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▼ Chapter
44 Scabies, Notoedric Mange,
and Cheyletiellosis
Lauren R. Pinchbeck / Andrew Hillier
Sarcoptic mange, notoedric mange, and cheyletiellosis in the cat, and an underlying immunosuppressive
are parasitic dermatoses caused by acarine mites living disease (i.e., feline immunodeficiency virus infec-
on or within the skin of the host animal. Exposure to tion) is likely to be concurrent and should be
these mites and the corresponding incidence of para- investigated.
sitic dermatoses are closely related to environmental • The adult mite is microscopic (200–400 mm), roughly
factors, especially animal contact and living in endemic circular in shape. It is characterized by two pairs of
areas. Although these mites are not completely host short legs anteriorly that bear long, unjointed stalks
specific, they exhibit host preference and have zoonotic with suckers and two pairs of rudimentary legs pos-
potential for causing dermatoses in humans. teriorly that do not extend beyond the border of the
Ectoparasitism is a differential diagnosis in all veteri- body.
nary patients presenting with a primary problem or • The parasite completes its life cycle (egg–larva–
clinical signs suggestive of pruritus. The level of pruri- nymph–adult) in 12 to 21 days in tunnels and molting
tus can be variable, especially among cats, and the pockets in the stratum corneum of the epidermis.
recognition of pruritus may be underappreciated by Mites burrow into the lower stratum corneum but
owners. Assess parasitism prior to pursuing primary rarely penetrate further. The female may reach the
allergic diseases such as atopic dermatitis or cutaneous stratum spinosum as she creates the tunnel and
adverse food reaction. Parasitism is generally a curable deposits eggs.
disease, and the diagnosis of a primary allergy can only • Although scabies mites live in the superficial layers of
be definitively diagnosed after parasitism is ruled out. the skin, the mite antigen can reach the lower epi-
Lesions resulting from infestation with these mites dermal and dermal skin and induce a humoral and
are primarily due to self trauma. In addition, lesions cell-mediated immune response. Dogs may develop a
may be due to mechanical damage from burrowing protective immunity after successful treatment and
of the mite into the superficial layers of the skin, cure of a scabies mite infestation. Thus, subsequent
pruritogenic substances secreted by the mite, or the reinfestation may not result in clinical signs. The
hypersensitivity reaction developed against extracellular exact mechanism of protective immunity is not
products of the mite. The variability of clinical mani- fully understood, and its elucidation is further com-
festations of these dermatoses probably reflects varia- plicated by crossreactivity and cross-sensitization to
tions in duration and intensity of the hypersensitivity house dust mites.
reaction and variations in the capacity of the host to • Although the parasite is susceptible to high temper-
limit parasite multiplication. ature and drying, it can live in the environment for
up to 21 days under ideal environmental conditions.
▼ Key Point Always consider parasites in patients • Scabies is highly contagious and is primarily trans-
presenting with pruritus. mitted by direct contact with an infested animal.
Fomite and fur transmission to humans or other
animals can occur via contact with grooming
equipment or at kennels.
SCABIES • The incubation period is highly variable and is
dependent on factors such as the number of mites
Etiology present, the time required for the development of
• Scabies (sarcoptic mange) is a non-seasonal, intensely hypersensitivity, and the treatments prescribed. The
pruritic papulocrustous dermatosis of dogs caused by use of systemic corticosteroids may allow the mite
the epidermal mite Sarcoptes scabiei var. canis (Fig. 44- population to increase more rapidly.
1). Although fairly host specific, the mite can affect • Observable dermatologic changes are often out of
cats, foxes, and humans. Sarcoptic acarosis is rare proportion with the number of mites present on the
465
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History
• Rapid onset of intense pruritus and rapid progres-
sion of lesions with inconsistent response to
Figure 44-1. Sarcoptes scabiei. corticosteroids.
• Likely source of infection. Inquire about visits to
training or boarding facilities, dog shows, dog parks,
grooming parlors, etc., approximately 1 month prior
animal, suggesting that cutaneous hypersensitivity to to the onset of the pruritus.
mite antigen plays an important role in the course of • Potential exposure of the affected animal to other
disease. species known to harbor the mite, especially fox.
• Pruritic dermatitis involving dogs and humans in
Clinical Signs contact with the affected animal. The absence of
pruritus in in-contact animals does not rule out the
▼ Key Point Scabies is typically characterized by possibility of infestation.
papular dermatitis and intense pruritus that
is incompletely or minimally responsive to Physical Examination
corticosteroids. • Characteristic cutaneous lesions and typical distribu-
tion pattern as described.
• The body sites typically involved include the ear • Generalized peripheral lymphadenopathy may be
pinnae margins, elbows, hocks, and ventral chest. palpated in an affected dog.
Lesions and pruritus can become widespread, but the
dorsum is usually spared. Diagnostic Tests
• Early lesions are characterized by erythematous
papular eruptions that develop thick crusts that may • To make a definitive diagnosis, the clinician must
be yellow in color. With time, self-excoriation results demonstrate the presence of any life stage of the
in patchy to widespread alopecia, and generalized mite and/or eggs. Perform superficial skin scrap-
papulocrustous dermatitis develops. Hyperpigmenta- ings and fecal flotation. Remember that the mite is
tion and lichenification are the most dominant often very difficult to find, even with multiple skin
lesions in chronic cases due to constant self trauma scrapings.
at affected body sites.
• Some dogs are intensely pruritic but have few, if any, ▼ Key Point Failure to find the mite does not elimi-
lesions other than mild erythema and occasional nate the diagnosis of scabies. Always use trial
excoriations. Others may have less severe pruritus therapy if the diagnosis remains in question and
with many mites present (so-called Norwegian the degree of suspicion is high enough to justify its
scabies). use.
dorsal neck is reported by the manufacturer to be • Adverse reactions to ivermectin may include
100% efficacious for the treatment of scabies by day tremors, ataxia, mydriasis, stupor, coma, and death.
60. Field and laboratory trials were comparable to As there is no known antidote for ivermectin toxi-
a reference positive-control product. We frequently city, only supportive therapy (fluids, parenteral
use selamectin every 14 days for two to three treat- nutrition) is available.
ments for the treatment of confirmed or suspected • The 0.5% pour-on preparation of ivermectin is
scabies acarosis. This regimen would be extra-label effective at 0.5 mg/kg applied topically to the
usage. Environmental treatment may not be dorsum twice 14 days apart. This may be consid-
necessary. ered if a large number of dogs must be treated.
Systemic absorption must be considered, and the
Milbemycin Oxime same precautions should be taken.
• Milbemycin oxime (Interceptor, Novartis Animal Fipronil Spray
Health) is a macrolide antibiotic made from the fer-
mentation of Streptomyces hygroscopicus and is approved • A 0.25% fipronil spray (Frontline Spray; Merial
for monthly heartworm prophylaxis. It is not Animal Health) at a dose of 3 ml/kg applied every 21
approved by the FDA for the treatment of scabies, days for three treatments has been safe and effective
but it may be an alternative treatment, especially in in 4-week-old puppies. Decreased pruritus was recog-
breeds of dogs in which ivermectin is contraindicated nized 1 week after the first application. It has also
and the FDA-approved product cannot be used. been used effectively as a sponge-on preparation in
• Dosing regimens of either 2 mg/kg PO twice at 14- dogs when applied at a dose of 6 ml/kg applied twice
day intervals or 2 mg/kg PO at 7-day intervals for 3 7 days apart. These treatments would be extra-
to 5 weeks have been effective. Other regimens that label usage. Recently, use of this product has been
may be effective include 1 mg/kg PO every 2 days recommended only for early cases of scabies or
for eight treatments and 2 mg/kg PO twice weekly for use in pets for which alternative products are
for 3 to 4 weeks. contraindicated.
• Accurate dosing of milbemycin oxime is essential
in at-risk breeds. When administered at doses of Dips
less than 3 mg/kg, adverse effects are rare. Milbe-
mycin is fairly well tolerated in collies and related • Dips traditionally were routine in the treatment of
scabies. Although less commonly used today, dips
breeds, but some dogs may be sensitive even at
may be indicated in certain situations. Clip the hair
doses of less than 3 mg/kg. Always use caution in
when the dog has medium to long hair or a dense
at-risk breeds and their crosses.
coat. When scale and crust are present, bath with a
• Lack of response to milbemycin when mites are not
keratolytic shampoo prior to dipping. Treat the
observed on scrapings does not necessarily rule out
entire coat; spot treatment is ineffective.
the disease. Reevaluate patients after the second or
third treatment to look for clinical improvement. • Dips known to be effective include the following:
• Lime sulfur (LymDyp, DVM Pharmaceuticals): A
Treatment duration may need to be extended.
2.5% to 5% solution every 5 to 7 days. It is the safest
dip for young animals or sick and debilitated
Ivermectin patients. The animal may appear worse after
• Ivermectin (Ivomec, Merial Animal Health) is very the first treatment but will likely be 50% to 75%
effective in the treatment of scabies, but it is not improved after the second application. Reevaluate
approved by the FDA for the treatment of scabies. after the third dip and continue treatment until the
Ivermectin is only licensed in the dog for the pre- dog is asymptomatic and negative skin scrapings
vention of dirofilariasis at a dosage of 0.006 mg/kg are obtained. The foul odor and potential for
PO monthly. For cats the dosage is 0.024 mg/kg PO staining light haircoats, fabrics, paints, metal, and
monthly. Extra-label doses of ivermectin preparations jewelry make lime sulfur less appealing. These
that are marketed for use in other species are problems are not significant once the coat is dry.
reported for the treatment of scabies. Staining of the pet’s haircoat is temporary, and the
• A dosage of 0.2 to 0.4 mg/kg PO every 7 days for discoloration and associated dry skin resolve once
three to four treatments or SC every 14 days for two treatment is discontinued.
to three treatments is effective. • Amitraz (Mitaban, Pfizer Animal Health): A 0.025%
• Any dog may have an idiosyncratic reaction to solution applied 3 times 14 days apart. This
ivermectin. Some recommend a step-up dose treatment would be extra-label usage. A response is
regimen to identify dogs that are sensitive. Do usually seen after the second application. Care and
not administer to collies, Shetland sheepdogs, Old appropriate precautions must be taken in applying
English sheepdogs, Australian shepherds, or their the dip. Do not use amitraz in toy breeds, pregnant
crosses. or nursing bitches, or puppies less than 3 months
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Other Treatments
• Doramectin at a dose 0.2 mg/kg SC or IM adminis-
tered once.
• Moxidectin 1% injectable at a dosage of 0.2 to
0.25 mg/kg PO or SC every 7 days for 3 to 6 weeks.
Side effects of this medication may include urticaria,
angioedema, and ataxia. Side effects seem to occur Figure 44-2. Notoedres cati.
more frequently when administered subcutaneously,
so the oral route is preferred.
• These treatments would be extra-label usage. • In comparison to S. scabiei var. canis, N. cati is smaller;
has medium-length, unjointed sucker-bearing stalks
Treatment Principles on the legs; and has more body striations. The major
• Treat all dogs in contact with the affected animal. Do differentiating characteristic is the dorsally located
not allow affected and in-contact animals to socialize anus in N. cati.
with other dogs or travel where there may be fur-
bearing animals. ▼ Key Point Notoedric mange is highly contagious
• Cats may be reservoirs but do not usually need to be and is usually transmitted by direct contact.
treated. If there are cats in the household, treat with
selamectin every 2 to 4 weeks while the affected dogs • It commonly affects entire litters and all in-contact
in the household are being treated. adult cats in cattery situations. Characteristically, it is
• Mites die after a few days when off the host, but a disease of adult cats, but it may present as a fulmi-
general cleanup of the environment and application nating dermatitis in kittens.
of a parasiticide containing permethrin may be ben- • N. cati survive for only a few days off the host, but
eficial when a number of animals are affected (e.g., fomite transmission should be considered in cases
a kennel or pet shop). Environmental treatment that do not respond to therapy.
may prevent reinfestation from point sources. Con- • The exact pathogenesis of notoedric mange is
sider environmental treatment if there is a poor unknown, but the intense pruritus and inflammation
response to parasiticidal therapy in proven cases or may be due to the proximity of the burrowing tunnels
in recurrences. to the nerve endings in the skin.
• If a therapeutic trial does not result in the reduction
and subsequent resolution of clinical signs within Clinical Signs
3 to 4 weeks, reassess the animal for other causes • Classically, the ear pinnae, head, and neck are the
of pruritus (most notably infection and allergic der- affected body sites.
matitis) and pursue further diagnostics. • Initially there are erythematous papular eruptions on
the medial aspect of the pinnae as the mites burrow
between hair follicles. The papules may have a well-
defined center representing the location of the burrow.
NOTOEDRIC MANGE • Lesions can then spread rapidly to the head, neck,
perineum, and feet. This distribution is consistent
Etiology with the grooming and nesting behaviors of most
• Notoedric mange (feline scabies) is an intensely cats. The abdomen, flanks, base of tail, and inner
pruritic, crusting dermatosis of cats caused by the thighs become affected with time.
sarcoptiform mite, Notoedres cati (Fig. 44-2). The mite • As the disease progresses, the affected body sites
may also infest dogs, fox, and rabbits and may cause become thickly crusted. The intense pruritus results
transient lesions in humans. in self-excoriation that leads to alopecia and licheni-
• Notoedric mange is uncommonly diagnosed, but it fication. A matted haircoat may be noted in medium-
may be endemic in a few localities. and long-haired cats.
• This obligate parasite is a burrowing mite similar to • Persistent self-trauma can lead to secondary
S. scabiei, and the life cycle is approximately 17 to 21 infection.
days. • Peripheral lymphadenopathy is usually present.
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Clinical Signs
• The hallmark of cheyletiellosis is excessive scaling
and associated pruritus. A crusting or papular der-
matitis may also characterize the disease. The hair-
coat may be greasy. Cats may have a papulocrustous
eruption (miliary dermatitis).
• Dorsal truncal distribution is typical in dogs and cats,
but a generalized distribution may occur. Puppies
tend to be affected over the caudal dorsum initially,
and the lesions then spread up the back to the head.
• Pruritus is highly variable, ranging from absent to
constant. Asymptomatic carriers can also exist. Intro-
duction of a susceptible pet into the household may
be the first indication that there is a carrier animal.
Figure 44-3. Cheyletiella yasguri.
• Make a definitive diagnosis by demonstration of the eradicate. Treatment of the patient, all in-contact
mite or egg on the animal. Mites are usually present animals, and the premises is mandatory. Successful
in high numbers, but occasionally they can be diffi- treatment plans are 6 to 8 weeks in duration.
cult to detect. The absence of mites does not rule out • There are no veterinary products specifically licensed
this disease when there are compatible clinical signs. by the FDA for the treatment of cheyletiellosis in dogs
or cats.
Diagnostic Tests • Flea shampoos, powders, foams, and sprays have not
been efficacious as sole therapies for cheyletiellosis.
• Several diagnostic tests may be needed. Techniques
Historically, organophosphates, carbamates, and
used to demonstrate the mite or its eggs include the
following: amitraz have been advocated. However, there are
• Direct examination of the surface of the skin and newer treatments that provide an effective and safer
haircoat using a magnifying lens. The mites are alternative.
very large; hence the name “walking dandruff.” • Dips traditionally were routine in the treatment of
• Flea combing is the most reliable method for finding cheyletiellosis and may still be indicated in certain sit-
mites in both symptomatic and asymptomatic uations. Clip the hair when the animal has medium
patients. Comb the entire coat for several minutes. to long hair or a dense coat. When scale and crust are
Brushing the collected material onto a dark back- present, bathing with a keratolytic shampoo prior to
ground may facilitate recognition of mites. If no dipping is beneficial. The entire coat must be treated;
mites are found at the initial diagnostic appoint- spot treatment is ineffective.
ment, instruct the owner to similarly brush the coat Treatments for cheyletiellosis that have been effec-
of the pet several times a day for several days and tive include the following:
collect the material in a container for examination
at the clinic. • Lime sulfur (LymDyp; DVM Pharmaceuticals) as a 2%
• Superficial skin scrapings performed as previously solution applied as a dip every 7 days for six to eight
described for scabies and notoedric mange. In treatments. Lime sulfur can be used safely in kittens,
animals with thick coats, clip an area so that the puppies, pregnant or lactating animals, or debilitated
affected hair and skin can be visualized and animals.
sampled. • Weekly pyrethrin sprays or L-pyrethrin dips diluted
• Adhesive acetate tape (Scotch tape) preparation is the according to label instructions. Products used on cats
classic diagnostic test; however, it only samples a should be approved for use in this species and should
small area. If used, sample several sites. Press a always be diluted according to the label instructions.
small piece of tape repeatedly over affected hair • Amitraz (Mitaban, Pfizer Animal Health) as a 0.025%
and skin. Place the tape strip onto a glass slide with solution applied as a dip every 14 days for four treat-
a few drops of mineral oil. ments. This treatment would be extra-label usage.
• Potassium hydroxide (KOH) digestion. Mix epidermal Use extreme caution in cats. Monitor as described for
material collected with flea combing with 10% scabies.
KOH and heat for 10 to 20 minutes. Centrifuge • Ivermectin (Ivomec; Merial Animal Health) at a
with a saturated sugar solution and examine micro- dosage of 0.2 to 0.3 mg/kg PO every 7 days or SC
scopically under 40-power magnification. every 14 days for 6 to 8 weeks in dogs and cats.
• Fecal flotation. Double centrifugation with a stan- • This treatment would be extra-label usage. Con-
dard sucrose solution may be performed to sider risks of adverse reaction, and have the owner
examine feces for ova and ingested mites. This may give informed consent. Due to the low cost, iver-
provide supportive evidence for the diagnosis of mectin may be appealing if there is a kennel or
cheyletiellosis in pets with low mite numbers. multi-pet environment. Consider safer alternatives
first.
• Evaluate heartworm status before administration.
▼ Key Point The most effective diagnostic techniques
for cheyletiellosis are the acetate tape preparation
• Do not administer to herding breeds such as
and the collection of epidermal debris with a flea
collies, collie crosses, Shetland sheepdogs, Old
comb.
English sheepdogs, or Australian shepherds. Any
patient can show clinical signs of ivermectin toxic-
ity, so careful patient monitoring is indicated. Clin-
• In some cases, the mite or its eggs cannot be demon- ical signs of toxicity include vomiting or diarrhea,
strated, and a therapeutic trial is indicated. Such
trials can only definitively rule out cheyletiellosis. mydriasis, depression, persistent lethargy, ataxia,
tremors, ptyalism, recumbency, excitability, stupor,
coma, and death.
Treatment • Administration of the bovine 0.5% alcohol-based
• Although Cheyletiella mites appear to be susceptible to ivermectin (Ivomec Pour-On for cattle, Merial
most insecticides, they may be extremely difficult to Canada) applied topically to the interscapular skin.
W0422-Ch044.qxd 11/10/05 5:16 PM Page 473
This was recently reported in cats using a dose of may need to be treated if the pet rides in the vehicle.
0.5 mg/kg (0.1 ml/kg). Four to six treatments may Treat any visiting fur-bearing mammals.
be required. This treatment would be extra-label • Client compliance is central in the effective resolu-
usage. tion of Cheyletiella dermatitis and environmental
• Fipronil spray, 0.25%, at a dose of 3 ml/kg or the contamination. If a treatment failure is suspected,
10% concentrated solution (Frontline Spot-on Dog, first ensure that all instructions were followed as
Merial Animal Health) applied every 30 days for two prescribed. Always ask the clients if they are able
to three treatments. Frontline Plus (Merial Animal to perform rinses or dips at home. Alternatively,
Health) should be similarly effective. This treatment these can be performed in the hospital by trained
would be extra-label usage. technicians.
• Selamectin (Revolution, Pfizer Animal Health). For
cheyletiellosis, apply every 30 days for three treat-
ments. This treatment would be extra-label usage. We SUPPLEMENTAL READING
routinely use selamectin every 2 weeks for three
treatments in adult cats and dogs. Arlian LG, Morgan MS: Serum antibody to Sarcoptes scabiei and house
• Selamectin is reportedly safe in ivermectin-sensitive dust mite prior to and during infestation with S. scabiei. Vet Para-
sitol 90:315, 2000.
collies. Bishop BF, Bruce CI, Evans NA, et al: Selamectin: A novel broad-
• Milbemycin oxime (Interceptor, Novartis Animal spectrum endectocide for dogs and cats. Vet Parasitol 91:163, 2000.
Health) at a dosage of 2 mg/kg PO every 7 days in Chailleux N, Paradis M: Efficacy of selamectin in the treatment of
dogs. Treatment may take 9 weeks. The efficacy of natural acquired cheyletiellosis in cats. Can Vet J 43(10):767, 2002.
milbemycin oxime has not been demonstrated in Curtis CF: Current trends in the treatment of Sarcoptes, Cheyletiella, and
Otodectes mite infestations in dogs and cats. Vet Derm 15:108, 2004.
cats. This treatment would be extra-label usage. Delucchi L, Castro E: Use of doramectin for treatment of notoedric
• Clean and spray the animal’s quarters and bedding mange in five cats. J Amer Vet Med Assoc 216(2):215, 2000.
with a residual insecticide appropriate for killing Itoh N, Muraoka N, Aoki M, et al: Treatment of Notoedres cati infesta-
adult fleas. Discard any bedding or grooming sup- tion in cats with selamectin. Vet Record 154:409, 2004.
Lower KS, Medleau LM, Hnilica K, Bigler B: Evaluation of an enzyme-
plies that cannot be effectively cleaned to prevent linked immunosorbent assay (ELISA) for the serologic diagnosis of
fomite-mediated reinfestation. Launder washable sarcoptic mange in dogs. Vet Derm 12:315, 2001.
fabrics at 55∞C and then treat. Professional extermi- Mueller RS, Bettenay SV: Efficacy of selamectin in the treatment of
nators may be required. Perform frequent vacuum- canine cheyletiellosis. Vet Record, 151(25):773, 2002.
ing with disposal of the collected material. Paradis M: Ivermectin in small animal dermatology: Part II. Extra-
label applications. Compend Contin Educ Pract Vet 20(4):459,
• Treat all in-contact animals throughout the treatment 1998.
period and reevaluate the affected animals at regular Scott DW, Miller WH, Griffin CE: Small Animal Dermatology.
intervals to assess for mites and eggs. Continue treat- Philadelphia: WB Saunders, 2001, p 423.
ing for 2 to 4 weeks beyond resolution of clinical signs Shanks DJ, McTier TL, Behan S, et al: The efficacy of selamectin in
the treatment of naturally acquired infestations of Sarcoptes scabiei
and pruritus and until a negative examination for on dogs. Vet Parasitol 91:269, 2000.
mites and eggs has been made. Wagner R, Wendlberger U: Field efficacy of moxidectin in dogs and
• Treat the environment every 2 weeks with a premise rabbits naturally infested with Sarcoptes spp., Demodex spp., and
spray appropriate for killing fleas. In addition, the car Psoroptes spp. mites. Vet Parasitol 93:149, 2000.
W0422-Ch045.qxd 11/10/05 5:16 PM Page 474
▼ Chapter
Flea allergy dermatitis (FAD) is a hypersensitivity reac- dogs have an IgE response to Cte f 1, making this a
tion to one or more components of fleas, especially major allergen involved in the pathogenesis. It is not
allergens in flea saliva. Several types of hypersensitivi- the only allergen, and some flea-allergic dogs do not
ties, such as cutaneous basophil hypersensitivity, react to Cte f 1, nor do all have IgE-mediated disease.
immunoglobulin E (IgE)-mediated immediate hyper-
sensitivity, late-onset IgE reactions, and delayed-type Important Flea Life Stages
hypersensitivity, can occur alone or in combination.
Effective control of flea populations and prevention of
The hypersensitivity reactions cause inflammation
exposure to adult fleas requires an understanding of
leading to pruritus and the generation of most of the
many aspects of the flea life cycle and biology. Adult
lesions.
fleas only represent a small percentage of the total flea
In most geographic areas, FAD is still a common
population. Eggs, larvae, and pupae make up the vast
cause of skin disease in dogs and cats. During the
majority.
summer it is often the most common disease seen by
the small animal practitioner and is a common reason
Larval Stage
for exacerbation of pruritus in patients with concurrent
FAD and atopic dermatitis. In some areas, and when • Larvae are positively geotactic and negatively photo-
indoor infestations occur, FAD may be non-seasonal. taxic and therefore migrate deep into carpets and
The advent of newer, more effective flea control prod- under furniture.
ucts has been both beneficial and detrimental to clini-
cal practice. The new products have greatly minimized Pupal Stage
the impact of FAD in many practices and allowed much • Of the pre-adult stages, the pupal stage is most
more effective flea control. At the same time, many troublesome.
clients utilizing these products no longer believe fleas • This stage is most resistant to environmental changes,
can be the cause of disease. Thus, establishing the diag- such as low humidity, and is also most resistant to
nosis and client acceptance of the diagnosis is more environmentally applied insecticides, partly due to
troublesome, as clients do not see fleas but FAD is still their location deep in the carpet. The pupa’s exter-
occurring. nal sticky cocoon attracts a coating of environmental
Atopic dermatitis or adverse food reactions (“food debris that also helps protect the developing adult
allergy”) may occur in combination with FAD, and occa- inside the cocoon from insecticides.
sionally all three reactions will be present in one • The pre-emerged adult flea inside the cocoon will
patient. The prevalence of FAD in patients with atopic wait for optimal environmental and local host factors
dermatitis is generally higher; up to 80% of dogs with before emerging. Emergence of the adult from the
atopic dermatitis that are exposed to fleas were cocoon may be delayed up to 5 months and can be
reported to have FAD. responsible for pet owners seeing young adult fleas
even after environmental therapy. Delayed emer-
gence and resurgence of fleas after effective use of
ETIOLOGY environmental insecticides has been termed the
pupal window.
• Ctenocephalides felis is the species that usually infests Newly Emerged Adult Fleas
both dogs and cats. Pulex irritans and less commonly
Ctenocephalides canis may be responsible in some areas. • The newly emerged adult flea will rapidly find its host
• Investigations with purified flea saliva led to the dis- in response to stimuli such as positive phototaxis,
covery of several antigens, and one named Cte f 1 has carbon dioxide, body heat, light changes from move-
been cloned. Eighty percent of clinical flea-allergic ment, and negative geotaxis.
474
W0422-Ch045.qxd 11/10/05 5:16 PM Page 475
• Even residual types of environmental insecticides and diagnosis of FAD. The caudal thighs, groin, and
insect growth regulators (IGRs) are not rapid enough abdomen are frequently affected, although less
in killing fleas to prevent these newly emerged adults severely than the dorsal lumbar region. In chronic
from finding their host. The time necessary for even and severe cases, there is extension of the lesions
effective topical or systemic therapies to eliminate all cranially on the trunk.
the developing stages from an enclosed environment • Ear disease, otitis externa, perioral lesions, and podo-
has been termed the developmental window. As a result dermatitis (especially of the front paws) are usually
of these pupal and developmental windows, owners not seen and are highly discriminant for a diagnosis
may see emerging young adult fleas and feel that the other than FAD. When these signs are present in a
products are not beneficial, leading to poor compli- dog suspected of FAD, they suggest either that flea
ance or premature termination of treatments that allergy is not present or that flea allergy is present
would eventually be effective. with a concurrent disease, such as atopic dermatitis
or food adverse reaction.
Other Environmental Sources of Fleas • Cats with FAD commonly have miliary crusts in the
Other environmental sources for newly emerged or cervical as well as the dorsal lumbar region. Lesions
mature adult fleas must also be considered. may be limited to the abdomen and groin or cervical
area.
• C. felis commonly infest opossums, raccoons, skunks,
coyotes, foxes, and some rodents. Areas outdoors fre- Secondary Problems
quented by these other hosts will keep flea popula-
Secondary problems that may occur often represent
tions present in locations that pets may frequent,
focal sites of infection; foci of severe trauma, possibly
exposing the pet to more fleas.
from the itch-scratch cycle; or a different pathologic
• In these circumstances, even the use of the newer
reaction.
topical or systemic flea-killing products may not
prevent clinical allergy from occurring. As the prod- • Acute moist dermatitis (hot spots), acral pruritic
ucts with the most rapid killing effect take 4 to 6 nodules, eosinophilic plaques, and eosinophilic gran-
hours to kill newly emerged adult fleas, enough of ulomas may be seen in dogs and cats.
these newly emerged fleas (or fleas from other envi- • Superficial or deep pyoderma may develop, especially
ronmental sources) may be present to keep signifi- in animals repeatedly treated with corticosteroids.
cant disease occurring for days. Thus, active FAD may • Animals with superficial pyoderma will present with
be present even though an infestation in the pet’s pustules, crusted papules, or circular spreading rings
home environment may be prevented. of crust over erythematous erosions, lichenified
plaques, or papules.
• Deep pyoderma may be present as furuncles, hem-
CLINICAL SIGNS orrhagic bullae, fistulous tracts, crusted ulcers, and
proliferative pruritic nodules.
• Pruritus is the primary clinical sign, which the owner
may observe as chewing (as if eating corn on the
cob), rubbing, rolling, or scratching. Cats may groom
excessively or pull out their hair. Severe chewing may
DIAGNOSIS
lead to excessive wear of the incisor and canine teeth.
FAD is diagnosed presumptively in pruritic animals with
• Primary lesions are papules and erythematous
typical patterns of involvement. Flea involvement that
macules in dogs and focal crusted erosions or papules
may be determined by finding fleas, flea feces, or a
(miliary eczema) in cats. Exudation and crusting may
history of possible exposure to fleas is supportive of the
be seen.
diagnosis. In cases with no direct evidence of fleas,
• Secondary lesions result from the chronic inflamma-
response to flea control is used as evidence that fleas
tion and pruritus-induced trauma and include alope-
were present. Always consider the presence of coexis-
cia, excoriations, broken hairs, dry hair, scaling,
tent allergies as they are frequently overlooked.
hyperpigmentation, and lichenification.
▼ Key Point The most definitive diagnosis of FAD
Pattern of Involvement requires typical lesions, a typical pattern, a positive
Lesions are localized to areas of flea bites, and distant intradermal or in vitro test to Cte f 1 (flea antigen),
lesions and significant disease from one flea bite is and a complete response to effective flea control.
unlikely. Generalized disease does not occur without
generalized biting. History
• Involvement of the tail-base and dorsal lumbar region • Identify typical patterns of involvement and season-
has been shown to be highly discriminant for the ality compatible with fleas.
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• A history of otitis externa or paw licking suggests that • A positive test indicates that flea hypersensitivity is
other or concurrent allergies are present. present, but it does not document that all clinical
• Obtain information regarding the number and type signs are related to fleas, that is, there may be sub-
of pets, housing, the type of floor covering, current clinical hypersensitivity.
pesticide use, and client concerns regarding the use • A negative test at all observation times usually indi-
of pesticides. cates (approximately 90%) that flea allergy is not
• Possible sources of exposure to fleas should also be present.
investigated. A history of cats living in the same envi- • False-negative results may occur if glucocorticoids
ronment also has a positive correlation with a diag- and antihistamines are not properly withdrawn
nosis of FAD. Investigate how much time is spent before testing.
outside, the type of outdoor environments the pet has
access to, and the possible presence of stray or feral Serum In Vitro Testing
cats as well as opossums and other wildlife. Recent advances have led to an in vitro test that is valu-
• A history of prior favorable response to flea control able in the diagnosis of FAD (Heska Corporation). This
also supports a diagnosis of FAD. Adverse food reac- test utilizes a recombinant flea salivary antigen.
tion is one of the few differential diagnoses for the
lesions and pattern of involvement seen in FAD, and • A positive test is strongly correlated with FAD.
a gastrointestinal history (bowel movements, bor- • A negative test does not preclude a diagnosis as some
borygmus, flatulence, etc.) may be helpful in this dogs and cats react to a different allergen or have
regard. FAD by other allergic mechanisms.
Borates Dustmite and Flea Environment, Wettable powder sprayed Long-term effects, safety. Powder can be
Control/Aveho ingests and on or added to carpet messy, and both are
Biosciences desiccates larvae. shampooer. Powder labor intensive to
Rx for Fleas/ applied and brushed apply.
Fleabusters into carpets.
Fipronil Frontline/Merial Dogs and cats Monthly topical spot Rapid kill.* Shown Cannot be applied
topical, application spreads to resist depletion more often than
adulticide. over body and spray. by shampooing or monthly. External
water. insecticide.
Fipronil/ Frontline Plus/ Dogs and cats Monthly topical Rapid kill. One product As above, and IGR
methoprene Merial topical, adulticide spot application delivers integrated not photostable.
and IGR. spreads over body. flea control.
Imidacloprid Advantage/Bayer Dogs and cats Monthly up to weekly Rapid kill. More frequent Expense when used
topical, topical spot application application can make it more often than
adulticide. spreads over body and more effective in FAD monthly. External
spreads local into dogs and cats. insecticide.
environment where
pets sleep.
Imidacloprid/ Advantix/Bayer Dogs only. Two Monthly topical As above, plus As above. Not for cats.
permethrin types of spot application. integrated flea
adulticide, control and
possible suspected to have
repellent. flea repellent effect.
Lufenuron Program/Novartis Dogs and cats Oral for dogs and Systemic very Not adulticidal and
Animal Health oral or injectable. cats, and long- effective for whole not as effective for
IDI larvae. acting injection for month and not FAD as sole therapy
cats. affected by topical in dogs and cats that
therapy. spend much time
No external drug. outdoors.
Methoprene Various Dogs and cats Varies on delivery Effective against UV susceptibility limits
topical, systemic, system and what is multiple stages with environmental use.
and environment. treated. large margin of safety.
IGR to multiple
stages.
Nitenpyram Capstar/Novartis Dogs and cats Oral systemic Extremely rapid kill† Short half-life limits
Animal Health oral, adulticide. therapy. To and safe to use daily long-term use due to
maintain levels, makes it most effective expense.
q24h in cats and as trial therapy and
q48h in dogs. short-term prevention.
No external insecticide
on pet.
Permethrin Multiple Dogs only most Varies with product Suspected repellent Most products not
formulations. type and where effect makes allowed on cats, and
Topical and applied. particularly useful ones allowed must
environment. for FAD-affected dogs. be low concentration.
UV resistant.
Longer effect than
pyrethrin.
Pyrethrin Various shampoos Topical and Apply up to daily to Rapid kill and large Short residual action
and spray environmental pets or environment. safety margin makes and rapid UV
products, it useful on puppies, degradation.
adulticide. kittens, and
environment where
it is allowed when many
other products are not.
Pyriproxyfen Various Dogs and cats Varies with form Photostable, so Concern for effect
topical and and use. longer-term effect. on other insects
environment. since long-term
IGR multiple environment
stages. persistence.
Selamectin Revolution/Pfizer Dogs and cats Monthly topical Rapid kill. Not readily Expense if only use
topical. administration, washed off for long. is for fleas. Although
which is absorbed Broad spectrum, so rapid kill, some
systemically. multiple-use product. suggest still slower
than other rapid kill.
*
Rapid kill means over 90% of fleas applied to the pet’s haircoat are killed in 24 hours or less.
†
Extremely rapid kill is over 90% of fleas killed in 4–6 hours.
FAD, flea allergy dermatitis; IDI, insect development inhibitor; IGR, insect growth regulator; UV, ultraviolet.
W0422-Ch045.qxd 11/10/05 5:16 PM Page 478
lufenuron inhibits chitin synthesis and also prevents the • These stages are mainly found in carpets and cracks
development of larvae. or spaces in flooring. Most tile, linoleum, and smooth
Complete flea control requires treating the affected wood floors do not readily support flea development.
pet, other pets in the same environment, and the pet’s Therefore, treatment can be applied to carpeted
environment. Modern product developments have areas, pet bedding, and upholstered furniture that
totally changed the approach to flea control in the last pets have access to.
few years (see Table 45-1). Compliance and flea control • Since larvae are mobile and negatively phototaxic,
success have greatly improved because of long-acting, treatment under furniture and behind doors is an
total-body protection that can be achieved with topical important aspect of control.
focal spot applications, systemic therapy from monthly • Hand-held application is preferred for making sure
oral or topical spot formulations, and improved flea products reach the important areas.
collar technology. These products have made the use of • Vacuuming, especially with vacuums that have beater
flea shampoos, dips, and sprays for on-pet use obsolete bars, is also helpful in decreasing the number of eggs
for long-term flea control. Pyrethrin shampoos may still and larvae. The cleaner bags should be removed fol-
be used to rapidly remove fleas in infested puppies, lowing vacuuming to prevent any fleas from return-
kittens, or adults when quick elimination of fleas on a ing to the environment.
pet is required. However, they are not routinely recom- • Treat linoleum and tile floors by frequently mopping
mended as compliance and efficacy are less than newer with routine disinfectants.
products.
Resistance to some flea products has been seen in the
Insect Growth Regulators
past. The cat flea has been described as the most resis-
tant of the flea species, and to more types of products. The newer systemic and topical formulations with IGRs
Integrated pest management decreases the probability for rapid adult kill in under 24 hours are also very
of this developing to the newer products now being helpful in keeping an indoor environment flea free (see
used extensively. The international imidacloprid flea Table 45-1). Imidacloprid has also been shown to be
susceptibility monitoring program developed an in vitro transferred to treated pets bedding and is an effective
assay to test for the development of flea resistance. Eval- ovicidal and larvacidal agent if the bedding is not laun-
uations of natural strains of fleas from around the world dered. IGR-containing products that have residual
have not yet detected any resistance. effects and bind to the pets hair are likely to also have
Compliance is still a key component of a successful an environmental effect.
flea control program. Even the newer products require
regular use to prevent the development of viable eggs
Borate Products
from being laid. Therefore, to assure that the flea life
cycle is broken, owners must be diligent about proper In houses in which floors are primarily carpeted, borate
application of these products at correct intervals. This products are most effective, lasting up to 1 year. They
involves the use of different ingredients or techniques are also safe, with no reported toxicity.
on pets and in the environment. In severely infested
environments, effective control may take 4 to 8 weeks
• An electrostatically charged sodium polyborate
powder (Rx for Fleas, Fleabusters) is applied as a
to achieve. Once flea control is achieved, clients may powder and brushed into carpets and pet-exposed
find that only one or two aspects of flea control are suf- furniture.
ficient for maintenance, but the long-term use of an
integrated pest control plan is optimum.
• Disodium octaborate tetrahydrate (Dustmite and
Flea Control, Aveho Biosciences) is a wettable
powder that once mixed with water is sprayed on. It
▼ Key Point The optimum control will utilize inte- may also be added to carpet shampooers or steam
grated pest management as the most effective way cleaners providing excellent penetration to deeper
to eliminate multiple stages of the flea life cycle carpet fibers.
and decrease the chance that resistant strains of
fleas will develop.
Permethrin or Pyrethrin Combined with
Insect Growth Regulators
Environmental Treatment for Indoor Areas
Another alternative is spraying all carpeted surfaces and
Because the majority of flea eggs, larvae, and pupae are
furniture that pets have access to with permethrin or
located in the environment, it is essential to treat envi-
with pyrethrin in conjunction with an IGR.
ronmental areas. Treatment of indoor areas is critical
when the affected animal spends most of the time • Effective products include methoprene, permethrin,
indoors. This is the habitat that can be controlled most phenothrin (Vet Kem Siphotrol Plus II House Treat-
effectively. The main life stages being targeted are the ment, Wellmark), pyriproxyfen, pyrethrin and per-
larvae and eggs. methrin (Virbac Knockout ES Area Treatment,
W0422-Ch045.qxd 11/10/05 5:16 PM Page 479
Virbac), and tetramethrin with pyriproxyfen (Ectokyl and 2 days in dogs. It may be used when pets are
IGR Pressurized Spray, DVM Pharmaceuticals). known to be going into areas where fleas may be
• Frequency of use varies with products selected, but in present. It is also helpful as a trial therapy to see if
general these IGR combinations last at least 1 month. flea control is effective and help establish FAD as the
diagnosis.
Environmental Treatment for Outdoor Areas • The newest generation products have improved these
products by combining another topical agent that
Treat outdoor pens and similar enclosures weekly for 3
works by another mechanism. Fipronil is combined
weeks and then monthly.
with an IGR methoprene and imidacloprid is com-
• A liquid application of chlorpyrifos, permethrin, or bined with an adulticide and repellent permethrin.
diazinon is preferred. Repellent activity for mosquitoes has been docu-
• Although helpful in long-term control, granular and mented; effectiveness for repelling fleas is still to be
microencapsulated insecticides have been less bene- determined.
ficial for obtaining initial control. • Permethrin is toxic for cats and cannot be used on
• Pyrethrins are safe and have minimal environmental cats. Use water-based pyrethrin spray for cats, and for
impact, but weekly applications are required as they dogs use either pyrethrin or permethrin sprays
have no residual activity. (Duocide LA, Allerderm/Virbac) that contain a
• The IGR pyriproxyfen is photostable and therefore a repellent. Apply daily if approved for such use.
useful adjunct to outdoor therapy when used with
adulticides. Increase Allergic/Pruritic Threshold
• Consideration should also be given to areas that are
occupied by both pets and wildlife that may carry • Control concurrent allergic diseases such as atopic
fleas, for example, under trees that may harbor opos- dermatitis and food allergy.
sums or raccoons. • Treat secondary pyoderma, which often increases
pruritus, with systemic antibiotics (see Chapter 38).
Treatment of Unaffected Pets • Eliminate dry skin by use of baths, moisturizing sprays
or rinses, and fatty acid supplements.
Treat unaffected animals in the same environment with • Remove other irritants or allergens on the skin
adulticidal and/or insect development inhibitor flea surface, which may aggravate inflamed skin, by fre-
products that lack flea repellent effects. quently bathing the animal. Use this option cau-
• Regular use of the topical adulticides fipronil or imi- tiously with most topical treatments, although
dacloprid or of lufenuron helps prevent unaffected fipronil and imidacloprid and selamectin still have
animals from contributing to reintroduction of fleas efficacy if bathing is 48 hours from application time.
into the home environment. Combination products Selamectin is absorbed systemically, excreted in epi-
or combining IGR products will improve environ- dermal secretions, and replenished, although
mental control of population levels and is an inte- bathing may temporarily decrease surface levels. Do
grated pest control strategy. not bath for 48 hours following application.
• In cases in which topical treatments are not wanted
by owners or pets react, systemic products such as Block Allergic Reactions
lufenuron or collars may be helpful.
• Use an approved flea collar with at least an IGR on A variety of systemic drugs may be used to alter the aller-
cats that cannot be treated with topical spot applica- gic reaction. This approach is often used at the begin-
tions, dips, sprays, or foams. ning of the flea control program and to break the
itch-scratch cycle. Resort to long-term use of systemic
drugs only when clients cannot effectively control fleas.
Treatment of Affected Pets This most often occurs with outdoor or roaming pets,
Treat affected animals with an adulticidal product and especially cats.
repellents as frequently as allowed for these products.
Glucocorticoids
• The new topical adulticides, fipronil, imidacloprid,
and selamectin, have been shown to be efficacious for • Topical triamcinolone 0.015% spray (Genesis spray,
treating FAD in dogs and cats, even when environ- Virbac) has been shown to be effective in the man-
mental treatment is not done. Fipronil in the spray agement of experimentally induced FAD and has
formulation appears to be more efficacious than the been effective in some clinical cases.
spot application and is preferred for the affected pet • Systemic glucocorticoids are often effective. Initially,
if client compliance is not a problem. use prednisone or prednisolone, 1 to 2 mg/kg PO
• Nitenpyram is the most rapid flea-killing systemic q12–24h, to stop the pruritus associated with FAD.
product available, with the drawback of a short half- • Use either oral triamcinolone acetonide (Vetalog,
life. This means there is duration of only 1 day in cats Fort Dodge), 0.25 to 0.5 mg/kg q12–24h, or methyl-
W0422-Ch045.qxd 11/10/05 5:16 PM Page 480
prednisolone (Medrol, Pfizer), 0.8 to 1.6 mg/kg low level of efficacy. A recent trial with flea salivary
q12–24h, if polyuria, polydipsia, or polyphagia asso- antigen did show efficacy in a blinded, controlled trial,
ciated with prednisone or prednisolone is unaccept- suggesting that if done in type I allergic dogs with the
able to the client. exact allergen they tested positive to, then this form of
• When pruritus is controlled, change to an alternate- therapy may be beneficial. This is not commercially
day program and then taper to the lowest effective available at this time.
dose.
Cyclosporine PREVENTION
Although not approved for FAD, some dogs with FAD
Prevention is achieved by long-term continuation of a
have responded well to this new treatment for atopic
flea control program. Long-term treatment may not
dermatitis. Relative effectiveness compared to gluco-
have to be as complete or as frequent as the initial treat-
corticoids is not known. Atopica (Novartis) at 5 mg/kg
ment program. Another option is to use prevention by
q24h has been effective with fewer side effects than
anticipating increases in flea population and increasing
glucocorticoids.
the use of parasiticidal therapy just before the onset of
environmental conditions favoring these increases.
Antihistamines
Antihistamines are infrequently effective for FAD. They
may be used in conjunction with glucocorticoids and SUPPLEMENTAL READING
have a synergistic effect that makes possible a reduction
in the glucocorticoid dose. Blagburn, BL: Flea and tick control: Ensuring efficacy while mini-
mizing resistance. In: New Developments in Ectoparasite-Related
• Diphenhydramine HCl, 2 mg/kg PO q8h; hydrox- Diseases. Advanstar Veterinary Healthcare Communications and
yzine HCl or pamoate, 2 mg/kg PO q8h; doxepin Bayer Healthcare, 2004, p 2–8.
HCl, 1 to 2 mg/kg PO q12h; or clemastine, 0.05 to Dryden, MW: Understanding persistent and recurrent flea problems.
0.1 mg/kg q12h PO may be useful in dogs. In: New Developments in Ectoparasite-Related Diseases. Advanstar
Veterinary Healthcare Communications and Bayer Healthcare,
• Chlorpheniramine may be helpful in dogs at a total 2004, p 9–12.
dosage of 2 to 6 mg PO q8–12h. It is especially useful Dryden, MW, Brace, AB: Integrated flea control for the 21st century.
in cats at a total dosage of 2 mg PO q12h. Compend Cont Educ 24(Suppl 1):36–39, 2002.
Frank GR, Clarke KB, Goodman FW, et al: Efficacy of a 0.015% tri-
Fatty Acid Supplements amcinolone acetonide topical spray in experimental canine flea
allergic dermatitis. Proceedings of the AAVD/ACVD, Monterey,
Fatty acid supplements containing omega-3 fatty acids Calif, 2003, p 210.
and dihomogammalinolenic acid alone rarely control Kunkle G, Halliwell R: Flea allergy and flea control. In Foster A and
Foil C (eds): BSAVA Manual of Small Animal Dermatology, 2nd ed.
FAD. However, they may be helpful in controlling con- British Small Animal Veterinary Association, 2003.
current atopy, alleviating dry skin, and modulating the Kwochka KW, McCall CA, Hillier A, et al: Flea salivary antigen rush
production of inflammatory mediators. These effects immunotherapy for flea allergy dermatitis in dogs: Double-blinded,
may raise the pruritic/allergic threshold and have a syn- placebo-controlled clinical study. Proceedings of the AAVD/
ACVD, San Antonio, Texas, 1998, p 107.
ergistic effect with other treatments, allowing a reduc- Lee SE, Johnston IP, Lee RP, et al: Putative salivary allergens of the
tion in the glucocorticoid dose. cat flea, Ctenocephalides felis. Vet Immunol Immunopathol
69:229, 1999.
Allergen-Specific Immunotherapy McDermott MJ, Weber E, Hunter S, et al: Identification and cloning
of a major cat flea salivary allergen (Cte f 1). Molecular Immunol
Allergen-specific immunotherapy (ASIT), previously 37:361–375, 2000.
referred to as hyposensitization with standard allergens Prelaud, PZ, Alhaidari, Gauguere E, et al: Abstract: Discriminant diag-
and protocols, has not been shown to be efficacious in nostic criteria for the clinical diagnosis of canine FAD. Vet Derm
14:259, 2003.
studies. However, ASIT has been reported to be occa- Schiessl, B, Cavaliero T, Peel JE, et al: Abstract: Localized exposure of
sionally effective in individual cases, but it is not con- dogs to Ctenocephalides felis does not cause generalized signs of flea
sidered cost effective for most clients, considering the allergy dermatitis. Vet Derm 14:245, 2003.
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▼ Chapter
46 Atopic Dermatitis
Andrew Hillier
481
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Table 46-1. PHARMACOLOGIC AGENTS USED FOR THE SYMPTOMATIC CONTROL OF CLINICAL
SIGNS OF ATOPIC DERMATITIS IN DOGS
Drugs with Weak Evidence for Efficacy in Treatment of AD
▼ Chapter
47 Food Hypersensitivity
Stephen D. White
Adverse reactions to foods have been well documented reported. Any dietary protein, even in small (mg)
in small animals. The terms food allergy and food hyper- quantities may be the cause of food hypersensitivity.
sensitivity have been used interchangeably in the human • Food contaminants such as pathogenic bacteria and
and veterinary medical literature to describe clinical toxins, food additives such as tartrazines, and vasoac-
signs induced by food ingestion in which there are tive amines such as tyramine in cheese have all been
demonstrable or highly suspected immunologic reac- implicated or suspected as mimicking food hyper-
tions. The terms food intolerance and occasionally food sensitivity in humans. Their importance in small
sensitivity have been used when an immunologic etiol- animals is unknown and is likely to be low.
ogy is unlikely or has not been established. Although
the causes of abnormal reactions to ingested foods have
not been well established in small animals, food hyper- CLINICAL SIGNS
sensitivity and food allergy are the terms commonly
used. I prefer the former as being more accurate in ▼ Key Point Although the age of onset is variable,
describing an abnormal response of the immune predisposition is noted for young dogs (£1 year of
system. Allergies to inhalant aeroallergens cause atopic age). Owners seldom relate the onset of clinical
dermatitis (see Chapter 46). signs to any change in diet.
488
W0422-Ch047.qxd 11/10/05 5:14 PM Page 489
• Commercially prepared pet foods, including diets • Consider other, concurrent hypersensitivities, such as
containing no preservatives and diets marketed as fleas and atopic dermatitis. Literature reports indi-
“natural,” are not adequate test diets. These products cate that approximately 30% of dogs with food hyper-
do not meet the criteria for a true restricted test diet sensitivity have concurrent atopic dermatitis; in these
because of the many foodstuffs they contain and the patients, residual pruritus is to be expected and is
processing of these ingredients. associated with the atopic dermatitis.
• Use of a commercially prepared diet will give an
approximately 90% chance of determining a food
allergy; however, none of these diets will work for all
animals, and failure of an animal to improve on such
TREATMENT
a diet may warrant trying another one or a home-
Once improvement is noted, several treatment alterna-
cooked diet in another trial.
tives are open to the clinician.
Hydrolyzed Protein Diets • Challenge the animal with its original diet in order
• Another option for animals who already have been to substantiate the diagnosis. A recurrence of clinical
fed many foods, or whose dietary history is unknown, signs is usually seen within 72 hours of initiating the
is the use of hydrolyzed protein diets, in which the dietary challenge, but it may take as long as 2 weeks,
protein source is hydrolyzed to small molecular particularly when a hypersensitivity to cereals is
weights, thus avoiding the body’s “immunologic involved.
radar.” Such foods for dogs include Purina HA • This rechallenge procedure is particularly impor-
(hydrolyzed soy and corn starch), Hills Z/D Ultra tant when the clinical improvement with the restric-
(hydrolyzed chicken and chicken liver and corn tion test occurred over the course of a change in
starch), and Hills Z/D Low allergen (hydrolyzed season, as this may cause a decreased exposure to
chicken and chicken liver and potato). For cats I have environmental aeroallergens; that is, pollens may
used Hills feline Z/D Low allergen (hydrolyzed have led to improvement in a pet with atopic der-
chicken and chicken liver and rice protein) or Purina matitis, rather than improvement from the change in
HA (not yet available at the time of writing of this diet.
chapter). • If clinical signs recur with the original diet and food
hypersensitivity is confirmed, then revert back to the
Concurrent Medical Therapy restricted diet. Once clinical signs have resolved
again, add individual foodstuffs to the restricted diet
• Occasionally, an animal may be presented to the clin- at 5- to 10-day intervals until a balanced diet is
ician with pruritus so severe that administration of achieved or the offending allergen(s) is discovered.
oral corticosteroids is justified while the diet is in • Many owners are unwilling to exacerbate a clinically
progress. Administer prednisone or prednisolone, improved animal or separate various components of
0.5 to 1.0 mg/kg PO q24h, for 10 to 14 days, and then foods to determine potential allergens. Instead, they
stop. Continue the diet for a minimum of 2 weeks are more interested in achieving a balanced, less
beyond discontinuation of the medication in order to expensive diet as soon as possible.
properly evaluate response to diet. • Once the diagnosis of food hypersensitivity is con-
• Identification, treatment, and resolution of sec- firmed, if the pet’s restricted diet has been home-
ondary bacterial and yeast infections are critical if the made, the diet may be changed to one of the
clinician is to be able to evaluate the response to the commercially available limited-allergen diets men-
restricted diets. tioned in the previous section (see “Restricted Diet
Test”). If the new diet is not tolerated, most animals
Interpreting Results show a recurrence of clinical signs within 72 hours,
• Clinical improvement is observed in most animals although a few pets may take longer.
within 24 hours to 4 weeks after starting the restricted • If the animal cannot tolerate a commercial diet, use
diet. It may take longer than this for complete reso- a home-prepared diet consisting of a protein and car-
lution of pruritus. bohydrate source supplemented with vitamins, min-
• In my experience, 8 weeks is a reasonable length of erals, and, for cats, 60 to 100 mg of taurine daily.
time in which to expect some improvement. Improve- Supplementation with 0.5 teaspoon of clam juice per
ment is best defined as a reduction of pruritus (or day, recommended by some, is not adequate taurine
other clinical signs if pruritus is absent). supplementation. For further information on addi-
• If only partial improvement is noted, the diet may not tive-free supplements for homemade hypoallergenic
have been given long enough for full effectiveness. diets, see the article by Roudebush and Cowell
• Alternatively, evaluate the restricted diet’s content (1992). Consultation with a veterinary nutritionist
and consider a change (e.g., substitute potatoes for is strongly advised in the formulation of home-
rice). prepared diets.
W0422-Ch047.qxd 11/10/05 5:14 PM Page 491
Jeffers JG, Meyer EK, Sosis EJ: Responses of dogs with food allergies
to single-ingredient dietary provocation. J Am Vet Med Assoc
SUPPLEMENTAL READING 209:608, 1996.
Jeffers JG, Shanley KJ, Meyer EK: Diagnostic testing for canine food
Carlotti DN, Remy I, Prost C: Food allergy in dogs and cats: A review hypersensitivity. J Am Vet Med Assoc 198:245, 1991.
and report of 43 cases. Vet Derm 1:55, 1990. Mueller RS, Friend S, Shipstone M, et al: Diagnosis of canine claw
Declercq J: A case of diet-related lymphocytic mural folliculitis in a disease: A prospective study of 24 dogs. Vet Dermatol 11:133, 2000.
cat. Vet Dermatol 11:75, 2000. Patterson S: Food hypersensitivity in 20 dogs with skin and gastroin-
Fujimura M, Ohmori K, Masuda K, et al: Oral allergy syndrome testinal signs. J Small Anim Pract 36:529, 1995.
induced by tomato in a dog with Japanese cedar (Cryptomeria japon- Rosser EJ: Food allergy in the cat: A prospective study of 13 cats. In:
ica) pollinosis. J Vet Med Sci 64:1069, 2002. Ihrke PJ, Mason IS, White SD (eds): Advances in Veterinary Der-
Guaguère E: Food intolerance in cats with cutaneous manifestations: matology, vol. 2. Oxford, England: Pergamon Press, 1993, p 33.
A review of 17 cases. Eur J Comp Anim Pract 5:27, 1995. Rosser EJ: Diagnosis of food allergy in dogs. J Am Vet Med Assoc
Harvey RG: Food allergy and dietary intolerance in dogs: A report of 203:259, 1993.
25 cases. J Small Anim Pract 34:175, 1993. Rosser EJ, White SD: Diet and the skin in companion animals. In:
Ishida R, Masuda K, Kurata K, et al: Lymphocyte blastogenic responses Kwochka KW, von Tscharner C, Willemse T (eds): Advances in
to inciting food allergens in dogs with food hypersensitivity. J Vet Veterinary Dermatology, vol. 3. Oxford, England: Pergamon Press,
Intern Med 18:25, 2004. 1998.
Ishida R, Masuda K, Sakaguchi M, et al: Antigen-specific histamine Roudebush P, Cowell CS: Results of a hypoallergenic diet survey of
release in dogs with food hypersensitivity. J Vet Med Sci 65:435, veterinarians of North America with a nutritional evaluation of
2003. homemade diet prescriptions. Vet Derm 3:23, 1992.
Jackson HA, Hammerberg B: Evaluation of a spontaneous canine White SD: Food allergy in dogs. Compend Contin Educ 20:261, 1998.
model of immunoglobulin E-mediated food hypersensitivity: White SD: Food hypersensitivity in 30 dogs. J Am Vet Med Assoc
Dynamic changes in serum and fecal allergen-specific 188:695, 1986.
immunoglobulin-E values relative to dietary change. Comp Med White SD, Mason IS: Proceedings of the Dietary Allergy Workshop.
52:316, 2002. In: Von Tscharner C, Halliwell REW (eds): Advances in Veterinary
Jackson HA, Jackson MW, Coblentz L, et al: Evaluation of the clinical Dermatology, vol. 1. London: Baillière Tindall, 1990, p 404.
and allergen-specific serum immunoglobulin-E responses to oral White SD, Sequoia D: Food hypersensitivity in cats: 14 cases
challenge with cornstarch, corn, soy, and a soy hydrolysate diet in (1982–1987). J Am Vet Med Assoc 194:692, 1989.
dogs with spontaneous food allergy. Vet Dermatol 14:181, 2003.
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▼ Chapter
48 Immune-Mediated Dermatoses
Karen Helton-Rhodes
Immune-mediated dermatoses are relatively uncom- from the other autoimmune diseases by the produc-
mon diseases in domestic animals. This group may be tion of lesions that are vegetative (i.e., proliferative)
divided into autoimmune and immune-mediated rather than pustular or ulcerative.
categories according to immunopathogenesis.
• Autoimmune diseases include the pemphigus Etiology
complex, bullous pemphigoid, mucous membrane The exact cause or stimulant for the production of the
pemphigus, and uveodermatologic syndrome (Vogt- pemphigus antibody is unknown. Theories involve
Koyanagi-Harada syndrome). These are character- either abnormal immune regulation or abnormal
ized by a specific antibody-mediated or cell-mediated antigen stimulation.
immune response directed against a normal compo-
nent of the skin or body. • A virus spread by an insect vector has been proposed
• Immune-mediated dermatoses include systemic as the initial stimulus. This theory gains support from
lupus erythematosus and cutaneous (discoid) lupus an endemic form of pemphigus (fogo selvagem) in
erythematosus. In these diseases, antigen-antibody humans in South America.
complexes are formed and then deposited in various • Genetic factors may be equally important as there are
locations (vessel walls, glomeruli of the kidney, or breed predilections for the disease.
basement membrane zone of the skin). This deposi- • In humans, once formed, the antibody binds with
tion of immune complexes may then trigger an components found in the core of the desmosome
inflammatory response that results in tissue (desmoglein I or plakoglobin). Desmosomes func-
destruction. tion as attachment areas between keratinocytes of the
• Vasculitis can be either autoimmune or immune skin. This binding stimulates plasminogen activators
mediated, depending on the underlying etiology. (i.e., serine proteases), which subsequently cause the
conversion of plasminogen to plasmin.
• The production of plasmin causes the disruption of
PEMPHIGUS COMPLEX the desmosome attachments and therefore a loss of
keratinocyte adhesion. This loss of adhesion between
The pemphigus complex of diseases includes pemphi- adjacent cells is called acantholysis, and the individual
gus foliaceus, pemphigus erythematosus, pemphigus cells are termed acantholytic cells.
vulgaris, pemphigus vegetans, panepidermal pustular • All of the diseases in the pemphigus complex appear
pemphigus, paraneoplastic pemphigus, and drug- to have the same immunopathogenesis, but the target
related pemphigus. protein will vary depending on the type of pemphi-
gus. The location of the bulla or separation within the
▼ Key Point Pemphigus foliaceus is the most epidermis differs; for example, pemphigus foliaceus
common autoimmune skin disorder in dogs and has a more superficial bulla than pemphigus vulgaris.
cats.
Clinical Signs
• Pemphigus erythematosus is considered a variant of Pemphigus Foliaceus
pemphigus foliaceus. It may have clinical and
histopathologic features of lupus erythematosus and • Breeds that are predisposed include Akitas, chow
is therefore considered a “crossover” between the chows, bearded collies, dachshunds, Doberman pin-
pemphigus and the lupus erythematosus complexes. schers, schipperkes, and rottweilers.
• Pemphigus vegetans is an extremely rare variant of • Lesions consist of erythematous macules that progress
pemphigus vulgaris that is distinguished clinically rapidly to a pustular phase and then appear as a dry,
492
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• IPS is not very specific; positive results are obtained Paraneoplastic Pemphigus
in 73% of animals with pyoderma, 67% with der-
matophytes, 50% with demodicosis, and 100% with
• Histologic lesions appear to be a mixture of pemphi-
gus foliaceus (PF), pemphigus vulgaris (PV), and ery-
scabies. Also, IPS is positive with the immunoreactant thema multiforme.
immunoglobulin G in an intercellular pattern in
biopsies obtained from normal canine planum nasale
• Autoantibody targeted appears to be different than
those recognized in PF and PV (desmoplakin II and
and foot pads. IFA is positive with the immunoreac- a 190 kDa protein).
tant immunoglobulin M in a basement membrane
zone pattern in 75% of normal canine nasal biopsies Drug-Related Pemphigus
and 45% of biopsies of normal foot pads, thus yield-
ing false-positive results. • Most cases resemble pemphigus foliaceus.
Differential Diagnoses
▼ Key Point Indirect pemphigus titers using serum The major differential diagnoses for pemphigus foli-
are unreliable in dogs and cats.
aceus include the following.
• For initial therapy, choose prednisone. If the • Treatment of choice for pemphigus complex in small
response is poor, add a chemotherapeutic agent such dogs and all cats when lesions are severe.
as azathioprine to the protocol. • Toxicity from this protocol is mild and includes vom-
• For more rapid and complete resolution of clinical iting, anorexia, and diarrhea (usually resolves when
signs with less resistance to therapy, start with a the dosage is changed from a daily to an alternate-
regimen of prednisone and an adjunctive chemother- day regimen), as well as a mild, gradual, and rapidly
apeutic drug. reversible myelosuppressive effect.
• Maintain medications at a high dose until clinical • Monitor CBC and platelet count every 2 weeks.
signs have resolved at least 75% to 85%, then gradu-
ally decrease dosages while monitoring for exacerba-
tion of disease.
Tetracycline and Niacinamide
• Taper either the prednisone or the chemother- • Used for mild or localized cases.
apeutic agent first, depending on side effects noted. • Tetracycline has anti-inflammatory properties affect-
• Another option is to alternate the dosage reductions ing complement activation, antibody production,
of the two medications until there is complete remis- chemotaxis, prostaglandin synthesis, lipases, and
sion and therapy is no longer necessary or until the collagenases.
minimum dosage of drug needed to control the • Niacinamide inhibits mast cell degranulation and
disease is found. phosphodiesterase.
• Initially, monitor CBC and platelet count every 2 • Adverse reactions include vomiting, diarrhea,
weeks. After the disease is controlled and the level of anorexia, and increased serum liver enzymes.
medication is being tapered, gradually decrease the • In dogs with >10-kg body weight, give 500 mg of each
frequency of monitoring to every 1 to 2 months. Eva- drug q8h (higher doses have been used in some
luate periodic (every 3–6 months) urine cultures for large- and giant-breed dogs).
occult lower urinary tract infections. • In dogs with <10-kg body weight, give 250 mg of each
• It is typically very difficult to induce remission of drug q8h.
lesions without the initial use of glucocorticoids. • Clinical response may take 1 to 3 months; then
taper the medication dose according to clinical
Prednisone as a Single Therapeutic Agent response.
• Prednisone, 1 to 2 mg/kg PO q12h (dogs) or 1 to
3 mg/kg PO q12h (cats). Cyclosporine
• Use in conjunction with over-the-counter sunscreens
and topical glucocorticoids and/or topical tacrolimus • Cyclosporine blocks regulatory proteins that up-
regulate activation genes of T-helper inducer and
(see later section).
cytotoxic cells.
• Treatment of choice for pemphigus erythematosus.
• The clinical response is variable in autoimmune and
immune-mediated diseases.
Prednisone with Azathioprine
• Give 5 mg/kg/day PO without food (2 hours before
• Prednisone, 1 to 2 mg/kg PO q12h in combination and after dosing).
with azathioprine (Imuran, Burroughs-Wellcome), 1 • May be used with glucocorticoids if needed.
to 2 mg/kg PO q24–48h (dogs). • Side effects include vomiting, diarrhea, anorexia,
• Treatment of choice for pemphigus foliaceus, pem- weight loss, hepatotoxicity, gingival hyperplasia,
phigus vulgaris, and pemphigus vegetans when involuntary shaking, hirsutism, and papillomatosis.
lesions are advanced. • Use caution when using in conjunction with other
• Side effects of azathioprine include vomiting, diar- drugs that influence the hepatic microsomal iso-
rhea, pancreatitis, dermatitis, anemia, bone marrow enzyme P450 system (e.g., ketoconazole)—use half
suppression, and hepatotoxicity. the dose of cyclosporine to avoid toxicity.
• Monitor CBC and platelet count every 3 to 4 weeks. • Monitor the serum chemistry panel every 3 months.
• Cyclosporine is very expensive, especially in medium-
▼ Key Point Do not use azathioprine in cats because to large-breed dogs. As the reported success rate of
of idiosyncratic reactions characterized by severe, this therapy is not very high, it should be regarded as
non-responsive leukopenia and thrombocytopenia a distant choice of treatment.
most pronounced in feline leukemia virus– and
feline immunodeficiency virus–positive cats.
Tacrolimus (Topical)
Prednisone with Chlorambucil • 0.1% topical formulation
• Prednisone, 1 to 2 mg/kg PO q12h in combination • Often used for pemphigus erythematosus and discoid
with chlorambucil (Leukeran, Burroughs Wellcome), lupus erythematosus but in focal cases only, especially
0.2 mg/kg PO q24–48h. involving the face
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Dapsone
• Dapsone (Jacobus) is rarely used for pemphigus and SUBEPIDERMAL BLISTERING DERMATOSES
may be combined with glucocorticoids.
This category includes bullous pemphigoid, mucous
• Dapsone decreases complement activation, antibody membrane pemphigoid, and epidermolysis bullosa
production, lysosomal enzyme synthesis, and neu-
acquisita.
trophil chemotaxis.
• Dosage is 1.0 mg/kg q8h; use for dogs only.
• Lag phase of 4 to 8 weeks. Etiology
• Side effects include anemia, neutropenia, throm- The immunopathogenesis of bullous pemphigoid and
bocytopenia, hepatotoxicity, gastrointestinal signs, mucocutaneous pemphigoid involves antibody produc-
neuropathies, and cutaneous drug eruptions. tion directed against the hemidesmosomes located in
• Monitor CBC, platelet counts, serum chemistries, and the lamina lucida (BPA II/ collagen type XVII) region
urinalysis every 3 weeks for the first 4 months. of the basement membrane zone of the skin. The com-
plement cascade is then activated, causing the release of
components C3a and C5a, which triggers mast cell
Sulfasalazine degranulation. Mast cell mediators attract inflammatory
• Sulfasalazine (Azulfidine, Pharmacia) is rarely used cells that release lysosomal enzymes, resulting in tissue
for pemphigus and may be combined with glucocor- destruction and subepidermal blisters. The target
ticoids. antigen for epidermolysis bullosa acquisita is the anchor-
• Sulfasalazine has anti-inflammatory properties. ing fibrils of the lamina densa (type VII collagen).
• Dosage is 10 to 40 mg/kg q8h; consider it for cases
with marked neutrophilic component. Clinical Signs
• Monitor as for dapsone and check tear production
(keratoconjunctivitis sicca is common side effect). Bullous Pemphigoid
• This is a relatively uncommon autoimmune
dermatosis.
Gold Therapy • Collies, Doberman pinschers, and Shetland sheep-
• Aurothiomalate (gold salts) (Myochrysine, Merck) is dogs may be predisposed.
rarely used, and no published reports exist regarding • Clinical signs and lesions mimic those of pemphigus
its effectiveness in animal patients. vulgaris.
• Prednisone, 1 mg/kg PO q12h, also may be needed • Vesicles and bullae of bullous pemphigoid are more
until remission is achieved. stable than those seen with pemphigus, most likely
• Gold therapy is suitable for both dogs and cats; due to the depth of the lesion.
however, results appear to be much better in cats. • Oral cavity lesions are common and occur in 80% of
• Auranofin (Ridaura, SmithKline Beecham), an oral cases, but they are not usually the initial presenting
form of gold salts, has been tried in a limited number clinical sign. Cutaneous or mucocutaneous vesico-
of cases but needs further investigation for use in bullous lesions generally precede oral cavity
dogs and cats. involvement.
• Side effects include thrombocytopenia, aplastic • Pruritus and pain are variable.
anemia, toxic epidermal necrolysis, stomatitis,
nephrotic syndrome, hepatotoxicity, dermatitis, and Mucous Membrane Pemphigoid
pancreatitis. Eosinophilia may herald toxicity. (Cicatricial Pemphigoid)
• Monitor CBC, platelet count, and urinalysis every 2
weeks during the first 3 months of treatment and a • This is relatively common, accounting for half of the
serum chemistry panel monthly. reported subepidermal blistering diseases.
• Common in the German shepherd breed; no age or
sex predilection.
Prognosis • Transient vesicles that rapidly evolve into erosions,
ulcers, and crusts.
• The prognosis for control of pemphigus foliaceus is • Lesions concentrate around the oral cavity, nasal
fair to good.
planum, eyes, ear canals, genitalia, and anus.
• If glucocorticoids cannot be administered, then the • Oral mucosal lesions are common and are often
prognosis is poor to guarded.
present from the outset of disease.
• It is important that the clinician always remember the
following:
• The drugs are more likely to kill the patient than
Epidermolysis Bullosa Acquisita
the disease. • This is extremely rare. It is mostly seen in young dogs
• 100% control of all lesions is not always necessary. and is clinically similar to bullous pemphigoid.
W0422-Ch048.qxd 11/10/05 5:21 PM Page 497
• Great Danes appear to be at a greater risk than other • Dermatologic lesions (leukoderma, leukotrichia)
breeds. affect primarily the nose, lips, foot pads, eyelids, and
• Lesion is deeper in the skin since the anchoring anus.
fibrils (type VII collagen) of the lamina densa are the • Erosions and ulcerations may or may not be present
target antigen. in conjunction with leukoderma.
Diagnosis Diagnosis
• Direct smears are negative for acantholytic cells • Direct smears are negative.
because this disease does not affect intercellular • CBC, serum biochemical profile, and urinalysis are
adhesion. non-diagnostic.
• CBC, serum biochemical profile, and urinalysis are • ANA test is negative.
non-diagnostic. • Histopathologic findings include a histiocytic inter-
• ANA test is negative. face dermatitis with pigmentary incontinence
• Histopathologic findings include a subepidermal (histiocytes contain fine melanin granules).
cleft or bulla with a lichenoid infiltrate of neutrophils • IFA and IPS are negative.
and/or eosinophils.
• IFA and IPS are positive (see under “Pemphigus Foli- Treatment
aceus”), with a linear band of staining along the base-
ment membrane zone.
• Treatment is similar to that for the pemphigus (see
“Treatment” under “Pemphigus Complex”).
• VKH syndrome is very difficult to control and usually
Treatment requires high levels of prednisone and azathioprine.
Therapeutic options for subepidermal blistering dis- • Ocular changes usually dictate the therapeutic
eases are the same as those available for the pemphigus course. For treatment of uveitis, see Chapter 136.
(see “Treatment” under “Pemphigus Complex”).
• The planum nasale is the area most commonly • ANA test is positive in 5% of cases of DLE. This may
affected, although lesions have been noted on the indicate those animals with the potential for conver-
eyelids, lips, foot pads, and concave surface of the sion to SLE that therefore should be closely moni-
pinnae and in the oral cavity. tored.
• Profuse hemorrhage may occur following minor • Histopathologic findings include a lichenoid inter-
trauma to the planum nasale. face dermatitis composed primarily of lymphocytes
• Sunlight exacerbates the lesions and may play a role and plasma cells, thickened basement membrane
in the pathogenesis of DLE. zone, hydropic degeneration of the basal cell layer,
apoptotic keratinocytes in the lower layers of the epi-
Systemic Lupus Erythematosus dermis, pigmentary incontinence, and excess of
• Collies and Shetland sheepdogs are predisposed. dermal mucin.
• SLE is a multiorgan disease with dermatologic mani- • IFA and IPS are positive, with a granular or rough
festations in 32% to 54% of cases. band of immunoglobulin and/or complement
• Cutaneous signs associated with SLE include ulcer- deposited at the basement membrane zone.
ative stomatitis, seborrhea, mucocutaneous ulcera-
tion, foot pad ulceration, panniculitis (lupus Systemic Lupus Erythematosus
profundus), urticaria, and purpura. • Direct smears are non-diagnostic.
• Non-cutaneous signs of SLE (see Chapter 24) include • CBC, serum biochemical profile, and urinalysis may
polyarthritis, fever, glomerulonephritis, hemolytic show a variety of abnormalities, depending on the
anemia, thrombocytopenia, polymyositis, neurologic non-cutaneous organs involved (see Chapter 24).
signs, pleuritis, myocarditis, and lymphadenopathy. • ANA test is positive in 85% to 90% of cases.
• The negative titers in 10% to 15% of ANA tests may
Exfoliative Cutaneous Lupus Erythematosus be a laboratory “fault” because of the current inabi-
• This hereditary disease (autosomal recessive) is also lity of most laboratories to test for extractable nuclear
known as lupoid dermatosis of German shorthaired antigens.
pointers. It usually occurs in the first year of life. • The lupus erythematosus cell preparation is unreli-
• It is characterized by localized to generalized scale able and not routinely used in veterinary medicine.
with follicular casting and alopecia. Pruritus is • Histopathologic findings include epidermal and
minimal. The course may wax and wane. dermal lesions similar to those seen in DLE and may
• Dogs may also have blood dyscrasias, joint disease, include leukocytoclastic vasculitis and mononuclear
and features of sebaceous denitis. panniculitis.
• IFA and IPS are positive, with a band of staining at
Vesicular Cutaneous Lupus Erythematosus the basement membrane zone of the skin and
involved dermal and subcutaneous vessels.
• This is also known as ulcerative dermatosis of collies and
Shetland sheepdogs and was previously thought to be
a variant of dermatomyositis. It has an adult onset. Exfoliative Cutaneous Lupus Erythematosus
• Lesions are annular, polycyclic, and serpiginous • Histopathology reveals hyperkeratosis, basal cell
(wavy, indented) ulcerations and are located primar- degeneration, and apoptotic epidermal cells, as well
ily in the inguinal and axillary regions. as features of sebaceous adenitis.
• Apply topical glucocorticoids to the planum nasale. cold hemagglutinin disease. (See Chapter 153 for
This may be the only form of corticosteroid needed more information on vasculitis.)
to treat and control mild cases.
• Topical tacrolimus (Protopic 0.03% or 0.1%) may be Clinical Signs
beneficial.
• Apply topical sunscreens to the planum nasale during
• Vasculitis is a polysystemic disease.
periods of sun exposure.
• Dermatologic signs include petechiae, ecchymoses,
hemorrhagic bullae, ulcerations, urticaria, and
• Administer vitamin E 400 IU PO q12h. Give 2 hours
edema.
before or after a meal.
• Vitamin E has a 30- to 60-day lag phase, and therapy
• Non-cutaneous signs are similar to those described
for SLE.
usually is maintained for the life of the dog.
• No side effects have been reported in dogs. Prob-
lems noted in humans include thrombophlebitis,
Diagnosis
hypertension, fatigue, cardiac disease, and diabetes • Direct smears are non-diagnostic.
mellitus. • Diascopy, the application of a glass slide pressed to an
• Tetracycline and niacinamide in combination may erythematous lesion, may help rule out vascular
be effective. In dogs over 10 kg, the initial dosage is fragility. The lesion clears if the erythema is due to
500 mg of each drug PO q8h, and in dogs under vascular dilatation but remains if hemorrhage or vas-
10 kg, the dosage is 250 mg of each drug PO q8h. cular leakage has occurred.
Once response is noted, the dosage can be decreased • CBC, serum biochemical profile, and urinalysis
to q12h and then to q24h. Side effects include changes are dependent on the underlying etiology
anorexia, vomiting, and diarrhea. and on the target organ system.
• Severe cases may require the use of azathioprine, as • ANA test is negative unless SLE is the underlying
described for the pemphigus complex (see “Pred- cause of the vasculitis.
nisone with Azathioprine”). • Histopathologic findings include leukocytoclastic
• Gold salts are contraindicated in SLE because of the vasculitis, fibrinoid degeneration of vessel walls,
potential for both the drug and the disease to thrombosis, and endothelial swelling.
produce glomerulonephritis. • IFA and IPS may be positive in early lesions, with
• In severe cases of anemia and thrombocytopenia, immunoglobulin and complement detected in and
splenectomy may be indicated (see Chapter 25). around vessel walls. Affected animals have high levels
• Trental (pentoxifylline) has been helpful in rare of circulating immune complexes and low levels of
cases, especially for lupoid onychitis. complement.
• Essential fatty acid supplementation may be used as
an adjunct therapy for all of the disorders. Treatment
• Treatment is similar to that described for the pemphi-
gus (see “Treatment” under “Pemphigus Complex”).
VASCULITIS • Do not use glucocorticoids if there is an infectious
etiology.
Etiology • Dapsone (Jacobus), 1 mg/kg PO q24h, may be used
• Most of the recognized vasculitic syndromes are in cases of idiopathic neutrophilic vasculitis.
caused by deposition of immune complexes within
vessel walls. Complement components are then acti-
vated and act as chemoattractants for neutrophils. SUPPLEMENTAL READING
Neutrophils infiltrate the vessel wall and release lyso-
somal enzymes such as elastase and collagenase, Crawford MA, Foil CS: Vasculitis: Clinical syndromes in small animals.
which damage the vessel wall. Thrombosis, occlusion, Compend Contin Educ 11:400, 1989.
Rosenkrantz W: Immunomodulating drugs in dermatology. In Kirk
hemorrhage, and necrosis may develop. Blood flow RW (ed): Current Veterinary Therapy X. Philadelphia: WB
turbulence and hydrostatic tension may also play a Saunders, 1989, p 570.
role in the immunopathogenesis of vasculitis. Scott DW, Miller WH Jr, Griffin CE: Muller and Kirk’s Small Animal
• Inciting causes of vasculitis are varied and include Dermatology, 5th ed. Philadelphia: WB Saunders, 2001, pp
667–779.
allergic diseases, bacterial and viral infections, drug Gregory CR: Immunosuppressive agents. In Bonagura JD (ed):
reactions, chemicals, neoplasia, SLE, rickettsial dis- Current Veterinary Therapy XIII. Philadelphia: WB Saunders,
eases, polyarteritis nodosa, rheumatoid arthritis, and 2000, pp 509–513.
W0422-Ch049.qxd 11/10/05 5:21 PM Page 500
▼ Chapter
Necrotizing dermatitis refers to those skin conditions in ough as possible from the outset to increase the chance
which there is death of tissue. With many cases of necro- of a definitive diagnosis.
tizing dermatitis, eschar (slough) formation and ulcer-
ation is often the visible clinical sign, and it occurs when ▼ Key Point Specific diagnosis is best made by
there is cell death, especially within the epidermis and routine histopathology from representative
the hair follicles. In other necrotizing skin diseases, the primary skin lesions and/or tissue samples adja-
tissue destruction may arise in the dermis or even from cent to necrosis, in conjunction with a careful
compromise of deeper vessels. In these cases the first history and thorough physical examination.
clinical signs may be discoloration, swelling, or coolness
to the skin followed later by cutaneous ulceration.
Causes of necrotizing skin disease are categorized in
History
Table 49-1. • Identify or exclude several of the potential causes of
necrotizing dermatoses.
▼ Key Point Dependent on the depth of necrosis or • Record a thorough drug history and take note of
the percentage of surface area which is ulcerated, environmental factors.
necrotizing dermatoses can be life-threatening. • Record a careful timetable of events in addition to
the owner’s description of the earliest cutaneous
An overview of necrotizing dermatitis will be pre- lesions and their temporal relationship to any noted
sented in this chapter, followed by discussion of the systemic signs.
specific diseases that cause the disorder.
Physical Examination
CLINICAL SIGNS • Thoroughly examine all of the skin, including the
inside of the ears, the oral cavity (and other mucosal
Necrotizing skin diseases are characterized clinically by surfaces), and haired as well as non-haired skin.
well-defined areas of devitalized skin (eschar), which • Note any primary lesions.
may vary from pinpoint sized to involving of a large • Look for secondary lesions and for evidence of how
portion of the skin surface. The area may be discolored, they may have developed.
ranging from dark red to purple to yellow to black. • Palpate all peripheral lymph nodes for enlargement.
There may be swelling and even gas production within • Take the body temperature.
the tissues. In time, the devitalized skin develops into a • Perform a general physical examination, including
thick adherent crust, revealing deep ulceration if examination of the eyes, auscultation of the thorax
removed. Common sequelae are systemic signs of and palpation of the abdomen, to evaluate for sys-
toxicity. temic signs.
500
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saline. When the cause cannot be identified, supportive cells may attack components of the vessel walls in
care is the mainstay of treatment. Hydration and provi- other connective tissue conditions.
sion of a high-quality protein diet are important aspects • Focal cutaneous vasculitis has been reported at the
of therapy. site of rabies vaccination. This is usually a deep
panniculitis, and the cutaneous clinical sign most
often is alopecia instead of necrosis. Similar lesions
SPECIFIC NECROTIZING DERMATOSES may develop later at sites distant from the site of
vaccination.
Vasculitis/Vasculopathy • Post-vaccination ischemic dermatopathy and familial
dermatomyositis in the acute stages may exhibit
Etiology erosions or ulcerated lesions on the extremities in
Vasculitis is an inflammatory process that occurs within association with vasculitis. However, in the majority
blood vessel walls and that can lead to necrosis of the of these cases the signs are more chronic and are
vessels and subsequent death of the adjacent tissue. evidence of a vasculopathy.
Histopathologic evidence of vasculitis can be subtle and
transient. When surrounding tissues suggest vascular Clinical Signs
compromise or there is vessel wall damage without
cells, many pathologists refer to this as vasculopathy. • Vasculitis signs usually consist of necrosis and ulcera-
Acute cutaneous vasculitis is most likely to result in tion. These commonly occur on the pressure points,
necrotizing skin signs including hemorrhage (ecchy- foot pads, pinnae, and extremities. Mucocutaneous
moses or purpura), hemorrhagic bullae, necrosis ulcerations may be present as well as fever, lym-
(eschar), and punched out ulcers. Hemorrhage can be phadenopathy, anorexia, and depression. Acute signs
confirmed clinically by diascopy (the skin remains dis- are more often necrotic or erosive lesions whereas
colored when pressure is applied with a glass slide. In chronic signs may show alopecia and scarring.
comparison, erythema blanches under pressure).
Chronic vasculitis or cell-poor vasculitis (vasculopathy) Treatment
is more likely to present with ischemic changes such • Vasculitis/vasculopathy is best managed by treatment
as alopecia, scaling, hyperpigmentation and some of the underlying disease. Unfortunately, a specific
erythema. Both often involve the ears, tail tip, face, cause of vasculitis/vasculopathy cannot be identified
and extremities. Cutaneous vasculitis and vascu- in a significant number of cases.
lopathies are rarely primary in the dog. The list of • If sepsis or generalized bacterial, fungal, or rickettsial
secondary causes is quite extensive; for prognosis and disease is identified, treat the infectious agent.
treatment purposes it is useful to separate these into • If the vasculitis is drug induced, discontinue the
infectious and non-infectious etiologies. In spite of an offending drug immediately. Corticosteroids at anti-
extensive search for an underlying cause, many cases inflammatory dosages (prednisone or prednisolone,
are idiopathic. 1.1 mg/kg q12–24h PO) are advocated by some for
the management of drug-induced vasculitis.
Non-immunologic Causes • If immune complexes are being deposited in vessel
• Necrotizing vasculitis can be seen with a variety of walls, give immunosuppressive doses of glucocorti-
infections caused by bacteria, viruses, disseminated coids (2–4 mg/kg q12–24hr PO) or other drugs.
fungi, and tickborne organisms such as Rickettsia • Corticosteroids may be beneficial in some cases of
rickettsii. Bacteria may directly invade the vessel walls, vasculitis/vasculopathy. Other cases are self-limiting.
especially with sepsis. Other infections such as E. coli In some, alternative treatments may be beneficial.
can produce toxins that result in specific signs of vas- Pentoxyfylline (10–15mg/kg q8h PO) has a wide
culopathy as seen in the cutaneous and renal range of properties, few side effects, and can be used
glomerular vasculopathy of greyhounds. for successful management in idiopathic cases.
• Neoplasia can result in vessel wall necrosis through Dapsone (Avlosulfone, Jacobus) (dogs only) as well
toxin production or direct invasion of the vessel wall as sulfasalazine reportedly have been effective. The
by neoplastic cells. initial dosage of dapsone is 1 mg/kg q8–12h PO;
• Specific drugs can induce lesions of vasculitis in when the disease is controlled, gradually reduce the
animals; the antifungal drug, itraconazole, at a dosage. Both of these drugs have potential side
dosage of 5 mg/kg q12h PO has been observed to effects, and should be used accordingly.
cause vasculitis in some dogs.
Neoplasia-Related Skin Necrosis
Immunologic Causes
• Neoplasia can cause skin necrosis and cutaneous
• With autoimmune disease immune complex deposi- ulceration through a variety of mechanisms. As men-
tion may occur in vessel walls. Antibodies or cytotoxic tioned previously, neoplasia can cause vasculitis.
W0422-Ch049.qxd 11/10/05 5:21 PM Page 503
Through release of necrosis factors generated by • Drug reactions to topically applied drugs can occur
tumor cells, there may be local death of tissues. Also, if the animal has an idiosyncratic reaction or, more
the encroaching growth of a rapidly advancing lesion often, if prior exposure has induced hypersensitivity.
may cause circulatory compromise, leading to cuta- Contact allergic dermatitis can be the result of a
neous tissue necrosis. There are several neoplastic topical drug, and extensive ulceration can occur,
conditions that may result in dermal necrosis, includ- especially if the diagnosis is not made early.
ing cutaneous lymphoma.
Treatment
Clinical Signs • For treatment of drug-induced necrosis, discontinue
• Clinical signs depend on the type and location of the the offending drug immediately. New lesions may
tumor as well as the stage of the disease. In epider- continue to develop after discontinuation of the
motropic lymphoma and in some cases of cutaneous drug. If the adverse effects resolve and are known to
lymphoma, ulceration and necrosis of the tissues at be dosage dependent, resume therapy at a much
the mucocutaneous junctions and inside the oral lower dosage if the primary disease mandates con-
cavity may be seen with or without well-defined tinuation of the drug. In most instances, it is prefer-
tumors. In other cases of cutaneous lymphoma, mul- able to substitute a different drug and to avoid giving
tifocal cutaneous necrotic lesions may occur without the suspect drug to the animal in the future. The effi-
mucocutaneous lesions. In lymphomatoid granulo- cacy of corticosteroids, both at immunosuppressive
matosis (angiotropic lymphoma) neoplastic cells are and at anti-inflammatory levels, for drug reactions is
noted around and within the walls of vessels with the highly controversial. Assess each case individually for
result of ischemic necrosis. potential advantages and disadvantages.
• The medium- to long-term prognosis is generally lesion and keep the patient quiet. Application of
poor, and an outcome of euthanasia is common, tourniquets is controversial, as is glucocorticoid
often due to the painful feet of the patient. The therapy. When polyvalent antivenom (Antivenin, Fort
reported mean survival time from diagnosis is less Dodge) is indicated, give one vial slowly IV as soon as
than 6 months, but some dogs live for months with possible after the bite and repeat injections as neces-
waxing and waning of their symptoms. sary. Monitor the patient closely for anaphylaxis.
Broad-spectrum antibiotics are generally indicated
Environmental Injury of the Skin because both anaerobic and aerobic infections are
Environmental factors can cause necrosis and ulcera- often sequelae to the bite. Keep the lesions clean and
tion of the skin. The clinical signs of environmental debride wounds regularly.
injuries of the skin vary depending on the specific eti-
ology and location of exposure.
Spider Bite
• Spiders (e.g., brown recluse and brown spider) cause
Contact Irritant Chemicals necrotizing skin lesions by injection of a potent der-
• Contact irritant chemicals can caustically burn or monecrotic toxin into the tissue when they bite. The
necrose the skin after topical exposure. The list of enzymes in the venom and the immunologic
primary irritants is extensive and includes soaps, response of the host both play a role in dictating the
detergents, insecticidal sprays, fertilizers, and caustics clinical response.
such as strong acids or alkalies. Medications and • These toxins can continue to damage the surround-
hypertonic solutions delivered extravascularly can ing tissue for an extended time after the bite.
also result in necrosis of the underlying tissue and the
Treatment
skin.
• Excise the bite wound if the lesion is identified early
Clinical Signs as a bite from one of these spiders.
• Lesions of cutaneous necrosis can occur wherever the • Corticosteroids and antivenom do not appear to
reduce local necrosis.
skin was exposed to the irritant. Usually the feet,
scrotum, and ventral abdomen are involved if the
• When systemic signs are present, corticosteroids
combined with supportive care are beneficial.
animal walked or lay down on the causative agent.
Intravascular hemolysis and renal failure are possible
The muzzle or oral cavity may be involved if the
sequelae.
animal tried to remove the compound by licking.
Radiation Injury
Treatment
• Radiation injuries may be acute or chronic, and
• Treatment requires removal of the irritant followed necrosis and ulceration of the tissue can occur days
by supportive care. to weeks after exposure.
• Radiation injury occurs in the anatomic area previ-
Snake Bite ously exposed to radiation.
• Snakes, including pit vipers (copperhead, cotton-
mouth, and rattlesnake) and coral snakes, produce Clinical Signs
venoms that alter the integrity of blood vessels, blood • The clinical signs include erythema of the skin, moist
cells, and coagulation; affect the nervous system; and desquamation, pigmentation or change in hair color,
result in necrosis at the site of envenomation. and loss of hair.
• Snake bites most frequently occur during the warmer
months in geographic areas with an indigenous Treatment
population of venomous snakes.
• Treat acute radiation damage with gentle topical
Clinical Signs cleansing, followed by topical creams. Use medica-
tions to control pain as needed.
• The face and extremities are the common sites of • Chronic radiation injury and areas of cutaneous
involvement. Initial signs are localized soft tissue atrophy caused by acute damage may later necrose
swelling that spreads rapidly. Local hemorrhage and slough. This condition usually is progressive.
occurs, followed by necrosis of tissue and sloughing. Supportive care is the primary treatment.
• Burns can cause significant necrosis and loss of skin. • Decubitus ulcers usually are secondary to pressure
Depending on the depth of the burn, necrosis may necrosis in recumbent animals.
involve only the epidermis or may extend deeper into
the tissues. Clinical Signs
Bristol-Myer), and chlorambucil (Leukeran, Burroughs- • In diabetes mellitus, vasculopathies may occur rarely
Wellcome) may be necessary in severe or refractory in the extremities of dogs and cats. In these cases a
cases. chronic ulcerated lesion on an extremity usually fails
to heal even with symptomatic treatment.
Infection-Induced Necrosis
Clinical Signs
• Infection from deep bacterial or fungal invasion can
lead to local areas of cellulitis or abscessation and • Vascular compromise can lead to sloughing or ulcer-
subsequent necrosis of surrounding tissues. ated lesions. In mechanical occlusion of the circul-
• Both streptococcal and staphylococcal infections n ation, the necrotic lesion is distal or beneath the
the dog can result in a rapidly progressing deep obstruction. For example, an elastic band tightened
necrotizing fasciitis. Although staphylococcus can around the tail over time causes underlying tissue
produce exfoliative toxins that result in a more super- death and sloughing of the distal tail.
ficial peeling of the skin (staph scalded skin
syndrome), staphylococcus and streptococcus can Treatment
produce exotoxins similar to those that produce toxic
shock syndrome in humans.
• Treat vascular compromise based on the etiology and
the location of the necrosis. In thrombovascular
necrosis of the ears, resect all affected tissue. When
Clinical Signs mechanical occlusion causes incomplete circulation
Canine patients with necrotizing fasciitis will have to the tissue, remove the mechanical device. In dia-
intense pain, swelling, and necrosis of the fascia, fat and betes mellitus, the optimal approach to the vascu-
overlying skin. These patients can rapidly deteriorate lopathy is to carefully monitor and control the
and die if aggressive treatment is not elected. diabetes.
• Embedded foreign bodies may result in central
necrosis of the tissue due to release of neutrophilic
enzymes. The lesion ruptures and drains externally at
SUPPLEMENTAL READING
the most necrotic site.
Affolter VK: Cutaneous vasculitis and vasculopathy in Clinical
• Infection can also cause sepsis and vasculitis resulting Program Proceedings 4th World Congress of Vet Derm, 206–211,
in necrolytic dermatitis. 2000.
Foster A, Foil C, BSAVA Manual of small animal dermatology Quedge-
Treatment ley Gloucester UK BSAVA (Publisher)2003, 200–205.
Jackson HA. Eleven cases of vesicular cutaneous lupus erythematosus
• Treat by administering systemic antimicrobial agents in Shetland sheepdogs and rough collies: clinical management and
against the offending etiologic agent, based on prognosis. Vet Dermatol 15:37–41, 2004.
March PA, Hillier A, Weisbrode SE et al. Superficial necrolytic der-
culture and sensitivity testing. Establish and maintain matitis in 11 dogs with a history of phenobarbital administration
local drainage. (1995–2002), J Vet Intern Med 18:65–74, 2004.
Medleau L, Hnilica KA Small animal dermatology Philadelphia, W.B.
Vascular Compromise Saunders Co 2001, pp 157–163.
Moriello K: Ulcerative Skin Lesions. In Moriello K, Mason I, eds.:
• Vascular compromise can occur whenever there is Handbook of Small Animal Dermatology. Oxford: Pergamon
interruption of the normal circulation to an area of (Elsevier) 1995, pp 105–117, 183–192.
tissue. This is involved in many of the aforemen- Outerbridge CA, Marks SL, Rogers QR. Plasma amino acid concen-
trations in 36 dogs with histologically confirmed superficial neu-
tioned conditions and also can be the result of a rolytic dermatitis Vet Dermatol 13:177–186, 2002.
thrombus, vasculopathy, or mechanical or pressure Scott DW, Miller WHM, Griffin C: Small Animal Dermatology, 6th
constriction (e.g., elastic bands). edition, Philadelphia: 2001:WB Saunders. pp 180–182, 742–755,
• There is a unique thrombovascular problem in some 940–947, 1081–1090.
Vitale CB et al: Vaccine-induced ischemic dermatopathy in the dog.
dachshunds that affects the dependent portion of the Vet Dermatol 10:131–142, 1999.
aural pinnae.
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▼ Chapter
50 Keratinization Defects
Kenneth W. Kwochka
Clinical Signs
PRIMARY DEFECTS OF KERATINIZATION
• Disorders of keratinization are characterized clini-
cally by mild-to-severe dry, waxy, or greasy scales.
Primary defects of keratinization are dermatoses that are
Some degree of “seborrheic odor” may be associated
manifested clinically by localized or generalized excess
with the skin condition. Because hair follicles and
scale formation. The scale may be formed from the
glandular structures may also be involved, it is not
interfollicular epidermis or may emanate from hair fol-
unusual to see comedones and follicular casts. Come-
licles as comedones and follicular casts. Histologically,
dones are blackheads resulting from dilation of hair
the most striking abnormalities involve the keratinizing
follicles with keratin plugs. Follicular casts are tightly
structures of the body including the epidermis, hair
adherent scales around hair shafts, giving the
follicle outer root sheath, and hair cuticle.
so-called candle wax appearance. Common sec-
ondary findings include alopecia, inflammation,
▼ Key Point Cutaneous scaling of dogs is a very crusts, pruritus with secondary excoriations, and pyo-
common clinical sign. In most cases, it is not due derma. Secondary Malassezia colonization may also
to a primary keratinization defect but is secondary be associated with primary and secondary causes of
to other dermatologic diseases. Common condi- scaling, especially with greasy scales.
tions causing secondary scaling include demodi-
cosis, scabies, cheyletiellosis, atopic dermatitis, ▼ Key Point Primary keratinization defects are usually
adverse food reaction (“food allergy”), flea allergy, hereditary and appear during the first 2 to 3 years
pyoderma, yeast infection, dermatophytosis, hypo- of life. A breed incidence for these disorders is
thyroidism, hyperadrenocorticism, sex hormone known. An observant owner usually indicates that
abnormalities, pemphigus foliaceus, mycosis fun- the scaling was present before the development of
goides, and environmental influences. The veteri- secondary signs.
narian must determine whether the scaling is
secondary to one of these conditions or associated
with a primary keratinization defect. A primary Diagnosis
keratinization defect is never diagnosed until No specific laboratory test exists for definitive diagnosis
the secondary causes of scaling have first been of a primary keratinization disorder. A combination of
considered. factors is used, including age of onset, breed, history,
diagnostic elimination of more common secondary
In this chapter, an overview of the etiology, clinical causes of scaling, findings on histologic examination of
signs, diagnosis, and treatment of keratinization disor- skin biopsies, and response to therapy.
ders is presented, followed by a description of each
specific disease. ▼ Key Point Skin biopsy is the most important diag-
nostic tool for primary keratinization defects (see
Chapter 37). Biopsy results not only help make a
Etiology definitive diagnosis but also help rule out der-
• For most of the diseases classified as primary kera- matoses associated with secondary scaling.
tinization defects, the pathophysiology is unknown.
For others, the cause is known and the primary patho- Take several biopsies from lesions of various ages.
physiology involves a defect in the keratinizing Send samples to a veterinary pathologist who specializes
epithelium or the cutaneous glandular function. in dermatopathology.
508
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Treatment Diagnosis
After a definitive diagnosis of a primary keratinization • A definitive diagnosis of primary idiopathic sebor-
defect is established, warn owners that the condition is rhea requires a number of different supporting
most likely controllable but not curable. factors, including age of onset, breed, history, diag-
nostic elimination of secondary causes of scaling, and
▼ Key Point Some type of topical and systemic treat- findings on histopathologic examination of skin
ment will probably be needed for the remainder of biopsy specimens.
the patient’s life. • The most important aspect of the diagnostic plan is
a full investigation for secondary causes of scaling.
▼ Key Point It is imperative to treat any secondary The primary differentials are allergic dermatitis,
bacterial and/or yeast infections before a decision scabies, dermatophytosis, demodicosis, bacterial fol-
is made on the type of specific treatment that will liculitis, Malassezia dermatitis, hypothyroidism, and
be needed for the primary keratinization disorder. vitamin A–responsive dermatosis. Additional differ-
entials in Doberman pinschers are color-dilution
alopecia and adult-onset follicular dysplasia.
PRIMARY IDIOPATHIC SEBORRHEA • Biopsy samples are usually characterized by ortho-
keratotic and parakeratotic hyperkeratosis, follicular
Primary idiopathic seborrhea is the most common chronic hyperkeratosis, and dyskeratosis. Often, the follicular
keratinization disorder encountered in dogs. Predis- abnormalities are more impressive than are the
posed breeds include cocker spaniels, English springer changes in the surface epidermis.
spaniels, West Highland white terriers, basset hounds,
Irish setters, German shepherds, dachshunds, Dober-
man pinschers, Chinese Shar-Peis, and Labrador re-
Treatment
trievers. Topical Therapy
• As in most primary keratinization disorders, the treat-
Etiology ment goal in primary idiopathic seborrhea is to
• In cocker spaniels and Irish setters, at least part of the control scale formation, not to cure the disease. Mois-
pathophysiology of scale formation involves hyper- turize the skin and haircoat when dry scaling is
proliferation of basal epidermal keratinocytes. present. This task is accomplished with twice-weekly
moisturizing hypoallergenic shampoos (HyLyt EFA,
▼ Key Point Many dogs with primary idiopathic seb- DVM Pharmaceuticals; Allergroom, Virbac; Micro
orrhea will have concurrent dermatoses that con- Pearls Advantage Hydra-Pearls, EVSCO) and fre-
tribute to the severity of the cutaneous scale and quent moisturizing rinses (HyLyt EFA Bath Oil
inflammation. Coat Conditioner, DVM Pharmaceuticals; Humilac,
Virbac) after each shampoo.
For example, it is not unusual to see a seborrheic • When dry scaling is severe and some keratolytic acti-
cocker spaniel with concurrent allergic dermatosis and vity is needed, the treatment usually consists of sulfur
secondary pyoderma and/or yeast dermatitis. When and salicylic acid shampoos (SebaLyt and SeboRex,
these conditions are diagnosed and treated properly, DVM Pharmaceuticals; Sebolux, Virbac; Micro Pearls
the remaining scale caused by the primary seborrhea is Advantage SebaMoist and SebaHex, EVSCO) fol-
much less severe and easier to control. lowed by moisturizing rinses. Dietary supplementa-
tion with an omega-6 and omega-3 essential fatty acid
combination is also beneficial (e.g., DermCaps, DVM
Clinical Signs Pharmaceuticals).
• Depending on the breed, clinical signs may range • Use keratolytic and keratoplastic degreasing sham-
anywhere from dry scaling (seborrhea sicca), to poos to control the scale and odor associated with
greasy scaling (seborrhea oleosa), to scaling and seborrhea oleosa. Effective topical agents include
greasiness with inflammation and pruritus (sebor- coal tar (NuSal-T, DVM Pharmaceuticals; T-Lux,
rheic dermatitis), and any combination of these Virbac; LyTar, DVM Pharmaceuticals; Allerseb-T,
clinical abnormalities on the same animal. Breeds Virbac), benzoyl peroxide (OxyDex and Sulf
affected with the seborrhea sicca form of idiopathic OxyDex, DVM Pharmaceuticals; Pyoben, Virbac;
seborrhea include Doberman pinschers, Irish setters, Micro Pearls Advantage Benzoyl Plus, EVSCO), and
German shepherds, and dachshunds. Breeds most selenium sulfide (Selsun Blue, Ross). If significant
predisposed to the seborrhea oleosa form include bacterial and/or yeast infections are playing a major
cocker spaniels, English springer spaniels, basset role in the greasy scaling dermatitis, it is better to use
hounds, West Highland white terriers, Chinese Shar- an antibacterial and antifungal shampoo combin-
Peis, and Labrador retrievers. ation (Malaseb Shampoo, DVM Pharmaceuticals;
W0422-Ch050.qxd 11/10/05 5:20 PM Page 510
Diagnosis Etiology
• Epidermal dysplasia is diagnosed clinically by early • Lichenoid-psoriasiform dermatosis is an extremely rare,
probably inherited, keratinization defect reported
age of onset of severe ventral erythema and pruritus
only in English springer spaniels.
rapidly progressing to chronic lesions in West High-
land white terriers. This diagnosis is supported by
skin biopsy findings consisting of hyperplastic perivas-
Clinical Signs
cular dermatitis with epidermal abnormalities, • Clinical signs include non-pruritic, erythematous,
including hyperchromasia, excessive keratinocyte lichenoid papules and plaques involving the pinnae,
mitosis, crowding of basilar keratinocytes, epidermal external ear canal, preauricular and periorbital skin,
“buds,” loss of epidermal cell polarity, and paraker- lips, prepuce, and inguinal region. Chronic cases
atosis. Budding yeast organisms and gram-positive have papillomatous-type lesions, which may involve
cocci may also be found in surface and infundibular the face, ventral trunk, and perineum. A more gen-
keratin. eralized distribution of greasy scales and crusts may
• The principal diagnostic challenge in these dogs is to also be present.
determine if the condition is caused by epidermal
dysplasia, some other pruritic skin disease, or a Diagnosis
combination. Primary diagnostic differentials that
must be considered include atopic dermatitis,
• Lichenoid-psoriasiform dermatosis is diagnosed clini-
cally by early age of onset of refractory, plaque-like
adverse food reaction dermatitis, scabies, and lesions involving the face, ears, and ventrum in
primary idiopathic seborrhea. Evaluate all of these by English springer spaniels. Perform skin scrapings and
appropriate testing or response to therapy in the fungal culture to rule out demodicosis and dermato-
diagnostic workup. phytosis.
• A definitive diagnosis of epidermal dysplasia can be
• The definitive diagnosis is based on skin biopsy
made only with characteristic clinical and histologic results. Histologic examination reveals lichenoid der-
findings and elimination of other diagnostic differ- matitis (i.e., a band of mononuclear cells in the
entials. Another challenge is to determine how much superficial dermis) with psoriasiform epidermal
secondary bacterial infection or Malassezia coloniza- hyperplasia, intraepidermal microabscesses, and
tion is contributing to the severity of the clinical con- Munro microabscesses. Advanced lesions may show
dition. This can only be assessed by evaluating papillated epidermal hyperplasia and papillomatosis.
response after treatment with appropriate topical and
systemic antimicrobial agents. Treatment
• Lichenoid-psoriasiform dermatosis is a waxing and
Treatment waning dermatitis. Minimal responses usually follow
• Epidermal dysplasia has generally been thought to be medical therapy with most antibiotics, low-dose glu-
nonresponsive to medical therapy. However, this cocorticoids, vitamin A, levamisole, dapsone, auto-
observation has changed with the realization that genous vaccines, and topical antiseborrheic agents.
most of these dogs manifest the syndrome secondary Cephalexin may be helpful when secondary pyo-
to allergies and skin infections, especially yeast. derma is present. Prednisone at 2.2 mg/kg PO q24h
• In patients with secondary Malassezia colonization, has improved lesions in some cases but has not
there may be significant improvement in pruritus and resulted in complete remission.
skin condition with ketoconazole (Nizoral, Janssen),
5 to 10 mg/kg PO q24h, or itraconazole (Sporanox,
Janssen), 5 mg/kg PO q24h, and twice-weekly appli-
cation of a topical antifungal shampoo. Alternate-day
SCHNAUZER COMEDO SYNDROME
or twice-weekly pulse dosing with the systemic anti-
fungal agents may be used after initial treatment
Etiology
for long-term control of redevelopment of the • Schnauzer comedo syndrome is a follicular keratinization
infection. defect of miniature schnauzers characterized clini-
• Similar to what was described above for dogs with cally by multiple comedones along the dorsal midline
idiopathic seborrhea, cyclosporine (Atopica, Novartis) of the back. The etiology is probably genetic because
at a dosage of 5 to 10 mg/kg PO q24h has been effec- of the exclusive occurrence in miniature schnauzers.
tive because of the strong allergic component associ- A developmental defect may affect the hair follicle,
ated with this disease. leading to abnormal keratinization, comedo forma-
W0422-Ch050.qxd 11/10/05 5:20 PM Page 513
Diagnosis
CANINE EAR MARGIN DERMATOSIS
• Idiopathic nasodigital hyperkeratosis is diagnosed by
finding nasal and/or digital hyperkeratosis without Etiology
evidence of other concurrent diseases. Consider all
diseases that may cause the lesions. Unfortunately, • Canine ear margin dermatosis is a rare, idiopathic kera-
the list is long and includes canine distemper virus, tinization defect characterized by greasy plugs that
pemphigus foliaceus, pemphigus erythematosus, adhere to the skin and hairs of the pinnae of the ears
lupus erythematosus, nasal solar dermatitis, hypo- in a bilaterally symmetrical pattern. This dermatosis
thyroidism, zinc-responsive dermatosis, generic dog occurs primarily in dachshunds but is also occasion-
food dermatosis, and superficial necrolytic dermati- ally seen in other breeds with pendulous ears. (See
tis. Pemphigus foliaceus, superficial necrolytic der- Chapter 58 for a discussion of pinnal diseases.)
matitis (hepatocutaneous syndrome), and lupus
erythematosus are the most common causes of nasal Clinical Signs
and digital hyperkeratosis. • Canine ear margin dermatosis has greasy plugs adher-
• Perform extensive diagnostic tests only when the con- ing tightly to the skin surface and hair shafts on the
dition is severe or when clinical signs suggest that one pinnal margins. Alopecia may develop with time. Pru-
of the other more serious diseases listed previously is ritus is usually absent. In severe untreated cases, a
present. progression to ulceration and necrosis has been
reported that is due to thrombosis of capillaries that
▼ Key Point Idiopathic nasodigital hyperkeratosis is supply blood to the pinnal margins. This condition
merely cosmetic for most dogs and requires may result in severe scarring and fissures.
neither extensive diagnostic workup nor treatment.
Diagnosis
• When warranted, perform a complete diagnostic
evaluation including a good history, complete blood • Canine ear margin dermatosis is tentatively diag-
count (CBC), serum biochemical profile, thyroid nosed in the early stages when only scale is present
evaluation with baseline thyroxine and a thyroid- by breed and clinical signs alone. Perform skin scrap-
stimulating hormone level, and biopsy for histologic ings and fungal culture to rule out scabies (a consid-
evaluation. Histopathologic findings are most helpful eration only if pruritus is present), demodicosis, and
in ruling out the diagnostic differentials. Abnormali- dermatophytosis. Skin biopsy findings reveal promi-
ties for idiopathic nasodigital hyperkeratosis are non- nent orthokeratotic and parakeratotic hyperker-
specific and consist of irregular epidermal atosis. However, biopsy is unnecessary and the ear
hyperplasia with severe orthokeratotic and parakera- margin is a difficult part of the body from which to
totic hyperkeratosis. remove tissue.
• When the condition has progressed to ulceration and
Treatment necrosis, the number of differential diagnoses to con-
sider is more extensive and includes lupus erythe-
• Medical treatment of idiopathic nasodigital hyper- matosus, pemphigus complex, cutaneous vasculitis,
keratosis includes hydration of the hyperkeratotic dermatomyositis, cold agglutinin disease, frostbite,
tissue by water soakings or wet dressings followed by drug reactions, and lymphoreticular neoplasms.
application of petrolatum jelly as an occlusive agent Diagnostic procedures to differentiate these diseases
to help seal moisture into the stratum corneum. include CBC, serum biochemical profile, urinalysis,
• Although simple hydration may be adequate for mild skin biopsy for routine histologic examination and
lesions, more severe hyperkeratosis requires a topical direct immunofluorescence, Coombs testing, and
agent with keratolytic activity. A gel containing sali- antinuclear antibody testing.
cylic acid, lactic acid, and urea (KeraSolv Gel, DVM • Skin biopsy specimens reveal necrosis and ulceration.
Pharmaceuticals) is helpful, as is topical 0.025% or Some sections may demonstrate vascular thrombosis.
0.01% tretinoin gel (Retin-A, Ortho). Apply the gel However, the changes are nonspecific and may
q12h until the condition is controlled, then use as be seen with many of the diagnostic differentials.
needed for long-term maintenance. Irritation may be Therefore, all of the suggested diagnostic tests are
a problem, especially with tretinoin. Corticosteroid recommended to eliminate the differentials and to
and antibiotic ointments, creams, or gels may be establish a definitive diagnosis of canine ear margin
needed when severe inflammation or secondary dermatosis.
infection is present.
• When very severe projections of keratin are present,
Treatment
especially on foot pads and causing lameness, they
may be surgically removed by trimming the dead • The mild scaling form of ear margin dermatosis is
tissue with scissors. usually controllable but rarely curable with topical
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▼ Chapter
51 Sex Hormone and Endocrine
Look-alike Dermatoses
Linda A. Frank
517
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• In male dogs, a clinical sign highly suggestive of Diagnosis of Gonadal Causes in Intact Dogs
excess estrogen production is linear preputial
dermatosis that appears as a narrow strip of hyper- • In intact animals, the excess sex hormone is most
pigmentation along the ventral midline from the likely gonadal in origin. Measure baseline concen-
prepuce toward the scrotum. trations of estradiol, progesterone, and testosterone
to establish a presumptive diagnosis. If any of these
hormones is substantially increased out of the normal
Female Reproductive Signs range, then there is good reason to suspect this is
causing the dermatosis.
• The nipples and vulva may be enlarged, similar to a
normal heat cycle. • Use diagnostic imaging, especially ultrasonography,
to identify gonadal tumors.
• The heat cycles may be abnormal, especially persis-
tent or irregular estrus. • Evaluate a complete blood count to assess bone
marrow status when hyperestrogenism is suspected.
• Confirm the diagnosis based on resolution of clinical
Male Reproductive Signs signs in response to neutering or ovariohysterec-
tomy.
• The testes may be palpably abnormal.
• The nipples may enlarge, similar to what occurs in • The intact animal may also respond to treatment with
females. an antagonistic hormone, such as androgen to treat
hyperestrogenism; however, this approach is not
• Males may attract other male dogs. recommended since the primary cause of the sex
hormone imbalance is a gonadal tumor.
Other Signs
• Hyperestrogenism can cause serious bone marrow
suppression and aplastic anemia. Diagnosis of Adrenal Tumors
• Adrenal tumors have been associated with abnormal
Hyperandrogenism sex hormone production; thus, in neutered dogs with
clinical signs suggestive of a sex hormone dermatosis,
• Intact male dogs are most commonly affected. Testes the excess sex hormones are most likely arising from
are palpably normal in most cases, but a testicular the adrenal glands.
tumor may be identified. • Perform abdominal ultrasonography to identify
• Hyperandrogenism is only rarely associated with adrenal tumors.
alopecia. • Measure the serum concentration of the sex
• Typical lesions include perianal gland hyperplasia, hormones as well as cortisol, before and after ad-
resulting in a “donut” ring around the anus. This can renocorticotropic hormone (ACTH) stimulation, to
result in anal sac impaction. identify substantial increases in one or more of these
• Generalized seborrhea oleosa is a presenting sign in adrenal hormones. Hyperandrogenism sometimes
some dogs. occurs concurrently with hypercortisolemia. To per-
• Local hyperplasia of the supracaudal gland may form the ACTH stimulation test, obtain baseline and,
appear as alopecia and seborrhea of the dorsal aspect 1 hour post-ACTH, serum samples. ACTH is admin-
of the tail approximately one-third the distance from istered at 5 mg/kg IV. The serum samples need to be
the tail base. frozen and mailed overnight to the following address:
Clinical Endocrinology Service, 2407 River Drive, Rm
Hyperprogesteronism A105 Veterinary Teaching Hospital, University of
Tennessee, Knoxville, TN 37996-4543 (telephone:
• Bilaterally symmetrical alopecia sparing the head and 865-974-5638).
extremities has been attributed to elevated proges-
terone in one dog.
Skin Biopsy
Diagnosis A skin biopsy may support the diagnosis of a sex
Suspect sex hormone dermatoses in dogs that have hormone imbalance; however, the findings are non-
typical clinical signs after routine diagnostic testing has specific. The biopsy can only document the presence
ruled out the more common causes of endocrine alope- of a non-inflammatory alopecia accompanied by hairs
cia, such as hypothyroidism or hyperadrenocorticism that are not cycling (typical endocrine histopathology
(see Chapters 31 and 33). In intact dogs, the resolution pattern). This is not specific for endocrine disease;
of clinical signs in response to neutering confirms the it also is seen in many of the endocrine “look-alike”
diagnosis. In neutered dogs with sex hormone der- alopecias discussed in the later sections of this
matosis, adrenal testing is required. chapter.
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• Interestingly, some respond to melatonin (see the • The pathomechanism of the alopecia is unknown;
“Alopecia X” section), suggesting that the alopecia however, it may involve defective melanization
may be associated with hair cycle arrest, similar to the and/or a hair defect.
other endocrine look-alikes discussed.
Clinical Signs
Post-Clipping Alopecia
Color Dilution Alopecia
Etiology
• Color dilution alopecia is seen in dogs with diluted
• Failure to regrow hair following clipping is a common haircoat colors such as blue Doberman pinschers or
sequel to the “summer cut” and surgical site prepa- fawn Irish setters. It also occurs in Yorkshire terriers.
ration. Possible explanations for this include an arrest Any breed of dog with a color dilution can in theory
of the cycling hair follicle due to the clipping or sur- have this condition.
gical procedure or the clipping of the coat during a
normal telogen phase of the hair cycle in dogs with Black Hair Follicular Dysplasia
very seasonal growth phases.
• It may be seen more frequently with clip sites of • In black hair follicular dysplasia, the alopecia is
epidural anesthesia. restricted to the black-haired areas of the coat. This
condition is usually seen in piebald dogs (dogs with
Clinical Signs large patches of white and black) throughout
the coat, although it has also been seen in black
• Delayed hair regrowth is seen at clipped areas. This Doberman pinschers.
tends to be most noticeable over the trunk, causing • Alopecia occurs in dogs less than 3 years of age and
it to be easily confused with endocrine dermatoses. progresses. Seborrhea and pyoderma are often asso-
• Many times some hairs have regrown within the ciated with areas of alopecia.
alopecic area while the rest remain inactive.
Diagnosis
Diagnosis
• Suspect this condition when alopecia is restricted to
• History of a recent clip and clinical signs are highly a specific color region of the haircoat.
suggestive of this condition. • Microscopic examination of the hair (trichogram) is
• Because endocrinopathies may be associated with useful only in dogs with color dilution alopecia. This
lack of hair regrowth following clipping, it is impor- reveals large and irregular melanin aggregates within
tant to rule out hypothyroidism and hyperadreno- the hair shaft resulting in distortion and breakage of
corticism. the shaft.
• Biopsy supports a non-inflammatory cause of the • Histopathology is useful for both conditions, reveal-
alopecia. Biopsy may show telogen arrest with all hairs ing abnormal melanin clumping within the hair
in telogen. In some cases the biopsy is very similar to shafts and periadnexally within the dermis.
normal-haired areas of the same dog, suggesting that
the dog’s hair growth cycle was in a normal resting Treatment
phase. The biopsy may show anagen hairs, indicating
that hair regrowth has started. • Symptomatic treatment of seborrhea and pyoderma
is essential.
Treatment • There is no known treatment to reverse the clinical
alopecia. There are anecdotal reports of partial
• This condition is self-limiting and does not require response to retinoids and melatonin.
treatment. Hair usually grows back within 1 year,
especially after the dog completes a heavy shedding Telogen Defluxion
cycle.
• Melatonin appears to help stimulate hair regrowth, Etiology
although controlled studies have not been done (see • Illness or severe stress causes abrupt cessation of
the “Alopecia X” section for dosages). anagen and synchronizes hair follicles into the
telogen (resting) stage of hair growth.
Follicular Dysplasias • Telogen hairs synchronously shed in 1 to 3 months as
Follicular dysplasias include color dilution alopecia and the new anagen hair cycle begins.
black hair follicular dysplasia.
Clinical Signs
Etiology
• Hairs begin to shed in abnormal amounts, resulting
• This condition appears to be congenital and/or in alopecic patches, usually 1 to 3 months following
genetic. a stressful incident or illness.
W0422-Ch051.qxd 11/10/05 5:20 PM Page 522
• Hairs epilate easily. The skin appears otherwise Frank LA, Schmeitzel LP, Oliver JW: Steroidogenic response of
healthy with no evidence of pyoderma or adrenal tissues after administration of ACTH to dogs with hyper-
cortisolemia. J Am Vet Med Assoc 218:214, 2001.
inflammation. Medleau L: Sex hormone-associated endocrine alopecias in dogs.
J Am Anim Hosp Assoc 25:689, 1989.
Diagnosis Miller MA, Dunstan RW: Seasonal flank alopecia in boxers and
Airedale terriers: 24 cases (1985–1992). J Am Vet Med Assoc
• Suspect telogen defluxion based on history and 203:1567, 1993.
clinical signs. Paradis M: Melatonin therapy for canine alopecia. In Bonagura JD
• A trichogram of the epilated hairs will confirm that (ed): Kirk’s Current Veterinary Therapy XIII. Philadelphia: WB
Saunders, 2000.
all hairs are in telogen. Scott DW, Miller WH, Griffin CE: Small Animal Dermatology, 6th ed.
• Biopsy will support a non-inflammatory alopecia and Philadelphia: WB Saunders, 2001.
either confirm all hairs to be in telogen or reveal early Suess RP, Barr SC, Sacre BJ, et al: Bone marrow hypoplasia in a
regrowth of a new wave of anagen hairs. feminized dog with an interstitial cell tumor. J Am Vet Med
Assoc 200:1346, 1992.
Syme HM, Scott-Moncrieff JC, Treadwell NG, et al: Hyperadrenocor-
Treatment ticism associated with excessive sex hormone production by an
• Telogen defluxion is self-limiting, and hair eventually adrenocortical tumor in two dogs. J Am Vet Med Assoc 219:1725,
2001.
regrows normally without treatment.
SUPPLEMENTAL READING
Fadok VA, Lothrop CD, Coulson P: Hyperprogesteronemia associated
with Sertoli cell tumor and alopecia in a dog. J Am Vet Med Assoc
188:1058, 1986.
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▼ Chapter
52 Feline Symmetrical Alopecia
Vicki J. Scheidt / Andrew Hillier
Alopecia is defined as the absence of hair from skin climates, minimal hair growth occurs and the thick
areas where it is normally present. Feline symmetric winter coat is shed. Therefore, cats that live outside in
alopecia (FSA) is a cutaneous reaction pattern with colder climates may shed excessively in late spring and
many possible etiologies; FSA should not be a final diag- develop a transient thinning of the coat (hypotrichosis).
nosis, and it is important to determine the primary Secondary hairs undergo a growth phase in the fall and
cause for the most appropriate therapy to be instituted. winter that results in the thick, heavy coat needed for
In order to properly define the clinical problem and colder temperatures. Seasonal changes are less dra-
formulate an appropriate list of differential diagnosis, it matic in tropical regions or in environments with arti-
is helpful to further categorize alopecia as follows: ficial lighting (e.g., cats confined indoors). Under these
conditions, a small amount of hair loss may occur
• Whether the alopecia is self-induced (i.e., a result of continuously.
pruritus) or not
• Distribution of lesions (body locations involved, local-
ized or generalized)
• Duration (permanent or transient) ETIOLOGY OF ALOPECIA
• Degree (partial or complete)
Multiple factors play a role in normal hair follicle devel-
Alopecia in the cat, whether symmetric or asymmet-
opment and growth (Table 52-1). Absence or changes
ric, is most often associated with varying degrees of pru-
in one or more of the factors can alter the normal hair
ritus and skin reactivity depending on the underlying
growth process and result in alopecia. The underlying
disease.
causes of FSA can vary depending on the area or region
of the body affected. This chapter focuses on the causes
▼ Key Point Although self-trauma (pruritus) due to
of FSA that are primarily confined to the trunk
underlying inflammatory skin disease is the most
(dorsum, perineum, caudal thighs, flanks, ventral
common cause of FSA, visible skin inflammation
abdomen, and thorax). The underlying causes of FSA
may be minimal or absent, even in cases of severe
affecting the trunk region have been classified into
pruritus and alopecia.
those that are associated with self-trauma or pruritus
(e.g., licking or scratching) and those that are non-
pruritic (Table 52-2).
NORMAL SHEDDING OF HAIR
In animals, the haircoat aids in thermal regulation, pro- ▼ Key Point Determine whether pruritus and concur-
rent skin inflammation are present when formulat-
tects the skin, and has important aesthetic qualities.
ing a differential diagnosis for FSA in the cat.
Cats are fastidious and spend a great deal of time
grooming their coats. Normal grooming behavior aids
in hair removal and normal shedding. However, when
Self-induced (Pruritic) Alopecia
grooming becomes excessive, it may accentuate hair Allergic dermatitis and parasitic infestations are the
damage and skin disease. It may be difficult for some most common causes of self-induced alopecia. Other
owners who are inexperienced in the grooming behav- cutaneous reaction patterns associated with allergic and
ior of cats to be able to distinguish between normal parasitic dermatoses are feline miliary dermatitis (see
grooming and excessive grooming due to pruritus. Chapter 53) and eosinophilic granuloma complex
Hair follicles have specific cycles of growth (anagen) lesions (see Chapter 53). Allergic causes of self-induced
and rest (telogen) that are primarily stimulated by alopecia in cats typically do not have as strong a regional
changes in the photoperiod and to a lesser extent by distribution (i.e., involvement of specific body loca-
temperature. From winter to late spring in temperate tions) as is the case in dogs.
523
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Food Allergy
Table 52-1. INTERNAL AND EXTERNAL
FACTORS INFLUENCING HAIR FOLLICLE Food allergy in cats is associated with non-seasonal pru-
GROWTH AND DEVELOPMENT ritus and a variety of clinical presentations, including
FSA. The skin lesions and severe pruritus may be gen-
Internal Factors External Factors eralized or confined to the face and ears or trunk.
Genetic Nutritional Alopecia, whether diffuse or symmetric, results from
Hormonal Infectious excessive pruritus triggered by an allergic reaction to
Immunologic Bacterial specific food items ingested (see Chapter 47). Stubbled
Neoplastic Fungal (dermatophytes) or broken hairs, with or without concurrent focal ery-
Stress Parasitic
Physical (traumatic)
thema, papules, and crusting (miliary dermatitis), are
Chemical (toxins, drug therapy) usually present. Food allergy should be considered a dif-
ferential diagnosis in any cat with non-seasonal pruritus
and alopecia.
(FeLV), feline immunodeficiency virus (FIV), diabetes thighs, ventral abdomen, flanks, and perineum. Partial
mellitus, or neoplasia. to complete alopecia and stubbled hairs are observed,
A pruritic, symmetric alopecia of the trunk caused by and concurrent skin changes (e.g., erythema, erosions,
D. gatoi has been described in cats. Other body locations exudation, and crusting) are rare.
may occasionally be affected.
▼ Key Point As with most psychogenic conditions, it
Otodectic Mange is critical to rule out the more common and likely
pathologic causes of FSA before a diagnosis of
Otodectes mites are the most common cause of otitis psychogenic alopecia can be confirmed.
externa in cats (see Chapter 59). Otodectic mites can
live on the skin surface and infrequently cause a sym- Non–self-induced (Nonpruritic) Alopecia
metric alopecia over the lower back and tail base. Con-
current otitis externa may or may not be present. The Feline Endocrine Alopecia
degree of pruritus is variable. This is a disease of unknown cause. It is presumed to
result from hormonal imbalances or deficiencies based
Notoedric Mange on the positive response observed following treatment
Notoedres mites cause a severely inflammatory and pru- with specific hormones. The condition is character-
ritic dermatitis involving the head, pinna, and neck in ized by non-pruritic, symmetric hair loss on the per-
particular. Typically, miliary dermatitis is seen, but FSA ineum, ventral abdomen, and caudal or medial thighs.
may be an uncommon manifestation of infestation with Although the alopecia may spread to the flanks, lateral
this mite. thorax, and proximal tail, the dorsum is usually spared.
A thinning of the hair, rather than complete baldness,
Bacterial Infection (Pyoderma) with normal, non-inflamed skin is the classic presenta-
tion. Feline endocrine alopecia primarily affects
Bacterial infection (usually staphylococci bacteria) is neutered females and males. However, this syndrome
usually secondary to underlying primary disease, for has been reported in intact cats.
example, allergic dermatitis, parasitic infestations, or Significant controversy exists regarding the relation-
endocrinopathy. Secondary bacterial skin infections are ship of hypothyroidism to feline endocrine alopecia.
far less common in cats compared with in dogs. Affected cats usually have normal baseline serum thy-
However, occasional cats may have a secondary bacter- roxine (T4) levels; however, serum T4 levels at 6 hours
ial infection that will mask response to flea control or following stimulation with thyroid-stimulating hormone
food trials if not detected and treated to resolution. (TSH) have been low compared with TSH stimulation
results in normal cats. These findings suggest that some
Yeast (Malassezia) Dermatitis cats with feline endocrine alopecia may have a low
Similar to bacterial infections, yeast dermatitis is usually thyroid reserve.
a secondary problem associated with primary skin Some cats with hyperthyroidism may develop truncal
disease (allergy, parasites, endocrine, etc.) and is also alopecia, although typically the skin lesions of hyper-
far less common in cats compared with dogs. However, thyroidism are uncommon and more often associated
when present, yeast infections may induce moderate to with a dull, greasy, lusterless haircoat.
severe pruritus in their own right, even when the under- Feline hyperadrenocorticism is rare; however, spon-
lying primary disease is non-pruritic (e.g., endocrine). taneous and iatrogenic Cushing disease can produce
Once again, failure to detect and resolve yeast skin FSA of the trunk or pinnae associated with thin hypo-
infections will make it difficult to appreciate response tonic skin.
to flea control, food trials, immunotherapy, etc.
Telogen Effluvium
Psychogenic Alopecia This is a syndrome in which the anagen cycle is short-
This condition is often an enigma. Alopecia develops ened and a wave of hairs simultaneously enters the
because the cat excessively licks, bites, or pulls out hair resting phase. Conditions associated with physiologic
from those areas normally groomed (perineum, ventral stress (e.g., fever, shock, pregnancy and lactation, mal-
abdomen, flank). In most cases, a stressful event such nutrition, adverse drug reactions, or a severe debilitat-
as moving to a new surrounding, being hospitalized or ing disease) can precipitate rapid shedding in animals.
boarded, loss of a favorite companion, or introduction The resultant alopecia can be partial to complete, local-
of a new pet or person (baby) into the environment ized or generalized, and usually non-pruritic. Affected
precipitates the disease. Psychogenic alopecia is hairs are easily epilated by friction or grooming.
most common in nervous or “high-strung” cats, such as
Siamese, Abyssinian, or black-colored cats. Typically, the Anagen Defluxion
areas affected are regions the cat can easily lick, such as This is a syndrome in which there is a sudden inter-
the dorsal lumbosacral region, tail, medial and caudal ruption of growth of anagen hairs, causing deformity
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iatrogenic Cushing disease. Administer dexamethasone including signs of estrus in females, aggressive behavior
at a dosage of 0.25 to 1.0 mg/cat once daily with a taper or urine spraying in males, and hepatobiliary disease in
to 2 to 3 times weekly, or prednisolone at a dosage both, have been reported following androgen and/or
of 2 mg/kg q24h PO for 7 to 14 days with a taper to estrogen therapy.
an alternate-day schedule, and gradually taper to the
lowest effective dose. Methylprednisolone acetate Thyroid Hormone
(Depo-Medrol, Upjohn) given at a dose of 4 to 5 mg/kg Supplemental thyroid hormone has been found to be
or 20 mg/cat SC is also effective when administered effective in cats with feline endocrine alopecia, despite
every 2 to 3 weeks. When giving repeated corticosteroid normal serum baseline thyroid levels. Sodium levothy-
injections (Depo-Medrol) every 2 to 3 weeks, do not roxine is effective at a dosage of 0.05 to 0.1 mg q12–24h
exceed four treatments at this interval. If pruritus per- PO. Sodium liothyronine (Tertroxin, Glaxo) given at
sists, it is imperative to find the underlying disease or 50 mg q12h PO has been reported to produce complete
look for alternative treatments. hair regrowth in 73% of cats treated (Thoday, 1989).
Systemic Progestational Compounds
Progestational Compounds
These compounds have been used for years to treat
various feline skin diseases, including FSA, both pruritic These compounds can be effective in the management
(e.g., atopy and psychogenic alopecia) and non-pruritic of feline endocrine alopecia. Megestrol acetate (2.5–
(e.g., feline endocrine alopecia). In cats, progestational 5.0 mg/cat PO once every other day for 1–2 months) is
compounds such as megestrol acetate (Ovaban, Scher- preferred over repositol progesterone due to potential
ing-Plough) are immunosuppressive and have potent side effects of the latter in cats.
anti-inflammatory activity. They exhibit a wide spectrum
of actions and side effects. Serious side effects in Adrenalectomy
the cat include decreased spermatogenesis, pyometra, Either unilateral or bilateral adrenalectomy is the treat-
mammary gland fibroadenomatous hyperplasia and ment of choice for naturally occurring hyperadreno-
mammary neoplasia in both male and female intact and corticism in the cat (see Chapter 33). Discontinue and
neutered animals, permanent or transient diabetes mel- avoid future treatment with systemic corticosteroids
litus, adrenocortical suppression, and various behav- and progestational compounds in cats with iatrogenic
ioral abnormalities (e.g., polyphagia with subsequent hyperadrenocorticism.
weight gain, polyuria, polydipsia, and lethargy). The
oral dosage in cats is variable and starts with an induc-
tion dose of 2.5 to 5 mg per cat q24h for 5 days, Antianxiety Drugs and Tranquilizers
decreases to every other day, and is tapered to 2.5 to These drugs can be used in conjunction with behavior
5 mg every 5 to 7 days for 1 to 2 months. modification to treat cats with stress-induced symmetric
alopecia or psychogenic alopecia. Because response to
▼ Key Point Progestational compounds are not ap- systemic antianxiety medication is variable in cats and
proved for use in cats. Because of this and their requires much patience and effort on the part of the
numerous side effects, they are administered only owner, identification and removal (if possible) of the
as the last choice. predisposing cause is crucial. Use these drugs as adjunc-
tive therapy to behavioral modification. The main
goal is to calm the cat and eventually discontinue
Hormonal Therapy the antianxiety medication.
Hormonal therapy has been successfully used in the cat
to treat non-pruritic, FSA that is associated with normal-
• Examples include clomipramine, alprazolam, fluoxe-
tine, and amitriptyline.
appearing skin and classified as endocrine in origin.
Although various hormones have been effective in the
treatment of feline endocrine alopecia, relapses are
common and intermittent lifelong therapy is often SUPPLEMENTAL READING
necessary.
Halliwell REW: Efficacy of hyposensitization in feline allergic diseases
Combined Estrogen and Testosterone based upon results of in vitro testing for allergen-specific
immunoglobulin E. J Am Anim Hosp Assoc 33:282, 1997.
These have been used successfully in both neutered Kirk RW: Feline alopecia. In Kirk RW (ed): Current Veterinary
male and female cats with feline endocrine alopecia. Therapy VII. Philadelphia: WB Saunders, 1980, p 490.
Repositol testosterone (12.5 mg/cat) and repositol Miller WH, Scott DW: Efficacy of chlorpheniramine maleate for
management of pruritus in cats. J Am Vet Med Assoc 197:67,
diethylstilbestrol (0.625 mg/cat) are given IM separately 1990.
or in combination. Although hair regrowth is usually Muller GH, Kirk RW, Scott DW: Small Animal Dermatology, 4th ed.
present by 6 weeks, relapses are common. Side effects, Philadelphia: WB Saunders, 1989, p 701.
W0422-Ch052.qxd 11/10/05 5:19 PM Page 530
Scott DW: Feline dermatology, 1900–1978: A monograph. J Am Anim Thoday KL: Differential diagnosis of symmetric alopecia in the cat.
Hosp Assoc 16:334, 1980. In Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia:
Scott DW: Feline dermatology, 1979–1982: Introspective retrospec- WB Saunders, 1986, p 545.
tions. J Am Anim Hosp Assoc 20:537, 1984. Thoday KL: Aspects of feline symmetric alopecia (abstract). First
Scott DW, Miller WH, Griffin CE: Muller and Kirk’s Small Animal World Congress of Veterinary Dermatology, Dijon, France,
Dermatology, 5th ed. Philadelphia: WB Saunders, 1995. September 1989.
W0422-Ch053.qxd 11/10/05 5:19 PM Page 531
▼ Chapter
53 Miliary Dermatitis and Eosinophilic
Granuloma Complex
Wayne S. Rosenkrantz
Miliary dermatitis (MD) and eosinophilic granuloma implicated in EGC as a cause of a hypersensitivity reac-
complex (EGC) are extremely common cutaneous reac- tion. These parasites also produce lesions in MD by way
tion patterns in the cat. The term miliary is a descriptive of a hypersensitivity reaction. Refer to the respective
one, and it implies that the papules and crusts charac- chapters concerning these various parasites for addi-
teristic of the syndrome resemble millet seeds. The term tional information.
eosinophilic granuloma is also descriptive of a group of
lesions affecting the skin and oral cavity of the cat. The Infectious Diseases
three clinical histologic syndromes included in this Infectious causes for both entities include bacterial
complex are eosinophilic ulcer, eosinophilic plaque, infections and dermatophytosis. In EGC, viral infections
and eosinophilic (collagenolytic) granuloma. are an additional consideration and for MD consider
Malassezia (yeast) infections (see Chapter 41).
ETIOLOGY • The most common bacteria isolated in both entities
include Staphylococcus, hemolytic Streptococcus, Pas-
▼ Key Point MD and EGC are neither final diagnoses teurella, and Bacteroides species. Presence of bacteria
nor pathognomonic for any one disease. Many eti- on cytology and positive clinical response to a variety
ologies exist for both reaction patterns. The ability of antibiotics in both MD and EGC gives support to
to control or cure chronic or recurrent cases is a bacterial etiology. Although secondary bacterial
dependent on pursuing the underlying cause. The infections are uncommon in cats (less common than
two conditions share similar etiologies and there- in dogs), their role in disease and contribution to
fore are discussed together in this chapter. clinical signs is easily overlooked.
• The major dermatophyte species isolated from cats is
Microsporum canis (see Chapter 42). This dermato-
Underlying causes or predisposing factors for MD phyte can produce MD, but it can also be found on
and EGC (Table 53-1) include (1) allergies, (2) para- cats without MD. This dermatophyte is rarely isolated
sites, (3) infectious diseases, and (4) miscellaneous from EGC lesions, and its significance in this complex
conditions. is questionable.
Allergies Miscellaneous Causes
Allergies to biting insects (e.g., fleas, mosquitoes, and Miscellaneous conditions causing MD include genetic
flies), foods, environmental allergens, and rarely factors, immune-mediated diseases, drug reactions,
contact substances (irritants and allergens) have been nutritional factors, epitheliotropic lymphoma, and idio-
associated with MD in the cat. With the exception of pathic causes. Genetic factors, immune-mediated
contact allergies, all of these reactions have also been disease, and idiopathic causes have received attention
associated with EGC. In particular, flea and other biting as etiologies in EGC.
insect hypersensitivities have been emphasized as
etiologies in EGC. • Hereditary (genetic) factors have been implicated based
on reports of offspring from affected cats, which have
developed similar MD or EGC lesions.
Parasites • Immune-mediated disorders, such as pemphigus
Parasites, such as fleas, Demodex, Cheyletiella, Notoedres, foliaceus, can produce MD-like lesions. Immune-
chiggers, Otodectes, lice, cat fur mites, and endoparasites, mediated disease has not received much considera-
have been associated with MD. Fleas have also been tion in EGC, although antiepithelial antibodies
531
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HP), Royal Canin (Sensitivity VR and RD) and • Although treatment options for environmental aller-
Eukanuba (Response LB) diets. The elimination diet gen and mite reduction (Allerase and Dustmite,
is fed strictly for 6 to 8 weeks. Aveho Biosciences) are available, their efficacy has
not been determined in the feline. However, I com-
Intradermal Allergy Testing monly recommend the use of environmental control
based on positive experiences seen in HDM allergy in
Intradermal testing (IDT) helps demonstrate hyper-
the canine.
sensitivity to insect and environmental allergies. Allergy
testing in the cat is more difficult to perform and inter- • In addition to treating the premises, it is also recom-
mended to install a room air conditioner and dehu-
pret than in the dog. Testing is, therefore, best done by
midifier in the bedroom if the home does not have
an experienced veterinary allergist (see Chapter 46).
central air conditioning. Lowering humidity reduces
the number of mites, as well as mold and other
Serum In Vitro Allergy Testing
allergens.
Serum in vitro allergy testing (SIAT) has improved sig- • It is also recommended to use wood, vinyl, or leather
nificantly in the cat. I have had results comparable furniture instead of upholstery furniture; vacuum fre-
to skin testing using a liquid-phase enzymo-immuno- quently; avoid pet foam beds; and wash all bedding
metric assay (Veterinary Allergy Reference Laboratory; materials in hot water (>130∞F) weekly.
Pasadena, CA) for selecting antigens for allergen-
specific immunotherapy (ASIT). Glucocorticoid Therapy
▼ Key Point Positive allergy test results (IDT or SIAT) This therapy can be tried in first-time cases of MD and
should not form the basis for a diagnosis of atopic EGC. In chronic recurrent cases, alternative therapy is
dermatitis—positive results will help confirm the given based on information from an appropriate
clinical diagnosis of atopic dermatitis and are workup. Even with proper workup, refractory allergies
essential in the selection of allergens for inclusion or idiopathic cases of both MD and EGC may require
in immunotherapy. Allergy tests have not been long-term glucocorticoid therapy. A variety of gluco-
shown to be useful in the diagnosis of food allergy corticoids can be tried.
in cats. • Methylprednisolone acetate (Depo-Medrol, Pfizer) at
4 mg/kg IM is a commonly used, and often effica-
cious, long-acting injectable glucocorticoid. Cases of
TREATMENT refractory EGC may need three injections at 2-week
intervals. In general, after remission, do not use
▼ Key Point Many forms of therapy have been methylprednisolone acetate more often than every
described for both MD and EGC. The best long- 3 months.
term management is achieved when a definitive • As an alternative to methylprednisolone acetate, give
diagnosis of the underlying cause has been estab- anti-inflammatory doses of prednisolone or methyl-
lished and specific therapy for that disease is prednisolone at 2.2 mg/kg PO q24h for resolution of
prescribed. lesions. Decrease the dose to 1 to 2 mg/kg PO q48h
for maintenance.
Avoidance of Inciting Etiologies • Some cases can be successfully managed with initial
injections of methylprednisolone acetate and then
Avoidance strategies are commonly used for flea bite maintained with oral prednisone, prednisolone, or
hypersensitivities, other ectoparasitic hypersensitivities, methylprednisolone at a dosage of 1 to 2 mg/kg PO
food hypersensitivities, epithelial allergens (feathers, q48h.
cat, dog, or human dander) or mold allergies and most • Other oral glucocorticoids can be tried in refractory
recently for house dust mite (HDM) hypersensitivities. cases. Use triamcinolone at a dosage of 0.4 to 0.6 mg/
kg PO q24h, then tapering to 0.2 to 0.3 mg/kg PO
Control of House Dust Mites q48h–72h for maintenance; or use dexamethasone at
In my practice, HDM (Dermatophagoides farinae) is the a dosage of 0.25 to 0.75 mg PO q24h, then tapering to
most common non-seasonal allergic reaction seen in 0.25 to 0.125 mg q48h–72h for maintenance.
the feline. • Use intralesional triamcinolone (Vetalog, Squibb) in
refractory EGC lesions at a dose of 1 to 4 mg injected
• HDM detection can be performed by using an in- intralesionally.
home swipe test on any textile surface (MITE-T-Fast
Allergen Detection System, Aveho Biosciences). In
many cases testing is not necessary and treatment can
Antihistamine Therapy
be based upon the presence of a positive allergy test Antihistamines can be tried in atopic dermatitis, flea
or a strong clinical suspicion. allergy, and idiopathic MD and EGC:
W0422-Ch053.qxd 11/10/05 5:19 PM Page 535
life-threatening side effects (including pyometra, dia- Power HT: Eosinophilic granulomas in a family of specific pathogen-
betes mellitus, and mammary neoplasia). freed cats. Proceedings of the 6th Annual Meeting of the AAVD
and ACVD, 45, 1990.
Power HT, Ihrke PJ: Selected feline eosinophilic skin diseases. Vet Clin
N Am Small Anim Prac 25:833–850, 1995.
SUPPLEMENTAL READING Prost C: Diagnosis of feline allergic disease: A study of 90 cats. In:
Kwochka KW, et al. (eds): Advances in Veterinary Dermatology III,
Butterworth-Heinemann, Boston, 1998, p 516.
Colombini S, Hodgin EC, Foil CS, et al: Induction of feline flea allergy
Rosenkrantz W: Eosinophilic granuloma confusion. In: August JR
dermatitis and the incidence and histopathological characteristics
(ed): Consultations in Feline Internal Medicine. Philadelphia: WB
of concurrent indolent lip ulcers. Vet Dermatol 12:155–161, 2001.
Saunders, 1990, pp 121–124.
Mason KV, Evans AG: Mosquito bite-caused eosinophilic dermatitis in
Rosenkrantz W: Feline eosinophilic granuloma complex. In Griffin
cats. J Am Vet Med Assoc 198:2086, 1991.
CE, Kwochka KW, MacDonald JM (eds): Current Veterinary Der-
O’Dair H, et al: An open prospective investigation into aetiology in a
matology. St. Louis: Mosby-Year Book, 1993, pp 319–324.
group of cats with suspected allergic skin disease. Vet Dermatol
7:193, 1996.
W0422-Ch054.qxd 11/10/05 5:26 PM Page 537
▼ Chapter
54 Surgery of Intertriginous Dermatoses
Jamie R. Bellah
Intertriginous dermatoses are surface pyodermas that • Brachycephalic breeds: Pekingese, English bulldog,
are associated with skin folds. Chronic skin apposition pug, French bulldog, Boston terrier
results in friction, minor trauma, and poor air circula- • Persian cats
tion along with a moist environment conducive to col-
onization and infection by bacteria and yeasts.
Lip Fold
▼ Key Point Inflammation and exudates associated • Common in dogs with excessive mandibular labial
with skin fold pyoderma cause pain, pruritus, and tissue, such as spaniels, Saint Bernard, Irish setter,
malodor. Conservative treatment is only palliative. Newfoundland, golden retriever, and Labrador
Resolution of these conditions can be accom- retriever.
plished only by surgery. • Redundant lip fold is usually located behind the
mandibular canine tooth.
• Can be bilateral.
ETIOLOGY • Causes severe halitosis.
• May occur after partial mandibulectomy or maxillec-
Normal skin defense mechanisms are as follows: tomy if a skin fold is created during wound closure.
• Intact epidermis and stratum corneum
• Sebum that contains antibacterial and antifungal Body Fold
fatty acids
• Skin microflora that may secrete antibiotic-like • Usually affects obese or Chinese shar-pei dogs.
substances • With shar-pei puppies, body folds become less redun-
dant with growth but persist on the head and face.
Skin fold pyoderma is classified as a surface pyo- • May occur in female dogs or cats along the abdomi-
derma. (See Chapter 38 for a complete discussion of nal midline if mammary glands or body fat creates a
pyoderma.) skin fold.
• Bacteria and yeasts remain on top of the skin. • Moist seborrhea predisposes the animal to body fold
pyoderma.
• Warm, moist environment within recess of the skin • Pendulous cervical skin may result in body fold pyo-
fold allows colonization by Staphylococcus intermedius
derma, especially if generalized skin disease exists.
or Malassezia pachydermatis.
• Other infecting organisms include Streptococcus, • Folds left after surgery (i.e., total ear canal ablation)
or created by surgery may result in residual fold
Escherichia coli, Pseudomonas, Proteus, and Candida.
pyoderma.
• Surface bacteria and yeasts act on trapped secretions
and sebum, producing breakdown products that are
irritating and odoriferous. Vulvar Fold
• Superficial skin erosions and inflammation result.
• Most common in older, obese, spayed female dogs
• Self-trauma and obesity tend to worsen the condition.
and rarely cats.
Locations, characteristics, and breeds associated with • Seen in younger dogs with infantile vulvas.
intertriginous dermatoses include the following. • Accumulation of urine and vaginal secretions occur.
Facial or Nasal Fold ▼ Key Point Chronic or relapsing urinary tract infec-
• Frequently associated with secondary ulcerative tion is commonly secondary to vulvar fold pyo-
keratitis derma and recessed vulva.
537
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SURGICAL PROCEDURES
Objectives
A Area to be removed
• En bloc excision of the skin fold and associated
pyoderma
• Wound closure without excessive tension
• Resolution of wound infection
Equipment
• Standard general surgical pack.
• Suture material appropriate for infected wounds
(e.g., polydioxanone for subcutaneous tissues and
monofilament nylon for skin).
• Bone-holding forceps aid manipulation of the tail
during caudectomy for screw tail.
• Bone-cutting forceps or Gigli saw for caudectomy. B
• Penrose drains (most commonly for screw tail Figure 54-1. Facial fold excision. A, Incision boundaries (dotted
excision). lines) are planned so that enough skin for closure without tension
• Sterile skin marking pen remains. B, Final suture pattern.
W0422-Ch054.qxd 11/10/05 5:26 PM Page 539
h. Cut the suture ends short so that they do not from rolls of abdominal fat or from pendulous
contact the cornea. mammary tissue.
i. Alternatively, use an intradermal pattern using
fine absorbable suture, eliminating the need for 4. Vulvar Fold Excision (Episioplasty)
suture removal. a. Place the animal in ventral recumbency with the
perineal region at the end of the table. If the rear
2. Lip Fold Excision (Cheiloplasty) legs are draped over the end of the table, be sure
a. Position the animal in dorsal recumbency. to pad them sufficiently.
b. Clip and prepare the skin over the mandible from b. Express the anal sacs, and place a purse-string
its rostral tip to the mandibular angle (Fig. 54- suture around the anus.
2A). c. Prepare the perivulvar region for aseptic surgery.
c. Make an elliptical incision around the lip fold, d. Mark the proposed skin incision. Make an ellipti-
and remove the entire fold and infected region cal incision around the base of the vulvar fold,
(Fig. 54-2B). then undermine and remove the incised area of
d. It is very rare that the mucosal surface of the lip skin (Fig. 54-3A).
needs to be incised. e. Starting with the most dorsal suture, place simple,
e. Try to avoid incising the underlying muscles of interrupted cuticular sutures equidistant from
the lip. one another around the incision to approximate
f. Close the incision in two layers using fine the wound margins (Fig. 54-3B). This step helps
absorbable suture for subcutaneous tissue and determine if adequate skin and subcutaneous fat
fine non-absorbable suture for skin (Fig. 54-2C). have been removed.
g. Close the buccal mucosa, if incised, with fine, f. Close the skin in two layers using fine absorbable
interrupted absorbable sutures. suture for subcutaneous tissue and fine non-
absorbable sutures for skin (Fig. 54-3C).
3. Body Fold Excision g. Remove the purse-string suture.
a. Position the dog so that optimal access to the
body fold to be removed is accomplished.
b. Prepare the skin wide enough so the fold can be
excised in its entirety.
c. Make two incisions parallel to the fold near its
base, being certain to leave sufficient skin for
closure.
d. Closure is done in two layers using fine Vulvar fold
absorbable suture for subcutaneous tissues and
interrupted non-absorbable sutures for skin
apposition.
e. Mastectomy (see Chapter 29) may be required to
resolve body fold pyoderma that has resulted
Incision
A B
A
C
C Figure 54-3. Vulvar fold excision (episioplasty). A, Incision
Figure 54-2. Lip fold excision (cheiloplasty). A, Preparation of pattern around the base of the vulvar fold. B, Simple sutures approx-
skin. B, Excision of fold. C, Closure pattern. imate the wound margin. C, Suture pattern.
W0422-Ch054.qxd 11/10/05 5:26 PM Page 540
▼ Chapter
55 Management of the Traumatic Wound
by Primary Closure
Mark W. Bohling / Steven F. Swaim
Following proper initial management of a traumatic • Adequate hemostasis has been attained.
wound by debridement and lavage, the wound may be • Perform delayed primary closure when:
closed. Sufficient viable tissue must be present to allow • Wounds show evidence of heavy contamination,
closure without excessive tension. Wounds may be purulent exudate, residual necrotic or question-
closed by primary closure, delayed primary closure, or able tissue, edema, erythema at the wound
secondary closure. See Chapter 56 for a discussion of margins, lymphangitis, and skin tension.
open wound management. • Local infection has been controlled by staged
debridement, lavage, topical and/or systemic
antibiotics, and appropriate bandages. This is
ANATOMY usually 3 to 5 days after wounding.
• Perform a secondary closure when:
• Dogs and cats have abundant skin on the trunk and • The wound is in the reparative stage of healing at
neck but a sparsity of skin on the distal limbs, tail, ear, presentation, with a healthy bed of granulation
and rostral areas of the head. tissue and evidence of epithelialization.
• Direct cutaneous vessels run parallel to the skin’s • The wound has disrupted and has subsequently
surface and supply the subdermal plexus of the skin. developed a healthy bed of granulation tissue.
See Chapter 57 for more details regarding blood • It has been necessary to leave the wound open
supply to the skin. for longer than 5 days to control infection (see
• Some areas of the body have panniculus musculature Preoperative Considerations, Delayed Primary
underlying the skin. The skin’s blood supply runs Closure, Local Infection Control).
both superficial and deep to this musculature.
• Other areas of the body have loose areolar fascia deep
to the dermis in which vasculature is located, and in
other areas the skin is closely associated with under- SURGICAL PROCEDURES
lying fascia.
Primary or Delayed Primary
Closure without Tension
PREOPERATIVE CONSIDERATIONS
Objectives
▼ Key Point If a traumatically induced wound is to be • Close the wound.
closed, it is imperative that the tissues be viable • Provide drainage if necessary.
and clean enough that wound healing can progress
uneventfully. Perform adequate debridement and
lavage.
Equipment
• Standard general surgical pack
• Perform a thorough physical examination and appro- • Undyed polyglactin 910, polyglecaprone, dyed or
priate diagnostic tests on all traumatized animals to undyed polydioxanone, 2-0 to 4-0 (Vicryl, Monocryl,
rule out associated injuries. or PDS II; Ethicon, Somerville, NJ.) and polypropy-
• Perform primary closure when: lene or nylon, 2-0 and 3-0 (Prolene or Ethilon,
• The animal is in good condition. Ethicon, Somerville, NJ.)
• A short time (6–12 hours) has elapsed since injury. • Wound lavage solution of 0.05% chlorhexidine diac-
• Minimal contamination and tissue trauma have etate or gluconate (Nolvasan Solution, Fort Dodge,
occurred. IA. or ChlorhexiDerm Disinfectant, DVM Pharma-
• Adequate debridement and lavage have been done. ceuticals, Miami, FL.)
541
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Technique Equipment
1. Pack the wound with sterile surgical sponges moist- • See equipment under Primary or Delayed Primary
ened with physiologic saline, or with water-soluble Closure Without Tension.
sterile lubricant (K-Y Jelly, Johnson & Johnson, New
Brunswick, NJ.) or water-soluble sterile lubricant that Technique
contains chlorhexidine gluconate (Surgilube, E. 1. The general techniques for closure of wounds with
Fougera & Co., Mellville, NY.) tension are the same as those for primary or delayed
2. Prepare the area around the wound for aseptic primary closure without tension (see previous
surgery. section), with the exception of suture pattern (see
3. Remove the wound packing or sterile lubricant. tension-relieving suture patterns discussed subse-
4. Lavage the wound frequently with sterile isotonic quently).
fluids (or a solution of 0.05% chlorhexidine diac- 2. Wounds that are in the reparative stage of healing
etate or gluconate) during surgery along with with healthy granulation tissue and epithelialization.
removal of devitalized tissue and debris as indicated. a. Excise epithelium from the edge of the wound,
5. Use as few simple interrupted absorbable sutures as leaving healthy granulation tissue in the center.
necessary to close dead space in deep layers of the b. Gently clean the surface of the granulation tissue
wound. with 0.05% chlorhexidine solution (Fig. 55-1).
6. Be careful not to entrap major vessels or nerves in 3. Gently undermine the skin surrounding the wound.
the sutures. a. Undermine bluntly, using Metzenbaum scissors,
7. Place a drain (Penrose drain, or a closed suction leaving some loose areolar connective tissue on
drain [Jackson-Pratt]) if there is any possibility of the dermis or undermine beneath panniculus
residual dead space and/or wound drainage. musculature if present.
8. Place a simple continuous suture in the subcuta- b. Undermine sharply with scissors or scalpel blade
neous tissue at the wound edge using absorbable in areas where skin is closely associated with the
suture material. underlying fascia.
9. Close the skin with non-absorbable simple inter-
rupted sutures.
First
suture bite
a
b a b
a b b
Second Figure 55-3. Intradermal sutures. Using 3-0 or smaller absorbable
A suture bite B suture material in a continuous pattern, place intradermal sutures
with each bite being passed horizontally. (Redrawn from Scardino MS,
Swaim SF, Henderson RA, Wilson ER: Enhancing wound closure on
1 the limbs. Compend Contin Educ 18:919, 1996.)
Walking
2 sutures
Simple interrupted
closure sutures Simple interrupted
subcutaneous sutures
Figure 55-7. Presutures. A, The day before surgery, suture the skin
adjacent to the lesion over the lesion using a Lembert suture pattern.
B, The following day, remove the presutures and excise the lesion.
Stent sutures Inset, Close the resulting defect or wound using the stretched skin
made available by the presutures. (Redrawn from Scardino MS, Swaim
SF, Henderson RA, Wilson ER: Enhancing wound closure on the
limbs. Compend Contin Educ 18:919, 1996.)
A
the “presutures” are removed and the wound is
closed using the prestretched skin (Fig. 55-7).
g. On wounds that cannot be closed, or to help
B prevent further wound edge retraction, place a
monofilament non-absorbable intradermal con-
tinuous horizontal mattress suture. The ends are
left untied and a button and two fishing weights
(split shot) are placed on each end of the suture.
Traction is placed on each free suture end daily
C to advance the edges toward each other. Two new
split shots are placed on the suture adjacent to the
Figure 55-6. Stent sutures. A, Preplace stent sutures deep to the button after each tightening to hold the edges
wound tissues. B, Wound tissues are closed. C, Tie stent sutures over under tension and advance them toward the
a roll of gauze or rolled towel.
wound center (Fig. 55-8). Use “environmentally
friendly” (tin) split shots to prevent lead toxicity
sponges or a rolled towel to act as a tension suture in case the patient should chew at the wound site
as well as to obliterate dead space (Fig. 55-6). and swallow the split shots.
f. Place nonabsorbable Lembert sutures in the skin h. Another technique for closing wounds that are
adjacent to the wound the day before surgery. The under considerable tension is the “pulley” suture
sutures are tied under tension. The following day, (Fig. 55-9). This is a 4-bite buried interrupted
W0422-Ch055.qxd 11/12/05 10:39 AM Page 545
Fascia
Top of
skin
A
4
2 B
1
3
B A
C
Dermis Subcutaneous
Figure 55-9. Pulley suture. This is the same as a “buried” simple A=B
interrupted suture, except that four suture bites (two on each side of Figure 55-10. Unilateral bipedicle flap. A, Undermining the skin
the incision) are taken instead of two, creating two loops through the on the side of defect from which the flap will come. B, Checking to
tissue instead of the usual single one. All bites are placed in the deep see if undermining provided sufficient skin for wound closure. C,
layer (underside) of the dermis to provide solid purchase in the tissue Making an incision to create a bipedicle flap. Wound and flap width
for closure against tension. are equal (A = B).
W0422-Ch055.qxd 11/12/05 10:39 AM Page 546
E
Figure 55-10, cont’d D, Flap being sutured into position after Figure 55-12. Multiple punctate relaxing incisions. A, Make par-
walking sutures have advanced it (broken lines). E, Donor site sutured. allel staggered rows of incisions as needed on both sides of a wound
(After Swaim SF, Henderson RA: Small Animal Wound Management. while a simple continuous intradermal suture is placed and tightened.
2nd Ed. Philadelphia: Williams & Wilkins, 1997, p 176.) B, Final wound apposition with simple interrupted sutures. (After
Swaim SF, Henderson RA: Small Animal Wound Management. 2nd
Ed. Philadelphia: Williams & Wilkins, 1997, pp 189–190.)
A a
c' c
b
b'
d
B
c
a b'
c' d
b
C a b' c
c'
b d
Figure 55-14. V-to-Y plasty relaxing incision. A, Make a V-shaped
incision adjacent to the defect with point of the V away from the
D defect. Undermine skin between the defect and incision. B, Closure
of the defect with walking sutures holding the flap in position (broken
Figure 55-13. Z-plasty as a relaxing incision for wound closure. A, lines). C, Closure of the V-shaped incision, beginning at the ends. D,
Make a 60 degree equal-angle, equal-limb-length Z-plasty designed Closure of the stem of the Y. (After Swaim SF, Henderson RA: Small
adjacent to a wound, with the central limb in the direction relaxation Animal Wound Management. 2nd Ed. Philadelphia: Williams &
is needed. B, Z-plasty has been cut. Undermine Z-plasty flaps and adja- Wilkins, 1997, pp 181–182.)
cent skin (arrows indicate Z-plasty flap transposition). C, Closure of
the defect with automatic transposition of Z-plasty flaps. D, Suturing
the Z-plasty flaps into their new positions. (After Swaim SF, Hender-
son RA: Small Animal Wound Management. 2nd Ed. Philadelphia:
Williams & Wilkins, 1997, p 186.)
defect in half with each subsequent suture; this
ensures an even approximation of skin over the
unequal sides of the defect.
defects can be problematic, particularly when
6. Drains to prevent dead space are generally not
they are located on a limb or other location
needed in wounds sutured under tension, especially
lacking abundant adjacent skin for closure. The
if open relaxing incisions have been made.
combined-V closure (Fig. 55-15) is often useful
for such situations. Two V-shaped flaps, with width
and length equal to the radius of the defect, are
Postoperative Care
created as equilateral triangles. The central axis • Bandaging is similar to that for postoperative care of
of the triangles is 45 degrees from the long axis wounds closed without tension. Do not remove
of the wound along the line of greatest skin “walking” sutures and absorbable intradermal con-
tension. The skin flaps are made by incising only tinuous horizontal mattress sutures. Remove vertical
two sides of the triangles, forming two V-shaped mattress tension sutures after 3 to 4 days. Remove
incisions with their points directed towards the “far-near-near-far” and “far-far-near-near” sutures at
long axis of the wound. After the flaps are incised about 10 days. Remove stent sutures after 7 to 10 days,
and undermined, they are transposed and the and remove presutures within 24 hours after their
flap tips are tacked into position. When the flap placement. The adjustable horizontal mattress suture
tip is sutured to the side of the circular defect, the (see Fig. 55-8) may be left in place and tightened
original circular defect is converted into smaller, daily for several days to a week.
irregular fusiform defects. These defects are • Prevent self-mutilation of wounds with an Eliza-
closed with simple interrupted sutures, beginning bethan collar or other device such as a cervical collar
with a suture in the center of the defect to divide (Bite Not Products or Jorgensen Laboratories) or
its length in half and continuing to divide the side braces, as necessary.
W0422-Ch055.qxd 11/12/05 10:39 AM Page 548
45°
Figure 55-15. Combined-V closure of a
circular skin defect. A, Circular defect. B,
V-shaped flaps oriented 45 degrees off
Skin and pointing toward the line of greatest
tension
tension. Flap width (y) equals radius of the
defect (x). C, Arrows showing transposition
of the flaps. D, Flap tips sutured into place,
creating a series of irregular fusiform
X
defects. E, The completed closure. Skin
Y from each V-shaped flap closes half of the
A B C D E original circular defect. Inset, Central sutur-
ing technique. A suture is placed at the
2 center of each defect, subdividing it into
X=Y 1
2 smaller and smaller defects until it is
1 closed. (First sutures = 1, subsequent
2
sutures = 2.) (After Swaim SF, Henderson
RA: Small Animal Wound Management.
2nd Ed. Philadelphia: Williams & Wilkins,
Central 1997, p 266–67.)
suturing
▼ Chapter
56 Management of the Open Wound
David W. Knapp
549
W0422-Ch056.qxd 11/10/05 5:25 PM Page 550
• If active bleeding is encountered, controlling hem- • High-pressure systems (e.g., Water Pik) deliver solutions
orrhage is best accomplished with direct pressure or at pressures near 60 psi. Advantages are their
isolation and ligation of the vessel. Avoid placing ability to dislodge debris and bacteria. A potential
tourniquets, which will result in increased circulatory disadvantage is the possibility of driving bacteria
compromise of an area already suffering decreased into tissues near wound margins resulting in
vascular perfusion. microabscessation.
• Medium-pressure systems deliver solutions at pressures
near 7 to 8 psi, which has been shown to be effective
Clipping and General Cleaning in dislodging foreign material and bacteria without
Protect the wound from loose debris and hair during risk of driving bacteria into the wound. Such a system
the initial preparation and clipping of the adjacent can be developed by using a 35-ml syringe and an 18-
area. Use a sterile water-soluble gel to cover the defect, gauge needle. Systems which combine the syringe
cover with saline moistened surgical sponges, or sterile and needle with a three way stop cock and intra-
towel clamps, sutures, skin staples, or wound clips to venous tubing will speed the process.
provide an economical and efficient temporary closure. • Low-pressure systems are ineffective at dislodging bac-
Clip a generous margin surrounding a truncal wound teria and debris. Such systems include a syringe
or the expected bandaged portion of a limb and scrub without a needle, a bulb syringe, and tap water deliv-
with an antiseptic soap or solution. ered directly from the faucet.
• Removal of lavage solution from the wound by
suction, very light pressure on gauze sponges placed
Cleansing the Wound over the wound, or gravity avoids dilution of opsonins
Lavage Solution necessary for phagocytosis.
The ideal lavage solution is sterile, non-irritating, non-
cytotoxic, normothermic, and isotonic. Of available Debridement
solutions, warmed sterile isotonic saline best meets
these criteria. Lactated ringers solution may also be ▼ Key Point Surgical debridement is the most effec-
used. tive method for removal of dead or devitalized
tissue.
• The use of antibiotic or antiseptic solutions for
wound lavage is controversial. There is evidence for
both beneficial and detrimental effects. Controversy • Inspect and palpate questionable tissues to deter-
exists between in vitro versus in vivo studies and the mine tissue viability. Signs suggestive of non-viable
antibacterial versus the cytotoxic effects of varying tissue include the following:
concentrations of chlorhexidine and povidone- • Black, bluish-black, or a shiny white discoloration
iodine solutions. Use a 0.5% to 1.0% chlorhexidine (especially if there is a distinct demarcation
solution due to its broad-spectrum and extended between abnormal and normal color)
residual activity. • Lack of bleeding at wound margins
• Tap water is an economical alternative to other com- • Texture is leathery to touch or skin is very thin and
monly used sterile solutions, even though it does not no pain sensation is detectable.
meet all criteria for an ideal lavage solution. When • Skin temperature is cool.
large volumes are anticipated, tap water may be the • Hair is easily epilated.
most practical irrigation solution. Due to the hypo- • Other methods of tissue viability determination
tonic nature of distilled or sterile water, their use in include transcutaneous oxygen (PO2), transcuta-
lavage is not recommended. neous carbon dioxide (PCO2), and ultrasonic
• Effective lavage often depends more on the copious Doppler flow detection. The use of intravenous dyes
volume of fluid rather than the contents of the solu- is not a reliable method of evaluation.
tion. The effect of lavage is to loosen and flush away • Reddish discoloration or severe edema is not neces-
from the wound any foreign material, damaged, sarily indicative of non-viable tissue. Such tissue
necrotic or free tissue, wound exudates, and bacteria. should be managed conservatively in the initial treat-
• Do not scrub the wound, which results in increased ment period.
tissue damage due to mechanical trauma. Trauma to • During each surgical debridement it is best to main-
the tissue will result in increased inflammation, tain a conservative approach, leaving critical tissue of
delayed healing, and increased risk of infection. questionable viability while surgically excising only
confirmed non-viable tissue. Resect contaminated or
devascularized fat to decrease the risk of bacterial
Lavage Delivery Systems propagation. Use a scalpel rather than scissors to
Delivery systems are categorized based on pressures at decrease additional trauma to the wound. Preserve
which the lavage solution is applied to the wound. vessels, nerves, and tendons. Remove any devascular-
W0422-Ch056.qxd 11/10/05 5:25 PM Page 552
• Occlusive non-adherent dressings (e.g., Ulcer Dressing, fluid from the wound to dilute the thicker exudates
Johnson & Johnson) do not allow for absorption of resulting in easier transfer into the bandage. Some
wound exudate, and therefore are used in non- delay in epithelialization may be expected.
exudative wounds. Occlusive dressings also prevent • Acemannan acts as a synthetic growth factor, which
gaseous exchange. These dressings are left in place enhances wound healing through its effects on
for longer periods of time, often 2 to 4 days. Disad- macrophages and cytokines.
vantages of occlusive dressings include difficulty in • Bovine collagen has been used to stimulate fibroblast
accessing wound progress due to their nontranspar- ingrowth and deposition of collagen. When placed in
ent nature as well as delaying wound contracture. the wound it creates scaffolding for the patient’s own
• Occlusive dressings speed re-epithelialization of partial- fibroblasts and collagen. It is most effective during
thickness defects. Constituents of occlusive dressings the late inflammatory and early reparative phases of
include polyethylene, polyurethane, hydrocolloids, healing.
and hydrogels. • Tripeptide-copper complex acts as an attractant for
cells such as macrophages, monocytes, and mast cells.
Wound Medications The result is increased wound debridement, release
of additional cytokines, and increased collagen syn-
• Wound management continues to advance as increas- thesis.
ing knowledge of cellular and chemical mediators
within the wound environment are more clearly • Enzymatic debriding agents (Granulex, Elase, Prepa-
defined. The trend toward the use of natural and syn- ration H) function to chemically debride wounds
thetic growth factors is increasing. In addition, prod- through the effects of trypsin, deoxyribonuclease,
ucts used for dressing wounds with additional wound and fibrinolysin and to increase angiogenesis, epithe-
surface interaction and enhancement of healing are lialization and collagen synthesis.
available. • Ointments may leave residual material in or on
the wound surface. Water-soluble creams leave a
▼ Key Point Sugar can be used in open wounds. decreased amount of foreign material at the wound
Granulated sugar draws macrophages into the surface and are preferred.
wound thereby decreasing the need for surgical
debridement; facilitating the formation of a protein Secondary Layer
layer thereby providing additional surface layer
protection; creating a hyperosmotic environment
• The secondary layer of the bandage functions as the
absorptive constituent, drawing fluid away from the
which is bactericidal; providing a local nutritional
wound and then acting as a reservoir for wound
source for the wound; decreasing edema; and pro-
exudate or the absorbed lavage solution.
moting granulation and epithelialization.
• This layer is often composed of cotton pads or layers
• Application of a thin layer of sugar at each bandage of rolled cotton or cast padding.
change is not painful to the patient and easily accom-
plished at little expense. Tertiary Layer
• Honey has also proven successful in the management • The tertiary layer functions to hold the other layers
of open wounds. Principles of its use are similar to of the bandage in place and is a layer of rolled gauze
those of sugar. covered with adhesive tape or self-adherent tape
• Maltodextrin N. F. is a polysaccharide soluble powder, (e.g., Vetwrap, 3M). The more porous the layer, the
which also exhibits many of the same properties of more rapid the evaporation of fluids or drying of the
sugar. deeper layers. Porosity may also allow for transloca-
• Silver sulfadiazine (Silvadene cream) serves to pene- tion of bacteria across the bandage.
trate into the wound and is effective against gram- • Wounds over areas of increased motion or on limbs
negative and gram-positive bacteria and enhances with concurrent orthopedic injuries may require
epithelialization. There is some concern about cyto- splints incorporated into the tertiary layers for
toxicity to fibroblasts and an inhibition to lympho- support or immobilization. Increased motion will
cytes and polymorphonuclear cells. delay wound healing.
• Triple antibiotic ointment is a broad-spectrum treat- • When bandaging thoracic or abdominal wounds,
ment, which may promote epithelialization due to bandages should be snug but not restrictive of
the zinc component. It has little efficacy for treat- normal respiration.
ment of pseudomonads. Its use may be greater for
prevention of infection rather than treatment.
• Gentamicin sulfate is used to inhibit the growth of Tie-Over Bandage
Pseudomonas, Proteus, and E. coli organisms. • If the area of the wound is not amenable to standard
• Nitrofurazone is a broad-spectrum antibacterial in a bandaging techniques (e.g., over the shoulder,
polyethylene base, which promotes removal of body hip, or axilla), a tie-over bandage may be used to
W0422-Ch056.qxd 11/10/05 5:25 PM Page 554
secure the primary and secondary layers to the • In cases where additional skin is recruited with the
wound bed. use of Velcro skin stretchers, the cable portion of the
• To make a tie-over bandage, place six to eight “eyelet” stretcher device can be used in a similar manner as a
sutures around the wound (Fig. 56-1). Place primary tie-over bandage.
and secondary bandage layers over the wound, then
lace umbilical tape through the sutures to hold the
layers of the bandage in place (Figs. 56-2 and 56-3).
Antibiotics
• Antibiotic therapy, whether applied topically or given
systemically as a prophylactic measure, is controver-
sial. If an established local infection exists, topical
therapy is often all that is necessary.
Miller CW: Bandages and drains. In Slatter D (ed): Textbook of Small Swaim SF, Gillette RL: An update on wound medications and dress-
Animal Surgery, 3rd ed. Philadelphia: WB Saunders, 2003, pp ings. Comp Cont Educ Pract Vet 20:1133, 1998.
244–249. Swaim SF: Surgery of Traumatized Skin: Management and Recon-
Pavletic MM: Atlas of Small Animal Reconstructive Surgery. Philadel- struction in the Dog and Cat. Philadelphia: WB Saunders, 1980.
phia: JB Lippincott, 1993. Waldron DR, Pope-Zimmerman N: Superficial skin wounds. In Slatter
Pavletic MM: The integument. In Slatter D (ed): Textbook of Small D (ed): Textbook of Small Animal Surgery, 3rd ed. Philadelphia:
Animal Surgery, 3rd Ed. Philadelphia: WB Saunders, 2003, pp WB Saunders, 2003, pp 259–273.
250–259.
Pope ER: Skin healing. In Bojrab MJ (ed): Disease Mechanisms in
Small Animal Surgery, 2nd ed. Philadelphia: Lea & Febiger, 1993,
pp 151–155.
W0422-Ch057.qxd 11/10/05 5:24 PM Page 557
▼ Chapter
57 Selected Skin Graft and
Reconstructive Techniques
Stephen J. Birchard / Daniel D. Smeak
Large skin wounds can occur (1) from trauma directly • Structures that compose the skin adnexa, hair folli-
to the skin or to its blood supply; (2) secondary to cles, sweat glands, and sebaceous glands are located
necrotizing skin diseases (see Chapter 49); and (3) after in the dermis.
removal of large skin, subcutaneous, or body wall neo- • Besides adnexa, the dermis is composed of fibro-
plasms. Most open wounds eventually heal by the for- blasts, collagen fibers, and various other structures,
mation of granulation tissue, wound contraction, and such as blood vessels, nerves, tissue cells, and fluid.
epithelialization. Skin flaps or grafts are indicated when
wound healing is either not progressing or will take a
very long time for completion. Full-thickness skin is nec-
Subcutaneous Tissue
essary to prevent mechanical problems caused by The subcutaneous tissue is mainly composed of loose
repeated trauma (e.g., in the dorsum of the leg or paw). connective tissue, including elastic fibers, fat, blood
Skin reconstruction is also necessary if the open wound vessels, and nerves.
is so large it will cause significant patient morbidity
or wound contracture is likely to cause a significant Cutaneous Muscles
problem (e.g., the wound is over a joint and the scar
limits full extension and weight-bearing). Skin flaps are • Thin, superficial muscles, collectively called the pan-
usually preferred over skin grafts because they are niculus muscle, lie within the subcutis or hypodermis
simpler to perform and have a higher success rate. (the most superficial aspect of the subcutaneous
However, if a skin flap is not feasible due to lack of adja- layer) in certain body regions in both dogs and cats.
cent skin (such as the distal limb), consider a skin graft. Examples are the platysma muscle in the neck and
Consider several factors before performing skin flaps the cutaneus trunci muscle in the trunk.
or skin grafts, such as viability of adjacent tissue, sys- • Preservation of these muscles during undermining
temic illness that may affect wound healing, function of and flap creation is a very important principle in skin
the affected area of the body, tolerance of the wound reconstruction.
by the animal, feasibility of long-term bandaging of the
affected area, desired cosmetic result, and cost to the Blood Supply to the Skin
owner. Thoroughly discuss these factors with the owner
prior to performing any of these procedures.
• Deep or subdermal plexus
This chapter describes practical methods of recon-
• This plexus is the major source of blood supply to the
skin and of most importance to the surgeon.
structing skin using skin flaps and grafts. More compli-
cated methods of skin grafting that require specialized
▼ Key Point When creating skin flaps in dogs and
skill or equipment, such as using a dermatome for split-
cats, preserve the deep vascular plexus.
thickness skin grafts, microvascular flap transfer, or tube
grafts, are not discussed in this chapter. Primary closure
of skin wounds is reviewed in Chapter 55, and open
• In regions where cutaneous musculature is present,
this vascular network is present on the superficial and
wound management in Chapter 56.
deep layers of the muscle. Dissection beneath this
thin muscle layer is critical to flap survival.
SURGICAL ANATOMY • Direct cutaneous arteries are present in several areas
of the body. They arise from deep vessels that course
superficially and run parallel to the skin. These direct
Skin cutaneous arteries communicate with the deep vas-
The skin is composed of the epidermis and dermis. cular plexus.
557
W0422-Ch057.qxd 11/10/05 5:24 PM Page 558
SKIN FLAPS
Skin flaps are a means of reconstructing open wounds
by rotating, transposing, or advancing adjacent or
regional skin to allow wound closure. Blood vessels sup-
plying these flaps are maintained. Therefore, skin flaps
do not rely on a bed of granulation tissue in the defect
for their early blood supply and nutrition. Skin flaps can
be classified according to their blood supply, such as
random subdermal flaps versus axial pattern flaps, or
according to their location with respect to the recipient
bed, such as local flaps versus distant flaps.
Random Subdermal Flaps Figure 57-1. Simple advancement flap. Make the initial incisions
Random subdermal skin flaps are those constructed (A), then deeply undermine the flap and advance to the defect (B).
without regard to the presence of a direct cutaneous
artery. Viability of these skin flaps is dependent on the
availability of local subdermal blood vessels supplied in
the flap base, so they rely on a wide skin attachment to
insure adequate blood supply. Random subdermal skin
flaps can be further classified as advancement flaps, rota-
tion flaps, and transposition flaps, depending on how the
flap is moved to the defect; single pedicle and bipedicle
flaps, depending on how the flap is attached to the
body; and direct distant flaps, moving an extremity wound
to a distant region of redundant host skin for flap
coverage.
• Advancement refers to how the flap is moved to the
wound. These are usually rectangular flaps. Simple
advancement flaps are undermined and pulled (hor-
izontally or vertically) directly to the wound (Fig.
57-1).
• A transposition flap is a tongue-shaped flap, usually
constructed immediately adjacent to the wound. It is
rotated (clockwise or counterclockwise) to cover the
wound (Fig. 57-2).
• A rotation flap is a semicircular flap that pivots into
an adjacent recipient bed. Single or paired flaps can
be employed to close triangular defects (Fig. 57-3);
no secondary defect is created with this flap. Figure 57-2. Transposition flap. After measuring the length of
flap needed (A), make the incisions and rotate the flap to the defect
• Direct distant flaps include thoracic or abdominal
(B). Suture the flap first and then close the remaining defect (C).
single pedicle or bipedicle flaps that can be used
as a method for transferring skin to the distal
extremities. • Forelimb defects are more often reconstructed
• Single pedicle: Attached to the body only at one using this technique than are rear limb defects.
end (Fig. 57-4A, C). The pedicle provides the vas-
cular attachment to the flap. Indications
• Bipedicle: Attached to the body at both ends (Fig.
57-4B). Advancement, Rotation, and Transposition Flaps
• These flaps are transferred from a distance to the • For large skin wounds that are located in areas with
recipient defect. The lesion is advanced to the flap adjacent loose, redundant skin (e.g., neck, flank,
rather than the flap being transferred to the lesion dorsal trunk) that allows formation and closure of
as in construction of advancement flaps. defects remaining after flap transfer without tension.
W0422-Ch057.qxd 11/10/05 5:24 PM Page 559
B Preoperative Considerations
Figure 57-3. Create a curved incision in a stepwise fashion to close • Carefully plan the surgical procedure. Review vascu-
a triangular wound. lar anatomy of the region. The size, location, shape,
and condition of the wound dictate the type of flap.
• Check the health, looseness, and pliability of the skin
adjacent to the lesion or wound to determine feasi-
bility of the intended skin flap.
• Consider administration of prophylactic antibiotics,
given intravenously at induction of anesthesia, if sig-
nificant contamination of the surgical site is possible.
• Prepare the recipient bed preoperatively to ensure
that the area is free of infection, foreign material, and
necrotic tissue.
• Direct distant flap technique requires two surgical
procedures to complete. The owner is made fully
aware of the costs involved, the postoperative man-
agement, and the problems related to the prolonged
immobilization of the leg. Hair direction and cos-
metic problems are more common with distant tech-
niques than with local flap techniques.
Surgical Procedure
Objectives
Figure 57-4. Direct distant flap. Make the skin flap using the • To provide full-thickness reconstruction of a large
lateral thoracic or abdominal skin. Suture the flap to the limb defect. skin wound.
This flap can have a single (A) or double (B) pedicle. Secure the limb
to the lateral body wall with skin sutures placed between the leg and • To avoid tension along the suture line.
the body wall (C). Place a padded bandage around the body to help • To create flaps that maintain viability and provide
stabilize the elevated limb. satisfactory cosmesis.
W0422-Ch057.qxd 11/10/05 5:24 PM Page 560
Axial
pattern flap
Caudal
superficial
epigastric
artery Thoracodorsal Artery
Defect
Defect
the flap is planned and undermined to preserve the Figure 57-6. Thoracodorsal axial pattern flap reconstruction of a
vascular pedicle. proximal brachial wound. Incisions are created as described in the text.
3. Make incisions to create the flap as shown in Figure Undermine the flap in a dorsal to ventral direction to the level of the
origin of the thoracodorsal pedicle (caudal shoulder depression).
57-6. Direct the cranial incision along the spine of Rotate the flap into the wound and suture the flap to the defect edges.
the scapula. Create the caudal incision parallel to the
cranial incision. This incision line is made behind
the caudal shoulder depression equal to the distance Postoperative Care and Complications
between the scapular spine and the caudal shoulder
depression. The flap margins can be extended safely
All Flap Types
up to the level of the dorsal midline. • Restrict exercise until suture removal.
4. Elevate the flap just below the level of the cutaneous • If necessary, apply an Elizabethan collar as the patient
trunci muscle, beginning at the end of the flap. Be is recovered from anesthesia and leave on the animal
careful to avoid interrupting the thoracodorsal vas- until the flaps are completely healed.
culature, which is often hidden from view in the • Change wound dressings as necessary.
deeper subcutaneous fat. • Immobilize the limb for at least 14 days for direct
5. Pivot the flap into the host bed. Use a bridging inci- distant flap techniques.
sion between the host and donor beds if necessary. • Major complications resulting from skin flaps include
Alternately, tube the flap base to traverse the skin local problems, such as partial or total ischemia of the
interposed between the two areas. flap, infection, seroma, and dehiscence of the flap or
6. Prepare the host wound bed as explained for the donor suture line.
direct distant flap technique. • Carefully pad the elbow if the thoracodorsal (TD) flap
7. Avoid kinking or excess tension at the base of the extends over this area to avoid pressure necrosis over
flap, which could obstruct blood flow from the axial the olecranon.
vasculature. • Dehiscence of donor site incisions is usually due to
8. Use the drainage and closure directions as for the excessive skin tension. If dehiscence occurs, allow
CSE axial pattern flap. these areas to heal by second intention. Excise
W0422-Ch057.qxd 11/10/05 5:24 PM Page 563
ischemic areas of flaps when these areas are clearly wound are desired, consider pinch grafts. If complete
demarcated. Let the wounds heal by second inten- regrowth of hair and excellent cosmesis are neces-
tion, or reconstruct the skin wound after all wound sary, employ a different skin graft method, such as
surfaces are lined with healthy granulation tissue. mesh graft. If the recipient site is over a joint or area
that is frequently traumatized, the more durable full-
thickness grafts may be needed and pinch grafts may
FREE SKIN GRAFTS not be satisfactory.
Free skin grafts involve complete removal of skin from ▼ Key Point Maximize the chances of graft “take”
one area of the body and implantation to another. by properly preparing the wound bed before
These grafts are completely separated from their blood grafting.
supply, so they are solely dependent on the wound bed
for viability in the early stages of graft healing. For the Use standard techniques of wound debridement,
first 3 to 4 days after grafting, the skin graft obtains its lavage, and bandaging (see Chapter 56) for several days
nutrition from the wound bed by diffusion, a process prior to grafting to establish a healthy bed of granula-
called plasmatic imbibition. During this process, the tion tissue. Postpone the graft procedure if any evidence
graft acts like a sponge, soaking up fluid and oxygen of infection is present.
from the granulation tissue of the wound. Imbibition is
a very delicate process that is easily disrupted by exces-
sive movement of the wound, seroma formation, and Surgical Technique
infection. During this initial phase of healing, the graft
usually looks its worst, appearing congested and some- Objectives
times purple. After a few days, this appearance dramat- • To establish epithelial coverage of an open wound.
ically improves if the graft “takes.” • To atraumatically harvest small plugs of skin from an
After the first 3 to 4 days, viability of the graft depends area of healthy redundant skin.
on the growth of capillaries from the wound bed into • To implant these plugs of skin into an area of healthy
the graft (i.e., inosculation). These invading capillary granulation tissue for rapid epithelial coverage.
buds are very fragile structures and are easily damaged
by trauma (such as licking of the graft), excessive shear
Equipment
motion, and infection. Once this blood supply becomes
well established, viability of the graft is maintained. • Same as for skin flaps, plus:
Skin grafts vary in their final cosmetic result. The best • Several #15 scalpel blades
cosmesis is obtained from a full-thickness skin graft, • Skin biopsy punch (optional), size 4 and 5 mm.
because there is growth of hair over the area. However,
full-thickness grafts are the most difficult to establish Technique
because they are thicker than split-thickness grafts. This
greater thickness makes the initial process of imbibition 1. Aseptically prepare the wound bed and the harvest
and inosculation more difficult, resulting in a higher site.
incidence of graft failure. Some authors recommend 2. Gently pick up the skin with thumb forceps or stay
harvesting skin from areas where the skin is thin, such suture and excise a 1-mm piece of skin, using the
as the cranio-ventral aspect of the lateral thorax. Thin #15 scalpel blade. Be careful not to include subcu-
skin grafts are preferred because they are more readily taneous tissue with the skin pinch.
incorporated into the granulation tissue. 3. Alternatively, harvest a punch graft using a 5-mm
skin biopsy punch. Place the punch at the same
Pinch (or Punch) Skin Grafts angle as the hair follicle during harvesting.
4. Trim any subcutaneous tissue found deep to the
When rapid epithelization of a wound is needed, pinch
dermis of the graft plug.
grafts can be effective. Pinch skin grafting is performed
5. Place the skin pinch or punch in a saline-moistened
by simply harvesting small (2–3 mm) sections of full-
surgical sponge.
thickness skin and placing them into the wound gran-
6. Make a “vest pocket” stab incision in the granula-
ulation bed. They are not difficult to perform and are
tion tissue with a #15 scalpel blade (Fig. 57-7).
highly successful. However, the major disadvantage of
7. Slide the skin pinch into the incision in the granu-
pinch grafts is the final cosmetic result. Uniform full-
lation tissue (Fig. 57-7). Be sure the epithelial side
thickness skin does not form over the wound with pinch
of the pinch is facing out.
grafts; therefore, very little hair grows over the area.
8. Repeat this process as many times as necessary to
have skin pinches (punches) covering the wound at
Preoperative Considerations about 1 to 2 cm apart.
• Determine the desired result of the graft. If a high 9. If using a skin punch, use a 4-mm punch to make
degree of success and rapid epithelial coverage of the the hole in the granulation tissue. The slightly
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Preoperative Considerations
• These are the same as those for pinch grafts.
• Consider giving a prophylactic systemic antibiotic
(beginning preoperatively) to help prevent infection
of the graft.
C • Do not perform the procedure if any evidence of
Figure 57-7. Pinch skin graft. (A), Obtain small pinches of skin infection is present in either the donor or recipient
using a scalpel. (B), Make small “vest-pocket” incisions in the granu- sites.
lation bed, and slide skin pinches into these incisions with the
epidermal side facing out. Pinches can be approximately 1 to 2 cm
apart. (C), Wound will be filled in by epidermal growth from the pinch Surgical Procedure
grafts.
Objectives
• To establish epithelial and some full-thickness skin
smaller hole compared to the skin punch will allow coverage of the wound.
a snug fit of the graft in the granulation tissue. • To atraumatically harvest the donor skin from an area
10. Place a non-adherent dressing over the wound. The of redundant skin.
primary layer of the dressing can be petrolatum- • To meticulously prepare the graft for implantation by
impregnated gauze or Telfa pad with a thin layer of removing all subcutaneous fat and creating a mesh by
triple antibiotic ointment (Bacitracin-Neomycin- making multiple small holes in the skin.
Polymyxin, Pharmaderm).
11. Let the donor sites heal by second intention, or Equipment
close them with simple interrupted sutures of 4-0 • Same as for pinch grafts, plus:
nylon. • A sterile board (plastic, wood, or cardboard) for
stretching out and preparing the graft
Postoperative Care and Complications • #11 scalpel blade
• Restrict exercise to leash walking only. Technique
• Change the wound dressing every day for the first 5
to 7 days, then every 2 to 3 days if wound healing is 1. Aseptically prepare the donor and recipient sites.
progressing normally. 2. Estimate the size of the wound by measuring or
• Keep the wound dressed until it is completely covered cutting out a template using sterile drape material.
with epithelium. 3. Sharply excise the donor skin from an area of thin
• If necessary, place an Elizabethan collar on the and redundant skin (e.g., cranial ventral thorax and
animal to prevent damage to the bandage or the lateral flank area).
wound. 4. Avoid excising the subcutaneous tissue.
• Potential complications include dislodgement of the 5. Note the direction of hair growth in the harvested
pinch grafts due to self-trauma or excessive motion skin.
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▼ Chapter
The pinna is a mobile structure designed to localize and • In addition to the pinna, lesions may occur anywhere
collect sound waves and transmit them to the tympanic on the body.
membrane. The pinna has vastly different breed con- • The lesions are quite variable and commonly include
formations in the dog, while in the cat; there is very little erythema, papules, pustules, alopecia, and crusts.
breed variation. The auricular cartilage expands to
form the pinna, with the skin of the concave portion of
the pinna tightly adherent to this cartilage. The carti- Diagnosis
lage of the pinna becomes funnel shaped at the
opening of the external ear canal.
• Tentative diagnosis: Wood’s lamp examination, micro-
scopic examination of the hair (potassium hydroxide
The pinna is a region of the body prone to numer- [KOH] preparation, chlorphenolac), and histo-
ous skin diseases. In most cases, the pinnal lesions are pathology.
associated with lesions on other body areas. There are
a few diseases where lesions are limited to the pinna
• Definitive diagnosis: positive dermatophyte test med-
ium (DTM) culture.
(Table 58-1).
The work-up for all animals with pinnal disease
should include a complete history, general physical Treatment
examination, and dermatologic examination. Next, an
otoscopic examination is performed, as well as micro- • For localized lesions on the ear pinna only, topical ther-
scopic examinations of skin scrapings for mites and apy, such as miconazole (Conofite Lotion, Schering-
fungi, cytology for bacteria and yeast, and mineral oil Plough Animal Health) or clotrimazole (Clotrimazole
swabs for mites (Otodectes cynotis and Demodex spp.). A Solution, Vet Solutions), may be effective.
bacterial culture is indicated if rod bacteria are seen • In generalized conditions where the pinna is not the
cytologically. Further testing may be needed such as a only affected body site, topical rinses with lime sulfur
complete blood count, serum biochemical profile, uri- (LymDyp, DVM Pharmaceuticals) along with systemic
nalysis, allergy testing, food elimination trial, and skin therapy (ketoconazole [generics; Nizoral, Janssen] or
biopsy for histopathology of the ear pinna (see Chapter itraconazole [Sporanox, Janssen]) are necessary for
59 for diagnosis and treatment of otitis externa). resolution.
• Inform owners that this is a zoonotic disease.
▼ Key Point In some cases, the definitive diagnosis of
the pinnal disease is made based on the
histopathological results from the pinnal biopsy. Malassezia Dermatitis (also see Chapter 41)
The biopsy technique of the ear pinna can be diffi- Clinical Signs
cult. For lesions on the margin of the pinna, a wedge • Malassezia pachydermatis may cause a pruritic dermati-
biopsy is preferred, while for central lesions, a small tis and otitis in the dog; cats are less frequently
punch biopsy, size 3.5 to 4 mm, is used to obtain affected.
samples. For additional information on the skin biopsy • In addition, the concave and convex portion of the
technique, please refer to Chapter 37). pinna may be affected.
• Lesions include erythema, alopecia, scale, crusts,
hyperpigmentation, and lichenification.
INFECTIOUS DISEASES
Dermatophytosis (also see Chapter 42) Diagnosis
Clinical Signs • Obtain samples for cytology by skin scrapes, acetate
• The pinna is often affected in dogs and cats with der- tape preparations, swabs, and impression smears.
matophytosis. • The yeast organisms are identified microscopically.
566
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Pinna only
Canine eosinophilic pinnal folliculitis Erythema, papules, crusts
Ear margin seborrhea Scale, fissures
Fly bite dermatitis Ulcers, crusts, erythema, alopecia
Proliferative thrombovascular necrosis of the ear Ulcers, scale, hyperpigmentation
pinnae
Pinna and other body areas
Actinic keratoses Erythema, hyperkeratosis, crusts, hyperpigmented
plaques
Arteriovenous fistula Edema
Atopic dermatitis Erythema
Canine demodicosis Erythema, papules, scale, alopecia, crusts
Canine sarcoptic mange Erythema, papules, crusts, scale, alopecia, excoriations
Contact dermatitis Erythema, macules, papules, erosions, ulcers
Cutaneous adverse food reaction Erythema
Dermatomyositis Alopecia, erythema, scale, crusts, ulcers, scars
Dermatophytosis Erythema, alopecia, papules, pustules, crusts
Discoid lupus erythematosus Alopecia, crusts, ulcers
Feline demodicosis Erythema, papules, scale, alopecia, crusts
Feline sarcoptic mange Erythema, papules, crusts, scale, alopecia, excoriations
Frostbite Ulcers, necrosis
Hereditary lupoid dermatosis of German Scale, crusts
short-haired pointers
Juvenile cellulitis Papules, pustules, crusts
Malassezia pachydermatis Erythema, alopecia, scale, crusts, hyperpigmentation
lichenification
Melanoderma and alopecia in Alopecia, hyperpigmentation
Yorkshire terriers
Pattern baldness Alopecia, hyperpigmentation
Pemphigus erythematosus Erythema, scale, papules, pustules, alopecia, crusts
Pemphigus foliaceus Erythema, scale, papules, pustules, alopecia, crusts
Psoriasiform-lichenoid dermatosis of springer Erythema, hyperpigmentation, plaques, papules
spaniels
Sebaceous adenitis Papules, alopecia, scale, follicular casts
Systemic lupus erythematosus Alopecia, crusts, ulcers
Vasculitis Erythema, alopecia, ulcers, crusts, necrosis
Zinc-responsive dermatosis Erythema, scale, crust, hyperkeratotic plaques
the ipsilateral hind leg) for the diagnosis of sar- Old English sheepdogs, other herding dogs, or their
coptic mange in the dog was found to have a sen- crosses.
sitivity and specificity of 81.8% and 93.8%,
respectively. Feline Demodectic Mange (also see Chapter 43)
• In the absence of identification of the mites, make Clinical Signs
the diagnosis of scabies based on response to therapy. • Demodectic mange in the cat is caused by two mites,
Demodex cati and Demodex gatoi.
Treatment • D. cati is a rare disease.
• In multiple-pet households, treat all other in-contact • The localized form affects the head and neck while
animals. the generalized form affects the head, neck, trunk,
and limbs
• Conventional therapy consists of weekly lime sulfur
dips (LymDyp, DVM Pharmaceuticals) for 6 to 8 weeks. • Lesions consist of erythema, papules, alopecia, scales,
and crusts.
• Selamectin (Revolution, Pfizer Animal Health) is a
novel, semi-synthetic avermectin approved for treat- • Generalized demodicosis is usually associated with
ment of canine sarcoptic mange. an underlying disease (diabetes mellitus, feline
leukemia virus infection, feline immunosuppressive
• Extra-label treatments (see below) for sarcoptic
virus infection).
mange have also been used successfully, including
amitraz dips (Mitaban, Pfizer Animal Health), iver- • Mites have been isolated from skin scrapings of the
mectin (Ivomec 1% injection for cattle and swine, external ear canal.
Merial) (this form and dosage of ivermectin should • Lesions of D. gatoi consist of alopecia, scale, and
not be given to collies, Shetland sheepdogs, Old crusts of the head, neck, and elbows or non-inflam-
English sheepdogs, other herding dogs, or their matory alopecia of the ventral abdomen.
crosses), and milbemycin oxime (Interceptor Flavor • D. gatoi is contagious to other cats.
Tabs, Novartis) (low incidence of side effects in
collies). Diagnosis
• Diagnosis is based on identification of the mites on
Canine Demodectic Mange (also see Chapter 43) skin scrapings, deep scrapings for D. cati, and super-
ficial scrapings for D. gatoi.
Clinical signs
• Demodectic mange in the dog is caused by Demodex Treatment
canis.
• Both the localized and generalized form may affect • Treatment consists of weekly lime sulfur dips
the ear pinna, in addition to other areas of the body. (LymDyp, DVM Pharmaceuticals).
• Lesions of demodicosis in dogs consist of erythema, • For D. gatoi, treat all in-contact cats.
scale, alopecia, papules, pustules, crusts, and sec-
ondary bacterial infections. Stable Fly Dermatitis (Fly Bite Dermatitis)
Clinical Signs
Diagnosis
• Stable flies (Stomoxys calcitrans) are the most frequent
• Make the diagnosis by identifying multiple demo- cause of fly bite dermatitis.
dectic mange mites on deep skin scrapings. • The rasping mouthparts shred the skin while they
feed, which is highly irritating to the dog.
Treatment • The flies usually attack the tips of the ears or the
folded edge of the ear.
• The majority of localized demodicosis cases will • The flies produce small ulcers, which then may ooze
resolve without treatment; however, topical benzoyl blood and result in hemorrhagic crusts.
peroxide (Pyoben Gel, Virbac; OxyDex Gel, DVM • The affected area may also be alopecic and erythe-
Pharmaceuticals) may be used on the alopecic areas. matous.
• In cases of generalized demodicosis, the FDA- • Ulceration, fibrosis, and scarring with deformation of
approved treatment is bi-weekly dips with amitraz the pinna may result if the condition is chronic.
(Mitaban, Pfizer Animal Health). • The lesions may become recurrent due to head
• Extra-label daily high dose ivermectin (Ivomec 1% shaking or scratching by the dog.
injection for cattle and swine, Merial) or milbemycin
oxime (Interceptor Flavor Tabs, Novartis) is effective
in the treatment of generalized demodicosis. As
Diagnosis
stated previously, this form and dosage of ivermectin • Diagnosis is based on clinical signs and a history of
should not be given to collies, Shetland sheepdogs, exposure to stable flies.
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Treatment Diagnosis
• Handle frozen tissues gently and thaw by the appli- • Base diagnosis on history, physical examination, and
cation of warm water. demonstration of the fistula by contrast radiography.
• In severe cases, amputation of the affected part may
be necessary. Treatment
• Delay surgery until a distinction between viable and
• Treatment includes removal of the fistula or amputa-
necrotic tissue can be made. tion of the affected part.
Actinic Keratoses Neoplastic Disease (also see Chapter 28)
Clinical Signs
Clinical Signs
• Actinic (solar) keratoses are caused by excessive • Ears are common sites for skin tumors.
exposure to ultraviolet light.
• The lesions occur on lightly pigmented animals or on • Neoplasms that affect the ear pinnae include squa-
mous cell carcinoma, histiocytomas, mast cell tumors,
areas of the body that have sparse hair coverage (ear
basal cell tumor, sebaceous adenomas, hemangiomas,
pinnae, face, abdomen).
hemangiosarcomas, epitheliotropic lymphoma, and
• Actinic keratoses of the pinna occur rarely in dogs
fibrosarcomas.
and occasionally in white-eared cats in sunny areas of
the world. • Refer to Chapter 28 for a complete discussion of cuta-
neous neoplasia.
• The lesions may be single or multiple.
• Acute lesions consist of poorly defined areas of ery-
thema, hyperkeratosis, and crusting, while chronic
lesions are indurated, crusted, hyperpigmented HEREDITARY DISEASES
plaques.
Pattern Baldness
Diagnosis Clinical Signs
• Base the diagnosis on history, physical examination, • One form of pattern baldness affects the pinna of
and histopathology. male and rarely female Dachshunds.
• Hair loss from the pinna occurs at 6 to 9 months
Treatment of age and slowly progresses to complete pinnal
• Treatment for early lesions is reduction of ultraviolet alopecia.
exposure. • As the alopecia progresses, the skin hyperpigments.
• Actinic keratoses are premalignant lesions capable of • Complete baldness may occur by 8 to 9 years of age.
becoming squamous cell carcinomas. Surgery (pin-
nectomy, cryosurgery, laser surgery) is the treatment Diagnosis
of choice for advanced actinic keratoses or neoplas- • Base the diagnosis of pattern baldness on history,
tic lesions. physical examination, and histopathology.
• Histologically, there is a decrease in size (miniatur-
Arteriovenous Fistula ization) of the hair follicles with normal adnexal
Clinical Signs structures.
• An arteriovenous fistula is a direct communication Treatment
between an artery and vein that bypasses the capillary
circulation. • Studies evaluating melatonin (5 mg PO q24h and
• They are rarely reported in dogs and cats. constant-release implants, 1–3 implants containing
• They may be congenital or acquired, with acquired 12 mg each, SC) as a treatment for pattern baldness
being the more common of the two. have shown it to be effective for hair regrowth.
• Acquired arteriovenous fistulas may result from • Hair regrowth is apparent in 1.5 months after ini-
penetrating wounds, blunt trauma, infection, neo- tiation of therapy, with maximum growth in 3 to 4
plasia, and surgical procedures and mainly affect months.
the paws, neck, temporal region, pinna, legs, flank,
and tongue. Psoriasiform-Lichenoid Dermatosis
• Affected areas are edematous and painful. of English Springer Spaniels
• Superficial blood vessels proximal to the fistula may
Clinical Signs
be distinct and tortuous.
• The fistula is characterized by pulsating vessels, pal- • Psoriasiform-lichenoid dermatosis of English Springer
pable thrills, and continuous murmurs. spaniels is a rare disease.
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Diagnosis Diagnosis
• Diagnosis is made based on history, physical exami- • Base diagnosis on history, physical examination, and
nation, and histopathology. histopathology.
Treatment Treatment
• Dogs respond poorly to treatment. • Zinc supplementation is necessary for treatment of
• Treatments that have been tried include antisebor- Syndrome I. Supplementation is life long.
rheic shampoos, glucocorticoids, fatty acid supple- • Treatment for Syndrome II involves changing to an
mentation, and retinoids. appropriate diet.
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▼ Chapter
59 Otitis Externa
James O. Noxon
The external ear canal consists of skin overlying carti- Predisposing Factors
lage, which provides the structural support to keep the
canal open. The auricular cartilage is the framework for • Predisposing factors facilitate the inflammation by
the pinnae and vertical aspect of the ear canal, and the promoting an environment conducive to survival of
annular cartilage supports the horizontal component of perpetuating factors.
the external ear canal. The cartilage is covered by skin, • Examples include conformation of the ear canal
which contains sebaceous sweat glands, apocrine (ceru- (long canal with a deep vertical component),
minous) glands, and hair follicles. Otitis externa is moisture in the canal (dogs that swim, residual
defined as inflammation of the skin and adnexal struc- cleaning agents in the ear canal), hair in the ears
tures of the ear canal. This condition is one of the most (e.g., in poodles and terriers), breed predisposition
common and frustrating problems encountered in (e.g., Chinese Shar-Pei, stenotic canals), immuno-
small animal practice. deficiency syndromes, endocrine imbalances, iatro-
genic ear trauma (e.g., unnecessary hair removal
▼ Key Point Otitis externa is often a clinical manifes- and cleaning with cotton-tipped applicators),
tation of a generalized dermatologic condition. and obstructive disease (e.g., cancer, polyps, and
hyperplasia).
The cause of otitis externa in a patient is usually mul-
tifactorial especially when chronic and requires a sys- ▼ Key Point Predisposing factors do not initiate otitis
tematic diagnostic and therapeutic plan for resolution externa.
and to prevent recurrence.
Perpetuating Factors
ETIOLOGY AND PATHOGENESIS • Perpetuating factors sustain and aggravate the inflam-
matory process.
Primary Factors • Mechanisms include occlusion of the canal, which
prevents drying or proper application of medication;
• Primary factors are those conditions or disorders that secretion of irritating factors; alterations in pH of the
initiate the inflammatory process within the ear canal.
canal; and formation of a focus of infection (otitis
• Examples include parasites (Otodectes cynotis); allergies media).
(food, atopic dermatitis, contact); foreign bodies
(grass awns, foxtails); keratinization disorders • Examples include bacterial infections (Staphylococcus
intermedius, Proteus mirabilis, Pseudomonas aeruginosa,
(seborrhea); and, less frequently, trauma, autoim-
and Escherichia coli), and yeast infection (Malassezia
mune disease (pemphigus), sebaceous adenitis,
pachydermatis). Otitis media serves as a source of infec-
zinc-responsive dermatoses, and endocrinopathies
tious agents, and chronic hyperplastic changes of the
(hypothyroidism)
ear canal may obstruct the canal.
• Primary factors may initially induce disease outside
the external ear canal. Otitis externa may be an
extension of a pinnal disorder (see Chapter 58), otitis ▼ Key Point Medication may also act as a perpetuat-
media, or otitis interna (see Chapter 61). ing factor (or a primary factor) of otitis externa, by
causing secondary contact irritation or allergy
▼ Key Point Identification and management of the (e.g., neomycin and topical anesthetics), or by
primary factors is the key to long-term control of leaving residue in the canal (e.g., oil-based
otitis externa. preparation).
574
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Other Tests
▼ Key Point Cytology is a rapid, inexpensive diag-
nostic procedure that is indicated in all cases of • Miscellaneous diagnostic tests are helpful to identify
otitis externa. It should be repeated at every predisposing and primary factors. See respective
recheck examination and the results used to chapters for details on these tests. Tests frequently
modify and adjust therapy. Document the extent recommended include hematology, serum biochem-
(or severity) of bacteria and/or yeast for compar- istry profiles, urinalysis, thyroid function tests,
isons at follow-up visits. adrenal function tests, intradermal allergy tests,
serum (in vitro) allergy tests, skin scrapings, fungal
cultures, and dietary trials.
Culture and Susceptibility Testing
• Bacterial culture of the external ear canal is recom- TREATMENT
mended when:
• Cytologic examination of exudate from the exter-
The initial treatment of otitis externa is directed toward
nal ear canal shows a uniform population of gram-
control of the active inflammatory process, because this
negative bacteria (or rod-shaped bacteria if Diff
aspect of the disease is of immediate concern to the
Quick is the stain used).
client and patient. After the perpetuating factors are
• Ulcers are present in the external ear canal and
controlled, treatment is directed toward removing the
bacteria are present on cytologic examination of
underlying predisposing factors and managing the
exudate.
primary etiologic factor.
• A bacterial infection continues to be present (as
Successful long-term management of otitis externa
demonstrated by cytologic examination of smears
requires identification and treatment of perpetuating
from the ear canal) despite appropriate empiric
factors, predisposing factors, and primary etiologic
antimicrobial treatment.
factors.
• Otitis media should also be suspected in animals with
chronic (recurrent or persistent) otitis externa even
when the tympanic membrane is intact. Bacterial
Principles of Medical Treatment
culture of the middle ear (by myringotomy if the tym- • Most commercial ear preparations contain multiple
panic membrane is intact) may be indicated if the therapeutic agents. Select otic preparations carefully
tympanic membrane appears at all abnormal (see for the desired active agents (Table 59-1). Do not use
Chapter 61). products with agents that are not specifically indicated
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*Commercial otic cleansers may include both cleansing and drying agents. Products listed are examples—
many other effective medications are commercially available.
• Topical glucocorticoids are indicated in most cases of phenicol, chlorhexidine, enrofloxacin, iodophors,
otitis externa to reduce inflammation and swelling, propylene glycol, and silver sulfadiazine.
to alleviate pain, and to help minimize fibrosis. • Tris-EDTA alone or added to antimicrobials increases
• Otic glucocorticoid administration may interfere the sensitivity of resistant Pseudomonas spp. to several
with diagnostic procedures, such as intradermal skin antibiotics.
tests, adrenal function tests, thyroid function tests, • Several antibacterial agents, such as ticarcillin (see
and routine hematologic and biochemical tests under “Pseudomonas Infection”), are available in for-
(e.g., serum alkaline phosphatase activity); therefore, mulations for injection and may be formulated as
perform these tests prior to treating with topical glu- topical preparations for specific problems.
cocorticoids if possible. • Other antibiotic preparations, available as otic or
• Use the least potent glucocorticoid necessary to ophthalmic preparations for humans, may be app-
accomplish the desired effect. lied to the external ear canal. Examples include
• Most otic glucocorticoid preparations also contain colistin sulfate (Coly-mycin Otic, Parke-Davis) and
antiparasitic and/or antimicrobial agents. tobramycin (Tobrex Ophthalmic Solution, Alcon).
(EVSCO Pharmaceuticals) or with white vinegar and is indicated as the best therapeutic option (see
water in a 1:2 ratio will reduce yeast populations. Chapter 60).
• If there has been a partial reduction of the hyper-
Pseudomonas Infection plasia, continued prednisone therapy (either at the
same dose or at a reduced q48hr dose) may be
• Pseudomonas infections generally cause ulcers and necessary.
severe pain in the ears and are accompanied by a
• Perform cytology to monitor the type and extent of
mucoid to purulent exudate.
secondary infection.
• Suspected Pseudomonas infections (i.e., if rods are seen
on cytology) should be cultured to obtain a sensi- • Apply a topical glucocorticoid, such as fluocinolone
acetonide (Synotic Otic Solution, Fort Dodge) once
tivity pattern to allow for the best antibacterial
or twice daily to each ear canal. Instill medication as
treatment.
deeply into the canal as possible.
• Topical agents with some efficacy include tobramycin,
gentamicin, enrofloxacin, silver sulfadiazine, and
polymixin B sulfates.
• The effectiveness of topically-applied fluoroqu- PREVENTION
inolones, aminoglycosides, and some other antibi-
otics may be enhanced by co-treating with Tris-EDTA • Use behavioral modification directed toward decreas-
buffered solution (TRIZ-EDTA, DermaPet; T8 Solu- ing activities that predispose the animal to otitis, such
tion, DVM Pharmaceuticals). as swimming and running through the woods and
• Ticarcillin may be applied as a 3% solution (Ticar, fields.
GlaxoSmithKline) twice daily. Dilute the 3.1 gm vial • Use regular medical care to decrease the recurrence
for injection with 100 ml of sterile water for injection, of otitis externa in predisposed patients.
draw up in 1.0 ml aliquots with an additional 0.5 ml • Thoroughly clean and dry ears after swimming.
of air added to each syringe, cap each syringe, then Infuse a topical medication containing an astringent,
freeze. The content of one syringe is applied to each such as boric acid or Burow’s solution, into the ears
ear, after thawing to room temperature, twice daily of patients who swim to help keep the ears dry and
for 25 to 30 days. Reevaluate cytology or a bacterial make the local environment less favorable for bacte-
culture after completion of therapy. rial and yeast infections.
• Systemic antibacterial therapy is indicated when otitis • Regularly clean ears of pets with seborrheic disorders.
media is suspected or when owners are unable to
treat ears topically. The fluoroquinolone antibiotics, ▼ Key Point Remove hair only when indicated by the
especially marbofloxacin (Zenequin, Pfizer), are the patient’s history. Hair clipping or plucking is not
most likely systemic antibiotics to be effective. recommended as part of routine ear care in most
• Give prednisone (1.1 mg/kg, PO, q24h for 5–10 days) animals because the irritation associated with
to reduce pain and inflammation. these procedures may predispose them to otitis
externa.
Hyperplastic Changes
• Hyperplastic changes are seen clinically as lichenifi-
cation and proliferative changes within the external SUPPLEMENTAL READING
canal and on the pinnae. They are perpetuating
factors. August JR: Otitis externa: A disease of multifactorial etiology. Vet Clin
North Am 18:731, 1988.
• Manage bacterial and yeast infections with appropri- Chester DK: Medical management of otitis externa. Vet Clin North
ate medications. Orally administered or parenteral Am 18:799, 1988.
medications may be necessary due to the obstructive Cole LK, Kwochka KW, Kowalski JJ, Hillier A: Microbial flora and
nature of hyperplastic changes. antimicrobial susceptibility patterns of isolated pathogens from the
• Give prednisone (1.1–2.2 mg/kg, q24h for 14 days) horizontal ear canal and middle ear in dogs with otitis media. J Am
Vet Med Assoc 212:534, 1998.
then reevaluate the ears: Macy DW: Diseases of the ear. In Ettinger SJ (ed): Textbook of Veterinary
• If there has been no reduction in the degree of Internal Medicine. Philadelphia: WB Saunders, 1989, p 246.
hyperplasia, surgery (e.g., total ear canal ablation) Wilke JR: Otopharmacology. Vet Clin North Am 18:783, 1988.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 582
▼ Chapter
External ear canal surgery is performed to provide tions. Inflammatory polyps extending into the
exposure and drainage for the vertical and horizontal external ear canal from the tympanic cavity usually
ear canal or to remove irreversibly infected tissue or do not require external ear surgery for removal.
neoplasia. Procedures for the external ear canal include See middle ear surgery (see Chapter 62) for further
lateral ear canal resection, vertical ear canal ablation, information.
and total ear canal ablation. Drainage of auricular
hematoma is the most common surgical procedure of
the pinna; this is discussed later in this chapter. ANATOMY
Success of ear surgery relies on the following:
• An accurate diagnosis A clear understanding of ear anatomy and related struc-
• An appreciation of the severity and extent of the tures is critical to uncomplicated ear surgery. The
disease surgeon must identify and preserve several key struc-
• Correct choice and technical execution of the tures, especially during horizontal canal dissection.
procedure
• Appropriate postoperative medical treatment of the External Ear Canal
local disease and any underlying primary skin disor-
der (see Chapter 59) • The normal external ear canal (Figs. 60-1 and 60-2)
is a 5- to 10-cm–long pliable cartilaginous tube lined
▼ Key Point As a general rule, surgical intervention is by glandular epithelium, extending from the base of
considered when appropriate medical treatment the pinna to the tympanic membrane.
for otitis externa fails, or when medical treatment
is not expected to be successful. Vertical Ear Canal
• From the external opening (aditus), the vertical
As ear disease progresses, more extensive surgery is canal (auricular cartilage) runs ventrally and slightly
often required to relieve clinical signs. Risk of compli- rostrally, before bending toward the skull to form the
cations, however, also increases as the surgery becomes shorter horizontal canal.
more extensive.
Horizontal Ear Canal
GENERAL SURGICAL INDICATIONS • The horizontal canal consists of a circular (annular)
cartilage extending from the ligamentous attachment
• For ear disease that fails to respond to appropriate to the auricular cartilage medially to the short
medical treatment osseous ear canal (projection of the petrous tempo-
• For relapse of clinical signs after initial response to ral bone). The canal ends at the tympanic mem-
medical therapy brane.
• For extensive irreversible changes of cartilage and/or
epithelium Important Local Structures
• For certain predisposing factors causing the ear con-
Salivary Glands (Fig. 60-2B)
dition (congenital or acquired malformation, steno-
sis or atresia of the ear canal, or neoplasia) • The V-shaped parotid salivary gland overlays the
ventrolateral aspect of the vertical ear canal and
▼ Key Point External ear surgery rarely is indicated in extends ventral to the distal aspect of the horizontal
the cat except for traumatic or neoplastic condi- ear canal.
582
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Tubercle of antihelix
Tragohelicine
Tragus
incisure
Antitragus
Helix Intertragic notch
Antihelix Tragus
Blood Vessels (Fig. 60-2B) gical treatment of the external ear disease (see Chapter
62).
• Blood supply to the ear is via the great auricular The ear canal is difficult to prepare aseptically,
artery, arising from the external carotid artery and contamination is inevitable during surgery; so
located medial to the parotid gland and ventral to the antibiotics should be given during the procedure.
osseous bulla. Administer a broad-spectrum, bactericidal, intrave-
• Small branches of the great auricular and maxillary nous (IV) antibiotic (optimally based on preoperative
arteries run dorsally, parallel to the long axis of the culture and susceptibility) before and during surgery so
pinna, and medial to the pinna cartilage. that adequate levels are maintained in tissues during
dissection.
Nerves (Fig. 60-2B)
• The facial nerve arises from the stylomastoid foramen Ear Palpation
located just caudodorsal to the osseous ear canal. Carefully palpate the ear canal and surrounding struc-
• The nerve is closely associated with the caudal aspect tures and determine the degree of pain elicited and if
of the horizontal ear canal shortly after it exits the there is evidence of end-stage disease.
foramen, and courses directly under the horizontal
ear canal.
• Sharp pain elicited on deep palpation of the external
ear canal usually indicates concurrent middle ear
• Terminal branches of the facial and auriculotempo-
infection.
ral branch of the mandibular portion of the trigemi-
nal nerve are located just rostral to the ear canal.
• Palpation of severely thickened and firm ear canal
tissue indicates that irreversible changes have
occurred.
Vertical canal mine whether the walls of the canal have undergone
irreversible calcification.
Otoscopic Examination
Great auricular
• Perform a thorough ear cleansing after obtaining the
appropriate diagnostic specimens for culture and sus-
artery
ceptibility, cytology, and biopsy (see Chapter 59).
• Otoscopic examination is the most important diag-
nostic modality to evaluate the severity and extent of
disease and tympanic membrane rupture.
Parotid gland
Auriculotemporal ▼ Key Point Otoscopic examination usually requires
Facial nerve
(VII) nerve (V) general anesthesia to completely assess the entire
B ear canal and tympanum.
Figure 60-2. Important anatomic structures of the external ear
canal. A, Transverse section of the head showing ear canal regions and Staging of Neoplastic Disease
middle ear and inner ear structures. B, Location of branches of the
external carotid artery in relation to the ear canal and middle ear, • Perform regional lymph node aspiration, cytology,
and important neural structures in the external ear canal region. biopsy, and thoracic radiography if neoplasia is sus-
pected in the underlying ear disease.
Neurologic Examination
• Perform a neurologic examination, especially in LATERAL EAR CANAL RESECTION—ZEPPS
chronic cases of otitis externa, to evaluate for facial MODIFICATION (LECR)
nerve involvement (e.g., hemifacial spasm and slow
or absent palpebral reflex) and involvement of inner Surgical Procedure
ear structures (e.g., nystagmus and circling).
Objectives
• Evaluate the patient’s ability to hear and alert the
owner to any problems before contemplating bilat- • To expose the medial portion of the vertical canal
eral ear canal ablation. and horizontal ear canal. Exposure enhances medical
treatment of otitis externa and changes local ear con-
Radiographic Examination ditions favoring drainage. Ventilation of the area
improves the local environment by decreasing mois-
Perform any imaging tests before otoscopic examina-
ture, humidity, and temperature in the ear canal.
tion because irrigation fluid entering the bulla through
a damaged tympanic membrane could be misinter- • To resect the lateral portion of the vertical ear canal
to remove tumors or to relieve congenital or acquired
preted as middle ear disease.
non-proliferative vertical canal stenosis that is restrict-
• Ventrodorsal skull radiograph is the view of choice to ing ear drainage and interfering with medical
evaluate horizontal canal diameter and to help deter- treatment.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 585
Location of
horizontal
A canal
D G
Figure 60-3. Lateral ear canal resection technique. A, Two skin incisions are extended parallel to each other from the intertragic notch
and tragohelicine notch, tapering down to a distance of 1.5 to 2 cm between the incisions, about 1.5 to 2.5 cm (depending on the size of
the animal) ventral to the horizontal ear canal. A transverse incision joins the two vertical incisions. Undermine the skin flap dorsally up to the
margin of the aditus. B, Incise through the subcutaneous tissue to the level of the vertical ear cartilage. Expose the entire lateral aspect of the
vertical ear canal by blunt and sharp dissection of the subcutaneous tissue in a rostral and caudal direction and parotid gland ventrally. C, Place
an Allis tissue forceps on the tragus, and apply dorsal traction so that the vertical ear canal can be seen from the dorsal aspect of the head.
With serrated scissors, make two incisions through the vertical ear canal on the rostrolateral and caudolateral margins while maintaining dorsal
traction. Extend the rostral and caudal incisions ventrally in an alternating fashion until the floor of the horizontal canal is reached. The ver-
tical canal essentially is divided into lateral and medial halves. D, Extend incisions medially toward the head until the horizontal canal is fully
exposed after the lateral wall is reflected ventrally. The base of the lateral wall flap should approximate the width of the horizontal canal. More
cartilage can be removed from the remaining ear canal as necessary to fully expose the remaining vertical canal. Manipulate the flap rostrally
and caudally until the horizontal canal is held open as wide as possible. E, Remove the skin flap and all but the proximal portion of the lateral
wall. The 1.5- to 2-cm cartilage (drain board) flap remaining is modified to lie flat and fit the skin defect ventral to the horizontal ear canal.
F, Begin closure by placing simple interrupted 3-0 to 4-0 monofilament nonabsorbable sutures from the caudal and rostral margins of the most
proximal aspect of the drain board to the skin. Throughout closure, place sutures through ear canal epithelium and cartilage first and then
to skin to aid in skin coverage of cartilage. G, Appose the remaining portion of the flap to the skin with simple interrupted sutures so that the
flap is flat against the head. Place additional sutures so that the skin and ear canal epithelium edges are apposed but not crushed.
the ear region, including the pinna, is exposed and If chronic hyperplastic tissue is present in the verti-
all anatomic relationships are identifiable. cal canal, it usually extends into the horizontal canal.
2. Use forceps to determine vertical canal depth and Therefore this procedure is not commonly indicated,
position of the horizontal canal. but VECA may be an alternative method for those
3. Incise the lateral portion of the vertical ear canal patients requiring LECR. As with LECR, hearing is pre-
and reflect ventrally. served, but more diseased ear canal tissue is removed,
4. Preserve the proximal portion of the lateral canal reducing the need for extensive ear cleaning except at
flap for a “drain board.” the opening of the horizontal ear canal. Some clinicians
5. Begin closure at the base of the flap; then appose the believe that VECA may be performed in dogs with end-
distal flap to the skin. Appose the remaining ear stage inflammatory ear disease. Owners need to be
epithelium and skin so that no cartilage is exposed. aware that clinical signs may improve, but continued ear
cleaning and antimicrobial therapy may be necessary
Postoperative Care and Complications long after surgery.
Prognosis
VERTICAL EAR CANAL ABLATION (VECA) Prognosis is good provided the procedure is performed
for the correct indications. In a large retrospective study
This technique combines some of the advantages of the of 75 dogs undergoing VECA, 72 were asymptomatic
LECR (maintenance of horizontal canal drainage) and within 12 weeks postoperatively.
total ear canal ablation (removal of chronically infected
vertical canal tissue). VECA is a less complicated pro-
cedure than total ear canal ablation (TECA); however,
surgical treatment of concurrent chronic middle ear TOTAL EAR CANAL ABLATION (TECA)
disease must be made through a separate ventral bulla
approach (see Chapter 62). Total ear canal ablation is a salvage procedure that
involves removal of the entire vertical and horizontal
▼ Key Point VECA is contraindicated if irreversible ear canal cartilage and epithelium. If severe horizontal
hyperplastic thickening or neoplasia is present in canal disease is present, only TECA is successful in elim-
the horizontal canal. inating the associated clinical signs.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 587
Incision
D
A C
E
F
Figure 60-4. Vertical ear canal ablation technique. Begin with T-shaped skin incision over the ear canal. A, Continue blunt dissection medi-
ally until the entire vertical canal is isolated and freed up. Dissect just underneath the cartilage to avoid damaging vascular supply to the pinna.
B, Cut the auricular cartilage with heavy straight Mayo scissors, removing all affected tissue on the dorsal aspect of the medial vertical canal
and pinna. This step allows complete mobilization of the vertical canal, which remains attached only at its proximal aspect. C, Remove the ver-
tical canal approximately 1 to 2 cm distal to the annular cartilage junction. D, Incise remaining vertical canal rostrally and caudally, if neces-
sary, to fully expose the horizontal ear canal. E, Suture the ventral flap to the skin in a fashion similar to that in lateral ear resection. F, Suture
the dorsal flap to appose the cut edges of the canal and skin with simple interrupted 3-0 to 4-0 monofilament nonabsorbable material. Remain-
ing skin is apposed to form a T-shaped closure.
▼ Key Point Neglected chronic otitis externa results • Irreversible hyperplastic and proliferative ear disease
in extensive chronic inflammatory changes in peri-
or neoplasia extending into the horizontal canal.
annular tissue. These greatly increase the risk of • Persistent otitis externa after LECR or VECA. If signs
iatrogenic complications associated with difficult
stem from middle ear infection, drainage of the
ear canal dissection.
middle ear is all that may be required, provided the
horizontal ear canal is not affected irreversibly.
fentanyl patch (Duragesic, Janssen, Titusville, New 8. Carefully dissect the nerve out along its course adja-
Jersey) 12 hours before the procedure ensures that cent to the horizontal canal.
serum levels of the analgesic will be at therapeutic 9. In some patients with chronic proliferative otitis
levels before the procedure. Local nerve blocks or con- externa, a greenish-brown epithelial pouch forms
stant local anesthetic infusion devices can be used between the tympanic bulla and the annular carti-
successfully through the early postoperative period. lage. This epithelium extends lateral and ventral to
Supplemental systemic narcotics are also commonly the tympanic bulla. Removal of this tissue is critical
used to treat breakthrough pain postoperatively (see to the success of the surgery because chronic fistu-
Chapter 6). lation occurs if it is not removed fully. Use hemo-
static forceps to grasp the edges of the pouch and,
with traction, bluntly dissect the pouch out without
Surgical Procedure injuring major local vessels and nerves.
Objectives 10. Sharply amputate the annular cartilage from the
petrous temporal bone, excise the ear canal, and
• To remove the entire external ear canal without submit it for biopsy.
trauma to the facial nerve.
11. Carefully remove the secretory epithelial lining of
• To provide access to the tympanic bulla to observe the short osseous external auditory canal by curet-
and treat infection or other disease.
tage. Submit this lining for culture and susceptibility.
12. Examine the middle ear for exudates and chronic
Equipment thickened epithelium.
13. Routinely remove the ventral and lateral aspect of
• Standard general surgical pack and suture
the bulla with rongeurs (see Chapter 62).
• Gelpi or Weitlaner self-retaining retractors
14. Remove all epithelium and debris in the tympanic
• Senn retractors
cavity with irrigation and curettage.
• Heavy serrated Mayo scissors
15. Avoid inner ear structures on the craniodorsal
• Suction apparatus and Frazier suction tip
aspect of the tympanic cavity during curettage.
• Electrocoagulation unit and sterile electrode
16. If massive contamination has occurred during
• Lempert and Cleveland bone rongeurs
surgery, or signs of periauricular inflammation are
• Straight Simon and Daubenspeck curettes
present after the ear canal is removed, place a
1
• /4-inch Penrose drains (surgeon preference)
Penrose drain within the dead space remaining
where the ear canal was removed, exiting ventral to
Technique (Fig. 60-5) the T-shaped incision. Place a percutaneous suture
1. Use the same positioning, skin preparation, and through the dorsal end of the Penrose tube to
draping as for LECR. prevent premature dislodgement.
2. Lavage the ear canal repeatedly with iodinated anti- 17. Place subcutaneous and skin sutures to form a T-
septic solution to remove as much debris and con- shaped wound.
tamination as possible.
3. Administer appropriate prophylactic IV antibiotics
Postoperative Care
(preferably based on culture and susceptibility • Examine the wound for evidence of fluid accumula-
results) and maintain appropriate blood levels tion or ensuing infection.
during the surgery. Fluoroquinolone and ampicillin • If a Penrose drain is used, rebandage daily until
+ sulbactam (Unisyn) are appropriate antibiotics if drainage ceases.
no culture is available. Continue antibiotic admin- • Place an Elizabethan collar to prevent self-inflicted
istration until intraoperative culture results are trauma to the wound until suture removal.
available; revise the regimen if necessary. • If acute postoperative infection occurs, open the
4. Make a T-shaped skin incision to expose the ear wound for drainage. Flush and bandage the open
canal. wound daily.
5. Reflect loose connective tissue from the vertical ear • Administer systemic antibiotics based on susceptibil-
canal. ity testing for a minimum of 3 to 4 weeks, if otitis
6. Isolate the vertical and horizontal canal by blunt media is present (see Chapter 61).
and sharp dissection. Maintain dissection immedi- • If facial nerve injury has occurred, place eye lubri-
ately adjacent to the ear canal cartilage. Occasion- cants (e.g., Hypotears, Cibavision) in the affected eye
ally, the facial nerve is found embedded in the q6h, especially if the dog has decreased tear produc-
annular cartilage. tion or has an exophthalmic conformation.
7. Careful dissection along the caudal aspect of the • Remove skin sutures in 14 days.
proximal horizontal ear canal isolates the origin of • Remove Penrose tubes when drainage has decreased
the nerve. significantly. Generally, this is in 2 to 3 days.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 589
Area to be
removed
(in red)
Dotted lines
indicate
extent of
dissection
B C
Figure 60-5. Total ear canal ablation technique. Make a horizontal incision parallel and just below the upper edge of the tragus between
the tragohelicine and intertragic notches (also see Fig. 60-4B inset). Make a vertical incision perpendicular from the midpoint of the horizontal
incision to a point just ventral to the horizontal canal, forming a T-shaped incision. The two triangular skin flaps are undermined and retracted,
exposing the lateral aspect of the ear canal. After hemostasis is achieved, bluntly dissect the proximal aspect of the vertical canal free from the
surrounding tissues, avoiding the auricular vessels located medial to the canal (A). Use heavy serrated Mayo scissors to cut the medial aspect of
the proximal vertical ear canal connecting the ends of the original horizontal incision. Retention of as much of the normal medial vertical
canal as possible encourages ear support in cats and dogs with erect ears (see Fig. 60-4B). The parotid gland is retracted ventrally. By a
combination of blunt and sharp dissection, isolate the horizontal canal to the level of the tympanic bulla. While maintaining meticulous hemo-
stasis, dissection continues as close to the cartilage as possible, carefully exposing and retracting the facial nerve away from the line of dissec-
tion. Excise the ear canal and remove epithelium from osseous ear canal. B, Transverse section of head shows common location of epithelial
pouch between annular cartilage and petrous temporal bone. All epithelium must be removed to avoid chronic fistulation after surgery. If otitis
media is present, an aggressive lateral bulla osteotomy is performed to expose the bulla for curettage and to improve ventral drainage. Cross-
hatching indicates area of resection of the lateral and ventral osseous bulla. Be sure all exudate and abnormal tissue are moved from the tym-
panic cavity. A Penrose drain is shown exiting ventral to the skin incision. C, Completed ear ablation showing placement of drain and skin
closure.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 590
hematomas because it allows for thorough debride- 8. Place the remaining mattress sutures in a staggered
ment of organized clots. fashion 1 cm apart until the entire dead space area is
• A more cosmetic and less time-consuming technique obliterated.
is the drainage-only procedure. Use this technique 9. Tie sutures with just enough tension to appose
only in hematomas with fluid consistency (acute cartilage surfaces. Do not crush skin.
cases) and, preferably, those located toward the distal
aspect of the pinna. Owners must understand that
recurrence develops more often with drainage only Alternative Technique Using Biopsy
compared with incision and suture. Punch and Suture (Fig. 60-6)
• Simple aspiration alone is not the best option 1. For acute hematomas, this technique creates a cos-
because of a high rate of hematoma recurrence. metic result with minimal recurrence problems.
• A CO2 laser has been used successfully to create mul- 2. Prepare pinna for surgery as described for incision
tiple small incisions into the hematoma for drainage and drainage technique.
and to allow for evacuation of blood, similar to the 3. Punch staggered holes over hematoma on concave
punch technique. pinna surface. Avoid creating holes any closer than
1 cm from the ear margin.
Surgical Procedure 4. Tack skin adjacent to punch holes to underlying
cartilage.
Objectives 5. Bandaging after the first postoperative day usually is
• To treat the source of irritation. not necessary.
• To drain the hematoma.
• To maintain apposition of cartilage surfaces for an Drainage Only
adequate time to prevent recurrence.
1. Aseptically prepare the skin on the concave surface
of the pinna only. It is not necessary to clip the
Equipment convex, haired surface (unless the patient is long-
• Standard general instrument pack haired) because this creates more inflammation,
• Penrose drain, 1/4 inch (if drain-only technique is which could lead to continual head shaking or
planned) scratching. Place 4 ¥ 4 sponges in the ear canal to
• Skin biopsy punch (3.5 or 5 mm) for alternative soak up blood from the hematoma.
punch technique 2. Make a small (0.5–1-cm) incision extending into the
hematoma at its most proximal and distal extent on
the pinna.
Technique 3. Remove all fluid and fibrin tags with mosquito
hemostats and digital expression.
Incision, Drainage, and Bandage 4. Place a drain (1/4-inch Penrose or sterilized IV exten-
1. Clip both sides of the pinna and prepare the ear for sion tubing) through the dead space and exiting
aseptic surgery. Place sterile 4 ¥ 4 sponges in the ear both stab wounds.
canal to soak up blood from the hematoma. 5. Suture the drain to the skin near the stab incisions
2. Incise the hematoma with a #10 blade in a linear with a loose nonabsorbable suture.
fashion on the concave side no closer than 1 cm from
the margin of the pinna.
3. Make this incision along the long axis of the pinna
Postoperative Care and Complications
extending the length of the hematoma. Removal of • After treatment of the hematoma by the incision
a strip of skin to widen the incision and permit method, bandage the affected ear over the top of the
drainage is not usually necessary. head in pendulous-eared dogs. Bandage erect ears in
4. Explore the hematoma and remove any fibrin tags an upright position.
or blood clots. • Leave the ear canal exposed in each method to
5. Place 1-cm–wide mattress sutures (3-0 or 4-0 monofil- permit cleansing and medication as needed.
ament nonabsorbable material) parallel to and no • Leave the bandages on for at least 10 days and change
closer than 0.5 cm from the incision. as needed.
6. Hold the incised edges of the skin 2 to 3 mm apart • Remove sutures in 3 weeks (incision or punch
when placing the first row of sutures. Sutures need method).
not penetrate both skin surfaces because this creates • If aspiration of the hematoma is elected, remove reac-
another source of irritation and entry way for cumulating fluid daily with a 20-gauge needle, and a
contamination. tapering anti-inflammatory dose of prednisone is
7. Pass the needle carefully from the concave surface of given for 7 to 14 days to reduce head shaking from
the pinna, catching both cartilage planes. otic irritation.
W0422-Ch060.qxd 11/10/05 5:30 PM Page 592
Skin
Perichondrium
Cartilage Figure 60-6. Concave surface of the
Subcutaneous tissue pinna. Shaded area indicates hematoma
Skin location. Create staggered (3.5- or 5-mm)
A punch biopsies approximately 1 to 1.5 cm
apart over the hematoma. Use 4-0 fila-
ment nonabsorbable sutures to tack
through each punch into underlying car-
tilage to adjacent skin edge for dead
space obliteration.
Skin
Perichondrium
Cartilage
Subcutaneous tissue
Skin
Skin
Perichondrium
Cartilage
B Subcutaneous tissue
• No bandages are used after the first day for the Beckman SL, Henry WB, Cechner P: Total ear canal ablation com-
bining bulla osteotomy and curettage in dogs with chronic otitis
drainage-only method or punch method unless the externa and media. J Am Vet Med Assoc 196:84, 1990.
patient continues violent or persistent head shaking. Dye T, Teague HD, Ostwald DA, Ferreira SD: Evaluation of a tech-
• Use an Elizabethan collar to reduce the incidence of nique using carbon dioxide laser for the treatment of aural
self-trauma in all cases. hematomas. J Am Anim Hosp Assoc 38:385, 2002.
Gregory CR, Vasseur PB: Clinical results of lateral ear canal resection
• Leave drains in place for 3 weeks.
in dogs. J Am Vet Med Assoc 182:1087, 1983.
• Instruct the owners to watch for signs of infection and Harvey CE: Ear canal disease in the dog. J Am Vet Med Assoc 177:136,
to milk out any fluid (drain technique only) that may 1980.
accumulate within the hematoma during this time. Joyce JA, Day MJ: Immunopathogenesis of canine aural hematoma. J
• Instruct the owners about the proper treatment of Small Anim Prac 38:152, 1997.
Krahwinkel DJ: External ear canal. In: Slatter DH (ed): Textbook of
the primary source of the ear irritation. Small Animal Surgery, 2nd ed. Philadelphia: WB Saunders, 1993,
• The appearance of the ear after surgery is related to p 1560.
the drainage technique and to the chronicity of Krahwinkel DJ, Pardo AD, Sims MH, Bubb WJ: Effect of total ablation
the hematoma. Inadequate drainage or continued of the external acoustic meatus and bulla osteotomy on auditory
inflammation results in a permanently thickened function in dogs. J Am Vet Med Assoc 202:949, 1993.
Siemering GH: Resection of the vertical ear canal for treatment of
pinna. chronic otitis externa. J Am Anim Hosp Assoc 16:753, 1980.
• Make no guarantees to the owners regarding the final Smeak DD: Total Ear Canal Ablation. In Bojrab MJ (ed): Current
cosmetic appearance of the ear and the impossibility Techniques in Small Animal Surgery. Philadelphia: Lea & Febiger,
of recurrence, because these are often unpredictable. 1990, p 140.
Smeak DD, Crocker CB, Birchard SJ: Treatment of recurrent otitis
• Reevaluate the patient weekly after drainage to deter- media that developed after total ear canal ablation and lateral bulla
mine the response to primary treatment and any osteotomy in dogs: Nine cases (1986–1994). J Am Vet Med Assoc
problem related to wound management. 209:937, 1996.
Smeak DD, DeHoff WD: Total ear canal ablation. Clinical results in
the dog and cat. Vet Surg 15:161, 1986.
Sylvestre AM: Potential factors affecting the outcome of dogs with a
SUPPLEMENTAL READING resection of the lateral wall of the vertical ear canal. Can Vet J
39:157, 1998.
Bacon NJ, Gilbert RL, White RA: Total ear canal ablation in the cat: Wooley RE, Jones MS, Gilbert JP, Shotts EB: In vitro action of combi-
indications, morbidity, and long-term survival. J Small Anim Prac nations of antimicrobial agents and EDTA-tromethamine on
44:430, 2003. Pseudomonas aeruginosa. Am J Vet Res 44:1521, 1983.
W0422-Ch061.qxd 11/10/05 5:29 PM Page 593
▼ Chapter
61 Otitis Media and Otitis Interna
Lynette K. Cole
Otitis media: Otitis media is defined as inflammation of with ear forceps or a suction catheter. Removal of the
the middle ear and is an important perpetuating mucous plug and flushing the middle ear had to be
cause of recurrent otitis externa. repeated up to five times for resolution.
• Otitis media occurs as a direct extension from an • Neoplasia and polyps can cause otitis media. Tumors
existing otitis externa through a ruptured tympanic present in both the ear canal and tympanic bulla can
membrane. be malignant. Inflammatory polyps are common in
the cat, whereas they are relatively uncommon in the
▼ Key Point The presence of an intact tympanic dog.
membrane does not rule out otitis media since the • Otoliths (mineral opacities) of the middle ear have
defect in the membrane may have healed. been reported in three dogs; however, their signifi-
cance is unknown, since only one dog had clinical
• In a recent study, 72.5% of the ears in dogs with
signs of vestibular disease.
otitis media diagnosed by a myringotomy had an
intact tympanic membrane. • Cholesteatomas are abnormal growths of the epithe-
lium within the middle ear consisting of keratinizing
• Less common routes include extension through
stratified squamous epithelium, inflammatory cells,
the eustachian tube or hematogenous dissemina-
and ceruminous debris. These may occur congeni-
tion.
tally or secondary to chronic otitis media and require
Otitis interna: Otitis interna is defined as inflammation surgical removal.
of the inner ear structures, which include the • Other causes of otitis media include trauma and
cochlea, vestibule, and semicircular canal. Otitis foreign bodies.
interna usually occurs as a direct extension from an • Otitis media may lead to otitis interna.
existing otitis media. • Otitis media is uncommon in cats.
593
W0422-Ch061.qxd 11/10/05 5:29 PM Page 594
• Keratoconjunctivitis sicca (KCS) may occur if the • Perform a thorough physical examination and include
parasympathetic nerves that innervate the tear gland the lymph nodes, oral cavity, and nasopharyngeal
are injured. The parasympathetic nerve fibers course region.
with the facial nerve. Tear production can be evalu- • Perform a neurologic examination to evaluate for signs
ated with the Schirmer tear test. of facial nerve paralysis or Horner’s syndrome, which
would be consistent with otitis media, as well as nys-
▼ Key Point Otitis media is uncommon in dogs with tagmus and vestibular disease, which would support
acute otitis externa; however, it is quite common otitis interna.
in dogs with chronic, recurrent otitis externa, with
an incidence of 50% to 88.9%.
▼ Key Point Peripheral vestibular signs, which occur
in otitis interna, must be differentiated from central
Otitis Interna vestibular signs, which occur with diseases of the
• Signs of otitis interna are those typically associated brain stem.
with peripheral vestibular syndrome and include a
head tilt, circling, falling, or rolling toward the ▼ Key Point The absence of neurologic signs does
affected side; horizontal or rotary nystagmus with the not rule out the possibility of otitis media and otitis
fast phase away from the affected side; and asymmet- interna.
ric ataxia with strength preserved (Table 61-1).
• Perform an otoscopic examination to evaluate the exter-
nal ear canal and tympanic membrane. The exami-
DIAGNOSIS nation is performed with a hand-held otoscope or
video otoscope (see under Video Otoscopy, follow-
History ing). Palpate the external ear canals to determine if
• Obtain a thorough history in order to establish the there is any calcification indicating chronic disease.
age of onset, duration of clinical signs, and the extent
of the involvement of the skin (such as pruritus), ▼ Key Point In cases of chronic otitis externa, an oto-
to be able to identify the primary underlying derma- scopic examination on initial presentation may not
tologic disease. See Chapter 59 for details on the be possible, due to ulcerations, hyperplasia, or
primary underlying diseases causing otitis externa. stenosis. Two to three weeks of topical and sys-
• Identify past treatment protocols and response to temic glucocorticoids are often necessary in order
therapy to help guide decisions for future treatments. to be able to perform an otoscopic examination.
Table 61-1. VESTIBULAR SIGNS ASSOCIATED WITH INNER EAR VS. BRAIN STEM LOCATIONS
Sign Inner Ear Brain Stem
Ultrasonography Myringotomy
• An ultrasonographic technique has been described • If the tympanic membrane is intact, appears abnor-
to differentiate between gas and fluid in the bulla of mal, and otitis media is suspected, perform a
dog cadavers. Studies to determine the usefulness of myringotomy to obtain samples for cytology and
this technique in the clinical situation have not been bacterial C/S and to flush the middle ear cavity.
performed as yet. • Using a hand-held otoscope, insert a sterile otoscopic
cone into the horizontal ear canal, and identify the
Biopsy tympanic membrane. Use a sterile Calgiswab to make
an incision into the caudoventral quadrant of the
• Biopsy any mass found in the vertical ear canal, hor- tympanic membrane. Submit the swab used for the
izontal ear canal, and middle ear. Submit the biopsy
myringotomy incision for bacterial C/S. Insert a
specimens in formalin for histopathologic evaluation.
second swab into the original incision and submit the
sample obtained for cytologic analysis.
• If the video otoscope is used to perform the myringo-
TREATMENT tomy, place an open-end, sterile 31/2-Fr tomcat cathe-
ter through the port of the otoendoscope. Use the
▼ Key Point The goals of treatment are to clean the tomcat catheter to make the incision, and flush
external and middle ear; remove infected, inflam- 1 ml of warm sterile saline into the middle ear cavity
matory, or foreign debris; and allow drainage of for culture.
the middle ear. • A spinal needle may also be used to make the
myringotomy incision.
Deep Otic Flush and Myringotomy • After the myringotomy procedure, flush the middle
ear with warm sterile saline until all of the exudate is
Deep Otic Flush removed from the middle ear.
• Perform under general anesthesia. • The normal tympanum has been shown experimen-
• Soak the ear canal for 10 minutes with a cerumi- tally to heal in 21 to 35 days.
nolytic ear cleaner, then flush using warm saline:
first with a bulb syringe, then using an 8-French ▼ Key Point Possible complications of a deep otic
polypropylene urinary catheter attached to a 12-ml flush and myringotomy are Horner’s syndrome,
syringe passed through an otoscopic cone. facial nerve paralysis, vestibular disturbances, and
• Other flushing options include a red rubber feeding deafness. Although the occurrence of these com-
tube, water-propulsion dental device, or the Auriflush plications is uncommon to rare when the proce-
system (Shering-Plough Animal Health). dures are performed with care, owners should
• Once the exudate and debris are removed from the understand these complications and sign a
ear canal, evaluate the tympanic membrane with an consent form prior to the procedure. These com-
otoscope or video otoscope. plications occur more commonly in the cat than in
• If the tympanic membrane is not intact, perform the dog.
cytology and bacterial C/S from the middle ear cavity
using the hand-held otoscope or the video otoscope.
Using a hand-held otoscope, insert a sterile otoscopic Systemic and Topical
cone into the horizontal ear canal and a pass sterile Antimicrobial/Antifungal Agents
swab (Calgiswab, Hardwood Products Company
LLC) into the middle ear cavity. Use the first swab for Systemic
C/S. Pass a second swab into the middle ear cavity for • Once the ear has been cleaned and flushed, begin
cytologic analysis. systemic and topical antimicrobial/antifungal treat-
• If the video otoscope is used, place an open-end 31/2- ment based on cytologic results from the external
Fr tomcat catheter attached to a 12-ml syringe through and middle ear.
the port of the otoendoscope. Flush 1 ml of warm • The most common coccoid bacteria isolated from the
sterile saline into the middle ear cavity and aspirate middle ear of dogs with otitis media is S. intermedius;
back for culture. appropriate antibiotic choices include cephalexin,
22 mg/kg PO q12h (generics), and amoxicillin and
▼ Key Point Some ceruminolytic agents may be oto- clavulanate, 13.75 to 22 mg/kg PO q12h (Clavamox,
toxic. If the tympanic membrane is not intact, Pfizer Animal Health).
remove the ear cleaner by repeatedly flushing the • The most common rod bacteria is Pseudomonas aerug-
middle ear with warm saline after collection of inosa. A fluoroquinolone such as enrofloxacin, 5
samples. to 20 mg/kg PO q24h (canine only) (Baytril, Bayer
W0422-Ch061.qxd 11/10/05 5:29 PM Page 597
Animal Health), or marbofloxacin, 2.75 to 5.5 mg/kg Systemic and Topical Glucocorticoids
q24h PO (Zeniquin, Pfizer Animal Health), would be
appropriate. Once the C/S results are known, modi- • Anti-inflammatory doses (1 mg/kg PO q24h, then
fication of the treatments may be needed. taper) of oral glucocorticoids (e.g., prednisone
• Certain systemic antibiotics (primarily aminoglyco- [generics]) reduce hyperplasia and stenosis of the ear
sides) are ototoxic and should be used cautiously. canal to facilitate therapy.
• Use ketoconazole (generics; Nizoral, Janssen) or itra- • Topical glucocorticoids may be used solely or in com-
conazole (Sporanox, Janssen) at 5 mg/kg PO q24h bination with oral glucocortocoids to reduce hyper-
for yeast otitis media. plasia and stenosis of the ear canal.
• Administer antibiotics and/or antifungal agents until • Glucocorticoids are available in topical combination
the infection resolves, clinically, cytologically, and on products, with antibacterial and antifungal agents, or
bacterial C/S, and then for an additional 2 to 4 in combination with acetic acid (ClearX Ear Drying
weeks, or until resistance to the antibiotic is found on Solution, DVM Pharmaceuticals), acetic acid and
subsequent bacterial C/S. Burow’s solution (Bur-Otic-HC, Virbac), Burow’s
solution (CortAstrin, Vedco), and dimethyl sulfoxide
Topical (DMSO) (Synotic Otic Solution, Fort Dodge).
▼ Key Point With topical medications, one is able to Topical Cleaning and Drying Agents
achieve concentrations in the ear 100 to 1000 times
higher than if the drug were given systemically. An
• These are used to aid in keeping the external ear
clean by removing exudate. Most products contain an
antibiotic that is resistant on bacterial C/S may thus
acid to dry the ear. Some examples include lactic acid
be efficacious when administered topically.
and salicylic acid (Epi-Otic, Virbac); salicylic acid,
benzoic acid, and malic acid (OtiCalm Cleansing
• Numerous otic medications are available (e.g., Solution, DVM Pharmaceuticals); alcohol, salicylic
neomycin sulfate, polymyxin B sulfate, and hydro-
acid, lactic acid, and benzoic acid (OtiRinse Cleans-
cortisone [Neo-Poly-W/HC Otic Solution, generics],
ing/Drying Ear Solution, DVM Pharmaceuticals);
enrofloxacin and silver sulfadiazine [Baytril Otic,
and olefin and citric acid (Advanced pHormula Ear
Bayer Animal Health], gentamicin sulfate and
Cleanser, EVSCO).
betamethasone valerate [generics; Gentocin Otic
Solution, Schering-Plough Animal Health]; thiaben-
dazole, dexamethasone, and neomycin sulfate solu- Prevention of Recurrent Otitis Externa
tion [Tresaderm, Merial]). • Prevention of recurrence of otitis is dependent on
• However, none of these otic medications is labeled diagnosing and controlling the primary underlying
for use with a non-intact tympanic membrane. Do not disease.
use otic preparations in an ointment base with a non- • While the primary disease is being diagnosed or if the
intact tympanic membrane. primary disease has been diagnosed but has not con-
• In addition, ophthalmic solutions (e.g., tobramycin trolled the recurrence of the otitis, maintenance ear
[Tobramycin Ophthalmic Solution 0.3%, generics]), cleaning (i.e., ear cleaning and drying agents) and
as well as extra-label solutions (e.g., silver sulfadiazine topical therapy (i.e., glucocorticoids) may be helpful
[Silvadene Cream 1%, Monarch Laboratories], in preventing a recurrence.
enrofloxacin [Baytril Antibacterial Injectable Solu-
tion 2.27%, Bayer Animal Health]), are also used top-
ically for otitis, but again, their ototoxic potential has Surgical Management
not been established. • Consider surgical intervention in unresponsive or
recurrent cases of otitis media (see Chapter 62).
▼ Key Point Always warn the owner of the possibil- • Perform surgery if middle ear polyps, neoplasia,
ity of neurologic signs of ototoxicity while admin- foreign bodies, or osteomyelitis of the tympanic bulla
istering topical medications when the tympanic is present.
membrane is not intact. • The surgical technique depends on the specific
condition.
• Use enough topical medication to fill the ear canal,
and repeat the application q12h.
• Topical otic and/or systemic treatment in animals Other Treatments
with chronic otitis may need to be continued for • Treat exposure keratitis due to facial nerve paralysis
weeks to many months to achieve complete resolu- or KCS with artificial tears, lubricating eyedrops, or
tion of the infection, especially in animals with topical cyclosporine (Optimmune, Schering–Plough
chronic otitis. Animal Health).
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▼ Chapter
62 Surgery for Otitis Media and
Otitis Interna
Harry W. Boothe
599
W0422-Ch062.qxd 11/10/05 5:34 PM Page 600
3. Bluntly dissect between the parotid salivary gland ▼ Key Point Administer eye lubricant (artificial tears)
and the ventral aspect of the horizontal ear canal to animals with facial nerve damage to prevent
to reveal the facial nerve. corneal ulceration.
4. Retract the facial nerve ventrocaudally near its exit
from the stylomastoid foramen. • Remove the drain tube when drainage has decreased
5. Elevate the soft tissue overlying the lateral aspect of significantly, generally within 3 to 4 days.
the osseous bulla using a periosteal elevator. • Continue an appropriate systemic antibiotic for at
6. Enter the tympanic cavity ventral to the horizontal least 3 weeks.
ear canal with the Steinmann pin and hand chuck.
7. Enlarge the osteotomy site ventrally with rongeurs. Long-Term
8. Obtain microbiologic samples, and flush the
middle ear cavity using warm saline solution. If ▼ Key Point Incomplete removal of secretory epithe-
curettage is performed, avoid traumatizing the lium from the tympanic bulla can result in recur-
inner ear structures on the dorsomedial aspect of rent deep tissue infections. Clinical signs include
the bulla. pain on opening the mouth and on palpation of the
9. Place and secure a drain tube (e.g., Penrose drain) area over the tympanic bulla, and nonspecific signs
into the tympanic cavity by suturing it to the such as anorexia, lethargy, and fever.
adjacent soft tissue with fine absorbable suture
material. Prognosis
10. Routinely close the subcutaneous tissue (simple • Response to bulla osteotomy tends to be incomplete
interrupted, absorbable suture) and the skin in long-standing cases of otitis media and otitis interna.
(simple interrupted, nonabsorbable suture). • Immediate response following bulla osteotomy indi-
11. Position the drain tube so that it exits the skin adja- cates a more favorable prognosis.
cent to the primary incision.
Angular process
of mandible
Lateral Medial
Jugular
Incision
process
Caudal
Midline Figure 62-3. Use bone rongeurs to enlarge the opening in the
Figure 62-2. Skin incision for ventral bulla osteotomy. ventral tympanic bulla.
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• Removal of the mass from the nasopharynx or ear bulla osteotomy than following excision by traction
canal using a simple traction technique, while care- alone.
fully excising polypoid tissue from the tympanic cavity • Disruption of the otic ossicles from trauma to the
via a ventral bulla osteotomy. dorsal aspect of the tympanic cavity results in hearing
loss.
Equipment
• See Equipment for Lateral Bulla Osteotomy without Prognosis
Total Ear Canal Ablation. • The long-term prognosis following removal of
nasopharyngeal polyps using both the traction exci-
Technique sion and ventral bulla osteotomy techniques is good.
1. Position the cat in dorsal recumbency and prepare Recurrence is uncommon.
the ventral cervical region from the mid-mandibular
area to the wings of the atlas. Perform the procedure
with the cat’s mouth held open. SUPPLEMENTAL READING
2. Displace the soft palate rostrally using a soft tissue
Boothe HW Jr: Ventral bulla osteotomy: dog and cat. In Bojrab MJ
retractor or stay suture to provide adequate exposure (ed): Current Techniques in Small Animal Surgery, 4th ed.
of the mass. Philadelphia: Lea & Febiger, 1998, p 109.
3. Apply traction to the mass to remove the pharyngeal Evans HE, Christensen GC: Miller’s Anatomy of the Dog. Philadel-
component of the polyp. phia: WB Saunders, 1979, p 1062.
4. Perform a ventral bulla osteotomy, as previously Howard PE, Neer TM, Miller JS: Otitis media. Part II. Surgical con-
siderations. Compend Contin Educ Pract Vet 5:18, 1983.
described, and excise tissue proliferations within the Kapatkin AS, Matthiesen DT, Noone KE, et al: Results of surgery and
tympanic cavity using careful curettage. Perform a long-term follow-up in 31 cats with nasopharyngeal polyps. J Am
bilateral bulla osteotomy if it is unclear which middle Anim Hosp Assoc 26:387, 1990.
ear is involved. Little CJL, Lane JG: The surgical anatomy of the feline bulla tym-
panica. J Small Anim Pract 27:371, 1986.
5. Examine the ipsilateral ear canal, and excise any McAnulty JF, Hattel A, Harvey CE: Wound healing and brain stem
polypoid tissue. auditory evoked potentials after experimental total ear canal abla-
tion with lateral bulla osteotomy in dogs. Vet Surg 24:1, 1995.
Postoperative Care and Complications McAnulty JF, Hattel A, Harvey CE: Wound healing and brain stem
auditory evoked potentials after experimental ventral tympanic
Short-Term bulla osteotomy in dogs. Vet Surg 24:9, 1995.
Sharp NJH: Chronic otitis externa and otitis media treated by total
• Temporary Horner’s syndrome of 1 to 2 weeks’ dura- ear canal ablation and ventral bulla osteotomy in thirteen dogs. Vet
tion is common following curettage of the middle ear Surg 19:162, 1990.
cavity. Smeak DD, Kerpsack SJ: Total ear canal ablation and lateral bulla
osteotomy for management of end stage otitis. Semin Vet Med Surg
• See short-term complications following lateral bulla
(Small Anim) 8:30, 1993.
osteotomy. Trevor PB, Martin RA: Tympanic bulla osteotomy for treatment of
middle-ear disease in cats: 19 cases (1984–1991). J Am Vet Med
Long-Term Assoc 202:123, 1993.
▼ Chapter
63 Disorders of the Claw
Ralf S. Mueller
603
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ated with abnormal mineral composition. Young dogs another disease is responsible for the infection, iden-
tend to be affected more by contagious disease, tify and treat to prevent recurrence of claw disease.
whereas neoplastic diseases are more commonly seen
in old dogs. Bacterial Culture
• An acute onset may be seen with trauma or immune- • Bacterial culture is not performed routinely, since
mediated disease. A slow progression is to be ex- most bacterial infections (due to cocci) of the claw
pected with dermatophytosis or keratinization respond well to empirical therapy.
defects. Commonly, trauma affects only single claws • Indications for a bacterial culture and sensitivity are
or is restricted to one foot, while multiple paws are (1) bacterial infections not responding to appropri-
affected more often by systemic disease. Other sys- ate antimicrobial therapy and (2) infections where a
temic signs such as polyuria and polydipsia or recur- significant number of rod-shaped organisms have
rent lameness point to a systemic disease such as been identified on cytology. Obtain material for
lupus erythematosus. Investigate the possibility of bacterial cultures as for cytological specimens. Prior
other animals in the household or humans in contact clipping of the claw may decrease the risk of
having skin disease. Pay special attention to fungal contamination. Interpret results of culture in light of
infections such as athlete’s foot in the owner, which cytology results.
may serve as a source of infection for the dog.
Fungal Culture
Physical Examination • If the history and clinical examination indicate a pos-
• Perform a thorough overall physical examination to sible fungal infection or spores/hyphae are identified
look for evidence of generalized diseases. on cytology or histopathology, perform a fungal
• Carefully examine the claws. Twisted, curled, or mal- culture to confirm the diagnosis and to allow deter-
formed claws are usually due to disturbed growth of mination of the fungal species involved. Different
the claw horn frequently associated with a damaged fungal organisms have different zoonotic potential.
claw matrix, trauma, or congenital defects. This mal- • Obtain scales from the claw fold and/or proximal
formation can lead to shedding of the claw. part of avulsed or intact claws and hair from the area
directly adjacent to the claw fold for culture agars.
Diagnostic Tests Use Sabouraud’s agar and dermatophyte test
medium. Apply shaved thin slices of the claw to the
Cytology culture medium to improve the probability of fungal
• Many patients with claw disease have inflammation of growth. Cleaning of the claw and surrounding skin
the tissue surrounding the claw. In these animals, with alcohol may reduce bacterial contamination.
material (pus, debris, keratinaceous material) may be • Transient contamination of claws with Trichophyton
squeezed out and applied to a glass slide with a small, spp. and Microsporum gypseum is possible. Identify
soft paint brush. Alternatively, use a swab to remove organisms not only on culture, but also directly on
material deep inside the claw fold and roll it onto a hairs, in hair follicles, or in claw material cytologically
slide. Impression smears may be useful, if the skin and/or histopathologically to confirm the diagnosis.
adjacent to the claw fold is abnormal.
• If the claws and claw folds are dry, moisten swabs with Skin Scrapings
saline prior to sampling the claw fold. Alternatively, • Deep skin scrapings for Demodex canis may be useful
in patients with changes of the claw horn, use a #10 since they may cause claw disease in some dogs. After
scalpel blade and scrape material from the most prox- gently clipping the skin adjacent to an affected claw,
imal portion of avulsed or affected claws. Apply the perform scrapings with a #15 scalpel blade until cap-
material to the slides and use the staining techniques illary bleeding is observed. Typically, heavy sedation
and methods of microscopic evaluation of specimens or general anesthesia is required to achieve proper
discussed in Chapter 37. skin scrapings in dogs with claw disease.
• Interpretation of results of cytology may be difficult at • An alternative to the scraping may be a trichogram,
times. The presence of bacteria alone is not diagnos- where numerous hairs adjacent to the claw fold are
tic of bacterial infection. However, if bacteria are plucked and examined under the microscope. If
present in large numbers, suspect infection and ini- mites are identified, the diagnosis is confirmed. If no
tiate trial therapy with antibiotics. Numerous yeast mites are present, perform a skin scraping.
organisms or inflammatory cells with intracellular
bacteria confirm clinically relevant infection and the Biopsy
need for appropriate therapy. If these bacterial or
yeast infections are secondary to trauma, treatment ▼ Key Point Claw biopsy is the diagnostic tool of
with antimicrobial agents alone may be successful choice for neoplastic disease, but may also confirm
without a relapse of the claw disease. However, if immune-mediated diseases such as the various
W0422-Ch063.qxd 11/12/05 10:38 AM Page 606
Biopsy Technique Figure 63-2. Positioning of the biopsy punch for onychobiopsy.
Place the punch horizontally such that the direction of the cutting
• To obtain appropriate specimens of claw matrix, sur- edge is perpendicular to planes A and B. The medial edge of the
gically remove the distal phalanx (see Chapter 114) punch needs to cut through the lateral edge of the claw. (From
Mueller RS, Olivry T: Onychobiopsy without onychectomy: descrip-
to allow the pathologist to evaluate the changes most tion of a new biopsy technique for canine claws. Vet Derm 10:55, 1999,
thoroughly. However, amputation of the digit is often with permission.)
met with owner resistance.
• Recently, a biopsy technique was developed that
allows evaluation of the claw matrix while avoiding
onychectomy. To minimize postsurgical discomfort,
take specimens from claws bearing no or little weight.
If dew claws are not present or not affected, obtain
samples from P2 and/or P5 of one hind paw.
• Place the animal under general anesthesia, and clip
the affected paw. Apply a tourniquet to reduce hem-
orrhage during the procedure.
• Obtain the biopsy specimen by rotating a biopsy
punch slowly in one direction deep into the tissue,
initially cutting medially through the horn of the claw
and then through the bone of the distal phalanx and
Figure 63-3. Localization of the excised biopsy specimen. Areas A
laterally through normal skin on the lateral aspect of and B depict the incision direction of the punch throughout the pro-
the claw fold (Figs. 63-2 and 63-3). Cut the base of cedure, and area C delineates the area evaluated histopathologically.
the sample with iris scissors or scalpel blades. (From Mueller RS, Olivry T: Onychobiopsy without onychectomy:
• Place the specimen in 10% buffered formalin. Close description of a new biopsy technique for canine claws. Vet Derm
10:55, 1999, with permission.)
the incision with two monofilament nonabsorbable
sutures. Bandage the paw for 2 to 3 days postopera-
tively. Analgesic therapy may be used postoperatively
for the first 8 to 10 hours. Remove the sutures after Radiography
2 weeks.
• Radiographs can identify lysis of bone, soft tissue
swelling, and periosteal elevation and thus may be
Blood Tests helpful in diagnosing secondary osteomyelitis and
invasive neoplastic lesions in dogs with severe pain
• Blood samples have been reported to be rarely useful and swelling of the affected digit.
in patients with exclusive claw disease. However,
complete blood counts, serum biochemistry, and
urinalysis may be helpful in individual patients
(particularly in older pets). They are essential when
TREATMENT
systemic diseases such as lupus erythematosus are sus-
pected. Antinuclear antibody titers or determination
General Therapy of the Claw
of cold agglutinins may also be useful in individual • To decrease pressure and associated pain, keep the
patients. claws very short so that the foot pads absorb most of
W0422-Ch063.qxd 11/12/05 10:38 AM Page 607
the weight. Distorted or brittle claws also benefit ative fungal culture in conjunction with clinical
greatly from frequent clipping. In addition, clipped remission.
claws are less likely to catch on material. However, • Griseofulvin at 50 mg/kg PO daily has been used suc-
take care not to cause significant hemorrhage by clip- cessfully. Administer with a fatty meal to maximize
ping beyond the cornified part of the claw. absorption. Griseofulvin is teratogenic; do not give to
• Remove the claw plate if it is partially separated from breeding bitches.
the claw bed and causes constant pain or discomfort. • Other options include ketoconazole at 10 mg/kg PO
Sedation or even general anesthesia may be neces- q12h or itraconazole at 10 mg/kg PO q12h. Both of
sary. Removal will typically diminish clinical signs of these drugs are occasionally hepatotoxic and may
discomfort quickly. Apply antimicrobial ointments lead to vomiting and nausea, although these side
and a bandage for 1 to 3 days to minimize pain and effects are much more common with ketoconazole
bleeding. The prognosis for regrowth is good as long than with itraconazole.
as the claw matrix is not significantly damaged. • Terbinafine (25–30 mg/kg q24h) may also be used
• Topical antimicrobial solutions such as chlorhexidine for onychomycosis in dogs. Pulse therapy may be
at 0.05% to 0.1% (or available in 1–2% concentra- useful with itraconazole or terbinafine; the drugs are
tion in some products such as Malaseb [DVM given at their normal dose every other week.
Pharmaceuticals], Resichlor [Virbac]) may be bene- • Consider amputation of the distal phalanx for clients
ficial with bacterial or fungal paronychia and can be with financial constraints. If the disease recurs after
used as a spray or shampoo daily to weekly. discontinuing extended therapy, onychectomy is rec-
• When an underlying etiology cannot be identified or ommended. Another reported alternative is long-
treated successfully, and multiple claws are affected, term, low-dose daily therapy with systemic antifungal
amputation of all affected distal digits can be per- agents.
formed. However, long-term lameness may be seen
following exercise.
Therapy for Neoplasia
Therapy for Bacterial Infection ▼ Key Point In all patients with neoplasia of the claw,
• Perform antibacterial soaks or shampoos two to three amputation of the digit is the therapy of choice.
times daily. Alternatively use 2% mupirocin ointment
twice daily. Apply the ointment before walking or Obtain lymph node aspirates or biopsies and radi-
feeding the dog or before play time to prevent foot ographs to evaluate the extent of tumor invasion and
licking for the first 10 minutes after application. the possibility of metastases. If the local lymph nodes
However, any topical therapy of the feet is cumber- show evidence of neoplastic cells, consider excision of
some and often not tolerated easily by the patient, the affected lymph node and limb amputation, or
and systemic therapy may be preferred. adjunctive therapy, depending on tumor type (see
• If cytology has revealed an infection with cocci, Chapter 115).
cephalexin (20–30 mg/kg PO q12h), enrofloxacin
(for dogs, 5–10 mg/kg PO q24h), or clavulanic acid/
amoxycillin combination (12.5–25 mg/kg PO q8h) Idiopathic Onychomadesis
are all reasonable choices. If rod-shaped organisms (Lupoid Onychodystrophy)
predominate on cytology, perform culture and sensi-
tivity to determine the choice of antibiotics. Continue • I have had reasonable success with a combination of
treatment for 3 to 8 weeks depending on the under- tetracycline and niacinamide at 250 to 500 mg/
lying disease and the severity of the infection. If radi- animal PO q8h. If a good response is seen within 8
ographs have indicated the presence of bacterial to 12 weeks, treatment may be changed to doxycy-
osteomyelitis, long-term systemic antibiotic therapy cline hydrochloride or preferably doxycycline mono-
will be necessary (see Chapter 120). hydrate at 5 to 10 mg/kg PO once daily. Many
patients will stay in remission with this once-daily
• Consider amputation of the distal phalanx in con-
therapy, which is less cumbersome than administra-
junction with antibiotic therapy to avoid the risk of
treatment failure and financial obligation associated tion of tetracycline/niacinamide and thus preferred
with long-term antimicrobial therapy. by many owners.
• In a recent study, some patients also responded to
pentoxifylline at 200 to 800 mg/dog PO once daily.
Therapy for Fungal Infection However, the condition in some dogs may wax and
• Onychomycosis is a refractory or recurrent disease wane, and spontaneous remission has been seen.
that needs to be treated aggressively. Administer anti- • Supplementation with essential fatty acids (omega-6
fungal agents for extended time periods. Clinical and omega-3 fatty acids (DermCaps, DVM Pharma-
improvement is an indicator of effective therapy, but ceuticals) or vitamin E (at 400 IU twice daily) has
continue treatment for several months beyond a neg- been reported to be very effective. However, in my
W0422-Ch063.qxd 11/12/05 10:38 AM Page 608
experience, response to supplements has been less Mueller RS, Rosychuk RAW, Jonas LD: A retrospective study regard-
reliable. ing the treatment of lupoid onychodystrophy in 30 dogs. J Am
Anim Hosp Assoc 39:139, 2003.
Mueller RS, Sterner-Kock A, Stannard AA: Microanatomy of the
canine claw. Vet Derm 4:5, 1993.
SUPPLEMENTAL READING O’Brien MG, Berg J, Engler SJ: Treatment by digital amputation of
subungual cell carcinoma in dogs: 21 cases (1987–1988). J Am Vet
Med Assoc 201:759, 1992.
Bergvall K: Treatment of symmetrical onychomadesis and onychodys-
Paradis M, Scott DW, Breton L: Squamous cell carcinoma of the nail
trophy in five dogs with omega-3 and omega-6 fatty acids. Vet Derm
bed in three related giant schnauzers. Vet Record 125:322, 1989.
9:263, 1998.
Rosenkrantz W: Immunomodulating drugs in dermatology. In
Boord MJ, Griffin CE, Rosenkrantz WS: Onychectomy as a therapy for
Kirk RW (ed): Current Veterinary Therapy X. Philadelphia: WB
symmetric claw and claw fold disease in the dog. J Am Anim Hosp
Saunders, 1989.
Assoc 33:131, 1997.
Rosychuk RAW: Diseases of the claw and claw fold. In Bonagura JD
Foil CS: Disorders of the feet and claws. In Proceedings of the 11th
(ed): Kirk’s Current Veterinary Therapy XII. Philadelphia: WB
Annual Kal Kan Symposium for the Treatment of Small Animal
Saunders, 1995.
Diseases. Vernon: Kal Kan Foods Inc., 1987, p 23.
Scott DW, Miller WH: Disorders of the claw and clawbed in dogs.
Foil CS, Conroy J: Dermatoses of claws, nails and hoof. In
Comp Cont Educ 14:1448, 1992.
Von Tscharner C, Halliwell REW (eds): Advances in Veterinary
Scott DW, Miller WH, Griffin CE: Diseases of eyelids, claws, anal sacs
Dermatology I. Philadelphia: Baillière Tindall, 1990.
and ear canals. In Small Animal Dermatology. Philadelphia: WB
Harvey RG, Markwell PJ: The mineral composition of nails in normal
Saunders, 2001.
dogs and comparison with shed nails in canine idiopathic ony-
Scott DW, Rouselle S, Miller WH: Symmetrical lupoid onychodystro-
chomadesis. Vet Derm 7:29, 1996.
phy in dogs: A retrospective analysis of 18 cases (1989–1993). J Am
Mueller RS: Diseases and management of canine claw diseases. In
Anim Hosp Assoc 31:194, 1995.
Campbell KL (ed): Veterinary Clinics of North America: Small
White SFD, Rosychuk RAW, Reinke SI, et al: Use of tetracycline and
Animal Practice—Dermatology, vol 29, no 6. Philadelphia: WB
niacinamide for treating autoimmune skin disease in 31 dogs. J Am
Saunders, 1999.
Vet Med Assoc 200:1497, 1992.
Mueller RS, Friend S, Shipstone MA, et al: Evaluation of canine claw
disease—a prospective study of 24 dogs. Vet Derm 11:133, 2000.
Mueller RS, Olivry T: Onychobiopsy without onychectomy: Descrip-
tion of a new biopsy technique for canine claws. Vet Derm 10:55,
1999.
W0422-Ch064.qxd 11/12/05 10:40 AM Page 609
▼
Section
6 Digestive System
Susan E. Johnson
▼ Chapter
Dental disease and diseases of the oropharynx are • The dentition, including root structure, of dogs and
common in dogs and cats. These diseases can be divided cats is illustrated in Figures 64-1 and 64-2, respec-
into categories including oral surgical disease, tively. Tooth roots for both species are listed in Table
periodontal disease, endodontic disease, orthodontic 64-2.
disease, stomatitis/gingivitis, neoplastic disease, and • Basic anatomic structures of the teeth and related
salivary gland disease. Neoplastic disease of the maxilla areas are illustrated in Figure 64-3 and defined in
and mandible is discussed in Chapter 99. Table 64-3.
609
W0422-Ch064.qxd 11/12/05 10:40 AM Page 610
Alveolar mucosa
Mucogingival line
Attached gingiva
Figure 64-1. Dental root structure in the dog.
In Dogs
client’s ability and desire to pursue alternatives to Incisor 1
extraction, such as periodontal, endodontic, and Canine 1
orthodontic therapy. Maxillary (upper) cheek teeth:
1st (1st P) 1
▼ Key Point If a client is unwilling to pursue alter- 2nd and 3rd (2nd and 3rd P) 2
natives for treatment of a painful tooth, then the 4th–6th (4th P; 1st and 2nd M) 3
tooth should be extracted. Mandibular (lower) cheek teeth:
1st and last (1st P; 3rd M) 1
2nd–6th (2nd–4th P; 1st and 2nd M) 2
Overly Retained Deciduous and Supernumerary Teeth
Deciduous teeth are considered overly retained if they In Cats
Incisor 1
are firmly attached following the initial stage of erup- Canine 1
tion of the permanent tooth. Failure to extract decidu-
Maxillary (upper) cheek teeth:
ous teeth during this initial stage may result in 1st (2nd P) 1
malocclusion of the permanent teeth. Retained decidu- 3rd (4th P) 3
ous teeth and supernumerary teeth can be diagnosed as All others 2
extra teeth present in the dental arcade. Deciduous Mandibular (lower) cheek teeth:
teeth may be differentiated from supernumerary per- All 2
manent teeth by their smaller crown size grossly and
smaller root structure radiographically. M, molar; P, premolar.
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displacement of teeth, severe root resorption of adja- • Examine the maxillary teeth for fractures or deep
cent teeth, and bone loss. periodontal pockets.
• Dentigerous cysts may give rise to ameloblastomas. • Take dental radiographs of the maxillary teeth to
• Radiography can diagnose impacted teeth. Perform check for periapical lysis.
extraction if they are causing problems and when • Extract teeth that are causing secondary ophthalmic
associated with a dentigerous cyst. Remove the disease.
entire cyst lining to prevent recurrence of the cyst
and submit cyst lining for histopathology to confirm
Preoperative Considerations
diagnosis.
• Before performing dental extractions, perform a
Deformed Teeth thorough physical examination, standard laboratory
tests including a complete blood count (CBC), serum
Diagnose deformed teeth based on gross and radio- biochemistry, and urinalysis.
graphic appearance. Usually they result from trauma or • Perform appropriate radiographic procedures, based
fever that occurred during tooth development. Abnor- on the animal’s clinical signs, physical examination
malities in development of teeth occur rarely and findings, and age.
include dens-in-dente and gemination of teeth, which • Correct any underlying metabolic abnormalities such
results when a single tooth bud attempts to divide into as dehydration, azotemia, electrolyte imbalances,
two teeth. Dens-in-dente results when there is invagina- hyperglycemia, and hypoglycemia.
tion of enamel and dentin into the pulp space often
resulting in secondary endodontic disease. Surgical Procedure
• Diagnose minor dental deformities such as enamel There are three basic types of extractions: simple, multi-
hypoplasia based on the observation of symmetric rooted, and complicated surgical. An alternative to
defects and staining of enamel combined with a routine extraction techniques, feline crown amputation
history of illness during tooth development. No treat- with intentional root retention can be utilized in feline
ment is required in most cases. teeth with advanced odontoclastic resorptive lesions
• Extract severely deformed teeth that are causing following proper screening.
pain.
• Gemination of the teeth usually requires no treat- Equipment
ment. When a tooth has this developmental defect
and extraction is necessary, perform dental radiogra- • See Tables 64-4, 64-5, and 64-6.
phy before extraction to determine the location of
abnormal roots. Simple Extraction
Simple extraction refers to the extraction of a small
Ophthalmic Manifestations of Dental Disease
single-rooted tooth such as an incisor.
Tooth roots of the maxillary fourth premolar and first
and second molars in dogs are in close proximity to Technique
the orbital floor and globe. Periodontal and endodon-
1. Place an appropriate-size dental elevator in the
tic disease of these teeth can result in ophthalmic
periodontal ligament to sever the attachments of the
signs, including orbital, periorbital, conjunctival, naso-
gingiva around the tooth.
lacrimal, and neuro-ophthalmologic abnormalities.
2. Advance the elevator apically (toward the apex or tip
• When signs of ophthalmic disease are suggestive of a of the root) between the alveolar bone and root.
primary dental disorder, do a complete oral exami- 3. Rotate the elevator and hold for 15-second intervals
nation under general anesthesia or sedation. to tear the periodontal ligament (Fig. 64-4A).
Portable electric dental drill with low-speed hand piece and prophy angle Sectioning teeth, removal of alveolar bone, polishing
(Vetroson Millennium Motor Pack, Henry Schein, Inc.; Port Washington, NY) teeth
Mobile delivery system with high-speed handpiece, low-speed handpiece, water Sectioning teeth, removal of alveolar bone, polishing
and air syringe (Vet-Base, Henry Schein, Inc.) teeth, cavity and crown preparations
Piezoelectric scaler, electric or air driven (Spartan USA, Inc.; Fenton, MO) Permits rapid, easy removal of dental calculus
Dental radiography unit (AFP Imaging, Elmsford, NY) Permits rapid, easy exposure of dental radiographs
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Technique
1. Locate the furcation with a dental elevator.
2. Place a tapered fissure bur (#701 in small animals
and #702 in larger animals) at the furcation and
direct it through the crown (Fig. 64-5A).
3. Advance the elevator apically between two roots.
4. Gently rotate the elevator and hold for 15 seconds to
gently force the roots apart (Fig. 64-5B).
Figure 64-4. A, Dental elevator in periodontal ligament space is 5. Advance the elevator further apically, rotate it 90
rotated 90 degrees. Tooth is rotated with extraction forceps. degrees, and hold for 15 seconds.
Oral Surgery
Dental elevator Tears periodontal ligament during extraction
Dental luxators Has a thinner, sharper blade than traditional elevators
Extraction forceps Completes breakdown of periodontal ligament and removal of tooth from alveolus during
extraction
Root tip pick Removal of small-breed deciduous teeth or broken root tips
Bone curette Debridement of alveolus following extraction
Periosteal elevator Elevation of mucoperiosteum during oronasal fistula repair and palatal surgery
Periodontic
Periodontal probe/explorer Measurement of depth of periodontal pocket (probe); detection of pulpal exposures and carious
lesions (explorer)
Hand scalers Subgingival scaling
Curette (Columbia #13/14) Removal of accretions on the root surface and removal of granulation tissue from the pocket wall
Prophylaxis paste Polishing teeth following scaling
Endodontic
Endodontic files (Hedstrom/K-Files) Debridement of necrotic pulpal tissue from canal
Root canal plugger Compression of gutta percha into the apex
Light-Speed and SimpliFil System†
*Available from Henry Schein, Inc.; Port Washington, NY and from Cislak Manufacturing Inc, Niles, IL.
†Available from Light Speed Endodontics, San Antonio, TX.
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Composite resins (Prodigy, sdsKerr, Orange, CA) Aesthetic restorations following endodontic therapy or cavity preparation
Glass ionomers (Vitrebond, 3M EPSE, St. Paul, MN) Restoration of feline external root resorptive lesions
Endodontic sealers (AH Plus, Dentsply, Konstanz, Germany) Endodontic filling material
Mineral trioxide aggregate (ProRoot MTA, Dentsply Tulsa Stimulates closure of an apex and reparative dentin formation following
Dental, Tulsa, OK) spulpotomies
Gutta percha (Successfil, Hygenic) Fills the pulp canal following debridement during root canal therapy
Figure 64-7.
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Palatine foramen
Palatine arteries
Figure 64-8. Elevation of root tip with root tip pick.
Figure 64-10. A, Proposed incision sites in mucosa for oronasal fistula repair. B, Elevation of mucoperiosteal flap. C, Incision of periosteal
layer of flap. D, Removal of rough edges of buccal alveolar bone with rongeurs or round bur. E, Mucoperiosteal flap is replaced and sutured.
3. Fold over and suture the flap to the periosteum of dental arcade. The rostral and caudal aspects of
the edge of the defect with 3-0 or 4-0 poliglecaprone these incisions are connected to the rostral and
(Monocryl) in a simple interrupted pattern (Fig. 64- caudal aspects of the hard palatal defect (Fig. 64-
11B). 12A).
4. Elevate a buccal mucoperiosteal flap from the lateral 2. Incise the opposite side of the palatal defect along
aspect of the oronasal fistula (see Fig. 64-10C). the entire length of the defect and gently elevate with
5. Advance the buccal mucoperiosteal flap palatally to a periosteal elevator to create a recipient site for the
cover the inverted flap and the denuded palatine mucoperiosteal flap. Carefully elevate the muco-
bone (Fig. 64-11C). periosteal flap with a periosteal elevator, preserving
6. Suture the flap to the palatal and gingival mucosa the palatine artery (see Fig. 64-9) that arises approx-
with 3-0 or 4-0 poliglecaprone (Monocryl) in a simple imately 1 cm palatal to the upper fourth premolar
interrupted pattern (Fig. 64-11D). (Fig. 64-12B).
3. Hinge the mucoperiosteal flap at the end of the
palatal defect and place beneath the mucosa on the
Overlapping Flap Technique other side of the defect.
• Use for repair of hard palatal defects, especially on 4. Preplace 3-0 PDS (polydioxanone) sutures in an
the midline. interrupted vest-over-pants suture pattern through
the recipient site and the flap.
5. Tie the sutures from caudal to rostral to complete
Technique the procedure (Fig. 64-12C).
1. Make an incision the length of the palatal defect 6. Make an incision along the edges of the soft palatal
in the palatal mucosa just palatal to the maxillary defect and close in two layers by apposing nasal
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A
C
B
D
Figure 64-11. A, Periosteal elevation of palatal flap. B, Palatal flap is sutured to debrided edges of defect. C, Buccal mucoperiosteal flap is
elevated and advanced palatally. D, Flap is sutured to palatal and gingival mucosa.
PERIODONTAL DISEASE
▼ Key Point Periodontal disease is the most common
cause of oral infection and tooth loss in dogs.
a Gingivectomy site
Bottom of pocket
b Mucogingival line
c
d
2. Make a beveled incision in the gingiva, slightly apical interproximally (between the teeth) to preserve
to the pocket mark, to create a natural gingival most of the gingival tissue.
contour to the gingiva following the gingivectomy 3. Elevate the mucoperiosteal flaps 3 to 5 mm from the
(Fig. 64-15B). The incision can be made with a gin- edge of the incision, using a sharp periosteal
givectomy knife, scalpel blade, or electrosurgery tip. elevator (Fig. 64-16B).
If electrosurgery is used, surgical cutting modes are 4. Remove the collar of gingival tissue around the tooth
recommended. with curettes.
3. Following removal of excessive hyperplastic tissue 5. Perform scaling and root planing on the exposed
and pocket elimination, scale and polish the exposed tooth surface.
tooth surface. 6. Polish the tooth and liberally irrigate the area with
sterile saline.
Open-Flap Curettage 7. Reposition the flaps and hold in place with 4-0
chromic catgut sutures in a simple interrupted
This technique is used to treat periodontal pockets that
pattern, placed interdentally (Fig. 64-16C).
extend beneath the level of the alveolar crest. Open-flap
curettage permits access to intrabony defects without
loss of attached gingiva. Postoperative Care and Complications
• To retard the recurrence of plaque and calculus accu-
Technique mulation, instruct the owner to irrigate the animal’s
mouth with a 0.2% chlorhexidine solution (CET
1. Make an incision with a #11 or #15 scalpel blade
chlorhexidine solution; Virbac, Fort Worth, TX) for
1 to 2 mm from the tooth and directed toward the
2 weeks. Additionally, recommend daily toothbrush-
alveolar crest (Fig. 64-16A).
ing with CET toothpaste (Virbac, Fort Worth, TX).
2. Make a scalloped incision on the buccal and lingual
or palatal surfaces of the affected tooth, dipping • If significant stomatitis (discussed later in this
chapter) or abscess secondary to periodontal disease
occurs, give broad-spectrum antibiotics such as
amoxicillin clavulanate (Clavamox, Pfizer, 14 mg/kg
PO q12h).
• Reevaluate the animal in 2 weeks. Annual or semian-
nual scaling is recommended.
• Complications are minimal when procedures are
properly performed.
ENDODONTIC DISEASE
Endodontic disease refers to disease of the pulp (the
inner aspect of the tooth). It occurs frequently in small
animals and may cause significant pain. Pulp cap,
pulpotomy, apexogenesis, apexification, and non-
surgical and surgical endodontic therapy can result in
the resolution of endodontic disease and retention of a
functional, painless tooth.
Anatomy
Figure 64-16. A, Open-flap curettage is initiated with an incision
directed toward the alveolar crest. B, Mucoperiosteal flaps are ele- Surgical anatomy varies with each tooth. The endo-
vated 3–5 mm to permit open curettage. C, The flaps are repositioned dontic system is divided into two parts: the pulp
with 4-0 chromic sutures. chamber and the pulp canal.
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• The endodontic system generally follows the external • When dental attrition is the cause of a shortened
anatomic contours of the tooth, including its root crown, the explorer will not penetrate the tooth
structure. but will be stopped by the reparative dentin, or
• The size of the endodontic system also varies with the “brown spot,” that fills in the area of receded pulp.
age of the patient. Young animals have immature • Evaluate the color of the tooth. A discolored tooth
teeth with open apices. As the tooth develops, the (red, purple, or gray) may be diseased.
apex is formed and, as the tooth matures, the denti- • Percussion of a tooth with endodontic disease may be
nal layer thickens, resulting in a thinner endodontic painful because of periapical inflammation.
system. • Soft tissue fistulas may occur secondary to endodon-
tic disease. Usually they are located apical to the
Etiology mucogingival line. When probed, they will be found
to originate from the apex of an endodontically dis-
• The most common cause of endodontic disease eased tooth.
in small animals is a fractured tooth with pulpal
exposure. • Severe maxillary or mandibular swelling may be
present with endodontic disease when the disease
• Less common causes include rapid dental attrition
process has progressed to severe periapical inflam-
(tooth wear), deep odontoclastic resorptive lesions in
cats, deep dental caries, severe periodontal disease mation and/or osteomyelitis.
with secondary endodontic disease, and dental
trauma with secondary internal pulpal hemorrhage Radiography
or damage to the apical vessels.
Perform dental radiography to delineate the endo-
dontic system and confirm endodontic disease. Radio-
Clinical Signs graphy reveals the stage of apical development.
Pulpal exposure can result in the progressive develop- • Chronic endodontically diseased teeth have an area
ment of the following conditions: of periapical lysis around one or more roots.
• Bacterial pulpitis • When soft tissue fistulas are present, radiopaque
• Pulp necrosis material such as a gutta percha point may be placed
• Periapical granuloma into the fistula before radiography to confirm
• Periapical inflammation that the fistula arises from the apex of the affected
• Acute alveolar periodontitis tooth.
• Osteomyelitis
• Sepsis
Preoperative Considerations
The time required for this progression varies from
months to years. When a tooth is fractured and the pulp
• Examine the teeth for concurrent periodontal
disease with a periodontal probe.
is exposed, the pulp will bleed.
▼ Key Point Pulpal exposure is extremely painful, ▼ Key Point Teeth with combined periodontal and
and animals with a fractured tooth with pulpal endodontic lesions have a poorer prognosis than
exposure may hypersalivate, may be reluctant to teeth with only endodontic lesions.
eat, and may exhibit other abnormal behaviors.
4. Introduce progressively larger files into the canal. cal tissues around the apex are packed off with
Flush the canal with 2.5% sodium hypochlorite cotton pellets.
solution before changing files. 2. An apical approach for most teeth is through a
5. Debridement is complete when white dentinal shav- mucoperiosteal incision just apical to the muco-
ings are present on the file and there is no further gingival line. However, access to the apex of the
bleeding from the canal. An alternative technique mandibular canine is most easily gained through a
to hand filing canals is an engine-driven rotary file cutaneous incision overlying the ventral border of
system (Light Speed Endodontics, San Antonio, the mandible.
TX). 3. Access to the apex is achieved by removing the alve-
6. Flush canal with sterile saline. olar bone overlying the apex with a #4 or #6 round
7. Dry the canal with paper points. bur.
8. Apply a sealer (AH Plus, Dentsply, Konstanz, 4. Perform apical curettage to remove necrotic and
Germany) into the canal with a paper point or fibrotic granulation tissue surrounding the periapi-
endodontic file rotated in a counter-clockwise cal region.
direction. 5. Perform an apicoectomy (amputation of the apex
9. Obturate (fill) the root canal with gutta percha. of the tooth) using a #701 bur. The exposed face of
a. Gutta percha may be applied using a vertical the cut root tip is beveled at a 45° angle to increase
condensation using hot gutta percha. In this exposure of the canal access site.
technique small amounts of hot gutta percha 6. Flush the periapical region with sterile saline
(Successfil, Hygenic) are placed on the end of a solution.
sterile file and rotated counterclockwise into the 7. Pack the periapical region with #0 cotton pellets or
canal and then vertically condensed with a a hemostatic agent to control hemorrhage.
plugger. This process is repeated until the canal 8. Create an undercut in the root canal of the apex
is adequately filled. with a #33 inverted cone bur.
b. An alternative technique for preparing and 9. Place at least a 4-mm layer of mineral trioxide
filling canals is the Light Speed and SimpliFil aggregate (ProRootMTA, Dentsply Tulsa Dental,
technique (Light Speed Endodontics, San Tulsa, OK) in the apical end of the canal, using a
Antonio, TX) in which a 5 mm gutta percha plug retrograde carrier, and condense the MTA with a
is placed in the apex followed by a solitary gutta small plugger.
percha master cone. 10. Before closure, remove all cotton pellets and flush
10. Remove any excess gutta percha and sealer from the periapical region with sterile saline solution.
the access site. 11. Reposition the mucoperiosteal flap and suture with
11. Apply a restorative material such as a compactible 3-0 chromic catgut in a simple interrupted pattern.
composite (Prodigy, sdsKerr, Orange, CA) to the Procedures involving the mandibular canine teeth
access site to complete the procedure. are closed with non-absorbable suture material in
the skin.
Surgical (Non-conventional) Endodontic Therapy Postoperative Care and Complications
This is the treatment of endodontic problems with an
approach through oral soft tissue and bone rather than • Immediately following endodontic therapy, take a
radiograph to document and assess the procedure.
through the crown of the tooth. In a non-surgical root
canal procedure, the pulp canal is accessed by the • Administer a broad-spectrum antibiotic, such as
amoxicillin clavulanate, for 1 week.
crown only.
Indications for surgical endodontic therapy include • Reexamine and radiograph the treated tooth 6
months postoperatively, and then annually, to evalu-
• Apical root resorption ate the success of the endodontic therapy.
• Incomplete root development
• Complications during conventional root canal Intraoperative Complications
therapy (broken files)
Intraoperative complications usually are associated with
• Recurrent apical abscessation following non-surgical
improper use of instrumentation or inappropriate tech-
root canal therapy (recurrent swelling over the apex of
nique. Examples are:
the tooth root or periapical draining fistulous tracts)
• Size, length, or curvature of the canal that makes • Broken endodontic files lodged in the root canal
instrumentation impossible • Perforation of the root canal or pulpal floor
Technique Postoperative Complications
1. Perform a conventional root canal procedure Postoperative complications usually are associated with
before surgical endodontic therapy. Do not flush or improper technique, inadequate apical seal, or inade-
fill the canal, if the apex is open, until the periapi- quate follow-up.
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Extraction of overly retained deciduous teeth is and prognosis. When a specific cause cannot be identi-
referred to as interceptive orthodontics. Extract a decidu- fied or specific therapy is not available, treatment is
ous tooth that is still firmly attached when the perma- symptomatic and supportive. Chronic relapsing stom-
nent tooth starts to erupt to allow the permanent tooth atitis can be particularly frustrating to manage.
to erupt in its normal position. Perform extraction care-
fully to avoid disruption of the permanent tooth. Etiology
Causes of stomatitis/gingivitis are listed in Table 64-8.
Correction of Lingually Displaced Many systemic diseases that cause stomatitis/gingivitis
Mandibular Canines are discussed in detail elsewhere in this book, including
viral upper respiratory infections of cats (see Chapter
A technique that can be easily applied in one visit is the 11), feline leukemia virus (FeLV) (see Chapter 8),
intraorally fabricated acrylic inclined plane. feline immunodeficiency virus (FIV) (see Chapter 9),
renal failure (see Chapter 77), autoimmune diseases
Technique such as systemic lupus erythematosus (SLE) (see
1. Clean and polish the teeth with pumice. Chapter 24) and pemphigus (see Chapter 48), and
2. Fabricate an inclined plane with a self-curing com- eosinophilic granuloma complex (see Chapter 53).
posite material (Pro-temp 3 Garant, 3MESPE, St.
Paul, MN) until the splint is approximately 1 cm Periodontal Disease
thick.
3. When the composite material becomes hard, create Periodontal disease is a common predisposing cause of
the appropriate inclined plane with an acrylic bur, so stomatitis/gingivitis in dogs and cats (see previous
that when the lingually displaced mandibular canine discussion).
hits the side of the inclined plane it will be deflected
labially and mesially into a normal position. The ▼ Key Point In any animal with stomatitis/gingivitis,
incline path for the affected tooth should be formed perform a complete periodontal examination and
so that the sloping angle is approximately 60° toward dental prophylaxis, including tooth extractions if
its target site. necessary, to eliminate periodontal disease as a
4. Add additional composite to create a band around contributing factor.
the canine teeth to provide retention for the splint.
Physical Injury
Postoperative Care and Complications Foreign bodies (plant awns, sticks, bones), oral trauma,
• Instruct the client to: and thermal, electrical, and radiation burns can cause
• Restrict the animal’s chewing activities and to feed stomatitis/gingivitis. A history of exposure combined
a soft diet. with the oral examination may be diagnostic.
• Observe the orthodontic device daily, making sure
that it is not displaced or causing excessive soft
• Plant awn stomatitis (bur tongue, vegetative stomati-
tis) occurs in outdoor dogs that groom burs from
tissue trauma. their coat or eat horse feces containing burs. The
• Gently clean the device daily with a stream of water awns become embedded in the tongue and gingiva,
from a curved-tip syringe. causing glossitis, gingivitis, and gingival hyperplasia.
• Leave the orthodontic appliance in place until the • On oral examination, close inspection will reveal
appropriate movement has been achieved. This tiny plant spicules embedded in tissue, and plant
usually takes about 6 weeks. material may be seen on biopsy.
• Complications usually are caused by inappropriate
techniques or inadequate postoperative care.
• Misapplication of orthodontic forces can result in Chemical Injury
resorbed roots, devitalized teeth (necrotic pulp), Strong alkalis (lye solutions) and acids, petroleum dis-
avulsed teeth, periodontal pockets, gingivitis, tillates, and phenols can damage the oral cavity. In many
and failure to achieve the desired orthodontic cases, the specific agent is not identified and the diag-
movement. nosis is based on circumstantial evidence. Concurrent
esophageal and gastrointestinal mucosal injury supports
the diagnosis of ingestion of a caustic substance.
STOMATITIS/GINGIVITIS
Stomatitis/gingivitis is a common clinical problem.
Nocardia Infection
Always attempt to identify a specific underlying cause, Nocardia spp. have been associated with severe halitosis,
because this can determine the therapeutic approach gingivitis, and oral ulcerations in dogs. In severe cases,
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*Symptomatic therapy appropriate for all causes of stomatitis may include systemic, oral antibiotics, especially for severe gingivitis or necrotic oral ulcerations,
such as amoxicillin (10 to 20 mg/kg q12h), metronidazole (25 mg/kg q12h), clindamycin (10 mg/kg q12h), and tetracycline (20 mg/kg q8h); oral rinses with
0.1% to 0.2% chlorhexidine or 1% hydrogen peroxide, three to four times daily; dental prophylaxis as needed; and soft food (canned or gruel).
†Rare in clinical practice.
ANA, antinuclear antibody; BUN, blood urea nitrogen; CBC, complete blood count; GI, gastrointestinal; IFA, indirect fluorescent antibody; LE, lupus erythe-
matosus; T4, thyroxine; TSH, thyroid-stimulating hormone.
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• Differentiate lesions from neoplasia (especially mast • If general anesthesia is required for complete oral
cell tumor), mycotic infections, and foreign body examination, obtain results of laboratory tests before
reaction. anesthesia.
• Perform ancillary tests as suggested by specific
Clinical Signs historical and physical examination findings, such
as FeLV, FIV, and Bartonella tests in cats with
Clinical signs of stomatitis/gingivitis include hypersali- chronic stomatitis/gingivitis; fine-needle aspiration
vation, drooling, halitosis, oral bleeding, reluctance to of enlarged mandibular lymph nodes for suspected
eat dry food, dysphagia, anorexia, and weight loss. neoplasia; and antinuclear antibody (ANA) and
lupus erythematosus (LE) tests for suspected SLE.
▼ Key Point Chronic stomatitis/gingivitis can be extre-
mely painful and can cause behavioral changes
• Bacterial and fungal cultures of the oral cavity can be
performed on scrapings, swabs, or pieces of tissue.
such as reclusive behavior, dropping food while
Unfortunately, cultures are not usually helpful, owing
eating, and running away from the food dish
to the large number of potentially pathogenic organ-
because of pain on eating.
isms present as normal flora. Exceptions include
isolation of Candida and Nocardia organisms.
Diagnosis • If bacterial cultures yield a large growth of a single
Base the overall strategy for diagnosis of stomatitis/ organism, antibiotic therapy based on sensitivity pat-
gingivitis without an obvious underlying cause (e.g., terns may be warranted.
foreign body) on the following measures: • Specialized laboratories can use virus isolation tech-
niques to detect calicivirus infection, but the clinical
• Rule out underlying systemic disorders with appro- significance of a positive result in cats with chronic
priate laboratory testing. stomatitis is poorly understood.
• Pursue specific diagnostics such as dental evaluation
and oral biopsies and cultures.
• Perform dental prophylaxis (as needed) and initiate Radiography
symptomatic therapy while awaiting test results (see • In animals with periodontal disease, radiograph in-
Table 64-8). volved areas to identify periodontal defects, retained
root tips, and odontoclastic root resorptive lesions, as
History discussed elsewhere in this chapter.
• Obtain a complete history, with special emphasis on • Skull radiographs may show lysis of bone secondary
potential exposure to foreign bodies, chemicals, to neoplastic disease.
drugs, and toxins.
• Look for signs suggesting underlying systemic disease Biopsy and Histopathologic Evaluation
(see Table 64-8).
Tissue biopsy is essential when evaluating chronic stom-
Physical and Oral Examinations atitis, especially when proliferative lesions are present.
Histopathology is useful to characterize the cellular
• Perform a general physical examination. In parti- response, identify specific causes, and differentiate neo-
cular, evaluate for concurrent dermatologic lesions, plastic from non-neoplastic lesions.
especially at mucocutaneous junctions (e.g., nail
beds, anus, vulva, prepuce) that suggest an underly- • If autoimmune disease is suspected, evaluate oral and
ing autoimmune disorder. skin biopsies as described in Chapter 37.
• Oculonasal discharges and fever in a cat supports the • Cytology can be performed on impression smears
diagnosis of an underlying viral upper respiratory of exudates or biopsied tissue and may be useful to
infection (see Chapter 11). diagnose underlying neoplasia (e.g., melanoma) and
• Perform a complete oral examination, including infection (e.g., Nocardia and Candida spp.).
periodontal evaluation, to identify and characterize
the nature and extent of the lesions. This usually
requires sedation or general anesthesia. A specific Treatment
diagnosis can sometimes be made on oral examina- Treatment is based on the initiating cause. Whenever
tion (e.g., foreign body, periodontal disease). possible, institute specific therapy, such as removal of
foreign bodies, immunosuppressive therapy for auto-
Laboratory Evaluation immune diseases, corticosteroids for eosinophilic
• Perform routine laboratory tests including a CBC, granuloma complex, sulfadiazine for nocardiosis, and
biochemical profile, and urinalysis to identify under- ketoconazole for candidiasis (see Table 64-8). Sympto-
lying systemic diseases such as renal failure (see matic treatment of stomatitis usually is warranted,
Chapter 77) and diabetes mellitus (see Chapter 34). regardless of whether specific therapy is available.
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TONSILLITIS Treatment
Secondary tonsillitis is usually resolved with identifica-
Tonsillitis is seen occasionally in dogs and less fre- tion and treatment of the predisposing disorder. When
quently in cats. a predisposing disorder cannot be identified, adminis-
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Prognosis
The prognosis is poor.
Sublingual
gland
Mandibular
SALIVARY GLAND DISEASES gland
Orifice of sublingual duct
Diseases of the salivary glands that may be encountered Orifice of mandibular duct
include Figure 64-18. Salivary glands in the dog.
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Neoplasia Diagnosis
Tumors of the salivary glands (e.g., adenocarcinoma) The diagnosis of salivary gland disease is based on
are rare. The parotid and submandibular salivary glands history, clinical signs, clinical pathologic findings, radi-
are most susceptible to tumor formation. ography, and histopathology.
• The diagnosis of mucoceles usually is based on pal-
Clinical Signs pation and aspiration of a clear or blood-tinged,
Clinical signs depend on the salivary gland affected and viscid, mucinous fluid that is consistent with saliva.
the type of disease present.
▼ Key Point Perform aspiration of mucoceles under
Mucoceles aseptic conditions to prevent infection of a
mucocele.
Clinical signs depend on the location of the mucocele.
• Animals with cervical mucoceles usually are pre- • Sialography also can be used; however, it is somewhat
sented because of a soft, fluctuant non-painful mass difficult to perform and is usually not necessary.
in the cervical area. • Base the diagnosis of sialoadenitis on clinical signs,
• Animals with a ranula often are presented because of an elevated white blood cell count, and histopathol-
abnormal tongue movements, reluctance to eat, ogy.
dysphagia, and blood-tinged saliva. • Histopathology is necessary to diagnose salivary gland
• Animals with a pharyngeal mucocele usually are pre- neoplasia. Thoracic radiography can evaluate for
sented because of difficulty breathing or swallowing. metastatic disease.
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Preoperative Considerations
• Prior to salivary gland surgery, perform a thorough
physical examination and appropriate laboratory
tests and radiographic procedures, based on the
animal’s clinical signs, physical examination findings,
and age. Figure 64-19. Surgical excision of the mandibular and sublingual
• Diagnosis of the type of salivary disease is necessary salivary glands. See text for details.
before surgical intervention.
Drainage of Zygomatic Salivary Gland • Remove the ipsilateral mandibular and sublingual
(Treatment of Sialoadenitis) salivary glands to prevent recurrence of the mucocele
(see previous section in this chapter).
Technique
1. Place the animal in lateral recumbency and swab the Postoperative Care and Complications
mucosa caudal to the maxillary second molar with • Administer broad-spectrum antibiotics periopera-
dilute povidone-iodine (Betadine) solution. tively.
2. Gently advance a small mosquito forceps through a • Feed a soft diet for 1 week postoperatively.
small stab incision in the inflamed oral mucosa
caudal to the last maxillary molar. Complications
3. Use caution to prevent damage to the maxillary
artery and nerve that course ventromedial to the Complications vary according to the initial problem.
orbit. • Salivary mucocele recurrence —re-explore for residual
salivary tissue. Ligation of the mandibular and sub-
Surgical Excision of Zygomatic Salivary lingual salivary ducts with a non-absorbable suture
during the initial surgery will aid in the localization
Gland (Treatment of Mucocele) of residual salivary tissue. Removal of residual tissue
Technique is curative.
1. Place the animal in lateral recumbency and routinely • Sialoadenitis—clinical response is good if drainage is
prepare the surgical site. adequate and appropriate antibiotics, based on bac-
2. Protect the animal’s eyes from irritants with oph- terial culture and sensitivity testing, are given.
thalmic ointment. • Neoplasia—recurrence is possible. Postoperative
3. Make an incision along the dorsal aspect of the zygo- adjuvant chemotherapy and/or radiation therapy
matic arch. may be beneficial in animals with salivary gland
4. Reflect the periosteum of the zygomatic arch ven- adenocarcinomas.
trally and retract the palpebral fascia dorsally.
5. Remove the dorsal aspect of the zygomatic arch,
using rongeurs. SUPPLEMENTAL READING
6. Retract the globe dorsally to expose the zygomatic
Harvey CE, Emily PP: Small Animal Dentistry. St. Louis: CV Mosby,
salivary gland beneath the periorbital fat. 1993.
7. Retract the gland dorsally, ligate the vessels supply- Holmstrom SE, Frost P, Eisner E: Veterinary Dental Techniques.
ing the gland, and remove the gland. Philadelphia: WB Saunders, 1998.
8. Suture the palpebral fascia to the periosteum of the Knecht CD: Salivary glands. In Bojrab MJ (ed): Current Techniques
zygomatic arch, using absorbable sutures. in Small Animal Surgery, 4th ed. Baltimore: Williams & Wilkins,
1998, p 183.
9. Close the subcutaneous tissues and skin routinely. Manfra Marretta S: Maxillofacial surgery. Vet Clin North Am Small
Anim Pract 28:1285, 1998.
Ramsey DT, Manfra Marretta S, Hamor RE, et al: Ophthalmic
Management of Pharyngeal Mucoceles manifestations and complications of dental disease in dogs and
cats. J Am Anim Hosp Assoc 32:215, 1996.
• Treat by marsupialization or by excision of the entire Wiggs RB, Lobprise HB: Veterinary Dentistry: Principles and Practice.
mucocele. Philadelphia: Lippincott-Raven, 1997.
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▼ Chapter
636
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Oral Dysphagia
Morphologic Disorders
(Abnormalities Teeth, tongue, Difficulty Dental disease Oral exam, radiography See Chapter 64 for
of prehension hard palate, prehending food Oral foreign body Oral exam, radiography treatment of
and mastication) bony or lapping water morphologic
structures, Excessive chewing Oral neoplasia Oral exam, radiography, disorders.
and TMJ and chomping biopsy
Exaggerated head Severe stomatitis Oral exam, biopsy
movements Cleft palate Oral exam
when eating Persistent frenulum Oral exam
Submerging muzzle Skeletal disorders Oral exam, skull
to drink (e.g., TMJ, radiography
Dropping food craniomandibular
from mouth osteopathy)
Pawing at face
Excessive salivation
No weight loss or
aspiration
pneumonia
Functional Disorders
CNS disease or Oral exam (atrophy or See Chapters 126
peripheral deviation of tongue and 129.
neuropathy secondary to
(cranial nerves denervation),
V, VII, XII) neurologic exam,
EMG, nerve biopsy,
CSF tap, CT scan
(see Chapter 125)
Neuromuscular Neurologic exam, EMG See Chapter 130.
disease (e.g., with repetitive nerve
myasthenia gravis, stimulation, Tensilon
botulism) test, ARA titer
(see Chapter 130)
Myopathy or myositis EMG, muscle biopsy, See Chapter 130.
(e.g., masticatory CK, AST, ANA, LE, T4
myositis, immune and TSH assay (see
polymyositis, Chapter 130)
hypothyroidism)
Pharyngeal
Dysphagia
Morphologic Disorders
(Abnormalities Pharyngeal Normal food and Inflammatory or Oral exam, skull and See Chapter 64 for
of bolus constrictor water uptake neoplastic pharyngeal radiography, treatment of
transport muscles, but repeated diseases of the biopsy of inflammatory morphologic
from the soft palate, unsuccessful pharynx, tonsils, or mass lesions, disorders.
oropharynx cranial attempts to or retropharyngeal fine-needle aspiration
through the esophageal swallow lymph nodes of lymph nodes,
cranial sphincter Spitting out endoscopy
esophageal saliva-covered food
sphincter) Eating with head Retropharyngeal Oral exam, pharyngeal
and neck tucked foreign body or radiography, fine-
ventrally abscess needle aspiration,
endoscopy
Pharyngeal food Soft palate disorders Oral exam
retention and (e.g., cleft soft
pharyngitis palate or iatrogenic
Gagging, retching shortening)
Regurgitation
Nasal discharge
Cough, fever
(pneumonia)
Table continued on following page
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Pharyngeal
Dysphagia
(cont’d)
Functional Disorders
CNS disease or Neurologic exam, EMG, See Chapters 126
peripheral nerve biopsy, CSF tap, and 129
neuropathy CT scan (see Chapter
(cranial nerves 125)
V, VII, IX, X)
Weight loss Myopathy or myositis EMG, muscle biopsy, CK, See Chapter 130
(e.g., immune AST, ANA, LE, T4
polymyositis, and TSH assay (see
hypothyroidism) Chapter 130)
Neuromuscular Neurologic exam, EMG See Chapter 130
disease (e.g., with repetitive nerve
myasthenia gravis, stimulation, Tensilon
botulism) test, ARA titer (see
Chapter 130)
Congenital Barium swallow with Cricopharyngeal
cricopharyngeal fluoroscopy, response myotomy (see
achalasia to myotomy Chapter 66)
Cricopharyngeal Barium swallow with Cricopharyngeal
asynchrony† fluoroscopy myotomy is
contraindicated
Sialadenosis Diagnosis of exclusion Phenobarbitol
(see Chapter 64)
*The type of dysphagia is first characterized as oral dysphagia versus pharyngeal dysphagia based on observing the animal eat (e.g., prehension of food and
water, swallowing). Barium swallow with fluoroscopy is useful to characterize functional oropharyngeal dysphagia but is not indicated for evaluation of mor-
phologic disorders.
†Lack of coordination between cranial esophageal sphincter opening and pharyngeal contraction.
ANA, antinuclear antibody; ARA, acetylcholine receptor antibody; AST, aspartate aminotransferase; CK, creatine kinase; CNS, central nervous system; CSF, cere-
brospinal fluid; CT, computed tomography; EMG, electromyography; LE, lupus erythematosus; T4, thyroxine; TMJ, temporomandibular joint; TSH, thyroid-
stimulating hormone.
• When a neuromuscular disorder is the underlying and drinking. Evaluate for signs suggestive of aspiration
cause of oropharyngeal dysphagia, generalized signs pneumonia (cough, dyspnea, anorexia, depression) or
of muscle weakness, atrophy, and neurologic deficits a systemic neuromuscular disorder (weakness, muscle
are often present. pain, gait abnormalities).
Signalment and History ▼ Key Point Observation of the animal eating and
The signalment may suggest certain breed predisposi- drinking is an important extension of the physical
tions for congenital neuromuscular disorders associated examination to confirm that dysphagia is present
with oropharyngeal dysphagia (see Table 65-1). Obtain and to characterize it as an oral or pharyngeal
a complete history, including a description of eating problem (see Table 65-2).
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Radiography Etiology
• Perform survey radiographs of the skull and pharyn- • Esophageal hypomotility disorders may be congenital
geal area to identify morphologic disorders such as a or acquired. A familial predisposition for congenital
pharyngeal foreign body or retropharyngeal abscess idiopathic megaesophagus has been suggested for
that can cause oropharyngeal dysphagia. many breeds of dogs and Siamese cats (see Table
• Perform thoracic radiographs to detect aspiration 65-1).
pneumonia and associated megaesophagus.
• A barium swallow with fluoroscopic examination is
required for definitive characterization of functional ▼ Key Point Breeding of animals with congenital
swallowing abnormalities, and it is essential for the megaesophagus is not recommended because of
diagnosis of cricopharyngeal achalasia. Unfortu- potential hereditability of the trait.
nately, fluoroscopy is available only at large referral
centers. • Acquired megaesophagus may occur secondary to
many disorders, especially diseases causing diffuse
neuromuscular dysfunction (Table 65-3). However, in
Ancillary Testing most dogs, a cause is not identified and the diagno-
Ancillary tests are frequently necessary to determine the sis is idiopathic megaesophagus.
cause of functional oropharyngeal dysphagia. • Megaesophagus is less likely to be idiopathic in cats.
Esophagitis associated with hiatal hernia and gas-
• Use a Tensilon response test (edrophonium chlo- troesophageal reflux is an important cause of feline
ride) (Tensilon, ICN Pharmaceuticals), acetylcholine esophageal hypomotility.
receptor antibody titer, and electromyography (EMG) • The underlying pathophysiologic mechanism for
for myasthenia gravis (MG) (see Chapter 130). idiopathic megaesophagus is unknown. Efferent neu-
• Use an EMG and muscle biopsy for polymyositis and romuscular pathways appear to be intact, and a defec-
polymyopathy (see Chapter 130). tive afferent component of the neural reflex is
• Use a cerebrospinal fluid (CSF) tap, computed tomog- suspected. Mechanisms may be similar for both con-
raphy (CT) scan, or magnetic resonance imaging genital and acquired idiopathic megaesophagus.
(MRI) for primary CNS diseases (see Chapter 125).
Clinical Signs
Treatment • Regurgitation, which may or may not be related to
eating, is the primary clinical sign of megaesophagus.
• The treatment and prognosis for oropharyngeal dys- In most cases, the more liquid the food, the less likely
phagia depend on the underlying disorder (see Table
it is to be regurgitated. Weight loss and emaciation
65-2).
occur secondary to inadequate retention of food.
• Supportive care is especially important with pharyn-
• Dyspnea, cough, and fever are indicative of secondary
geal dysphagia. Identify and treat aspiration pneu-
aspiration pneumonia, a common complication of
monia (see Chapter 163) and provide appropriate
megaesophagus.
nutritional support, including a gastrostomy tube in
severely emaciated animals (see Chapter 3).
• Cats with esophageal hypomotility typically present
for either upper gastrointestinal signs (regurgitation,
vomiting) or chronic or recurrent respiratory tract
disease (acute or chronic cough, dyspnea, noisy
breathing, nasal discharge) due to secondary aspira-
ESOPHAGEAL HYPOMOTILITY tion pneumonia.
(MEGAESOPHAGUS) • In cases in which megaesophagus is associated with
an underlying disorder (see Table 65-3), additional
Esophageal hypomotility refers to a decrease in clinical signs may be detected, including the
esophageal tone or peristalsis that may be segmental or following:
diffuse. The term megaesophagus commonly is used when • Generalized muscle weakness with MG, polymyosi-
a diffuse, severe motility disorder results in a large, tis, polymyopathy, or hypoadrenocorticism
flaccid esophagus. In most cases, the primary distur- • Neurologic deficits with CNS disease or polyneu-
bance is an abnormality of the body of the esophagus ropathy
rather than a failure of the gastroesophageal sphincter • Generalized muscle atrophy or pain with polymyos-
to relax (achalasia), as occurs in humans. Clinical find- itis
ings associated with megaesophagus reflect impaired • Obesity and alopecia with hypothyroidism
esophageal transport with secondary complications • Oropharyngeal dysphagia with generalized neuro-
such as weight loss and aspiration pneumonia. muscular dysfunction
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Routine Laboratory Tests • Offer frequent small meals with the animal in an
Perform a minimum database of tests, including the upright position. Maintain the upright position for 10
following: to 15 minutes after eating so that gravity can assist
entry of food into the stomach. In most cases, the
• Biochemical profile to screen for changes associated more liquid the diet, the easier it is for it to reach
with underlying systemic disorders that cause mega- the stomach. However, different types of food
esophagus (e.g., hyponatremia and hyperkalemia should be given on a trial basis to identify those best
in hypoadrenocorticism; hypercholesterolemia in tolerated.
hypothyroidism; and increased creatine kinase [CK] • Place a gastrostomy tube for temporary nutritional
and aspartate aminotransferase [AST] levels in support of animals with severe malnutrition (see
polymyositis) Chapter 3).
• Complete blood count (CBC) to detect a neutrophilia • Give antibiotics for treatment of aspiration pneumo-
and left shift consistent with aspiration pneumonia nia based on results of culture and sensitivity testing
• Acetylcholine receptor antibody titer to evaluate for (see Chapter 163). Caution the owner that recurrent
acquired MG, even in the absence of generalized pneumonia is a common problem and that early
muscle weakness, because acquired focal MG may detection and treatment are essential for long-term
mimic idiopathic megaesophagus (see Chapter 130) success.
• Treat the underlying disorder whenever possible (see
Ancillary Tests Table 65-3). Institute treatment for esophagitis (as
Perform other tests as indicated by clinical and discussed later in this chapter) when esophagitis is
laboratory findings to identify underlying causes of confirmed endoscopically or when esophageal hypo-
megaesophagus. motility is associated with risk factors for reflux
esophagitis (post-anesthesia, hiatal hernia).
• Adrenocorticotropic hormone (ACTH) stimulation • Smooth muscle prokinetic drugs such as metoclo-
test for hypoadrenocorticism pramide (Reglan, Robins) or cisapride (Propulsid,
• Thyroid-stimulating hormone (TSH) assay and thy- Janssen) do not appear to be useful in the manage-
roxine level for hypothyroidism ment of idiopathic megaesophagus in dogs, because
• Antinuclear antibody (ANA) and lupus erythemato- the dog’s esophagus consists entirely of skeletal
sus (LE) tests for systemic LE muscle. These prokinetic agents (cisapride more so
• Blood lead assay for lead poisoning than metoclopramide) may be useful in cats with
• Tensilon test for MG motility disorders involving the distal esophagus
• EMG for polymyopathy, polymyositis, polyneuropa- because of the smooth muscle composition of this
thy, and MG segment of the feline esophagus.
• Muscle biopsy for polymyopathy and polymyositis • A therapeutic trial with the cholinergic drug
• CSF tap for CNS disease bethanechol may be warranted, since it has been
• Transtracheal wash for cytology, and culture and sen- shown to increase the amplitude of esophageal con-
sitivity testing if aspiration pneumonia is suspected tractions determined manometrically in some dogs
with idiopathic megaesophagus. Potential systemic
Esophagoscopy side effects of bethanechol include salivation,
Esophagoscopy is not routinely indicated for evaluation lacrimation, urination, and defecation.
of megaesophagus unless obstructive disease of the gas- • Surgical myotomy of the gastroesophageal sphincter
troesophageal sphincter or reflux esophagitis is sus- is not recommended because “achalasia” of the
pected. With idiopathic megaesophagus, the esophagus sphincter is not usually present.
appears flaccid and dilated throughout its entire length
and contains variable amounts of froth, fluid, or food.
The esophageal mucosa is usually normal.
Prognosis
Esophageal Manometry • Some animals with congenital idiopathic mega-
This is an extremely useful diagnostic tool to detect and esophagus may improve in time with diligent
characterize esophageal motility disorders in humans, supportive care.
but it is not widely used in veterinary medicine because • Idiopathic acquired megaesophagus is usually irre-
of the expense and the lack of patient cooperation. versible. The animal may do well for months to years
if the owner is dedicated to performing appropriate
Treatment feeding procedures and if pneumonia is detected and
treated early.
▼ Key Point Treatment of megaesophagus is primar- • Aspiration pneumonia and euthanasia are the
ily supportive and symptomatic, unless a reversible most common causes of death in animals with
underlying disorder can be identified. megaesophagus.
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Treatment
Clinical Signs
Esophageal foreign bodies should be considered an
• Most dogs and cats with esophageal foreign bodies emergency situation. Do not delay foreign body
are presented for evaluation of acute onset of removal, as the likelihood of complications increases
gagging, salivation, dysphagia, and regurgitation. with time. Institute fluid therapy as needed to correct
• If esophageal foreign bodies go undiagnosed initially, secondary fluid and electrolyte imbalances before
they may cause chronic regurgitation and dysphagia. general anesthesia.
oral medications, including nonsteroidal anti-inflam- • Contrast radiography is often normal. When
matory drugs and bisphosphonates, are reported esophagitis is severe, the mucosa may appear irregu-
to cause esophageal irritation in humans and have lar. Segmental luminal narrowing can occur with
the potential to cause mucosal injury in dogs and involvement of the submucosa and tunica muscularis.
cats. This radiographic appearance can be difficult to dis-
• Thermal injury may occur with ingestion of food that tinguish from a fibrous stricture.
has been heated to high temperature (e.g., in a
microwave). Endoscopy
• Gastroesophageal reflux of gastric or duodenal contents Endoscopic evaluation of the esophageal mucosa is the
is a common cause of esophagitis. Esophageal most sensitive method for detecting esophagitis.
damage is attributed to mucosal contact with gastric
acid, pepsin, bile acids, and trypsin. Predisposing • Findings include mucosal erythema, hemorrhage,
factors that may contribute to reflux esophagitis increased friability, erosions or ulcers, and in severe
include general anesthesia, use of a head-down tilt cases, pseudomembranes, indistensibility, and stric-
table for surgery, an indwelling nasogastric tube or tures.
pharyngostomy tube, hiatal hernia, chronic vomiting, • If gastroesophageal reflux is the cause of esophagitis,
and delayed gastric emptying. lesions are most severe in the distal esophagus, espe-
• Pythium insidiosum as a cause of severe necrotizing cially linear erythematous streaks and erosions, and
pyogranulomatous esophagitis has been described in the gastroesophageal junction may appear dilated.
two dogs from the southern United States. Infection • Reflux of gastric contents into the esophagus may be
is believed to occur from the ingestion of zoospores noted during endoscopy.
in stagnant fresh water. Diagnosis is confirmed by
demonstrating characteristic hyphae with Grocott’s Treatment
methenamine silver stain on an esophageal biopsy.
Mild esophagitis frequently resolves without treatment
Medical therapy of pythiosis is usually unsuccessful;
and may not require additional therapy, especially when
however, the combination of itraconazole (10 mg/kg
the cause (e.g., foreign body) can be easily resolved.
PO q24h) and terbinafine (5–10 mg/kg PO q24h)
has been effective in some dogs with pythiosis (see
Chapter 40). General Therapy
• Administer antibiotics (e.g., ampicillin, amoxicillin,
Clinical Signs or cephalosporins) routinely to prevent or control
infection of the altered mucosa by oral bacteria.
• Signs of esophagitis are nonspecific for esophageal • Maintain adequate nutrition in mild cases with fre-
disease in general and include dysphagia, regurgita-
quent oral feeding of small portions of a non-
tion, repeated swallowing, and excess salivation.
abrasive, soft food. Place a gastrostomy tube in
• Anorexia, depression, and fever suggest secondary
animals with severe esophagitis, prolonged anorexia,
aspiration pneumonia or perforation.
or inability to retain food.
• Weight loss and dehydration may occur with chronic
or severe esophagitis.
Therapy for Reflux Esophagitis
• With mild esophagitis, signs may be absent.
See Chapter 67 (Table 67-3) for pharmacology, adverse
Diagnosis effects, and prescribing information concerning each of
the following medications.
Consider potential predisposing factors in the patient’s
history, such as recent general anesthesia or exposure • Give a promotility agent, such as metoclopramide
to foreign bodies, doxycycline (cats), or caustic (Reglan, Robins) (0.2–0.4 mg/kg PO or SC q8h) or
materials. cisapride (Propulsid, Janssen) (0.25–0.5 mg/kg PO
q8–12h in dogs or 2.5–5.0 mg total dose per cat PO
Physical Examination q8–12h), to decrease gastroesophageal reflux (by
increasing gastroesophageal sphincter pressure) and
Oral ulcerations or stomatitis may be present if caustic promote gastric emptying.
injury occurred. Weight loss and dehydration may be
detected when esophagitis is severe.
• Decrease acidity of refluxed gastric juice by giving
an H2-receptor blocker such as famotidine (Pepcid,
Merck) (0.5–1.0 mg/kg PO or IV q12–24h) or raniti-
Radiography dine (Zantac, GlaxoSmithKline) (2 mg/kg PO or IV
• Survey radiographs usually are unremarkable. Occa- q8–12h in dogs or 3.5 mg/kg PO q12h in cats). H2-
sionally, small amounts of gas may be seen in the receptor blockers are preferable to antacids for
esophagus and mild to moderate focal esophageal control of acid secretion because of their potency and
dilatation may occur secondary to delayed motility. ease of administration.
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• Traction diverticula occur secondary to periesophag- • Most esophagobronchial fistulas occur in the caudal
eal inflammation that results in fibrosis and contrac- esophagus, probably due to the close anatomic prox-
tion, which pulls out the wall of the esophagus into a imity of the caudal esophagus and bronchi in this
pouch. region.
• Esophagobronchial fistulas commonly are accompa-
Clinical Signs nied by an esophageal diverticulum.
• Large diverticula interfere with orderly movement of • A traction diverticulum may develop secondary to
ingesta through the esophagus and cause clinical periesophageal inflammation and fibrosis in the
signs because they predispose to impaction with region of the fistula.
foreign bodies or food, which may lead to esophagi- • A pulsion diverticulum may develop secondary to
tis and even perforation. lodging of a foreign body.
• Signs include regurgitation, distress after eating, • The diverticulum may occur first and predispose to
anorexia, weight loss, intermittent thoracic or lodging of a foreign body and subsequent fistula
abdominal pain, and respiratory signs. formation.
• Clinical signs may not occur with small diverticula.
• Esophagoscopy and bronchoscopy can be per- Regurgitation of undigested food commonly occurs
formed, but a contrast esophagram is more reliable immediately after eating but is sometimes delayed, as
for detecting fistulas. ingesta is retained in a large esophageal pouch that
develops cranial to the obstruction. Liquids and semi-
Treatment solid food are preferentially retained because they
• Treatment of esophageal fistulas requires surgery for can pass through the constricted area.
esophagotomy, foreign body removal, fistula resec- • Weight loss or failure to gain weight despite a good
tion, and lobectomy. appetite is common.
• Perform culture and sensitivity testing of involved • Cough and dyspnea suggest aspiration pneumonia.
tissues for appropriate antibiotic therapy.
Diagnosis
Prognosis Regurgitation since weaning is very suggestive of a vas-
If severe complications such as pneumonia, pulmonary cular ring anomaly. Most animals are presented by 6
abscesses, and pleuritis are present, the prognosis is poor. months of age, although occasionally signs are mild and
a diagnosis is not made until later in life. Differentiate
vascular ring anomalies from other causes of regurgita-
VASCULAR RING ANOMALIES tion in young animals such as congenital megaesopha-
gus and, less frequently, esophageal foreign bodies.
Etiology Diffuse esophageal hypomotility (megaesophagus)
Vascular ring anomalies are congenital malformations occasionally complicates vascular ring anomalies in
of the great vessels and their branches that entrap the dogs.
intrathoracic esophagus and cause clinical signs of
esophageal obstruction. Physical Examination
The cervical esophagus may be distended secondary to
Persistent Right Aortic Arch partial obstruction and development of a pouch.
This malformation accounts for 95% of vascular ring Cough, dyspnea, pulmonary crackles, and fever indicate
anomalies in dogs and cats. Persistent right aortic arch aspiration pneumonia.
(PRAA) occurs when the embryonic right rather than
the left fourth aortic arch becomes the functional adult Radiography
aorta. The ductus arteriosus continues to develop from • Survey thoracic radiographs often suggest a vascular
the left side, forming a band that crosses over the esoph- ring anomaly. The dilated esophagus appears as a
agus to connect the main pulmonary artery and the food- or fluid-filled density cranial to the heart, which
anomalous aorta (Fig. 65-1). Esophageal compression tapers to normal at the base of the heart. In the ven-
occurs by the aorta on the right, the ligamentum arte- trodorsal (VD) view of PRAA, the normal bulge of the
riosum (remnant of the ductus arteriosus) dorsolater- aortic arch to the left is absent. Tracheal deviation
ally on the left, the pulmonary trunk on the left, and consisting of a leftward curvature near the cranial
the base of the heart ventrally. border of the heart on the dorsoventral (DV) (or VD)
PRAA appears to have a familial tendency, because radiographs is a consistent feature. Moderate to
certain breeds (see Table 65-1), especially German shep- marked focal tracheal narrowing may also be seen on
herds and Irish setters, appear to be predisposed and the DV (or VD) and lateral thoracic views.
multiple animals in a litter may be affected. The mech- • Perform a barium esophagram (see Chapter 4) to
anism of inheritance may involve single or multiple confirm the location of esophageal obstruction and
recessive genes. Breeding of affected animals is not severity of esophageal distention. Differential diag-
recommended. noses for this radiographic appearance include an
intramural stricture, segmental motility disorder, or
Other Anomalies congenital diverticulum.
Other anomalies that have been described include • Fluoroscopy is useful to evaluate generalized esoph-
double aortic arch, persistent right ductus arteriosus ageal hypomotility.
(with normal left aortic arch), aberrant left or right sub- • Angiography is seldom necessary but in selected cases
clavian arteries, and (in English bulldogs) esophageal can be used for definitive confirmation of the type
compression by the left subclavian and brachiocephalic and location of vascular ring anomaly prior to surgery.
arteries.
Endoscopy
Clinical Signs • Endoscopy can distinguish a mural lesion from extra-
• Affected animals are usually presented for regurgita- luminal compression. In animals with PRAA, the
tion of solid food that began at the time of weaning. indentation in the esophagus caused by external
W0422-Ch065.qxd 11/10/05 5:34 PM Page 651
Internal
Common
carotid
a. External
Aortic
arch
Main pulmonary artery Left
Right subclavian a.
subclavian a.
Esophagus
Right
subclavian a.
Internal
External
Common
carotid a.
Main pulmonary artery Left subclavian a.
Esophagus
B
Figure 65-1. Persistent right aortic arch. A, Normal development of the aortic arch viewed from the animal’s left side. Inset shows normal
embryonic development of the great vessels from a dorsoventral view. B, When the embryonic right fourth aortic arch becomes the adult aorta,
esophageal constriction occurs. Inset shows dorsoventral view of the vascular malformation.
quent elevated feedings of small amounts of a semi- to hiatal hernia since severe inspiratory dyspnea
moist or liquid diet. If this diet is poorly tolerated, results in negative intrathoracic pressure, which may
consider feeding through a gastrostomy tube (see pull the stomach into the thorax. Bulldogs with
Chapter 3). severe manifestations of brachycephalic syndrome
• Control aspiration pneumonia with antibiotics before appear to be at increased risk for hiatal hernia.
surgery (see Chapter 163). • Reversible hiatal hernia and megaesophagus may be
• Significant clinical improvement usually occurs after seen as a complication of tetanus in dogs.
surgery, although mild esophageal distention often • Congenital idiopathic megaesophagus predisposes
persists, especially if a large cranial diverticulum was to GEI, presumably due to decreased esophageal
present. motility and decreased gastroesophageal sphincter
• Manage as described for megaesophagus if regurgi- pressure.
tation persists.
• Recovery of normal esophageal function is more Clinical Signs
likely if surgery is performed at an early age and Small hiatal hernias or intussusceptions may not be asso-
esophageal dilatation is not severe. ciated with clinical signs unless complicated by reflux
esophagitis. If the hernia or intussusception occurs
intermittently, clinical signs also may be intermittent.
HIATAL DISORDERS Common signs include vomiting, regurgitation, hyper-
salivation, and weight loss. Dyspnea also is common and
Anatomic abnormalities of the hiatus include hiatal may be due to aspiration pneumonia or compression of
hernia and gastroesophageal intussusception (GEI). the lungs secondary to large hernias.
• A sliding hiatal hernia is a protrusion of any structure
(usually the distal esophagus and stomach) through the Hiatal Hernia
esophageal hiatus of the diaphragm into the thorax. Signs are due primarily to impaired gastroesophageal
• A paraesophageal hiatal hernia involves displacement sphincter function, which predisposes to gastro-
of a portion of the stomach through a diaphragmatic esophageal reflux, reflux esophagitis, and segmental or
defect adjacent to the esophageal hiatus and is rare diffuse esophageal hypomotility. Dogs and cats with
in veterinary medicine. asymptomatic hiatal hernia may become symptomatic
• Differentiate hiatal hernia from GEI, in which the after general anesthesia, when impaired gastro-
stomach (and occasionally other structures such as esophageal sphincter function predisposes to reflux
the spleen, proximal duodenum, pancreas, and esophagitis and esophageal stricture formation. If large
omentum) invaginates or prolapses into the distal portions of the stomach are displaced through the
lumen of the esophagus. Hiatal hernias and GEI may diaphragm, signs occur because of esophageal and
be intermittent or persistent. gastric obstruction.
Etiology Gastroesophageal Intussusception
Congenital or acquired enlargement of the esophageal GEI can cause both esophagitis and esophageal obstruc-
hiatus or laxity of the surrounding ligaments may pre- tion. When a large portion of the stomach is intussus-
dispose to hiatal hernias and GEI. cepted, rapid clinical deterioration is evidenced by signs
of dyspnea, hematemesis, profound depression, col-
Congenital Hiatal Disorders lapse, and sudden death.
• Most hiatal hernias are congenital and occur as
a developmental defect of the diaphragmatic Diagnosis
esophageal hiatus. Shar-Pei dogs and brachycephalic breeds are predis-
• Sliding hiatal hernia has been described in young posed to hiatal hernia, and GEI occurs most frequently
Shar-Pei dogs. Concurrent megaesophagus or in young male dogs. Regurgitation prior to the onset of
esophageal hypomotility, which resolved after surgi- GEI suggests that megaesophagus may be a predispos-
cal correction of the hernia, suggests that reflux ing factor. When GEI causes esophageal obstruction,
esophagitis rather than a primary motility disorder the acuteness of onset and rapid progression to death
was the underlying cause of these complications. often preclude an antemortem diagnosis.
Acquired Hiatal Disorders Physical Examination
• Acquired hiatal hernias may occur secondary to high Findings often are unremarkable unless a large hernia
positive intra-abdominal pressure (e.g., blunt abdom- or intussusception is causing esophageal obstruction. In
inal trauma or vomiting). this situation, dyspnea, collapse, and shock predomi-
• Chronic upper airway obstruction (e.g., laryngeal nate. Evaluate for evidence of concurrent upper airway
disease or brachycephalic syndrome) can predispose obstruction, which may worsen the hiatal hernia.
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▼ Chapter
66 Surgery of the Esophagus
Ronald M. Bright
In general, the signs of esophageal disease are related Body of the Esophagus
to loss of function, to obstruction, or to inflammation
of the esophagus and the surrounding structures. • The esophagus has a cervical and thoracic portion.
Surgery on the esophagus probably requires more skill • The esophagus has four layers—adventitia, muscu-
and precision than any other portion of the alimentary laris (striated in the dog, smooth muscle in the caudal
tract. The esophagus is constantly moving, lacks a one-third of the cat), a thin submucosal layer, and
serosal layer, and does not have omentum to help seal mucosa composed of stratified squamous epithelium.
small leaks. If suture line reinforcement is necessary, • The blood supply is from the thyroid and esophageal
adjacent muscle, diaphragmatic tissue, or pericardium branches of the carotid artery proximally; the bron-
may be used. Extra-abdominal movement of omentum choesophageal artery supplies the thoracic and distal
on a pedicle through a rent in the diaphragm can also portion of the esophagus. A few branches from the
be used for this purpose. left gastric artery are located just above and below the
lower esophageal sphincter.
The distal 2 cm of the esophagus is located intra- Surgical Procedure (Cricopharyngeal Myectomy)
abdominally below the diaphragm and is thought to
have a slightly thickened inner circular muscle that acts Objectives
as a sphincter. • Surgically relieve the constriction by removing fibers
of the cricopharyngeal muscle.
• Sling fibers from the lesser curvature of the stomach • Allow unobstructed movement of food from the
may reinforce the sphincteric function.
pharynx to the esophagus while decreasing the inci-
• The pinchcock effect of the diaphragmatic hiatus is dence of aspiration pneumonia.
thought to assist in preventing gastroesophageal
reflux.
Equipment
• Innervation is primarily from the vagus.
• The major portion of the blood supply is derived • Standard surgical pack
from the esophageal branch of the left gastric • Gelpi or Weitlaner retractors
artery. • Surgical suction and cautery
655
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Prognosis
• If there is no concurrent oropharyngeal or esophageal
neuromuscular disorder, the prognosis is fair to good.
• Debilitated animals may benefit from hyperalimenta- Postoperative Care and Complications
tion via a gastrostomy tube (see Chapter 3) for 7 to
10 days before surgery. Short-Term
• Evacuate the pleural cavity and administer mepiva-
Surgical Procedure caine through the indwelling chest tube to control
Objectives pain as necessary postoperatively. The chest tube
usually can be removed within 24 hours.
• Relieve the constricted portion of the esophagus • Regurgitation may continue to be a problem early in
caused by the vascular ring. the postoperative period. Feeding blenderized food
• Allow unobstructed passage of food to the stomach. with the animal in a standing position may be neces-
• Avoid perforation of the esophagus. sary because of concurrent esophageal hypomotility.
Equipment Long-Term
• Finochietto rib retractors • Amelioration of signs followed by a return of regur-
• Suction and cautery gitation several weeks after surgery may signal extra-
• Right-angle forceps luminal scar formation acting as a constricting band.
• DeBakey thumb forceps • Repeated endoscopic balloon dilatation (see Chapter
• Foley catheter or balloon dilator 65) of these strictures sometimes ameliorates signs.
• An esophagoplasty or resection of the stenotic
Technique segment may be necessary.
1. Place the animal in right lateral recumbency.
2. Aseptically prepare the left lateral thoracic wall from Prognosis
three intercostal spaces above to five spaces below • The prognosis is good in most animals. Animals with
the fourth intercostal space. severe dilatation of the esophagus cranial to the
3. To approach the vascular ring, perform a thoraco- obstruction have a poor prognosis.
tomy through the fourth intercostal space (see • Although not well documented, it is believed that the
Chapter 167 for thoracotomy technique). younger the patient at the time of surgical correction,
4. Identify the ligamentum arteriosus, which is a con- the better the prognosis.
stricting band encircling the esophagus. In a PRAA, • The prognosis is thought to be better in animals in
the aorta is on the animal’s right side and cannot be which preoperative fluoroscopy shows
seen through a left thoracotomy (see Fig. 85-1). • Normal or near-normal motility of the esophagus
5. If a PRAA is not the problem, consider vascular above and below the constriction.
anomaly variations, including a left subclavian artery • Absence of severe esophageal dilatation cranial to
originating from the brachiocephalic trunk and, less the obstruction.
commonly, a double aortic arch.
6. Double-ligate (e.g., with 3-0 or 4-0 silk) and divide
the constricting vessel.
7. Gently dissect the mediastinum and adventitia away ESOPHAGOTOMY
from the esophagus 1 to 2 cm above and below the
constricted portion. Dissect any restricting bands The most common indication for an esophagotomy is
of tissue away from the esophagus. to remove a foreign body that could not be removed by
intraluminal retrieval methods.
▼ Key Point The esophageal wall usually is very
thin; use great care to avoid perforation during Preoperative Considerations
dissection. • Place a large-bore tube in the esophagus just before
an esophagotomy to aspirate esophageal contents, act
8. Pass a large Foley catheter or balloon dilator into the
as a support while incising into the lumen of the
esophagus per os to further expand the esophagus
esophagus, and help immobilize the esophagus.
at the site of constriction.
• Treat concurrent aspiration pneumonia aggressively
before and after esophagotomy.
Closure
• Although surgery of the esophagus carries a low risk
1. Administer a long-acting local anesthetic agent (e.g., of postoperative infection, some contamination
mepivacaine) caudal to the head of the rib above and occurs. Perioperative antibiotics are recommended
below the thoracotomy incision. (given 30 minutes before surgery and repeated
2. Place a chest tube before closure. once or twice). The antibiotic chosen should be
3. Close the thoracotomy incision routinely (see effective against gram-positive pathogens (e.g., a
Chapter 167). cephalosporin).
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• If the site of anastomosis is unhealthy or compro- be performed. Injecting saline between the
mised, a reinforcement or grafting technique may be muscle layers helps to identify the outer layer.
necessary. b. Mobilizing the stomach cranially through an
• Many patients requiring esophageal resection are enlarged hiatal opening can also help to reduce
dehydrated and malnourished and may have aspira- tension across the suture line.
tion pneumonia. Ideally, correct these conditions 6. If necessary, reinforce the sutures by bringing
before resection and anastomosis. omentum on a pedicle through a small rent in the
diaphragm or by using pericardial tissue or inter-
Surgical Procedure costal musculature.
Approaches to the various parts of the esophagus are 7. Place a chest tube before thoracotomy closure.
described under Esophagotomy. Closure following
anastomosis and resection is described here. Postoperative Care and Complications
Short-Term
Objectives
• Resect the lesion and reappose the esophagus under ▼ Key Point Bypass the esophageal anastomotic site
minimal tension. and provide nutrition via gastrostomy tube for a
• Restore esophageal continuity while minimizing the minimum of 7 days.
risk of early postoperative leakage or later stricture
formation. • Monitor closely for fever, which often signals an infec-
tion secondary to leakage.
Equipment • Allow water consumption and return to oral feeding
beginning on day 7. Retain the gastrostomy tube until
• Similar to that for esophagotomy plus intestinal non- normal food and water intake can be restored.
crushing forceps
Long-Term
Technique—Closure
1. A two-layer closure, using a simple interrupted appo-
• Dysphagia or regurgitation occurring 3 to 6 weeks
postoperatively probably indicates a stricture.
sitional suture pattern, is preferred (Fig. 66-2).
a. Use non-crushing forceps (or fingers) to occlude
• Bougienage or balloon dilatation may be necessary to
relieve the postoperative stricture (see Chapter 65 for
esophageal ends during closure. discussion of esophageal stricture).
b. Use multiple stay sutures to maintain alignment
of the tissues.
2. Close the contralateral adventitial and muscular Prognosis
layers, using 3-0 or 4-0 synthetic non-absorbable • Esophageal surgery of any kind carries a poorer prog-
sutures. nosis than surgery on any other portion of the ali-
3. Appose the contralateral mucosal-submucosal layers mentary tract.
with 3-0 or 4-0 monofilament non-absorbable sutures • If the anastomosis is done with precision and the
with the knot tied in the lumen; follow with closure tension across the suture line is minimal, fair to good
of the ipsilateral mucosa-submucosa. results can be expected.
4. Close the ipsilateral superficial layers as in Step 2. • Any compromise of the tissue at the anastomotic site
5. To relieve excessive tension across the suture line: carries a guarded to poor prognosis.
a. A circular myotomy (including only the outer
muscular layer) adjacent to the anastomosis can
ESOPHAGOTRACHEAL/ESOPHAGOBRONCHIAL
FISTULAS
Preoperative Considerations
• These fistulas usually are sequelae to a chronic
foreign body.
• Most affected animals are high-risk patients because
of severe bronchopneumonia.
• It may be necessary to sacrifice a lung lobe to achieve
a cure.
Figure 66-2. Esophageal resection and anastomosis. Close the
esophageal layers in the following order: far wall, seromuscular layer; • The use of gas anesthesia may cause the stomach to
far wall, mucosal layer (knots in the lumen); near wall, mucosal layer become overinflated if the endotracheal tube is
(knots in the lumen); near wall, seromuscular layer. located cranial to the fistula.
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Long-Term
• Perform esophagography if signs of regurgitation
continue in spite of surgery and follow-up medical
therapy.
• If failure of the “pexy” procedure or if incompetence
of the lower esophageal sphincter is suspected, sur-
gical intervention is necessary.
• If a sphincter-reinforcement procedure is indi-
cated, perform the Nissen fundoplication (Fig.
66-4).
Figure 66-3. Hiatal plication for hiatal hernia. Place the stomach
in its normal position and put slight caudal traction on the stomach Prognosis
to expose the distal esophagus and esophageal hiatus. Plicate the
esophageal hiatus with non-absorbable sutures, then perform an • The prognosis is good if aspiration pneumonia is
esophagopexy by placing sutures from the diaphragm to the controlled.
esophageal wall, being careful not to penetrate the lumen and not to • Chronic reflux esophagitis associated with a hiatal
injure the vagus nerves. Perform a pexy of the fundus to the interior
body wall (insets). Incise the seromuscular layer of the fundus and then hernia may cause various degrees of esophageal stric-
incise the peritoneum and underlying muscle adjacent to the fundic ture. If the pathology is advanced to this degree, the
incision. Suture the stomach wall to the body wall as shown. prognosis is poor.
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Figure 66-4. Surgical treatment of hiatal hernia. A, Place traction on the distal esophagus and wrap the fundus around the esophagus.
B, Plicate the fundus around the distal esophagus and place a tube gastrostomy.
▼ Chapter
664
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Radiography Treatment
Perform routine ventrodorsal and lateral abdominal Treatment strategies in the vomiting animal are
radiographs to identify radiopaque foreign bodies, directed toward the following:
gastric or intestinal obstruction, and abdominal masses
or abnormalities of the kidneys, liver, and pancreas. • Correction of the underlying cause of vomiting,
whenever possible.
• Perform barium contrast radiography to evaluate for • Symptomatic and supportive therapy of vomiting and
GI causes of vomiting such as radiolucent foreign its metabolic complications.
bodies, obstruction, and mural thickening or irregu- • Surgery is indicated to remove large gastric foreign
larity. Use barium administered by stomach tube as bodies, excise localized tumors and deep ulcers, and
recommended in Chapter 4. correct gastric outflow obstruction.
• Barium mixed with food may be better than liquid
barium to detect gastric retention disorders. Fluid Therapy
• Double air-barium contrast gastrography is also
useful. • Give fluids parenterally because vomiting usually pre-
• Use aqueous iodide contrast (iohexol; Omnipaque, cludes adequate oral intake of fluid. Subcutaneous
Amersham Health) rather than barium if perforation fluid administration can be used to treat mild dehy-
is suspected. dration in the absence of other systemic signs, but IV
• Barium-impregnated plastic spheres (BIPS) are an fluid therapy is preferred for animals with moderate
alternative to liquid barium for evaluating gastric to severe dehydration. Daily fluid therapy require-
emptying and GI transit times. ments in the vomiting dog or cat depend on the
degree of dehydration, ongoing fluid losses, and
maintenance needs (see Chapter 5).
Ultrasonography
• Ideally, base the choice of replacement fluid on
Perform abdominal ultrasonography to evaluate for serum electrolyte concentrations and blood gas analy-
non-GI disorders associated with vomiting that are sus- sis, because the electrolyte and acid-base changes that
pected based on initial blood test results (e.g., pancre- occur secondary to vomiting may vary considerably.
atitis and hepatic or renal disease). Ultrasonography In the absence of such information, use a balanced
may also be helpful to evaluate for primary GI disorders electrolyte solution such as lactated Ringer’s solution,
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Phenothiazines
Increased GES tone
Phenothiazine derivatives are broad-spectrum, central-
acting antiemetics that inhibit the chemoreceptor
trigger zone (CRTZ) at low doses and depress the vom-
iting center at higher doses. Phenothiazines, especially
chlorpromazine (0.5 mg/kg SC, IM, or IV q6–8h), and Pyloric relaxation
prochlorperazine (0.5 mg/kg SC, IM, or IV q6–8h) are
the most widely used antiemetics. Increased
gastric
• Hypotension, a potentially serious side effect, is contractions
caused by alpha-adrenergic receptor blockade. Con-
sequently, use phenothiazines cautiously in patients
with preexisting dehydration.
• Sedation may occur because of concurrent tranquil-
izing properties.
Increased peristalsis
• Phenothiazine derivatives decrease the seizure
of duodenum and jejunum
threshold and should not be used in animals with
seizure disorders. Figure 67-1. Effects of promotility agents such as cisapride and
metoclopramide on the gastrointestinal tract. Promotility drugs
• Phenothiazine derivatives are the most effective increase gastroesophageal sphincter (GES) tone and promote gastric
central-acting antiemetic in cats, regardless of the emptying by coordinating increased gastric contractions with pyloric
underlying cause. relaxation and increased intestinal peristalsis.
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Treatment
GASTRIC FOREIGN BODIES
When a gastric foreign body is identified radiographi-
Gastric foreign bodies are most common in dogs owing cally, consider whether immediate removal is necessary.
to their dietary habits and indiscriminant chewing • Remove the object promptly if it is large, sharp, or
behavior. potentially toxic (e.g., pennies, nuts and bolts, and
lead objects) or if the animal is persistently vomiting,
Etiology anorexic, or dehydrated.
Gastric foreign bodies cause clinical signs because of • Small, non-toxic foreign bodies may pass through the
mechanical irritation (e.g., acute or chronic gastritis) or GI tract uneventfully and thus can be managed con-
gastric outflow obstruction. servatively if the animal is not symptomatic. Allow a
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Preparation
• Fast the animal 8 to 12 hours before anesthesia to be GASTRODUODENAL ULCERATION
sure that the stomach is empty, because food can
obscure the endoscopic view. Correct fluid, elec- For the purposes of this discussion, gastroduodenal
trolyte, and acid-base imbalances before general ulceration is defined as mucosal defects associated with
anesthesia. bleeding, which includes petechiae, erosions, and
• Repeat abdominal radiographs immediately before ulcers. Clinical recognition of gastroduodenal ulcera-
induction of anesthesia to confirm that the object tion as a complicating factor in many disorders is
remains in the stomach. This avoids an unnecessary becoming more common, most likely due to the
procedure if the object has already entered the increased use of endoscopy.
intestinal tract and is beyond the reach of the
endoscope.
Etiology
Many disorders have been associated with gastroduode-
Procedure nal ulceration (Table 67-2). Ulceration is more likely
The key to removing foreign bodies endoscopically is to when two or more risk factors are present. General
get a firm grip on the object, using a grasping forceps mechanisms of gastroduodenal ulceration include
or a basket retrieval instrument. direct damage to the gastric mucosal barrier, increased
gastric acid secretion, delayed gastric epithelial renewal,
• Use forceps for retrieval of needles, coins, and small, and decreased gastric mucosal blood flow.
soft objects. To remove the foreign body, grasp the
object, pull it up near the end of the endoscope, and
remove the endoscope, instrument, and foreign body Nonsteroidal Anti-Inflammatory Drugs
as one unit.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (see
• Use the basket for retrieval of small, round objects
Table 67-2) are frequent causes of gastric ulceration.
such as marbles or stones that cannot be grasped with
These drugs inhibit prostaglandin synthesis, which
the forceps. Large smooth objects are also removed
decreases mucosal blood flow and alters gastric mucus
with a basket, but they can be especially difficult to
production, thus predisposing to ulceration. Dogs are
maneuver back through the gastroesophageal sphinc-
more susceptible to the ulcerogenic effects of NSAIDs
ter (or upper esophageal sphincter).
than are humans.
• Use an overtube (a plastic tube that fits over the shaft
of the endoscope and can be advanced over the end • Both gastric hemorrhage and large perforating ulcers
of the endoscope) to protect the esophageal mucosa may occur. A predilection for ulceration of the
when sharp or pointed objects are withdrawn. An pyloroantral region has been recognized.
overtube is also useful to assist removal of objects • Ulceration is most likely to occur when NSAIDs
through the gastroesophageal sphincter by maintain- are given to animals with other risk factors (see Table
ing sphincter dilatation. 67-2).
• After removing the foreign body, perform a thorough • Newer NSAIDs that preferentially inhibit cyclooxyge-
examination of the stomach to look for other objects nase-2 (COX-2) rather than COX-1 enzymes such as
or mucosal lesions. This should be done even if only carprofen (Rimadyl, Pfizer), etodolac (EtoGesic, Fort
one object is seen radiographically, because radiolu- Dodge), deracoxib (Deramaxx, Novartis), meloxicam
cent objects may not have been detected or multiple (Metacam, Merial), and tepoxalin (Zubrin, Schering-
objects may have previously adhered to each other, Plough) are much less likely to cause GI bleeding.
appearing as one. If food obscures the endoscopic However, they should not be used in the presence of
view, reposition the animal in the alternate lateral ulcers or inflammatory GI disease or concurrently
position or in the ventral dorsal position. with glucocorticoids.
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Gastrinoma
Glucocorticoids
This rare gastrin-producing tumor, arising from the amine
Glucocorticoid therapy has been associated with gastric precursor uptake and decarboxylation (APUD) cells of the
erosions and bleeding but usually only when combined pancreas, causes gastric acid hypersecretion and gastro-
with other risk factors for ulceration such as NSAIDs or duodenal ulceration (Zollinger-Ellison syndrome).
in dogs with spinal cord disease (see Table 67-2). Dexa-
methasone, especially at high doses, is more likely to • Suspect gastrinoma when ulceration is associated
cause GI bleeding than is prednisolone. with gastric mucosal hypertrophy or when ulcers
respond to medical management but relapse when
Chronic Gastritis therapy is discontinued and no underlying cause can
be identified.
Various forms of chronic gastritis may be complicated • Diagnosis is made by documenting hypergastrinemia
by mucosal ulcerations, particularly eosinophilic gastri- and identifying the tumor on surgical exploration.
tis, lymphocytic-plasmacytic gastritis, granulomatous • Most pancreatic gastrinomas are small (<2 cm) and
gastritis, and gastric pythiosis (see the “Chronic Gastri- have metastasized to regional lymph nodes and the
tis” section). liver at the time of diagnosis.
Hepatic Disease
• Tumor cytoreduction may be a useful palliative pro-
cedure to temporarily control clinical signs along
Hepatic diseases of all types are commonly associated with medical therapy to control ulceration (see
with ulceration (duodenal more commonly than “Treatment” in this section).
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▼ Key Point Endoscopy is the most reliable proce- • Eliminate or control predisposing factors (see Table
dure for detection of gastric mucosal ulcers and
67-2).
erosions and is preferred over contrast radiogra- • Correct fluid, electrolyte, and acid-base imbalances.
phy, unless general anesthesia is contraindicated. • Control any GI bleeding and correct resulting anemia.
If the packed cell volume (PCV) is less than 15%, give
a blood transfusion (see Chapters 3 and 22).
• Concurrent gastric mucosal thickening or mass
lesions suggest an underlying neoplastic or inflam- • Control gastric acid secretion (Fig. 67-2).
matory disorder. • Promote mucosal cytoprotection.
• Perform mucosal biopsies, regardless of the gross
appearance, to identify predisposing causes such as Agents That Control Gastric Acid Secretion
gastritis or gastric neoplasia.
Antacids
• If perforation is suspected, perform exploratory
laparotomy. Antacids can effectively neutralize gastric acid secretion;
however, H2 blockers or proton pump inhibitors are
Laparotomy preferred because of their ease of administration and
greater potency (Table 67-3).
Laparotomy can be used to diagnose and resect gastro-
duodenal ulcers.
H2 Blockers
• Evaluate other abdominal organs, including the These drugs are most commonly used to control acid
kidneys and liver.
secretion. They inhibit basal, nocturnal, and meal-
• Carefully examine the pancreas to identify gastri-
stimulated acid secretion by blocking the H2 receptors
noma nodules.
on gastric parietal cells (see Fig. 67-2). Several H2 block-
ers (e.g., cimetidine, ranitidine, famotidine, and nizati-
Treatment dine) are available that are equally effective but differ
The goals of management of gastroduodenal ulceration in potency, frequency of administration, and potential
include the following: to inhibit hepatic P-450 enzymes (see Table 67-3).
Text continued on p. 677.
Antacids
Anticholinergic H+
agents
ATPase
H2-receptor
antagonists +
X Proton pump
Histamine inhibitors
–
Prostaglandin E2
Misoprostol
Gastrin
Figure 67-2. Representation of a gastric parietal cell showing the site of action of various therapeutic agents used to decrease gastric acid
secretion. H2 antagonists (blockers) competitively inhibit acid secretion stimulated by histamine, which is released from nearby en-
terochromaffin-like (ECL) cells by gastrin stimulation. Acetylcholine also indirectly stimulates histamine release from the ECL cells. Use of anti-
cholinergic drugs to inhibit acid secretion is limited by systemic side effects. Prostaglandin (PGE2) analogues, such as misoprostol, inhibit acid
secretion by blocking histamine-induced cyclic adenosine monophosphate production. Proton pump inhibitors such as omeprazole and pan-
toprazole have broad-spectrum antisecretory activity because they interrupt the final common pathway of acid secretion by inhibiting hydro-
gen potassium adenosine triphosphatase. Antacids neutralize luminal gastric acid.
674
Table 67-3. DRUGS USED FOR TREATMENT OF GASTRIC DISEASE
Product Special
(Manufacturer) Preparations Dosage Indications Comments*
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H2 Receptor Blocker
Cimetidine Tagamet Syrup: 60 mg/ml 5–10 mg/kg PO or Decreases gastric acid secretion Inhibits hepatic P-450 drug metabolizing enzymes.
(GlaxoSmithKline) Tabs: 100 mg (OTC), IV q6–8h Decrease the dose of the following drugs if used
200 mg (OTC), concurrently: lidocaine, beta-blockers, calcium
300 mg, 400 mg, channel blockers, theophylline, diazepam,
800 mg metronidazole, quinidine, phenytoin, warfarin. Does
Injectable: 150 mg/ml not decrease hepatic blood flow. Simultaneous oral
administration of cimetidine and sucralfate or
cimetidine and metoclopramide is acceptable if
using the higher dose range for cimetidine.
Separate oral administration from antacids by
≥1 hr. Decrease dosage in renal failure
Ranitidine Zantac Syrup: 15 mg/ml 2.0 mg/kg PO or Decreases gastric acid secretion. 4–10 times as potent as cimetidine. Minimal
(GlaxoSmithKline) Tabs: 75 mg (OTC) IV q8–12h (dog); Preferred over cimetidine when inhibition of hepatic P-450 enzymes. No effect on
150 mg, 300 mg 2.5 mg/kg IV q12h concurrently administering drugs hepatic blood flow. Separate oral administration
Injectable: 25 mg/ml or 3.5 mg/kg PO dependent on hepatic metabolism.† from antacids by ≥1 hr. Decrease dose in renal
q12h (cat) Less frequent administration than failure. Stimulates GI motility (stomach, small
cimetidine. Promotes gastric intestine, colon) by inhibiting
emptying acetylcholinesterase activity
Famotidine Pepcid Liquid: 8 mg/ml 0.5–1.0 mg/kg PO Decreases gastric acid secretion. 20–50 times as potent as cimetidine. No inhibition
(Merck) Tabs: 10 mg (OTC), or IV q12–24h Preferred over cimetidine when of hepatic drug metabolizing enzymes and no
20 mg, 40 mg concurrently administering drugs effect on hepatic blood flow. Decrease dose in
Injectable: 10 mg/ml dependent on hepatic metabolism.† renal failure
Once-a-day dosing convenience
Nizatidine Axid Tabs: 75 mg (OTC) 2.5–5.0 mg/kg PO Decreases gastric acid secretion. Similar potency as ranitidine. No effect on hepatic
(Lilly) Caps: 150 mg, 300 mg q24h Promotes gastric emptying. Once- P-450 enzymes. Stimulates gastric emptying at
a-day dosing antisecretory doses by inhibiting acetylcholin-
esterase activity, similar to ranitidine
Mucosal Protectant
Sucralfate Carafate Tabs: 1 g 1 g: large dogs, GI erosions or ulcers; Safe local-acting drug. Potential for nonspecific
(Axcam Liquid: 1 g/10 ml 0.5 g: small dogs, NSAID-induced gastritis; binding with impaired absorption of simultaneously
Scandipharm) 0.25 g: cats reflux esophagitis (susp) administered oral drugs. No effect (in dogs)
PO q8–12h on absorption of the following drugs: digoxin,
quinidine, propranolol, aminophylline, diazepam,
imipramine, and chlorpromazine. Minor effect
on cimetidine absorption, not clinically significant
at higher doses of cimetidine (and other H2
blockers?). Separate phenytoin, tetracycline, and
fluoroquinolone antibiotics from sucralfate by
≥2 hr. Antacids interfere with sucralfate binding;
W0422-Ch067.qxd 11/10/05 5:32 PM Page 675
Misoprostol‡ Cytotec Tabs: 100 mg, 200 mg 3–5 mg/kg PO Prevention of NSAID-induced GI Gastric mucosal cytoprotection at low doses, inhibits
(Searle) q6h injury gastric acid secretion at higher doses. Side effects:
diarrhea, abortion
Promotility Agent
Metoclopramide Reglan Syrup: 1 mg/ml or 0.2–0.4 mg/kg PO, IM, Central antiemetic (CRTZ) for Side effects: anxiety, agitation, tremors, twitching,
(Robins) 10 mg/ml or SC 30 min before drug-induced vomiting, constipation. Contraindicated in patients with
Tabs: 5 mg, 10 mg eating, q8h or parvoviral enteritis, and mechanical gastric outflow obstruction or epilepsy.
Injectable: 5 mg/ml 1–2 mg/kg/24 h uremic gastritis; promotility for Should not be used in combination with
given in fluids as reflux esophagitis, functional phenothiazines, butyrophenones, or narcotics.
constant-rate gastric emptying disorder, recurrent Atropine or other anticholinergic drugs
infusion gastric hairballs, reflux gastritis, antagonize effects of metoclopramide. When oral
gastric stasis 2° to gastric surgery, metoclopramide is given simultaneously with oral
ileus cimetidine, decreased cimetidine absorption occurs.
Probably not clinically significant if cimetidine
given at higher dosage range. Decrease dose in
renal failure. Metoclopramide is physically
incompatible when mixed with cephalothin
sodium, sodium bicarbonate, chloramphenicol
sodium succinate, or tetracycline. Light sensitivity
of metoclopramide occurs in dextrose solutions
after 24 hr
Table continued on following page
675
676
Table 67-3. DRUGS USED FOR TREATMENT OF GASTRIC DISEASE—cont’d
Product Special
(Manufacturer) Preparations Dosage Indications Comments*
Cisapride Propulsid Available through 0.25–0.5 mg/kg PO Same promotility indications as 5-HT4 agonist. Decrease dose in hepatic but not renal
(Janssen) compounding q8–12h (dogs); metoclopramide but has no central failure. Taken off the U.S. market due to fatal
pharmacies 2.5–5 mg PO q8–12h antiemetic effect; has effects on arrhythmias in humans
W0422-Ch067.qxd 11/10/05 5:32 PM Page 676
Many available Maalox (Al + Mg) Tabs and liquid 1–2 tabs or 5–10 ml Safe and inexpensive treatment of Potency varies between products. Crush tablets for
(OTC) Quick Dissolve PO q4–6h GI ulceration maximum effectiveness. Difficult to administer in
Maalox (CaCO3) animals. Potential side effects: constipation
Mylanta II (Al + Mg (AlOH, CaCO3), diarrhea (Mg salts),
+ simethicone) hypernatremia and alkalosis (NaHCO3),
Amphojel (AlOH) hypercalcemia and acid rebound (CaCO3),
Tums tabs (CaCO3) phosphate depletion (AlOH); impaired excretion
of aluminum and magnesium in renal failure;
nonspecific binding of concurrently administered
drugs (e.g., cimetidine, ranitidine); interference
with binding of sucralfate to GI ulcers
*All drugs that decrease gastric acidity could potentially decrease absorption of orally administered drugs that are weak bases (e.g., ketoconazole), and increase absorption of durgs that are weak acids (e.g.,
diazepam, aspirin, furosemide).
†Examples include lidocaine, propranolol, theophylline, diazepam, phenytoin, metronidazole, and warfarin.
‡Limited experience with use in cats.
§To prepare as oral suspension, dissolve 20 mg capsule or tab in 10 ml of 8.4% HCO3 to make a 2 mg/ml solution; good for 7 days.
CRTZ, chemoreceptor trigger zone; GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; OTC, over the counter (nonprescription); susp, suspension; 5-HT4 (serotonin) agonist.
W0422-Ch067.qxd 11/10/05 5:32 PM Page 677
mation further stimulates acid secretion, which, in turn, little information on the relationship of Helicobacter to
promotes further mucosal injury, altered cell mem- gastric disease in these species.
brane permeability, and decreased microvascular blood
flow. The end result is varying degrees of gastric Enterogastric Reflux
erosion, ulceration, hemorrhage, edema, and necrosis. Reflux gastritis (or bilious vomiting syndrome) refers to
gastric mucosal damage caused by persistent enterogas-
Idiopathic Chronic Gastritis tric reflux of potentially damaging constituents such as
The underlying etiology of chronic gastritis is seldom bile and pancreatic enzymes. Inappropriate pyloric
determined. Possible causes include all factors capable relaxation predisposes to excess reflux, and impaired
of causing acute gastritis (see Table 67-1) in which gastric motility contributes to delay in clearing previ-
repeated or persistent exposure occurs. ously refluxed material from the stomach. Reflux gas-
tritis is a poorly documented clinical entity in dogs.
• In cats, lymphocytic-plasmacytic gastritis is often
accompanied by diffuse inflammatory bowel disease
(see Chapter 69). Clinical Signs
• Gastroduodenal ulcerations may be associated with • Animals with chronic gastritis have intermittent vomit-
secondary lymphocytic-plasmacytic gastritis that ing, usually over a period of weeks to months. Vom-
resolves after ulcer therapy. Conversely, lymphocytic- iting is not consistently associated with eating.
plasmacytic gastritis may be complicated by gastric Hematemesis and melena may occur if gastritis is
erosions and ulcerations. associated with mucosal erosions or ulcers.
• Eosinophilic gastritis is discussed later in this chapter. • Other signs such as depression, anorexia, weight loss,
and abdominal pain are present less frequently.
Physaloptera Infection • Signs of reflux gastritis include nausea, vomiting of
The nematode parasite, Physaloptera rara, inhabits the bile-stained fluid or foam early in the morning when
stomach and duodenum of dogs and cats and is an the stomach is empty, and abdominal pain. Most
infrequent cause of lymphocytic-plasmacytic gastritis animals are otherwise healthy and do not usually
and chronic intermittent vomiting. In most infections, vomit any other time of day.
only one to five worms are found in the stomach of the
host. Diagnosis
• Embryonated eggs passed in the feces are ingested by Confirmation of chronic gastritis requires a gastric
an intermediate host (cockroach, cricket, or beetle) mucosal biopsy, obtained by endoscopy or laparotomy.
in which infected larvae develop. Infection occurs
when a dog or cat ingests an intermediate or trans- History and Physical Examination
port host (rodent or snake).
• Diagnosis of Physaloptera spp. is difficult. Fecal flota- Obtain a complete history, emphasizing potential expo-
tion using either sodium dichromate or magnesium sure to ingested drugs, foreign bodies, chemicals, irri-
sulfate solution is often recommended, but eggs may tants, and unusual diets (see Table 67-1).
not be detected due to the small number of parasites, • Response to previous therapy (e.g., a change in diet)
low fecundity of the female nematodes, and presence may indirectly suggest a dietary intolerance or allergy.
of single-sex infection. The clinical diagnosis is • The physical examination often is unremarkable.
usually made by endoscopic detection of the adult
worms attached to the stomach mucosa.
Laboratory Evaluation
Ollulanus Infection • A CBC, biochemical profile, and urinalysis are indi-
O. tricuspis is a nematode infection of cats associated cated to exclude non-GI causes of vomiting and to
with chronic fibrosing gastritis. characterize any fluid, electrolyte, or acid-base imbal-
ances resulting from vomiting.
Pythium Infection • Test results usually are normal in animals with
chronic gastritis unless vomiting is profuse, mucosal
Pythium insidiosum is a fungal infection that can lead to
erosions or ulcers cause blood loss anemia, or inflam-
pyogranulomatous gastritis in dogs.
mation of the antral and pyloric region results in
Helicobacter Infection gastric outflow obstruction.
• Upper GI contrast studies may be normal or show • Avoid further exposure to plants, chemicals, and
thickening of gastric rugal folds, mucosal irregularity, other irritants.
mass lesions, or delayed gastric emptying. These find- • In most cases, a specific cause of gastritis cannot be iden-
ings are nonspecific, and gastric biopsy is required to tified, and therefore specific therapy is unavailable.
distinguish chronic gastritis from other disorders
such as gastric neoplasia. Dietary Trials
Perform dietary trials in all animals with chronic gastri-
Endoscopy tis because dietary factors or antigens could be the incit-
Endoscopy is used to obtain mucosal biopsies and is the ing cause. Continue dietary trials for at least 2 to 4 weeks
diagnostic method of choice for confirming chronic before assessing response to therapy. Feed a controlled
gastritis. diet that is easily digestible, carbohydrate based, and
moderately fat restricted. Give frequent small meals.
• Endoscopically, the gastric mucosa may appear Avoid high-fiber diets or the feeding of only one large
grossly normal or show thickened rugae, mucosal meal per day.
irregularity or friability, hemorrhage, ulceration, or
firm areas of fibrosis. • If gastritis is mild, dietary modification may be all that
• Severe chronic gastritis may have a diffuse nodular is required to control clinical signs.
appearance that must be differentiated from gastric • Commercial or homemade hypoallergenic diets
lymphoma. (single-protein or novel-protein source) are benefi-
cial in some cases.
• Reflux gastritis often responds to frequent feedings
▼ Key Point Always obtain biopsies because histo- or feeding of a late bedtime meal. Food may be effec-
logic changes in chronic gastritis may be present tive because it buffers refluxed duodenal contents
despite a normal endoscopic appearance. and stimulates gastric motility. Metoclopramide also
may be effective (see “Gastric Motility Disorders” and
Table 67-3).
• Carefully examine the entire gastric and proximal
duodenal mucosa for adult Physaloptera, which appear H2 Blockers
as white, 1-cm-long nematodes that may be attached
to the mucosa or living free on the mucosal surface. Reduction of acid secretion with H2 blockers (discussed
Often only one worm is present. Remove any worms previously) may be useful in animals with chronic gas-
observed by use of the grasping forceps. tritis even if gross mucosal erosions or ulcerations are
• If O. tricuspis is suspected, aspirate gastric juice for absent (see Table 67-3). A 2-week trial is recommended,
microscopic examination for adult and larval forms. but long-term therapy may be required, depending on
• Gastric foreign bodies can be detected and removed. clinical response. Ranitidine and nizatidine also
• In patients with reflux gastritis, large amounts of bile- promote gastric emptying, which may be useful for sec-
stained fluid may be present in the stomach and the ondary motility disorders that may accompany chronic
pylorus may appear wide open. gastritis.
Anti-inflammatory or Immunosuppressant Drugs
Laparotomy
Prednisolone
• Perform laparotomy to obtain full-thickness gastric
biopsies and to correct associated gastric outflow • If no response is obtained with dietary control and
obstruction. H2 blocker therapy, give prednisolone (0.5–1 mg/kg
• Full-thickness biopsy may be necessary to differenti- PO q12h) for a 2-week trial period.
ate severe lymphocytic gastritis diagnosed by endo- • If remission occurs, taper this dose over a period of
scopic biopsy from gastric lymphoma. 6 to 8 weeks and maintain alternate-day therapy using
the lowest effective dose.
Treatment Azathioprine
Eliminate underlying causes of gastritis whenever
possible.
• Azathioprine (Imuran, Glaxo Wellcome), an immuno-
suppressive drug, may be useful for treatment of
• Discontinue implicated drugs (e.g., aspirin). chronic gastritis in dogs that have not responded to
• Remove gastric foreign bodies. prednisolone or when glucocorticoid side effects are
• Treat Physaloptera infections with fenbendazole a problem.
(50 mg/kg/day PO for 3 days) or pyrantel pamoate • The initial dose for dogs is 2 mg/kg PO q24h.
(15 mg/kg PO initially and repeat in 2–3 weeks). The dose can be tapered after a clinical response
• Treat O. tricuspis infections with fenbendazole is obtained, usually by giving the same dose on an
(50 mg/kg/day PO for 3 days) or pyrantel pamoate. alternate-day basis.
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Chlorambucil
• Chlorambucil, an alkylating antineoplastic or EOSINOPHILIC GASTRITIS AND GRANULOMA
immunosuppressive agent, can be used in cats that
fail to respond to corticosteroids. The dose is Eosinophilic gastritis is characterized by diffuse or focal
20 mg/m2 PO once every 2 to 3 weeks (refer to infiltration of mature eosinophils into the mucosa,
Chapter 26 for conversion of body weight to body submucosa, or muscularis. Variable increases in lym-
surface area in m2). phocytes, plasma cells, and neutrophils may also occur.
• Side effects are uncommon but may include • Eosinophilic inflammation of the stomach in dogs
myoclonus, cytopenia, and hepatotoxicity. occurs as two distinct pathologic forms:
• Diffuse eosinophilic infiltration of the gastric
Promotility Drugs mucosa and submucosa is most common and is
• Secondary motility disorders may accompany chronic usually associated with generalized eosinophilic
gastritis. If postprandial vomiting occurs, add meto- gastroenterocolitis.
clopramide, or cisapride to the above therapy (see • Single or multiple eosinophilic granulomatous
Table 67-3 and Fig. 67-1). lesions (scirrhous eosinophilic gastritis) with trans-
mural eosinophilic inflammation, severe arteritis,
Antibacterial Drugs for Helicobacter and fibrosis occur less frequently.
• Although the clinical significance of gastric spiral • In cats, eosinophilic gastritis is usually a manifestation
of inflammatory bowel disease, which is similar to
bacteria (Helicobacter spp.) in dogs and cats is unclear,
eosinophilic gastroenterocolitis in dogs. Rarely,
treatment is justified empirically when chronic gas-
eosinophilic gastroenteritis in cats is associated with
tritis is associated with large numbers of spiral bacte-
hypereosinophilic syndrome (see Chapter 69).
ria on biopsy.
• Therapy for Helicobacter spp. has been extrapolated
Etiology
from human medicine. Single antibiotics are not
effective and resistance rapidly develops; thus, effec- The cause of eosinophilic gastritis or granuloma in dogs
tive treatment usually requires “triple therapy” with a is unknown. The presence of increased numbers of cir-
combination of three antibiotics or a combination of culating and tissue eosinophils suggests an allergic or
two antibiotics plus an acid reducer such as omepra- immunologic hypersensitivity, possibly in response to
zole or an H2 blocker for potentiation. Antimicrobials dietary components or parasites.
commonly used in various combinations include clar-
ithromycin, amoxicillin, metronidazole, tetracycline,
• Food allergy or hypersensitivity has been proposed
but not proven as a cause of eosinophilic gastritis in
and bismuth. dogs.
• Only a few controlled therapeutic trials have been
• Microfilariae have been observed on histologic sec-
done in dogs and cats. It appears that some of the tions in a dog with diffuse eosinophilic gastritis.
treatment regimens effective for eradicating Heli-
cobacter pylori in humans only transiently suppress
• Eosinophilic gastroenteritis with multiple focal eosin-
ophilic granulomas has been described in German
Helicobacter in dogs and cats without eliminating the shepherds with visceral larva migrans but is not an
infection; thus, the optimal treatment protocol for important clinical cause of eosinophilic gastroent-
dogs and cats is not yet known. eritis.
• The combination of clarithromycin (7.5 mg/kg PO
q12h), amoxicillin (20 mg/kg PO q12h), and
metronidazole (10 mg/kg PO q12h) for 14 days suc- Clinical Signs
cessfully eliminated Helicobacter in 100% of cats in one
Dogs with eosinophilic gastritis usually have signs of
study and can be used to treat dogs.
chronic vomiting, anorexia, and weight loss.
• Other commonly used (but unproven) treatments for
Helicobacter in dogs include the combinations of clar- • Eosinophilic gastritis is more likely to be associated
ithromycin, amoxicillin, and omeprazole—or amoxi- with mucosal ulceration and bleeding (suggested by
cillin, metronidazole, and famotidine—given for 14 hematemesis and melena) than are other types of
to 21 days. chronic gastritis.
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• Additional clinical signs may be present if gastritis is tion requiring surgical decompression is present.
a component of diffuse eosinophilic gastroentero- Obtain multiple biopsies from the stomach and duo-
colitis. Small intestinal involvement is characterized denum.
by malabsorption and voluminous watery diarrhea, • Cytologic examination of mucosal biopsies reveals
whereas colonic or rectal involvement is character- increased numbers of eosinophils.
ized by bloody-mucoid diarrhea with tenesmus (see • A disadvantage of endoscopically obtained biopsies is
Chapter 69). that the depth of the biopsy generally is limited to the
mucosa, and deeper layers may be predominantly
Diagnosis involved in eosinophilic gastritis.
Determine previous diets and clinical responses to
dietary changes. A history of dramatic response to pre-
Laparotomy
vious corticosteroid therapy is consistent with but not • Exploratory laparotomy may reveal diffuse or focal
specific for eosinophilic gastritis. thickening in affected regions of the stomach and GI
tract.
Physical Examination • Diffuse involvement of the stomach wall or large focal
• Weight loss is common. granulomas may grossly resemble neoplasia.
• Less common findings include pain on palpation of • Regional lymphadenopathy is common.
the stomach, or the stomach may feel diffusely rigid
and firm. With large focal granulomas, a mass in the
Treatment
stomach wall may be palpated. The treatment of choice for eosinophilic gastritis in
• Additional findings that indicate more extensive dogs is glucocorticoid therapy combined with dietary
intestinal involvement include focal or diffuse thick- management.
ening of the small intestine or colon or mesenteric
lymphadenopathy.
• If a broad-spectrum anthelmintic has not been
administered recently, before initiating glucocorti-
Laboratory Evaluation coids, treat with fenbendazole (Panacur, Intervet),
50 mg/kg daily for 3 days, to eliminate undetected GI
• A hemogram often reveals eosinophilia, but not in all parasites as a potential cause of the clinical signs.
cases. • Treatment of eosinophilic gastritis in cats that is a
• Gastric erosions and ulcerations can cause anemia manifestation of hypereosinophilic syndrome is dis-
and hypoproteinemia. cussed in Chapter 69. Eosinophilic gastritis or gas-
• Heartworm and fecal flotation tests are indicated to troenteritis in cats that is associated with focal GI
identify underlying parasitism. involvement and resembles canine eosinophilic gas-
troenterocolitis can be managed as outlined next for
Radiography and Ultrasonography dogs.
• Abdominal radiography is usually normal unless Anti-inflammatory and Immunosuppressant Therapy
gastric outflow obstruction occurs secondary to trans-
mural involvement or granuloma formation at the • Administer prednisolone, 0.5 to 1 mg/kg PO q12h.
antral or pyloric region. Response is prompt and dramatic, usually occurring
• Contrast radiography may demonstrate irregularity of within 24 to 48 hours.
the gastric mucosa or diffuse or focal thickening of • Gradually taper the dosage over the following 6 to 8
the gastric wall. weeks, decreasing to once daily (given in the
• With concurrent intestinal involvement, associated morning) and then to alternate days. If the initial
radiographic changes may be identified. treatment period is too short, relapse may occur. If
• Abdominal ultrasonography may identify gastric wall relapse does not occur while tapering the dosage, dis-
thickening, masses, or enlarged mesenteric lymph continue therapy at the end of the 6- to 8-week
nodes. period. Continue to monitor for relapse.
• If side effects are a problem or if higher dosage or
Endoscopy continued daily therapy is required, give azathioprine
concurrently, as described previously for chronic
• Visual endoscopic findings are nonspecific and may gastritis.
mimic other inflammatory and neoplastic diseases.
The gross appearance may be normal in some cases.
• Involved areas of the stomach may appear diffusely Dietary Recommendations
thickened, with hemorrhages, erosions, or ulcers. Because food hypersensitivity is a potential cause of
Granulomas appear as focal mass lesions. eosinophilic gastritis, consider a trial with a hypoaller-
• Endoscopy is the preferred initial method for biopsy genic diet. Some animals with eosinophilic gastritis may
rather than laparotomy, unless mechanical obstruc- respond to a hypoallergenic diet alone. Institute a
W0422-Ch067.qxd 11/10/05 5:32 PM Page 682
dietary trial even if corticosteroids are being given, • Gastric ulcers at the pylorus may cause outflow
because it may decrease the dose of corticosteroids obstruction.
required to control clinical signs. • Gastric neoplasia, especially adenocarcinoma, can
obstruct outflow (see under “Gastric Neoplasia”).
• Suggested hypoallergenic diets include select protein • Gastric dilatation-volvulus (GDV) is a frequent cause
or novel protein commercial diets consisting of lamb,
of acute outflow obstruction and is discussed later in
egg, fish, rabbit, duck, kangaroo, or venison. An alter-
this chapter.
native approach is to use a diet containing hydrolyzed
proteins, which may be less antigenic (Prescription
• Extrinsic outflow compression may be caused by
hepatic or pancreatic inflammation, abscesses, and
Diet z/d, Hill’s, or HA Diet, Purina).
neoplasia; marked regional lymphadenopathy; and
• Choose a protein and carbohydrate source that has
diaphragmatic hernia with gastric displacement.
not been a part of the animal’s diet in the past 6
months.
• Feed the diet exclusively for at least 3 to 4 weeks Clinical Signs
before determining effectiveness.
• If a hypoallergenic diet is ineffective, try a controlled • Vomiting is a consistent sign of gastric outflow
diet that is easily digested, carbohydrate based, and obstruction. Typically, undigested food is present in
moderately fat restricted. the vomitus greater than 12 hours after eating (the
stomach normally empties by 8–10 hours after
Surgery eating).
Perform surgical resection of obstructing granulomas at
• Bile staining of vomitus is usually absent.
the antral and pyloric region and follow up with gluco-
• Projectile vomiting suggests gastric outflow
obstruction.
corticoid therapy.
• Complete obstruction results in severe, profuse
Prognosis vomiting.
• Abdominal distention caused by an enlarged fluid- or
The prognosis for eosinophilic gastritis in dogs is good. food-filled stomach may occur, especially after eating.
Most dogs respond to therapy and many have complete • Anorexia may occur because of a sense of fullness
resolution of clinical signs on a long-term basis. In from gastric overdistention.
others, relapses occur, and a hypoallergenic diet or cor- • Belching may indicate an attempt to release gas from
ticosteroid therapy is required on a long-term basis. the stomach.
• Weight loss and dehydration may result from chronic
vomiting.
GASTRIC OUTFLOW OBSTRUCTION
Etiology Diagnosis
Gastric outflow obstruction most commonly is caused by History and Signalment
mural, mucosal, and luminal abnormalities involving The history and signalment often indicate a possible
the antral and pyloric regions of the stomach (see Table underlying cause.
67-1). External compression of the gastric outflow tract
is identified less frequently. Common causes of outflow • Persistent vomiting since weaning in young animals
suggests congenital pyloric stenosis.
obstruction include the following:
• Acute onset of vomiting in young animals may indi-
• Foreign bodies often lodge in the pylorus and cause cate a foreign body.
partial or complete outflow obstruction. • Chronic vomiting with hematemesis is seen with
• Chronic hypertrophic pyloric gastropathy (CHPG) is gastric neoplasia, chronic gastritis, and gastric ulcer.
a benign disorder of middle-aged to older small- • Chronic intermittent vomiting over weeks to months
breed dogs that frequently results in outflow obstruc- in middle-aged and older small-breed dogs is consis-
tion (see “Hypertrophic Gastropathy”). tent with CHPG.
• Pyloric stenosis is hypertrophy of the circular muscle • Acute onset of non-productive retching and gagging
fibers of the pylorus. Congenital pyloric stenosis accompanied by abdominal distention in large-breed
occurs in young dogs and cats. Acquired muscular dogs suggests GDV.
pyloric stenosis is sometimes a component of CHPG
in older animals.
• Chronic gastritis, especially eosinophilic gastritis and Physical Examination
granuloma, that involves the antral and pyloric The examination may be unremarkable, or potential
region can result in outflow obstruction. findings can include abdominal distention and signs
• Obstructing granulomas may be a manifestation of associated with metabolic abnormalities secondary to
fungal gastritis caused by pythiosis or histoplasmosis. profuse vomiting, such as weakness and dehydration.
W0422-Ch067.qxd 11/10/05 5:32 PM Page 683
activity of the stomach. Control of gastric motility and metabolic abnormalities. For example, neutropenia
emptying is influenced by hormones, autonomic associated with acute onset of vomiting, bloody diar-
nervous input, and composition of the food. Emptying rhea, and gastric retention and hypomotility in a young
is prolonged as the fat and protein content, acidity, dog suggests parvoviral gastroenteritis.
osmolality, and viscosity of the gastric contents increase.
The following factors may be associated with func- Radiography
tional delays in gastric emptying:
• Perform abdominal radiographs. Delayed gastric
• Drug therapy with anticholinergic drugs, adrenergic emptying is suggested by the finding of a distended
agonists, or narcotic analgesics can delay gastric fluid-filled stomach or food present in the stomach
emptying. greater than 12 hours after eating.
• Inflammatory lesions such as gastritis, gastric ulcers, • Perform a contrast gastrogram to assess gastric emp-
Physaloptera infection, and parvoviral gastroenteritis tying, as described previously under “Gastric Outflow
can alter gastric motility. Obstruction.” Normal gastric emptying of barium
• Acute abdominal inflammation caused by pancreati- does not exclude a gastric motility disorder because
tis and peritonitis can alter gastric motility. it evaluates only the ability of the stomach to empty
• Nervous inhibition associated with stress, trauma, liquids and not solids. In functional gastric motility
pain, or psychogenic input may cause a transient disorders, the gastric outflow region appears normal,
delay in gastric emptying due to increased sympa- but barium may not leave the stomach in a timely
thetic stimulation. fashion.
• Metabolic disturbances such as hypokalemia, endo- • Commercially available BIPS have also been used to
toxemia, and hypothyroidism may delay gastric evaluate gastric emptying time.
emptying.
• Neurogenic causes of delayed gastric emptying Endoscopy
include dysautonomia and vagal nerve damage.
• Dogs recovering from GDV commonly have gastric
• Endoscopy is a useful non-invasive method to exclude
mechanical outflow obstruction as a cause of delayed
myoelectrical and motor abnormalities.
gastric emptying.
• Prolonged gastric obstruction may be complicated by
• Fast the patient for at least 24 hours before
secondary motility dysfunction.
endoscopy to ensure that the stomach is empty. Large
• In many cases, functional gastric emptying disorders
volumes of fluid are often present and should be
are idiopathic. These disorders may be associated
aspirated through the endoscope to improve
with abnormal gastric electrical conduction distur-
visualization.
bances such as tachyarrhythmias.
• Recurrent trichobezoar formation in cats may be
• In idiopathic gastric motility disorders, the gastric
mucosa and pyloric outflow area appear normal. If
related to abnormal migrating motor complexes that
gastritis is a predisposing cause, gross and micro-
impair gastric emptying of indigestible material
scopic changes will be detected.
during fasting.
Electrogastrogram
Clinical Signs
Electrogastrograms have been used on a research basis
The clinical signs of a gastric motility disorder causing to document abnormal gastric electrical rhythms and
delayed gastric emptying are similar to those of gastric may have clinical applications in the future.
outflow obstruction. These include the following:
• Vomiting of undigested food more than 12 hours Treatment
after eating Whenever possible, identify and correct the underlying
• Abdominal distention and discomfort after eating cause of a gastric motility disorder. For example, dis-
• Anorexia and belching continue any anticholinergic drug therapy.
Promotility Therapy
The treatment for idiopathic gastric motility disorders
HYPERTROPHIC GASTROPATHY
is a motility modifier such as metoclopramide, cis-
The term hypertrophic gastropathy is used to describe a
apride, erythromycin, or the H2 blockers ranitidine or
heterogeneous group of poorly understood disorders
nizatidine (see Table 67-3). The effects of metoclo-
associated with focal, multifocal, or diffuse hypertrophic
pramide and cisapride on the stomach are shown in
changes of the gastric mucosa of dogs. Hypertrophic
Figure 67-1.
gastropathy appears to be quite rare in cats. Various
other names have been used, including CHPG, hyper-
Metoclopramide trophic gastritis, gastric polyps, and acquired pyloric
stenosis or hypertrophy. These disorders may be varia-
• Although metoclopramide, a dopaminergic antago- tions of the same disease process. Microscopic changes
nist, has traditionally been used as a first choice are variable and include hyperplasia of mucosal epithe-
gastric promotility drug, its effectiveness in promot- lial cells, glandular hypertrophy, variable inflammatory
ing gastric emptying may be overstated. infiltrates, and mucosal ulceration.
• Give metoclopramide one-half hour before meals at The most commonly recognized form of hyper-
a dose of 0.2 to 0.4 mg/kg PO q8h. trophic gastropathy in dogs is a benign disorder associ-
ated with mucosal hypertrophy of the antral and pyloric
region, resulting in gastric outflow obstruction. Some
Cisapride affected dogs have a component of pyloric muscular
• Cisapride, a serotonergic (5-HT4) agonist, appears to hypertrophy. This disorder has been termed chronic
be more effective than metoclopramide for gastric hypertrophic pyloric gastropathy (CHPG).
emptying, but availability of cisapride is limited to com-
pounding pharmacies. Cisapride was taken off the Etiology
market because of fatal ventricular arrhythmias that
occurred in humans but have not been documented Little is known about the underlying etiology and patho-
in dogs and cats. Cisapride lacks the broad-spectrum physiologic mechanisms of hypertrophic gastropathy;
central antiemetic effects of metoclopramide. thus, the disease is idiopathic in most cases. Environ-
• Administer cisapride one-half hour before meals at a mental, hormonal, genetic, and immune-mediated
dosage of 0.25 to 0.5 mg/kg PO q8–12h in dogs and mechanisms may play a role.
at a dosage of 2.5 to 5.0 mg PO q8–12h in cats. • Chronic irritation associated with aspirin therapy can
result in focal gastric hypertrophy.
Other Serotonin Agonist Drugs • Hormones such as gastrin, cholecystokinin, acetyl-
choline, and histamine can be trophic to the gastric
• Tegaserod (Zelnorm, Novartis) is a newly marketed mucosa. Causes of hypergastrinemia such as chronic
5-HT4 agonist. However, the intestine and colon are renal failure, chronic gastric distention, liver disease,
the predominate site of its promotility effects and it gastrin-secreting tumors, and idiopathic hypertrophy
may not be useful for treatment of delayed gastric of the antral G-cells (gastrin-secreting cells) may be
emptying. important considerations in some cases.
• Prucalopride (Janssen Pharmaceutical), another 5- • Basenji dogs have hypertrophic gastritis in association
HT4 agonist, is more likely to be indicated in the with immunoproliferative enteropathy; genetic,
treatment of delayed gastric emptying in dogs, but it immune-mediated, and hormonal (gastrin) factors
is not yet available. may play a role.
• Hypertrophic gastritis involving the body of the
stomach has been described in the Drentse patri-
Ranitidine and Nizatidine jshond breed of dog. Affected dogs also have red
The H2 blockers, ranitidine and nizatidine, also have blood cell stomatocytosis and hemolytic anemia.
gastric prokinetic effects in dogs and cats (see Table • Hyperplastic polyps involving the pylorus have been
67-3). described in young, related French bulldogs with
chronic vomiting and gastric outflow obstruction.
• CHPG is most common in highly excitable, nervous
Erythromycin small-breed dogs; underlying neuroendocrine or
stress-related mechanisms have been proposed.
The antibiotic erythromycin has a prokinetic effect on
the stomach of dogs, mimicking the effects of the
hormone motilin. The promotility effect occurs at lower
Clinical Signs
doses (0.5–1.0 mg/kg PO or IV q8h) than the antimi- Chronic vomiting is the most consistent clinical sign.
crobial effect. Anorexia, weight loss, abdominal distention, and belch-
W0422-Ch067.qxd 11/10/05 5:32 PM Page 686
ing are less frequent signs. Vomiting occurs at variable tures of hypertrophic gastropathy are not specific
intervals after eating. and mimic other inflammatory and infiltrative
disorders.
• If hypertrophic changes cause outflow obstruction, • Ultrasonography can demonstrate thickening of the
undigested food may be present in the vomitus
gastric wall at the antral and pyloric region.
greater than 12 hours after eating.
• Hematemesis and melena may be detected in associ-
ation with mucosal ulceration. Endoscopy
• Dogs with CHPG often are otherwise healthy and are
presented because of chronic intermittent vomiting • Endoscopy can confirm focal, multifocal, or diffusely
for a duration of weeks to months (sometimes years). thickened mucosal folds. Moderate gastric distention
with air is required so that normal-sized gastric rugal
• Basenji dogs with immunoproliferative enteropathy
folds do not appear falsely thickened.
and hypertrophic gastritis usually have concurrent
chronic diarrhea, anorexia, and weight loss. • With CHPG, the lesions predominantly involve the
antrum and pyloric region, causing partial or com-
plete pyloric obstruction. Hypertrophied mucosa
Diagnosis may form polypoid masses. Mucosal ulceration or
Hypertrophic gastropathy is most common in middle- hemorrhage is not typical.
aged or older small-breed dogs such as Lhasa apsos, • Endoscopically obtained biopsies are inadequate to
Shih Tzus, and miniature poodles. Males are affected diagnose hypertrophic gastropathy because they are
more commonly than females. A history of chronic too superficial to demonstrate the lesion.
intermittent vomiting is typical.
Surgery
Physical Examination • Definitive diagnosis of hypertrophic gastritis requires
• Potential findings include weight loss and abdominal full-thickness biopsies obtained surgically.
distension due to a fluid- or food-filled stomach. • Excisional biopsies are indicated when possible to
• If significant GI blood loss occurs, pale mucous mem- help relieve the obstruction.
branes due to anemia may be detected.
Treatment
Laboratory Evaluation
• Surgical excision of abnormal tissue and relief of
• Laboratory evaluation often is unremarkable. outflow obstruction is the treatment of choice for
• If profuse vomiting has occurred, laboratory findings CHPG (see Chapter 68). Response to surgery is
may reflect dehydration or electrolyte imbalances. usually good to excellent, and most dogs are clinically
Metabolic alkalosis may occur secondary to gastric normal after relief of obstruction. If gastric atony per-
outflow obstruction. sists after surgery, a promotility drug such as cisapride
• If hypertrophic gastropathy is associated with gastric or metoclopramide may be needed.
ulceration, evaluate serum gastrin concentration • If hypertrophic gastropathy is associated with gastric
to detect underlying hypergastrinemia (e.g., erosions or ulcerations, institute antiulcer therapy
gastrinoma). with H2 blockers and sucralfate as described under
• Iron deficiency anemia may result from chronic GI “Gastroduodenal Ulceration.”
blood loss. • When hypertrophic gastropathy is accompanied by a
significant inflammatory infiltrate, consider treat-
Radiography and Ultrasonography ment with prednisolone as described under “Chronic
Gastritis.”
• Perform survey abdominal radiographs to detect a • For treatment of basenji dogs with hypertrophic
fluid-filled distended stomach or food remaining in gastritis and immunoproliferative enteropathy see
the stomach greater than 12 hours after eating. These Chapter 69.
findings are consistent with a gastric retention
disorder.
• Perform a contrast gastrogram (see under “Gastric
Outflow Obstruction”). Findings consistent with GASTRIC NEOPLASIA
CHPG include delayed gastric emptying, filling
defects in the antral and pyloric region due to The clinical presentation of gastric neoplasia in dogs
hypertrophied mucosa, and narrowing of the pyloric and cats is influenced by the size and location of the
canal. With other types of hypertrophic gastropa- tumor, whether it is benign or malignant, and whether
thy, potential findings include focal, multifocal, or it is associated with outflow obstruction, altered gastric
diffusely thickened gastric rugae. Radiographic fea- motility, or mucosal ulceration and bleeding.
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• Gastric lymphoma appears as single or multiple white viscera predisposes to local acidosis and disseminated
nodules or as diffuse infiltration of the mucosa with intravascular coagulation (DIC). The spleen often is
irregular thickening of the mucosal folds. With displaced concurrently, causing splenic vascular occlu-
diffuse infiltration of the gastric wall, the stomach sion, congestion, and splenomegaly. Strangulation
may lack distensibility. necrosis of the gastric wall eventually occurs secondary
• Leiomyomas are smooth mass lesions with a to twisting of the stomach.
normal overlying mucosa unless complicated by
ulceration. Etiology
• Polyps appear as small, smooth, or raspberry-like
masses on a stalk. The cause of GDV is unknown.
• An anatomic predisposition may play a role; large-
Surgery breed, deep-chested dogs are most commonly
affected, and the disorder is rare in small dogs and
Surgical exploration is an important diagnostic method
cats.
for gastric neoplasia.
• Whether gastric distention due to excess swallowed
• Palpate all areas of the stomach to identify affected air precedes volvulus is not known, but if this theory
areas. is true, it suggests causes of aerophagia such as
• Obtain full-thickness biopsies. gulping of food and water may be important.
• Evaluate regional lymph nodes and the liver for • Risk factors for GDV include increasing age, having
metastases. a first-degree relative affected by GDV, lean body con-
formation, rapid eating, eating from a raised bowl,
Treatment eating one meal daily, exercise, stress after a meal,
and a fearful temperament.
• The treatment of choice for gastric neoplasia is sur-
gical resection of the tumor by partial gastrectomy
(see Chapter 68). Because the antral and pyloric Clinical Signs
regions are often involved, a gastroduodenostomy or • Acute onset of abdominal distention with tympany
gastrojejunostomy may be necessary. • Non-productive retching
• For treatment of lymphoma, use chemotherapy as • Salivating, restlessness, and respiratory distress
described in Chapters 26 and 27, with or without
prior surgical resection of large solitary gastric Diagnosis
masses.
Consider GDV in the differential diagnosis of any large-
Prognosis breed, deep-chested dog with acute onset of abdominal
distention.
• The prognosis for benign neoplasms after surgical
removal is good. Physical Examination
• The prognosis for adenocarcinoma is poor. Examination usually reveals abdominal distention that
• Some cats with lymphoma localized to the stomach is tympanitic on percussion and findings indicative of
may have a good to excellent response to chemother-
apy. hypovolemia and/or shock, such as increased heart
rate, weak femoral pulses, decreased capillary refill
time, and pale oral mucous membranes.
GASTRIC DILATATION-VOLVULUS Laboratory Evaluation
GDV is an acute, life-threatening disorder that is a • After initial stabilization (see “Initial Medical Man-
medical and surgical emergency. Early recognition and agement”) submit blood for a CBC and biochemical
treatment are essential for a successful outcome. Gastric evaluation to characterize secondary metabolic
dilatation refers to distention of the stomach, usually imbalances and to identify any other coexistent
with swallowed air. Gastric dilatation may or may not be abnormalities.
complicated by volvulus. GDV occurs when the stomach • Hypokalemia is the most common electrolyte abnor-
rotates on its long axis, resulting in complete gastric mality in dogs with GDV. Although serum potassium
outflow obstruction. Concurrent obstruction of the gas- concentration may be normal initially, hypokalemia
troesophageal junction precludes relief of fluid and gas frequently develops after aggressive fluid therapy
accumulation by vomiting or belching. Massive gastric and, if surgery is necessary, postoperatively. Preven-
distention impairs venous return through the portal tion of hypokalemia may decrease the frequency
vein and caudal vena cava, causing hypovolemic and of postoperative cardiac arrhythmias and muscle
endotoxic shock. Passive congestion of the abdominal weakness.
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• Because a variety of acid-base imbalances may occur Place an Intravenous Catheter and Administer Fluids
secondary to GDV, repeated laboratory assessment
and frequent monitoring of blood gases and elec- • While decompression is being performed, place a
trolyte concentrations are recommended. large-bore catheter in each cephalic vein.
• Metabolic acidosis is most common and occurs • Treat for shock as described in Chapter 156. Give iso-
because of decreased effective circulating blood tonic crystalloid fluids such as lactated Ringer’s solu-
volume, arterial hypoxemia, and lactic acid accumu- tion at an initial rapid rate of 90 ml/kg for the first
lation. hour. After shock is controlled and dehydration is
corrected, lower to a maintenance rate of adminis-
• Metabolic alkalosis, respiratory alkalosis, respiratory
tration. Add potassium chloride to the fluid (30 to 40
acidosis, and mixed acid-base disorders may also
develop. mEq KCl per liter of fluid) after the initial shock dose
of fluids has been given. When blood gas analysis is
not available, routine addition of NaHCO3 to fluids
Radiography is not recommended, because many dogs with GDV
have relatively normal blood pH at presentation. Cor-
Perform abdominal radiography only after the patient rection of volume depletion and mild metabolic aci-
is stabilized medically (see the next section). Minimize dosis by lactated Ringer’s solution is sufficient unless
stress to the patient during the procedure. severe metabolic acidosis is present.
• Alternatively, administer small-volume fluid therapy
▼ Key Point Right lateral and ventrodorsal radi- using 7% NaCl (5 ml/kg) in 6% dextran 70
ographic views of the abdomen are the most useful (HS/D70) (see Chapter 156). Give over 5 to 10
for diagnosing GDV. minutes and follow with 20 ml/kg/hr of 0.9% NaCl.
• Place a Foley catheter in the bladder to monitor urine
• Radiographic findings suggestive of GDV include output.
overdistention of the stomach with gas, pyloric dis-
placement dorsally and to the left, gastric fundic
displacement caudally and to the right, and Control Infection and Endotoxemia
compartmentalization of the stomach on the lateral
view. Splenomegaly is also seen. • To treat endotoxemia, give prednisolone sodium suc-
• Pneumoperitoneum suggests gastric perforation and cinate (10 ml/kg IV). Give a single dose of flunixin
requires immediate surgery. meglumine (Banamine, Schering), 1 mg/kg IV,
• Thoracic radiography is not essential but may demon- during the initial phase of therapy.
strate microcardia (due to hypovolemia), mega- • Give a broad-spectrum antibiotic (cefmetazole, 15 mg/
esophagus, or aspiration pneumonia. kg IV) or a combination drug therapy (cefazolin,
• In cases of intermittent bloating or failure of surgical 20 mg/kg IV, and enrofloxacin, 5–10 mg/kg IV).
correction following tube decompression, perform a
contrast gastrogram (see Chapter 4) to identify mal- Monitor and Treat Cardiac Arrhythmias
position of the stomach.
• Ventricular arrhythmias are the most common.
• To treat ventricular arrhythmias, give a bolus of lido-
Initial Medical Management caine (1–2 mg/kg) IV while monitoring the electro-
cardiogram. If no conversion is noted within 3 to 5
Decompress the Stomach by Orogastric Intubation minutes, repeat this dose. For a comprehensive dis-
• Sedation may be necessary to pass an orogastric tube. cussion of diagnosis and treatment of arrhythmias,
Give diazepam (0.1 mg/kg IV slowly) alone or in com- see Chapter 145.
bination with butorphanol (0.5 mg/kg IV). An alter- • If only temporary conversion occurs, start a lidocaine
native is the combination of diazepam-ketamine drip. A maintenance effect is achieved with a constant
(50:50), 1 ml/10 kg IV. rate infusion of lidocaine at a dosage of 40 to
• Perform gastric decompression by passing a well- 60 mg/kg/min added to the IV fluids. Lidocaine’s
lubricated large-bore orogastric tube. Remove all air effectiveness may be impaired in the presence of
and fluid from the stomach and lavage the stomach hypokalemia.
with 4 to 5 L of warm saline or water. Repeat orogas- • If lidocaine boluses are ineffective for controlling
tric decompression as needed during the stabilization ventricular arrhythmias, consider giving pro-
period. cainamide (10–15 mg/kg IM q6h) or quinidine
• If orogastric decompression is not possible with a sulfate (6–15 mg/kg IM q6h). If arrhythmias are
tube, use several 18-gauge needles to trocarize the dis- controlled with parenteral administration of pro-
tended stomach. Following decompression with cainamide or quinidine, an oral antiarrhythmic can
needle trocarization, a subsequent attempt to pass later be substituted, as described in Chapters 145 and
the orogastric tube often is successful. 146.
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▼ Chapter
68 Surgery of the Stomach
Ronald M. Bright
691
W0422-Ch068.qxd 11/10/05 5:40 PM Page 692
Postoperative Care and Complications 3. Ligate and divide the appropriate short gastric
vessels. LDS stapler apparatus is optimal. This pro-
Short Term cedure may not be necessary because these vessels
• Give no food for 24 hours; water is allowed ad are frequently torn.
libitum. 4. After placement of stay sutures, apply intestinal
• Monitor the patient for leakage, especially if the gas- forceps 2 lateral to the junction of viable and non-
trotomy closure involves diseased tissue (neoplasia). viable tissue. The tips of the forceps meet at an
• Emesis may be noted once or twice following gastric approximately 45-degree angle.
surgery and treatment is usually not required. 5. Use a #10 scalpel blade to cut along the intestinal
• Systemic antacids are indicated if ulcers or severe gas- clamps, leaving a 1-cm margin of healthy tissue
tritis is observed during surgery (see Chapter 67). outside the intestinal clamps.
W0422-Ch068.qxd 11/10/05 5:40 PM Page 693
Closure
1. Use a single-layer interrupted appositional suture
pattern to appose the stomach and duodenum. With
unequal lumen sizes, first close the lesser curvature
side of the stomach until the lumen disparity is cor-
rected (see Fig. 68-1, top).
2. Appose the back (far) wall first, placing the knots
into the lumen. Synthetic 3-0 absorbable suture (e.g.,
polydioxanone [PDS]) is recommended.
3. Then appose the near wall.
Equipment
• Same as that for the Billroth I.
Technique
1. Ligate and divide the appropriate vessels and the
common bile duct.
2. Close the duodenal or jejunal stump with a simple
interrupted appositional suture pattern using 3-0
synthetic absorbable suture material or a TA stapler.
3. The original Billroth II reconstruction is done by
closing the gastric stoma followed by a side-to-side
anastomosis of the jejunum to an incision made in
the ventral aspect of the stomach (Fig. 68-2).
4. Use a simple interrupted appositional suture pattern
to appose the gastric and jejunal segments.
5. For more extensive resections, appose the entire
width of the gastric stump to a longitudinal incision
made in the jejunum (Fig. 68-3).
6. Use a suture pattern as described in Step 4 for Figure 68-3. Billroth II with anastomosis of the entire gastric
closure. stump to a longitudinal incision of the jejunum.
W0422-Ch068.qxd 11/10/05 5:40 PM Page 695
Submucosa
Prognosis Equipment
• Because the underlying disease in most cases is • See under “Pyloromyotomy.”
benign, the prognosis is good to excellent.
Heineke-Mikulicz Pyloroplasty
Technique
PYLOROPLASTY 1. Place temporary stay sutures or Babcock forceps on
the antrum and proximal duodenum proximal and
Preoperative Considerations distal to the pyloric ring.
• See under “Pyloromyotomy.” 2. Make a full-thickness stab incision into the pylorus
• Pyloroplasty is indicated for pyloric hypertrophy using a #11 Bard-Parker scalpel blade. Place a suction
involving muscle and mucosa or mucosa alone (see tip into the stomach to evacuate contents and bile.
Chapter 67). Dogs with severe pyloric hypertrophy 3. Extend the incision with scissors to 1 to 2 cm above
may require the Billroth I procedure (see previous and below the pylorus (Fig. 68-5).
discussion). 4. Remove the stay sutures or Babcock forceps.
• Manual and visual inspection of the lumen of the 5. Close the longitudinal incision transversely with 3-0
distal stomach, pylorus, and proximal duodenum is synthetic absorbable sutures in a simple interrupted
possible with a pyloroplasty. appositional pattern. Stay sutures can be placed on
W0422-Ch068.qxd 11/10/05 5:40 PM Page 697
both sides of the incision to help orient the tissues Postoperative Care and Complications
for closure.
6. Routine abdominal closure follows warm saline Short Term
lavage of the surgical site. • Same as that for pyloromyotomy.
Y-U Pyloroplasty (Antral Flap Advancement) Long Term
Technique • Emesis containing a significant amount of bile several
1. Mobilize the pylorus as described under Pyloromy- weeks after surgery may suggest duodenogastric
otomy. reflux. Consider treatment with metoclopramide.
2. Place temporary stay sutures 4 to 5 cm above and • Alkaline reflux gastritis resulting from duo-
below the pylorus. denogastric reflux may require long-term therapy
3. Make a Y-shaped incision through the seromuscular with metoclopramide or cisapride to promote
tissue overlying the pylorus and distal stomach normal gastric emptying and an H2 blocker for acid
(Fig. 68-6). control.
4. Each limb of the Y is approximately 3 to 4 cm in
length depending on the size of the animal. Prognosis
5. The base of the Y extends a small distance (3–4 mm)
into the antrum proximal to the pylorus.
• Good—if the disease being treated is benign.
6. Trim the V-shaped antral flap to a U-shape. Save the
resected tissue and submit for histopathology.
7. Thoroughly palpate and visually examine the ACUTE GASTRIC DILATATION-VOLVULUS
stomach and proximal duodenum.
8. Excise hypertrophied tissue via a submucosal resec- Preoperative Considerations
tion. Close adjacent mucosa/submucosa in a con-
tinuous pattern with 3-0 or 4-0 synthetic absorbable • Aggressive fluid therapy, cardiac arrhythmia therapy,
suture. and orogastric decompression are necessary before
9. Begin pyloroplasty closure by suturing the base of any surgical intervention (see Chapter 67).
the U-shaped flap distally to the proximal duode- • Stabilization of most patients can be accomplished in
num with 3-0 or 4-0 synthetic absorbable suture (see 2 to 3 hours.
Fig. 68-6). • Complicating gastric perforation is considered a sur-
10. A simple interrupted appositional pattern is rec- gical emergency.
ommended. If necessary, preplace the sutures to • Risk factors recently described by Glickman and col-
ensure accuracy. leagues (see “Supplemental Reading”) are encourag-
11. Appose the lesser curvature limb of the Y, followed ing many surgeons to perform a prophylactic
by the greater curvature limb (see Fig. 68-6). gastropexy in those dogs that are considered to be at
great risk for gastric dilatation-volvulus. Some of the
more important risk factors include rapid eating,
hyperactivity, lean body conformation, aggressive
nature, first-degree relative with known gastric dilata-
tion-volvulus, and signalment (Great Dane breed).
Pylorus
Surgical Procedure
Objectives
• Reposition stomach and spleen to their normal
anatomic relationship.
• Fix (“pexy”) the stomach (pyloric antrum) to the
right abdominal wall to prevent future episodes of
volvulus.
• Resect devitalized tissue (spleen, stomach).
Equipment
• General surgical pack
• Self-retaining abdominal retractor (Balfour)
• Foley catheter (22–26-French)
Figure 68-6. Technique for Y-U pyloroplasty. • Orogastric tube
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Technique
1. Place the dog in dorsal recumbency and surgically
prepare from the mid-sternum to 6 to 8 cm below the
umbilicus. If a tube gastropexy is used, prepare the
right side of the abdominal wall aseptically, halfway
up the side of the thoracic and abdominal wall that
corresponds with the length of the midline incision.
2. Gently place an orogastric tube into the esophagus
and advance it until there is resistance.
3. Derotate the stomach by grasping the pylorus and 4 2
2 4
duodenum, usually located near the gastro-
esophageal junction, and elevating them to the right 3
1 1 3
side of the body.
4. The fundus, usually on the right side, is depressed
and rotated to the left side while the pylorus is being
repositioned.
5. Place the orogastric tube within the stomach and
perform stomach decompression.
6. Assess the viability of the stomach, and resect Figure 68-7. Technique for tube gastropexy in the treatment of
necrotic tissue if necessary (see discussion of “Partial gastric dilatation-volvulus. Inset, Place an untied pursestring suture in
the midantrum area. Place a Foley catheter through the body wall,
Gastrectomy Related to Gastric Dilatation-Volvulus”). into the pyloric antrum. Connect the stomach and abdominal wall
7. Splenectomy is usually not done unless there is evi- with interrupted sutures. In the figure, points 1 are connected, as are
dence of splenic torsion or necrosis. points 2 to each other, and so forth. (Drawing by Carol Haynes, after
8. Perform a gastropexy procedure on the right side of Daugherty.)
the dog (regardless of the technique employed).
Each of the gastropexy techniques described subse-
quently is effective. The technique chosen depends
9. Tie the sutures starting dorsally and ending
on the surgeon’s preference.
ventrally.
10. Affix the catheter to the skin with a traction suture.
Tube Gastropexy (22–26-French Foley Catheter)
Technique Circumcostal Gastropexy
1. Tube gastropexy is not considered to be an accept- Technique
able “pexy” technique unless it is done concurrently 1. Place two retention sutures using 1-0 or 2-0 non-
with a partial gastrectomy. Under these circum- absorbable suture material in the antrum approxi-
stances, the tube gastrostomy may be beneficial to mately 6 cm apart and midway between the lesser
wound healing by keeping the remaining stomach and greater curvature.
decompressed. 2. Make a 3 ¥ 3 cm incision through the seromuscular
2. Place a full-thickness pursestring suture in the mid- layer forming an I-shaped configuration (Fig. 68-8,
antrum area using 2-0 or 3-0 non-absorbable suture. inset).
This suture is left untied (Fig. 68-7). 3. The seromuscular flaps are formed by careful dis-
3. Pull the tip of a Foley catheter through a small right section between the muscular and submucosa
paracostal incision using Carmalt forceps, approxi- tunics. Place two stay sutures on each flap.
mately 4 cm caudal to the costal arch and 4 cm 4. Isolate the 11th or 12th rib ventral to the costo-
lateral to the incision. chondral junction and rotate it laterally with two
4. Make a stab incision into the middle of the purse- towel clamps placed 6 cm apart.
string suture area and advance the tip of the Foley 5. Expose a 4- to 5-cm length of the rib by incising
catheter through this and into the stomach (see Fig. through the peritoneum and muscle.
68-7). 6. By blunt dissection remove all tissue attached to the
5. Inflate the balloon portion of the catheter. rib.
6. Draw the pursestring suture tightly and tie it. 7. Pass one arm of each stay suture under the rib.
7. Move the stomach to the abdominal wall with 8. Place another stay suture midway down the sero-
traction on the Foley catheter. muscular flap found on the greater curvature side.
8. Preplace six to eight interrupted sutures between This placement helps pull this flap around the
the stomach, being sure to penetrate to the sub- exposed rib.
mucosa and the abdominal wall. Use non- 9. Once the flap is pulled around the rib, tie the two
absorbable #1 or 1-0 suture material (see Fig. 68-7). retention sutures.
W0422-Ch068.qxd 11/10/05 5:40 PM Page 699
9 A
10
Lesser
11
curvature
12
Greater D
curvature
C
11th rib
Figure 68-9. Technique for belt loop gastropexy (for gastric
dilatation-volvulus). See text for details.
1. This can be done in a female dog at the time of ster- Long Term
ilization by extending the incision cranially.
2. In the older sterilized bitch or male dog, a laparo- • Remove the tube (tube gastropexy) 5 to 7 days after
scopic or laproscopic-assisted technique can be used. placement. Allow the fistula to heal by second inten-
3. The laparoscopic-assisted technique includes two tion (contraction and epithelialization).
small incisions, one just caudal to the umbilicus • Wean the animal slowly off antiarrhythmic drugs if
(2–3 cm) and the other approximately 3 to 4 cm cardiac arrhythmia was a problem and so treated.
caudal to the last rib and just lateral to the rectus • Encourage three to four feedings per day at home.
abdominus muscle.
4. The midline incision allows a trochar cannula (10– Prognosis
12 mm in diameter) to be placed followed by the peri- • Fair to good if partial gastrectomy is not indicated.
toneal infusion of carbon dioxide. Place a camera • Grave to poor when partial gastrectomy is done.
W0422-Ch068.qxd 11/10/05 5:40 PM Page 701
Gastrotomy
Pyloroplasty
Arnockzy SP, Ryan WW: Gastrotomy and pyloroplasty. Vet Clin North
Am 5:343, 1975. Bright RM, Richardson DC, Stanton ME: Y-U antral flap advancement
Dulisch ML: Gastrotomy. Current Techniques in Small Animal pyloroplasty in dogs. Comp Cont Educ Pract Vet 10:139, 1988.
Surgery II. Philadelphia: Lea & Febiger, 1983, p 157. Stanton ME, Bright RM, Toal R, et al: Chronic hypertrophic pyloric
gastropathy as a cause of pyloric obstruction in the dog. J Am Vet
Med Assoc 186:157, 1985.
Partial Gastrectomy Related to Walters MC, Goldschmidt MH, Stone EA, et al: Chronic hypertrophic
Gastric Dilatation-Volvulus pyloric gastropathy as a cause of pyloric obstruction in the dog. J
Am Vet Med Assoc 186:157, 1985.
Clark GN, Pavletic MM: Partial gastrectomy with an automatic stapling
instrument for treatment of gastric necrosis secondary to gastric
dilatation-volvulus. Vet Surg 20:61, 1991. Gastric Dilatation-Volvulus
Matthiesen DT: Partial gastrectomy as a treatment of gastric volvulus:
Results of 30 dogs. Vet Surg 14:185, 1985. Fallah AM, Lumb WV, Nelson AW, et al: Circumcostal gastropexy in
the dog, a preliminary study. Vet Surg 11:9, 1982.
Glickman LT, Glickman NW, Schellenberg DB, et al: Non-dietary risk
Partial Gastrectomy (Distal Stomach) factors for gastric dilatation-volvulus in large and giant breed dogs.
J Am Vet Med Assoc 217:1492, 2000.
Ahmadu-Suka F, Withrow SJ, Nelson AW, et al: Billroth II gastroje- MacCoy DM, Sykes GP, Hoffer RE, et al: A gastropexy technique for
junostomy in dogs: Stapling techniques and postoperative compli- permanent fixation of the pyloric antrum. J Am Anim Hosp 18:763,
cations. Vet Surg 17:211, 1988. 1982.
Bright RM: Esophagus and stomach. In Harvey CE, Newton CD, Rawlings CA, Foutz TL, Mahaffey MB, et al: A rapid and strong
Schwartz A (eds): Small Animal Surgery. Philadelphia: JB Lippin- laparoscopic-assisted gastropexy in dogs. Am J Vet Res 62:871,
cott, 1990, p 323. 2001.
Schulman AJ, Lusk R, Lippincott CL, et al: Muscular flap gastropexy:
Pyloromyotomy A new surgical technique to prevent recurrences of gastric dilata-
tion-volvulus syndrome. J Am Anim Hosp Assoc 22:339, 1986.
Fox SM, Burns J: The effect of pyloric surgery on gastric emptying in Whitney WO, Scavelli TD, Matthiesen DT: Belt-loop gastropexy:
the dog: Comparison of three techniques. J Am Anim Hosp Assoc Technique and surgical results in 20 dogs. J Am Anim Hosp 25:75,
22:783, 1986. 1989.
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▼ Chapter
702
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a high volume without urgency, tenesmus, or marked • Straining (tenesmus) may be noted as the patient
increase in frequency. Weight loss and decline in body remains in position for a prolonged time after defe-
condition (malnutrition) may occur. cation or makes repeated attempts to defecate within
a few minutes. These attempts may produce little or
• Because of unabsorbed nutrients that are degraded no feces or sometimes just a few drops of mucus,
and fermented by intestinal bacteria, the feces are exudate, and blood.
rancid and foul-smelling and the increased produc- • Because many colonic diseases are associated with
tion of luminal gas by bacteria results in excessive mucosal injury, inflammation, or ulceration, abnor-
flatulence and borborygmus. mal fecal constituents are frequently found in large
• Steatorrhea (feces containing an excess of unab- bowel diarrhea, including (1) fresh red blood
sorbed fat) can occur in maldigestive and malab- (hematochezia) that originates from sites of erosion
sorptive small bowel diarrhea. In extreme cases, the or ulceration, (2) mucus that originates from the
feces may appear oily, greasy, and pale. Hair around abundant goblet cells in the colon that respond to
the perineum may also have an oily texture from mucosal injury by an outpouring of mucus, and (3)
contact with fatty feces. exudate (leukocytes) that originates from the site of
• Small bowel diarrhea is generally free of grossly inflammation.
visible mucus or blood. When there is bleeding
from a lesion in the proximal GI tract, the blood ▼ Key Point Abnormal fecal constituents such as
pigment becomes dark black during transit fresh red blood, mucus, and leukocytes are local-
(melena). In the absence of gastric bleeding, melena izing signs indicative of colonic disease.
generally indicates small intestinal parasitism (e.g.,
hookworms), infection (viral, bacterial, fungal), • Blood may coat the feces, streaks of blood may be
ulceration (e.g., drug induced), severe inflammation, mixed within the feces, or drops of blood may be
or neoplasia. passed at the end of defecation.
• Excessive mucus may give the feces a glistening or
Large Bowel Diarrhea jelly-like appearance.
• Exudates are detected by the positive identification
Large bowel diarrhea is characterized by frequent urges
of fecal leukocytes using cytology stains.
to defecate (usually greater than 3 times normal fre-
quency), with each defecation producing small quanti-
• Because the principal function of the colon is absorp-
tion of water and electrolytes rather than digestion
ties of feces that often contain excessive mucus and
and absorption of nutrients, nutrient malabsorption
sometimes fresh red blood.
and steatorrhea are absent in large bowel diarrhea.
• Urgency resulting from irritability or inflammation Thus, dramatic weight loss and wasting are unlikely if
of the distal colon causes frequent premature expul- the animal is eating, and the daily fecal output
sions of small quantities of feces that would otherwise (volume or weight of feces) usually is only minimally
be insufficient to trigger the defecation reflex. Lapses increased.
in housetraining (“accidents”) may be caused by • Vomiting is a clinical sign in about 30% of patients
urgency and inability to control urges to defecate. with colitis.
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Hematologic Findings
Eosinophilia Parasitism, eosinophilic enteritis,
hypoadrenocorticism, mast cell tumor
Neutrophilia Bowel inflammation, necrosis, or neoplasia
Neutropenia or “toxic” neutrophils Parvovirus, FeLV, FIV, endotoxemia, or
overwhelming sepsis (e.g., leakage peritonitis)
Monocytosis Chronic or granulomatous inflammation (e.g.,
mycosis)
Lymphopenia Loss of lymphocytes associated with intestinal
lymphangiectasia
Anemia GI blood loss, depressed erythropoiesis (chronic
inflammation, neoplasia, malnutrition)
Elevated PCV Hemoconcentration from GI fluid loss
RBC microcytosis Iron deficiency (chronic GI blood loss),
portosystemic shunt
RBC macrocytosis RBC regeneration, feline hyperthyroidism, FeLV,
nutritional deficiencies (rare)
Serum Biochemical Findings
Panhypoproteinemia Protein-losing enteropathy
Hyperglobulinemia Chronic immune stimulation, basenji enteropathy
Azotemia Dehydration (prerenal), primary renal failure
Hypokalemia GI loss of fluid and electrolytes, anorexia
Hyperkalemia/hyponatremia Hypoadrenocorticism, trichuriasis (rare)
Hypocalcemia Hypoalbuminemia, lymphangiectasia, pancreatitis
Hypocholesterolemia Lymphangiectasia, liver disease
Elevated liver enzymes or bile acids Liver disease
Elevated amylase/lipase Pancreatitis, enteritis, or azotemia
Elevated thyroxine (T4) Feline hyperthyroidism
FeLV, feline leukemia virus; FIV, feline immunodeficiency virus; GI, gastrointestinal; PCV, packed cell
volume; RBC, red blood cell.
• Inspect the fecal material obtained on the palpation fecal collection and fat analysis, chemical determina-
glove for abrasive particles (such as bone chips), tions, cultures, toxin assays, virology, and nuclear scans,
blood, and mucus. If indicated, examine the fecal but these are used only in selective cases.
material microscopically for parasites, microorgan-
isms, and inflammatory cells or submit for culture. ▼ Key Point Examination of feces for parasites
should be part of the minimum database for all
Routine Laboratory Tests animals with diarrhea.
• Evaluate a CBC for leukocyte responses and anemia • In cases of chronic unresponsive diarrhea, expand
that may be associated with intestinal disease (Table the database to include microscopic examination of
69-3). stained fecal smears for fat, starch, and leukocytes.
• Perform a serum biochemical profile and urinalysis • If circumstances suggest infection, perform fecal
to identify metabolic or systemic disorders that could culture for specific enteropathogenic bacteria (Sal-
cause or result from diarrhea (see Table 69-3). monella, Campylobacter) or toxin assay for enterotoxi-
• Measure serum thyroxin (T4) concentration in all genic Clostridium perfringens.
cats over 5 years of age with diarrhea or weight loss • Diagnostic methods for intestinal parasites and infec-
to exclude hyperthyroidism as a cause (see Chapter tious agents are listed in Table 69-4.
31).
Fecal Examination for Parasites
Fecal Examinations Fecal examination for parasites can include fecal flota-
Fecal examinations are an important aspect of the tion, zinc sulfate centrifugation-flotation, direct wet
diagnostic approach to diarrhea and should involve smears, and immunoassays. Examine fresh feces within
visual inspection (for blood, mucus, and foreign 1 hour of collection. Alternatively, refrigerate feces
matter), parasite evaluation, and microscopic examina- within 1 hour and examine within 3 days, or preserve
tions. Specialized evaluations can include quantitative feces in formalin for later examination.
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Helminths
Ascarids (Toxocara, Toxascaris leonina) Routine fecal flotation for ova
Hookworms (Ancylostoma) Routine fecal flotation for ova
Whipworms (Trichuris vulpis) Routine fecal flotation for ova; fenbendazole trial
Tapeworms (Taenia, Dipylidium caninum) Fecal proglottids or flotation for ova
Strongyloides Fecal sediment or Baermann test for larvae
Others (flukes) Fecal zinc sulfate centrifugation-flotation for ova
Protozoa
Coccidia (Isospora) Fecal flotation for oocysts
Cryptosporidium spp. Microplate ELISA, direct immunofluorescence, PCR, Sheather’s flotation
Giardia Fecal zinc sulfate centrifugation-flotation for cysts; fecal ELISA or IFA; duodenal
wash for trophozoites; fenbendazole trial
Tritrichomonas foetus Fecal wet smear for trophozoites; InPouch TF culture; PCR
Entamoeba histolytica Fecal wet smear for trophozoites
Balantidium coli Fecal wet smear for trophozoites
Viruses
Canine parvovirus Fecal ELISA (SNAP-Parvo Test) for viral antigen (see Chapter 14)
Feline panleukopenia virus Signs, leucopenia (see Chapter 14)
Canine coronavirus Fecal EM, virus culture, PCR (see Chapter 14)
Feline enteric coronavirus and FIP Signs, serology, fecal EM, PCR, biopsies (see Chapter 10)
Rotaviruses Fecal EM, virus culture, PCR (see Chapter 14)
Astrovirus Fecal EM, PCR (see Chapter 14)
Canine distemper virus Signs (see Chapter 13)
Retroviruses (FeLV, FIV) FeLV antigen test (ELISA, IFA); FIV antibody test (see Chapters 8, 9)
Rickettsia
Salmon poisoning (Neorickettsia helminthoeca) Operculated trematode eggs in feces; rickettsia in lymph node cytology
(see Chapter 17)
Bacteria
Salmonella Fecal culture
Campylobacter jejuni Fecal microscopy and culture
Yersinia enterocolitica, Y. pseudotuberculosis Fecal culture
Bacillus piliformis (Tyzzer’s disease) Biopsy (gut, liver) for filamentous bacteria; mouse inoculation
Mycobacterium spp. Acid-fast bacteria in cytology/biopsy; culture, PCR (see Chapter 19)
Clostridium perfringens, C. difficile ELISA-based fecal enterotoxin assays; PCR
Enteropathogenic Escherichia coli (?) Fecal culture and toxin assays
Fungi
Histoplasma capsulatum Fungi in biopsies/cytologies; serology (see Chapter 20)
Pythium, Zygomycetes Pythium ELISA; poorly septate hyphae in biopsies (Chapters 20, 40)
Others (Candida albicans, Aspergillus, etc.) Yeast or hyphae in biopsies; fungal culture (see Chapters 20, 40)
Algae (Prototheca) Unicellular algae in cytology or biopsy; fecal culture (Sabouraud’s)
ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; FeLV, feline leukemia virus; FIP, feline infectious peritonitis; FIV, feline immunodefi-
ciency virus; IFA, immunofluorescent antibody; PCR, polymerase chain reaction test; Rx, therapeutic response.
• Use routine fecal flotation to identify nematode ova • Use a direct saline smear of fresh feces to detect
and coccidian oocysts other than Cryptosporidium. motile trophozoites of protozoan parasites, including
• In warm, humid regions (e.g., southern United Giardia, Tritrichomonas, Entamoeba histolytica, and
States) endemic for Strongyloides species, perform a Balantidium coli. This is an insensitive method for
direct wet smear, sedimentation, or Baermann pro- diagnosis of Giardia. The distinguishing characteris-
cedure to identify larvae in the feces. tics of each of these protozoa are discussed under
• For Giardia, use zinc sulfate centrifugation-flotation to “Protozoan Parasites.”
identify cysts or an immunoassay to identify fecal • For diagnosis of Tritrichomonas foetus infection in cats,
antigen. Reliable fecal immunoassays are the point- fecal culture using InPouch-TF and fecal polymerase
of-care SNAP Giardia Test Kit (IDEXX), the micro- chain reaction (PCR) assay are more sensitive than
plate enzyme-linked immunosorbent assay (ELISA) direct fecal smear microscopy.
(Remel), or an immunofluorescent antibody (IFA) • For Cryptosporidium parvum, a very small coccidian,
test at a commercial lab. Evidence suggests the rapid use fecal antigen immunoassay (microplate ELISA or
ELISA test for human Giardia is not reliable in animals. IFA), Sheather’s sugar flotation for oocysts, or modi-
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fied acid-fast staining. Evidence suggests the rapid • Affected tissues can be cultured for systemic fungi
ELISA test for human Cryptosporidium is not reliable and Prototheca (a rare cause of colitis), but culture
in animals. growth takes weeks and the isolation rate is low.
• Diagnosis of occult parasite infections (e.g., Giardia
and most nematodes including whipworms) can be Fecal Examination Using Special Stains
based on response to a therapeutic trial using fen-
bendazole (50 mg/kg PO q24h for 3–5 days). Feces can be examined microscopically for abnormal
constituents using Sudan, Lugol iodine, Gram, and
▼ Key Point Intestinal parasitism can resemble many various other cytologic stains. In each test, one to two
other small and large bowel disorders. Common drops of fresh feces are stained on a microscope slide
examples are hookworms, whipworms, and and examined. In general, these procedures are rela-
Giardia. tively insensitive and nonspecific and are affected by
many factors, including diet.
Fecal Examination for Infectious Agents
Sudan and Iodine Stain
The diagnosis of infectious diarrhea often depends on
the detection of the offending viral, bacterial, or fungal Fecal staining with Sudan for undigested fat and Lugol
organisms in the feces. Details of diagnosis of these iodine for undigested starch may suggest exocrine
various enteric infections are found in the respective pancreatic insufficiency (maldigestion); however, these
sections of this chapter. evaluations are too insensitive, nonspecific, and diet
dependent to be recommended. These procedures
Viruses have been replaced by more reliable diagnostic tests for
exocrine pancreatic insufficiency (see Chapter 73).
Viral diarrhea is generally acute and is confirmed by
detection of viral antigen in the feces (ELISA, PCR,
etc.) or virus particles by electron microscopy (see Cytology Stain
Chapter 14). Routine cytology staining (e.g., new methylene blue,
Wright, and Diff-Quik stains) identifies fecal leukocytes
Bacteria that are markers of exudative inflammatory colonic
The common enteropathogenic bacteria in dogs and disease. Cytology may occasionally identify neoplastic
cats are listed in Table 69-4. cells or Histoplasma or Prototheca organisms. It is advis-
able to follow up with patients that are positive for fecal
• Specific enteropathogenic bacteria, such as Salmo- leukocytes with colonoscopy and fecal cultures for inva-
nella and Campylobacter, can be isolated from fresh sive bacteria such as Campylobacter and Salmonella.
feces using appropriate culture media. Cultures are
particularly indicated when examination of fecal Gram Stain
cytology preparations reveals the presence of numer-
ous fecal leukocytes or Campylobacter-like bacteria or With gram staining, the experienced observer may iden-
when there is an outbreak of diarrhea in groups of tify large numbers of C. perfringens or Campylobacter-like
animals housed together. spiral bacteria; however, microscopy is much less reli-
• For diagnosis of Clostridium perfringens and Clostridium able than toxin assays for Clostridium and culture for
difficile enterotoxigenic diarrhea, use validated fecal Campylobacter.
ELISA (Techlab, Blacksburg, VA) and PCR assays to
detect clostridial enterotoxins. The finding of numer- Tests for Fecal Occult Blood
ous large gram-positive sporulating rods with a “safety
These include a simple, in-office qualitative screening
pin” appearance in stained fecal smears is not a reli-
test (Hemoccult test) and a more accurate, semiquan-
able indicator of toxin-producing C. perfringens. Non-
titative send-out test (HemoQuant, SmithKline). These
toxigenic C. perfringens is part of the normal intestinal
tests are sensitive for detecting even very small amounts
flora in dogs and cats; thus, cultures are not useful.
of GI hemorrhage. Because of this sensitivity, it is
recommended that the owner exclude meat from the
Fungi and Prototheca animal’s diet for at least 3 days prior to testing to avoid
The diagnosis of fungal (Histoplasma, Aspergillus, false-positive results.
Pythium, Candida) and protothecal infections is usually
based on identification of the organisms in feces or • The presence of fecal occult blood signifies a bleed-
ing lesion of the GI tract, which suggests an ulcera-
more often in rectal scrapings (Histoplasma), tissue aspi-
tive, inflammatory, or neoplastic condition, or a
rates, or intestinal biopsies (see Chapters 20 and 40).
hemostatic abnormality.
• Serodiagnostic tests for presumptive diagnosis of • The fecal occult blood test is also indicated to docu-
histoplasmosis and pythiosis also are available. ment GI bleeding as a cause of blood loss anemia.
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Quantitative Fecal Fat Analysis • Serum folate also may be increased by high dietary
intake of folic acid, low intestinal pH, exocrine pan-
This can be used as an intestinal function test to
creatic insufficiency (32% of cases), and artifactually
confirm steatorrhea, but it is rarely used because it is
by hemolysis or heating of the blood specimen.
cumbersome and impractical to perform and does not
differentiate pancreatic maldigestion from intestinal
Serum Cobalamin
malabsorption. Feces must be collected for a 24- to
72-hour period while the animal is confined and fed a Cobalamin, a water-soluble B vitamin, is plentiful in
standard diet. The feces are weighed and sent to a com- most commercial pet foods, and serum concentration
mercial laboratory for analysis. Normally, less than 10% depends on the secretion of pancreatic intrinsic factor
of ingested fat is excreted in the feces, or less than 0.3 necessary for normal cobalamin absorption and on the
g/kg/day in dogs and less than 0.4 g/kg/day in cats. absorptive function of the ileum.
• Serum cobalamin (normal, dog: 249–733 ng/L; cat:
Fecal Proteolytic Activity 290–1500 ng/L) is frequently decreased in exocrine
Fecal proteolytic activity can be assayed as an indicator pancreatic insufficiency (deficiency of intrinsic
of pancreatic secretion of proteases (trypsin) for the factor) and in enteropathies that impair absorption
diagnosis of exocrine pancreatic insufficiency (EPI). in the distal small intestine, including diffuse small
The serum trypsin-like immunoreactivity (TLI) assay is intestinal disease. It also is decreased in presumed
more accurate and is now preferred for the diagnosis of small intestinal bacterial overgrowth.
exocrine pancreatic insufficiency in both dogs and cats • Because cobalamin has a shorter half-life in cats, cats
(see Chapter 73). with chronic intestinal disease are particularly
susceptible to developing cobalamin deficiency.
Tests for Fecal Protein Loss • Prolonged exposure of the blood specimen to bright
light may artifactually decrease cobalamin.
See under “Tests for Protein-Losing Enteropathy.”
• An isolated hereditary defect in cobalamin absorp-
tion has been recognized in some dog breeds (giant
Enteropancreatic Function Tests schnauzer, Border collie, Shar-Pei).
The following tests are designed to evaluate digestive
and absorptive functions. ▼ Key Point In small intestinal bacterial overgrowth,
serum folate may be increased due to synthesis of
Tests for Exocrine Pancreatic Insufficiency folate by the proliferated bacteria, whereas cobal-
amin may be decreased because bacteria can
Tests for exocrine pancreatic insufficiency (pancreatic utilize or bind the vitamin, making it unavailable for
maldigestion), such as serum trypsin-like immunoreac- absorption.
tivity and fecal assays for proteolytic activity, are
described in Chapter 73. Breath Hydrogen Test
Serum Folate and Cobalamin Assays This assesses monosaccharide or disaccharide malab-
sorption or bacterial overgrowth, based on the princi-
Serum concentrations of folate and cobalamin (vitamin ple that intestinal bacteria ferment intraluminal
B12) are indicative exocrine pancreatic function (cobal- carbohydrate and produce hydrogen gas, some of which
amin), intestinal absorptive function, and the status of is absorbed into the blood and excreted by the lungs.
the intestinal bacterial flora. This test is impractical for routine clinical use and is
affected by diet, gastric emptying, intestinal transit, and
Serum Folate the status of the intestinal flora.
Folate, a water-soluble B vitamin, is plentiful in most
commercial pet foods, and serum concentration Five-Sugar Absorption Tests
depends primarily on the absorptive function of the for Intestinal Permeability
proximal small intestine.
These oral sugar absorption tests are variations on
• Serum folate (normal, dog: 6.5–11.5 mg/L; cat: the other carbohydrate absorption tests. A mixture
9.7–21.6 mg/L) may be decreased in enteropathies of sugars is used as a noninvasive molecular probe of
that impair absorption in the proximal small intestine mucosal permeability and injury based on urine recov-
or in diffuse small intestinal disease. Widespread ery (in a 6-hour urine sample) after oral administration.
malignancy and sulfasalazine treatment also may These sugar probes measure passive diffusion. Lactu-
decrease serum folate. lose, cellobiose, and raffinose are probes of the large
• Serum folate may be increased with overproliferation pores of the paracellular pathway, and urine recovery
of the normal intestinal flora because many species increases with mucosal epithelial damage. Mannitol and
of bacteria synthesize folic acid. rhamnose are probes of the numerous small pores of
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the transcellular pathway, and urine recovery decreases feces in cats. The assay requires submission of three
with loss of mucosal absorptive surface area (such fresh fecal specimens to the Gastrointestinal Labora-
as villous atrophy). An increase in the lactulose-to- tory, Department of Small Animal Medicine and
rhamnose ratio is typical of intestinal disease with Surgery, College of Veterinary Medicine, Texas A&M
mucosal damage and increased permeability. University, College Station, TX 77843-4474 (website:
One variation on this procedure involves giving a http://www.cvm.tamu.edu/gilab).
mixture of lactulose, rhamnose, xylose, methylglucose,
and sucrose, and the ratios are determined in 6-hour Tests for Bacterial Overgrowth
urine for lactose-to-rhamnose (permeability test), Direct evidence of small intestinal bacterial overgrowth
xylose-to-methylglucose (absorption test), and sucrose- is conventionally based on quantitative cultures of small
to-methylglucose (mucosal digestion test). intestinal juice; however, because of extensive overlap
In addition to reflecting absorptive function and in the bacterial counts found in normal and diarrheic
permeability, results are also affected by gastric empty- dogs and cats, the diagnostic criteria for small intestinal
ing, intestinal dilution and transit, systemic distribution, bacterial overgrowth in animal patients is uncertain.
metabolism, and renal clearance. Results have not Indirect evidence of small intestinal bacterial over-
shown good correlation with clinical disease activity and growth is indicated by the following:
histologic findings.
• Increased serum folate and decreased serum cobal-
Unreliable Absorption Tests amin, reflecting increased bacterial metabolic activity
In general, the reliability of oral absorption tests is
• Abnormal hydrogen breath test results, reflecting
increased bacterial fermentation activity
affected by gastric emptying time, intestinal dilution
and transit time, digestion and absorption, systemic dis-
• Increased serum unconjugated bile acids, reflecting
increased bacterial deconjugation activity
tribution, metabolism, and renal excretion. Because of
inconsistent results, the following absorption tests are
• Idiopathic chronic small bowel diarrhea that is antibi-
otic responsive
not considered clinically useful in dogs and cats:
• Absorption of glucose substrates (glucose, lactose, Tests for Intestinal Motility
starch)—Affected by insulin, etc.
Tests for clinically assessing intestinal motility have
• Xylose absorption—For detection of brush border
limited clinical usefulness except for identifying
monosaccharide malabsorption
obstruction to flow. These include intestinal transit time
• Quantitative fecal fat analysis—For detection of fat
of barium, barium-impregnated spheres, or radiophar-
malabsorption (steatorrhea)
maceuticals. The hydrogen breath indirectly reflects
• Oral triglyceride absorption
transit time of the proximal GI tract.
• Vitamin A absorption
• Bentiromide para-aminobenzoic acid (BT-PABA)
absorption Radiography and Ultrasonography
Plain Abdominal Radiography
Tests for Protein-Losing Enteropathy
Plain radiography is indicated for detection of intesti-
Excessive GI loss of plasma proteins can be documented nal masses or abnormal gas-fluid patterns, especially
using fecal assays that quantitate the intestinal loss of when mechanical or obstructive disorders are suspected
specific serum proteins, such as alpha-1-proteinase (e.g., intestinal mass, foreign body, or intussusception).
inhibitor, or an IV dose of 51chromium-labeled albumin,
a radiopharmaceutical. Gastrointestinal Barium Contrast Radiography
• Alpha-1-proteinase inhibitor is a serum protein Upper GI barium radiography is indicated when other
similar in molecular size to albumin. The intestinal evaluations fail to determine the cause of small bowel
loss of alpha-1-proteinase inhibitor in protein-losing diarrhea or when intestinal obstruction is suspected
enteropathy parallels the loss of albumin, except that (see Chapter 4). This may help detect obstructive
it is not digested and is excreted intact in the feces. lesions, neoplastic masses, and inflammatory lesions
Thus, using a canine-specific assay, alpha-1-proteinase that cause an irregular mucosal pattern or distortion of
inhibitor can be measured in the feces as a marker the bowel wall. In most cases, however, diarrhea involves
for intestinal protein loss in dogs. This test is useful microscopic and functional changes in the bowel that
for evaluation of dogs with unexplained hypopro- are not detected by barium radiography.
teinemia and for early detection of affected dogs in
high-risk breeds, such as the soft-coated wheaten
terrier.
Barium Enema Contrast Radiography
• Normal fecal excretion of the alpha-1-proteinase Barium enema radiography is indicated in selected
inhibitor is <5.7 mg/g feces in dogs and <1.6 mg/g cases of large bowel diarrhea for evaluating the colon
W0422-Ch069.qxd 11/12/05 10:43 AM Page 710
and cecum for intussusceptions, neoplasms, polyps, gated through the ileocolic sphincter for examina-
strictures, inflammatory lesions, and colonic displace- tion and biopsy of the ileum in some animals.
ment or malformation. Colonoscopy is generally pre- • The normal colonic mucosa appears pale pink
ferred over barium enema for evaluating the colon through the colonoscope and reflects light uniformly.
because it yields more definitive diagnostic information. It is non-friable, thin enough that the submucosal
vessels are visible, and free of erosions, ulcers, thick-
Abdominal Ultrasonography ened folds, masses, or strictures.
Ultrasonography is indicated for assessing intestinal wall
thickness and layering, for defining intestinal and other Intestinal Biopsy
abdominal masses, and for evaluating other abdominal The least invasive and, in many cases, preferred method
organs—e.g., lymph nodes, spleen, pancreas, liver, for procurement of intestinal biopsies is endoscopy. If
biliary tract, kidneys, adrenals, and prostate (see endoscopy is not available, or if endoscopic biopsies are
Chapter 4). inconclusive, consider full-thickness intestinal biopsy by
laparotomy (see Chapter 70).
Endoscopy
• Obtain multiple biopsies along the length of the gut
▼ Key Point Endoscopic examination with mucosal even if no lesions are visible by gross inspection,
biopsy is required for definitive diagnosis or which is often the case.
accurate characterization of the disease in many • Biopsy mesenteric lymph nodes and evaluate other
cases of chronic intractable diarrhea in which non- abdominal organs, especially the pancreas, liver, and
intestinal, dietary, parasitic, and infectious causes colon.
have been excluded. • Duodenal aspirates or duodenal mucosal impression
smears may be examined for Giardia trophozoites or
Gastrointestinal Endoscopy cultured quantitatively for aerobic and anaerobic
bacterial overgrowth.
Duodenoscopy with a flexible fiberoptic endoscope can
be performed in the anesthetized animal for visual
examination of the upper GI tract, including duode- Therapeutic Trials
num; for duodenal aspiration (for quantitative bacter- In some cases, the response to a dietary modification or
ial culture or detection of Giardia trophozoites); and for therapeutic drug trial is used as an empirical diagnostic
directed forceps biopsy of the intestinal mucosa (see approach, when supported by adequate clinical infor-
Chapter 67 for a description of endoscopic equipment mation. Common therapeutic trials are given in the
and discussion of gastroscopy). sections that follow.
• The normal duodenal mucosa appears pale pink with
a uniformly granular villus pattern. Diet Modification
• Biliary and pancreatic duct papillae and Peyer lym-
phoid patches are normally seen. • Commercial GI diet for optimal digestability
• The mucosa is non-friable and should be free of • Novel protein diet—For dietary hypersensitivity or
excessive granularity, hemorrhages, erosions, ulcers, food allergy
thickened folds, masses, or strictures. Villous lym- • Fiber supplemented diet—For fiber-responsive large
phatics (lacteals) should not be prominent in the bowel diarrhea (dogs)
fasted animal.
• The lumen is easily and uniformly distensible with air. Fenbendazole
Colonoscopy
• For helminths (especially whipworms)
• For Giardia
Colonoscopy allows direct visualization of the lumen of
the colon, sampling of luminal content for culture and Metronidazole
exfoliative cytology, and directed forceps biopsy of the
ileocolic mucosa.
• For Giardia
• For enteropathogenic bacteria (especially Clostridium)
• Suitable rigid colonoscopes are relatively inexpensive • To suppress flora in bacterial overgrowth
and easy to use. Because colonic diseases are often • To treat idiopathic inflammatory bowel disease (via
diffuse, examination and biopsy of the descending flora effects or immune modulation)
colon with a rigid instrument is sufficient for diag-
nosis in many patients.
• When lesions are located predominantly in the NONSPECIFIC TREATMENT OF DIARRHEA
ascending or transverse colon, areas inaccessible with
a rigid colonoscope, use a flexible fiberoptic or video Dietary, supportive, and symptomatic therapy often is
colonoscope. A flexible colonoscope can be navi- beneficial in diarrhea, especially acute diarrhea. In
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severe acute diarrhea, fluid and electrolyte therapy can Fluid Therapy
be lifesaving.
• In severe, acute diarrhea, such as occurs with par-
voviral enteritis, fluid and electrolyte replacement is
Dietary Management essential for management of intestinal fluid loss that
Acute Diarrhea may lead to serious dehydration, shock, and death
(see Chapter 5).
• The initial goal is to physiologically “rest” the GI tract • Parenteral methods of fluid therapy are preferred in
by restricting food intake for at least 24 hours.
most cases; however, over-the-counter oral glucose-
• When resuming feeding, give bland, low-fat foods in
electrolyte solutions (Pedialyte) are available for
small amounts at frequent intervals. Various com-
counterbalancing intestinal fluid losses in cases of
mercial diets are available that have been specially
mild diarrhea.
formulated for animals with GI disease. Recipes for
appropriate homemade diets are available as well.
Examples of appropriate foods include boiled rice
Antidiarrheal Drugs
combined with turkey, boiled skinless chicken, Symptomatic treatment is based on drugs that modify
yogurt, or low-fat cottage cheese as protein sources. motility, fluid secretion, and absorption or on drugs
• Examples of commercial “intestinal diets” appropri- that act locally within the lumen as protectants or
ate for nonspecific therapy of diarrhea include adsorbents.
Eukanuba Low Residue (Iams), Prescription Diet i/d
(Hill’s), Low Fat (Waltham), and EN Formula
• In most cases, these drugs are reserved for short-term
use, usually for periods of 5 days or less. Some com-
(Purina). Other highly digestible diets can also be monly used antidiarrheal drugs and their dosages are
used. listed in Table 69-5.
• When the diarrhea has been resolved for 48 hours,
• The purposes of antidiarrheal drugs are to provide
gradually reintroduce the animal’s regular diet. short term relief from diarrhea, to provide relief from
bowel discomfort (“crampiness”), and to control
Chronic Diarrhea intestinal fluid losses.
Divide daily food intake into three or four feedings, and
use (1) commercial diets designed for GI disease with Opiate and Opioid Narcotic Analgesics
high digestibility and mild fat restriction (for all types
of diarrhea); (2) novel protein diets (for dietary hyper- ▼ Key Point Opioid drugs such as loperamide are the
sensitivity and inflammatory bowel disease); or (3) fiber- most effective all-purpose antidiarrheal agents
enriched diets (for canine large bowel diarrhea). (see Table 69-5).
Narcotic Analgesics*
Diphenoxylate Generic Tab: 2.5 mg 0.1–0.2 mg/kg PO q6–8h
Liq: 0.5 mg/ml
Loperamide Imodium AD (McNeil) Cap: 2 mg 0.1–0.2 mg/kg PO q6–8h
Liq: 0.2 mg/ml
Codeine Many Tab, Cap, Liq 0.25–0.5 mg/kg PO q6–8h
Anticholinergics/Antispasmodics
Aminopentamide Centrine (Fort Dodge) Tab: 0.2 mg 0.01–0.03 mg/kg SC, q8–12h
Inj: 0.5 mg/ml IM, PO
Dicyclomine Generic Tab: 20 mg 0.2 mg/kg PO q8–12h
Cap: 10 mg
Propantheline Generic Tab: 15 mg 0.25 mg/kg PO q8–12h
Hyoscyamine Levsin (Schwarz) Tab: 0.125 mg 0.003–0.006 mg/kg q8–12h
Liq: 0.025, 0.125 mg/ml PO, SC
Antisecretory/Protectant
Bismuth subsalicylate† Pepto-Bismol (Procter & Gamble) Liq: 9, 16 mg/ml 0.5–1.0 ml/kg PO q6–8h
chronic small intestinal disease or exocrine pancreatic substances from the diet, and prevention of indiscrimi-
insufficiency. Cobalamin deficiency can impair intesti- nant eating or chewing behavior. Management of
nal mucosal regeneration and cause villous atrophy and dietary hypersensitivity is discussed under “Chronic
malabsorption, exacerbating diarrhea and contributing Inflammatory Bowel Disease” later in this chapter.
to anorexia and depression in patients with chronic GI
disease.
• Treat with parenteral cobalamin (1000 mg/ml) when DRUG- AND TOXIN-INDUCED DIARRHEA
serum levels are decreased, especially if <200 ng/L.
Give injections weekly for at least 6 weeks, then every Etiology
other week for 6 weeks, and then monthly. • Diarrhea is a frequent adverse side effect of many me-
• For cats and small dogs: Give 250 mg SC, weekly dications, including nonsteroidal anti-inflammatory
• For medium dogs: Give 500 mg SC, weekly agents (e.g., aspirin, ibuprofen, indomethacin,
• For large dogs: Give up to 1000 mg SC, weekly phenylbutazone, and flunixin meglumine), digitalis
and other cardiac drugs, dithiazanine (Dizan),
magnesium-containing compounds, lactulose (for
hepatic encephalopathy), some anthelmintics, most
DIETARY DIARRHEA anticancer drugs, and many antibacterial drugs
(partly from adverse effects on the flora).
Etiology • Dexamethasone has been associated with hemor-
• Diarrhea as a result of indiscriminant eating and rhagic gastroenterocolitis characterized by erosion,
chewing behavior is particularly common in dogs. ulceration, necrosis, and sometimes fatal colonic per-
Dietary indiscretions include overeating, ingestion of foration, especially in dogs treated for intervertebral
spoiled garbage or decomposing carrion, and inges- disc disease.
tion of abrasive or indigestible foreign material (e.g., • Many exogenous toxins cause diarrhea, including
bones, stones, hair, plants, wood, cloth, carpeting, biologic toxins such as the enterotoxins that cause
foil, or plastic) that can traumatize the GI mucosa. staphylococcal and clostridial food poisoning and
• Diarrhea may result from an abrupt change in diet. various diarrheogenic chemical poisons, such as
Any change in the composition of the diet should be heavy metals (lead, arsenic, thallium), insecticides
made in gradual increments over a period of several (organophosphate dips, flea treatments), lawn and
days to allow adaptation. garden products (insecticides, herbicides, fungi-
• Animals may be intolerant of certain foods, such as cides), and some houseplants.
lactose ingested as milk, fatty foods, spicy foods, and • Free-roaming animals may drink from stagnant or
food additives found in certain commercial diets. runoff water polluted or potentially contaminated
Food hypersensitivity to specific protein sources is with toxic industrial, petroleum, or agricultural
implicated as a cause of inflammatory bowel disease chemicals.
in dogs and cats.
• Fiber-responsive diarrhea is sometimes seen in dogs. Diagnosis
Suspect drug- and toxin-induced diarrhea on the basis
Diagnosis of history of exposure (or opportunity for exposure),
clinical signs, and exclusion of other causes of diarrhea.
Dietary causes of diarrhea usually are identified by
careful history-taking and the response to a restricted • Many medications and most toxins that cause diar-
diet. rhea also cause vomiting.
• Carefully question the owner about all aspects of diet • Some toxicities are associated with various extrain-
testinal signs (e.g., neurologic manifestations of lead
and environment, including recent changes in type
and organophosphate toxicity).
and brand of food, all supplemental feeding practices
using “people foods,” patterns of chewing behavior
involving non-food items (including toys, plants, and
Treatment
haircoat), likelihood of garbage ingestion, and • Drug-induced diarrhea usually resolves after discon-
potential for unobserved indiscretions in free- tinuation of the offending medication or a reduction
roaming animals. in its dosage.
• Examine the feces for abrasive particles. • Toxin-induced diarrhea resolves with symptomatic
antidiarrheal therapy, prevention of further exposure
to the toxin, and gradual elimination of the substance
Treatment from the body. However, if the exact toxin is known,
Dietary diarrhea is self-limiting with feeding of a consult other sources of information for additional
restricted diet, elimination of identifiable offending specific treatments and antidotes.
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Life Cycle
INTESTINAL PARASITES (HELMINTHS) Ascarid infection occurs by four routes:
The majority of intestinal parasite infections are asymp- • Prenatal infection results from transplacental migra-
tomatic: when clinical signs do occur, diarrhea and tion, which occurs only with T. canis. Many puppies
weight loss are most common. Young growing animals are born infected with ascarids because of transpla-
generally are more frequently and severely parasitized, cental migration of the bitch’s somatic T. canis larvae
but never overlook endoparasitism as a possible cause into the fetus (prenatal infection).
of acute or chronic diarrhea of either small or large • Milk-borne infection results from transmammary
bowel type in dogs and cats of all ages. Other intestinal migration, which occurs with both T. canis and T. cati.
diseases, such as viral or bacterial enteritis, often are Milk-borne infection during nursing is the major
complicated by intestinal parasite infection. source of ascariasis in kittens.
The diagnosis of parasitism depends on the identifi- • Infection by ingestion of infective eggs occurs with all
cation of eggs, cysts, larvae, trophozoites, or proglottids three ascarids (T. canis, T. cati, and T. leonine).
in the feces (see Table 69-4). Parasites that are notori- • Infection by ingestion of a paratenic (transport) host
ous for evading detection include Giardia in dogs and (T. canis, T. cati) or an intermediate host (T. leonina).
cats with small bowel diarrhea and whipworms in dogs
Three types of migration pattern occur when an
with large bowel diarrhea. In such cases, response to a
animal is infected:
therapeutic trial is an indirect method of diagnosis.
Anthelmintics used to treat the common parasites are • Liver-lung migration (T. canis, T. cati)
listed in Table 69-6. • Migration within the wall of the GI tract (all three
ascarids)
Ascarids • Somatic tissue migration (T. canis, T. cati)
Etiology Clinical Signs
Ascarid nematodes are the most prevalent intestinal • Signs of ascariasis occur most often in young
parasites of dogs and cats worldwide. The ascarids of the puppies and kittens, in which the adult worms in the
dog are Toxocara canis and the less common Toxascaris small intestine may cause abdominal discomfort,
leonina; those in the cat are Toxocara cati and Toxascaris whimpering and groaning, potbellied appearance,
leonina. dull haircoat, unthriftiness, stunted growth, and
diarrhea. Worms frequently are passed in vomitus or the most common routes of infection. With all routes
diarrhea. of infection, eggs are passed in feces after 2 to 3 weeks.
• Rarely, large, tangled masses of worms occlude the
lumen in young pups and cause death from in- Clinical Signs
testinal obstruction, intussusception, or intestinal
perforation. Pathogenicity is directly related to the hookworm’s
• In the neonatal pup, the migration of large numbers bloodsucking activity and capacity for causing intestinal
of T. canis larvae through the lungs can cause severe blood loss. Hookworms embed their mouthparts in the
damage and fatal pneumonia. mucosa to suck blood and tissue fluid, leaving bleeding,
• In young animals with light infections and in adults, punctiform ulcers as they “graze.” Hence, an important
infection is most commonly asymptomatic or is evi- consequence of severe hookworm infection is blood loss
denced merely by a loss of body condition. anemia.
• The clinical signs of ancylostomiasis include tarry
Diagnosis (melena) or bloody diarrhea accompanied by pallor,
• The diagnosis of ascariasis is readily established by weakness, emaciation, and dehydration.
the identification of ascarid eggs in routine fecal • Rapidly progressive blood loss anemia may result in
flotation. acute death of neonates. In other animals, chronic
• Most pups begin passing large numbers of eggs in blood loss may cause iron deficiency anemia charac-
their feces around 3 weeks of age and continue to terized by erythrocytes that show hypochromasia and
shed eggs for most of early puppyhood (4–6 months) microcytosis.
until treated. • Acute, pruritic dermatitis occasionally is associated
with the active penetration of skin by hookworm
larvae.
Treatment • Hookworm infections in mature animals often are
• Numerous effective anthelmintics for ascarids are asymptomatic.
available (see Table 69-6). Pyrantel pamoate is espe-
cially well tolerated and effective in puppies and Diagnosis
kittens; it also is effective in controlling hookworms.
• Because many pups are born infected with T. canis, Young dogs are most often affected, and the diagnosis
treatment is recommended at 2 weeks of age, before usually is readily established by identification of the
eggs are first passed in the feces, and repeated at 4, characteristic Strongyloides hookworm ova by routine
6, and 8 weeks to kill all worms derived from prena- fecal flotation. Ancylostomiasis often is associated with
tal, milk-borne, and ingestion routes of infection. eosinophilia on the CBC.
• Toxocaral visceral larva migrans (VLM) is a serious
disease of humans (especially children) produced by Treatment
the invasion of visceral tissues by migrating T. canis;
Anthelmintics effective for eradicating hookworms
thus, infected pups are considered public health
include pyrantel pamoate (safest for young animals),
hazards.
fenbendazole, and febantel (see Table 69-6 for product
names and dosages).
Hookworms
• In areas in which A. caninum is a frequent problem,
Etiology routinely treat bitches and pups. Because of prenatal
• Ancylostoma caninum, the most common hookworm in and milk-borne infection, initiate treatment of pups
the dog, is a voracious bloodsucker. at 2 weeks of age, along with treatment for T. canis.
• Ancylostoma tubaeforme, the common hookworm in the
cat, is more of a tissue feeder than a bloodsucker and ▼ Key Point Pyrantel pamoate suspension is an
is far less pathogenic than A. caninum in dogs. excellent anthelmintic for nursing pups because it
• Ancylostoma braziliense (southern United States) and is safe and is active against both hookworms and
Uncinaria stenocephala (Canada) affect both dogs and ascarids.
cats but are less common than A. caninum and A.
tubaeforme and are only mildly pathogenic. • Severely anemic animals should receive whole blood
transfusions, iron supplementation, and supportive
Life Cycle therapy as needed.
Hookworm infection can occur by five routes: prenatal,
milk-borne, ingestion of infective larvae (L3), skin pen- Prevention
etration by infective larvae, and ingestion of paratenic • Parasite control is aided by good sanitation and
hosts. Ingestion and cutaneous migration probably are impervious flooring in kennels and dog runs.
W0422-Ch069.qxd 11/12/05 10:43 AM Page 716
Life Cycle
Diagnosis
• Infection with third-stage larvae is by the oral or cuta-
• Definitive diagnosis of whipworm infection requires neous route, and adult worms develop in the small
identification of the characteristic brown, bipolar- intestine following migration in the circulation and
operculated, football-shaped ova by routine fecal lung.
flotation. • Parthenogenetic female adults produce eggs that
• Repeated fecal examinations may be necessary to hatch within the gut lumen so that first-stage (rhab-
identify ova because of the unusually long prepatent doid) larvae are passed in the feces. These larvae may
period and because it is not uncommon for active develop into infectious third-stage (filariform) larvae
infection to be characterized by prolonged periods or free-living adults.
when ova are not shed in the feces.
• Alternative means of diagnosis of ova-negative, or
Clinical Signs
so-called occult, infections, include the following:
• Colonoscopic observation of adult whipworms in • S. stercoralis is mainly a problem in pups, in which it
the bowel lumen causes acute hemorrhagic enteritis that is often fatal.
• Resolution of signs in response to a therapeutic • S. tumefaciens infection in cats is usually asymptomatic,
trial of fenbendazole or febantel but in some cats the parasite causes peculiar tumor-
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• Clinical disease usually is characterized by diarrhea sules, 100 mg q24h for small-breed pups or 200 mg
that varies from soft to fluid and is occasionally q24h for larger-breed pups, PO for 7 to 12 days; alter-
mucoid or bloody. Other signs can include vomiting, natively, 1/4 tsp of 20% powder per four pups mixed
lethargy, weight loss, and dehydration. Coccidia have with puppy ration or 1 ounce (30 ml) of 9.6% solu-
been associated with chronic malabsorption. tion per gallon of free-choice water
Diagnosis
Treatment
The diagnosis can be confirmed by direct fecal
Drugs that are effective for treating giardiasis include microscopy, fecal culture, or PCR assay.
metronidazole, fenbendazole, albendazole, febantel,
quinacrine, and furazolidone. • Motile trophozoites of Tritrichomonas foetus can be
identified in fresh fecal wet smears taken directly
▼ Key Point Fenbendazole is the initial treatment of from the rectum in about 14% of cases. The likeli-
choice for giardiasis. hood of detecting trophozoites is lower in formed
feces, desiccated feces, or in cats recently treated with
• Fenbendazole (Panacur) (50 mg/kg PO q24h for 3 antibiotics.
days) is very safe and effective for treating Giardia in • Fecal culture is more sensitive for diagnosis than
dogs and probably cats. microscopy. Culture requires 0.05 g of freshly voided
• Febantel (Drontal Plus, 15 mg/kg q24h for three feces inoculated in special media (InPouch TF,
doses or a single dose of 30 mg/kg PO) appears to be BioMed Diagnostics). The instructions on using this
effective but needs further study. culture system are found at the website below.
• Metronidazole (25–30 mg/kg PO q12h for 5–10 days) • Fecal PCR assay is the most accurate test (high
is usually effective, although up to one-third of infec- sensitivity and specificity) for detecting T. foetus, and
tions may be metronidazole resistant. Side effects information on submitting samples is found at
include anorexia, vomiting, and reversible CNS toxic- http://www.cvm.ncsu.edu/mbs/gookin_jody.htm.
ity (weakness, ataxia, disorientation, seizures, and • Trichomonads may be observed in the superficial
blindness). mucus and crypts in colonic biopsies.
• Albendazole (Valbazen) (25 mg/kg PO q12h for 5
Treatment
days in cats and 2 days in dogs) is effective but has
been associated with severe bone marrow toxicity. For T. foetus is virtually impossible to eradicate with antibi-
this reason, fenbendazole is preferred. otics. Numerous antibiotic agents have been evaluated
• Furazolidone (Furoxone, SmithKline) (4 mg/kg PO without success. Treatment can reduce the number of
q12h for 5 days) is effective and convenient for cats, organisms and improve clinical signs, but it usually does
as it is available in a suspension form. not eliminate the infection.
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• Diarrhea often improves with antibiotics but relapses prevalent worldwide. Coronavirus and rotavirus are
when antibiotics are stopped. less prevalent and cause relatively mild clinical signs
• Other measures include reducing housing density, except in neonates. For details concerning intestinal
reducing stress, improving diet, and treating concur- viruses, see Chapter 14.
rent infections such as Giardia and Cryptosporidium. • Because of its epitheliotropism, canine distemper
• The long-term prognosis is good based on findings virus also causes diarrhea (see Chapter 13).
that most infected cats resolve the clinical signs of T.
foetus infection within 2 years (median, 9 months). Feline Intestinal Viruses
However, many of these cats remain subclinically
infected for several years. Clinical disease may be pro-
• The most clinically important primary enteric virus
is feline panleukopenia virus (FPV), a parvovirus.
longed in cats living under dense housing conditions,
Other feline intestinal viruses include enteric coron-
possibly attributable to stress.
avirus, rotavirus, and astrovirus (see Chapter 14).
Entamoeba • The intestine may be involved as part of generalized
viral infections such as feline leukemia virus (see
E. histolytica, primarily a human pathogen, rarely may Chapter 8), feline immunodeficiency virus (see
cause amebic colitis (bloody-mucoid diarrhea) in dogs Chapter 9), and feline infectious peritonitis, a coro-
and cats that drink polluted water. navirus (see Chapter 10).
Diagnosis
Diagnosis is based on identification of ameboid tropho- BACTERIAL INFECTIONS OF THE INTESTINES
zoites with pseudopodial movement in saline smears of
fresh diarrheic feces, amebic cysts in zinc sulfate flota- Most enteropathogenic bacteria produce intestinal
tion of formed feces, or trophozoites in colon biopsies. disease by invading the epithelium (invasive bacteria)
or by liberating diarrheogenic enterotoxins (non-
Treatment invasive or enterotoxigenic bacteria).
Optimal treatment for amebic colitis in dogs and cats is Enteropathogenic bacteria of clinical importance
unknown, but response has been seen with metronida- include Salmonella species, Campylobacter jejuni, C.
zole (25–30 mg/kg PO q12h for 5–10 days) or furazoli- perfringens, and C. difficile. Yersinia species and Bacillus
done (2.2 mg/kg PO q8h for 7 days). piliformis are rare and are not discussed here. Salmonella
and Campylobacter are primarily invasive, causing
Balantidium mucosal damage that leads to inflammation, exudation,
mucus secretion, and bleeding. Bacterial enterotoxins
B. coli, a ciliated protozoan that primarily infects swine, may also play a role in the pathogenesis of these agents.
is a rare cause of chronic ulcerative colitis in dogs. C. perfringens and C. difficile are noninvasive and cause
diarrhea by an enterotoxigenic mechanism.
Diagnosis
Diagnosis is based on identification of large (40 to ▼ Key Point Because Salmonella, Campylobacter, and
80 mm ¥ 25 to 45 mm), oval, brown, rapidly swimming cil- Yersinia also are potentially zoonotic pathogens,
iated trophozoites with prominent macronuclei in pets occasionally are reservoirs for human infec-
saline suspensions of fresh feces or identification of pro- tion.
tozoal cysts in zinc sulfate or sedimentation prepara-
tions of feces. Salmonella
Etiology
Treatment
• Salmonellosis is caused by gram-negative bacilli
Optimal treatment is unknown, but metronidazole belonging to the genus Salmonella of the family Enter-
(25–30 mg/kg PO q12h for 5–10 days) appears to be obacteriaceae. Salmonella frequently are isolated from
effective. the feces of normal dogs and cats, but clinical signs
of salmonellosis are uncommon, indicating a preva-
lent asymptomatic carrier state.
VIRAL INFECTIONS OF THE INTESTINES • Salmonella infection is transmitted by the fecal-oral
route, mainly through ingestion of contaminated
food or water. The organisms can survive in the envi-
Canine Intestinal Viruses ronment for long periods outside the host; thus,
• Canine parvovirus, coronavirus, and rotavirus cause fomite transmission also can occur.
viral enteritis and diarrhea in dogs. Canine parvovirus • Infected migratory birds have been a source of fatal
is an acute, severe, highly contagious enteritis that is infections in cats, and raw meat, bone, and raw food
W0422-Ch069.qxd 11/12/05 10:43 AM Page 721
• Clostridial diarrhea is usually self-limiting after a few avoided), because the fecal toxin breaks down after
days, but in some animals diarrhea can persist chron- 24 hours.
ically for weeks to months. Some animals have recur- • Cultures are not useful because non-toxigenic C.
rent episodes of diarrhea. perfringens is part of the flora in normal dogs and
cats and cultures do not reliably distinguish toxigenic
Diagnosis and non-toxigenic strains.
Routine hematologic and serum chemistry evaluations • Assays using molecular probes and PCR are being
evaluated as improved diagnostic procedures for
are usually normal in animals with clostridial diarrhea.
enterotoxigenic C. perfringens.
Colonoscopy is not routinely necessary in these cases,
but endoscopic findings are usually nonspecific (diffuse
hyperemia, increased friability, fresh bleeding, and Treatment
increased mucus). Biopsies range from minimal abnor- Diarrhea caused by enterotoxigenic C. perfringens can be
malities to catarrhal, lymphoplasmacytic, or suppurative effectively treated with ampicillin (20 mg/kg PO q8h),
colitis. amoxicillin-clavulanate (12–25 mg/kg PO q12h), tylosin
A definitive diagnostic test for C. perfringens-induced (20–40 mg/kg PO q12h), or clindamycin (5–10 mg/kg
diarrhea is lacking. Further work is needed to deter- PO q12h) for 5 to 7 days. Metronidazole (10–20 mg/kg
mine the role of CPE in canine and feline diarrhea PO q12h) can also be effective but seems to work less
and to define the optimal diagnostic parameters for consistently.
clostridial diarrhea. Fecal spore counts in stained fecal
smears are commonly used for routine cage-side screen- • Clostridial diarrhea is usually self-limiting or respon-
ing; however, studies have not shown a correlation sive to antibiotics in 2 to 3 days; however, chronic or
between spore counts and positive assays for CPE or a recurrent clostridial diarrhea may require long-term
correlation between either of these diagnostic proce- antibiotics (e.g., tylosin once daily or every other day)
dures and the presence or absence of diarrhea. In and a fiber-supplemented diet to prevent relapses.
people, fecal assays for CPE are considered more accu- • Commercial fiber-containing diets or regular diets
rate than spore counts; however, the commercially avail- supplemented with psyllium (Metamucil at a dosage
able CPE assays used in people need to be validated for of 1–2 tbsp/day for dogs) may help reduce bacterial
dogs and cats. In principle, CPE assays should be valid proliferation and sporulation because fiber is
across species. fermented to short-chain fatty acids that acidify bowel
contents. Alkaline rather than acid conditions are
• The identification of more than five clostridial most favorable for C. perfringens. In addition, short-
endospores per oil immersion field (identified by chain fatty acids nourish colonic epithelium and
their “safety pin” appearance with Diff-Quik or protect against injury.
Wright staining) is considered by many to be pre-
sumptive evidence for a diagnosis of enterotoxigenic Clostridium difficile
diarrhea caused by C. perfringens. Clostridial spores
are generally larger than other bacilli found in feces. C. difficile is an anaerobic, gram-positive, spore-forming
Malachite green can be used as a special stain for bacillus. Toxigenic C. difficile and its toxin have been
endospores. Fecal leukocytes also may be present. isolated from normal dogs and cats and occasionally
Unfortunately, the appearance or absence of from animals with mild diarrhea or acute hemorrhagic
clostridial spores in the feces does not correlate well diarrhea; however, this organism does not appear to
with CPE assays or signs; thus, it might be advisable be a frequent enteropathogen in dogs and cats.
to take into account spore counts, CPE assays, and Pseudomembranous colitis as seen in people is not seen
clinical information before making a diagnosis of in dogs and cats.
clostridial diarrhea.
Diagnosis
▼ Key Point Fecal ELISA assay for CPE is generally C. difficile can be cultured using selective medium;
more reliable and specific than fecal spore counts. however, the organism is isolated from normal dogs as
well, and culture alone does not confirm the produc-
• Commercial fecal assays for CPE are available in kit tion of diarrheogenic toxins.
form for testing humans. The ELISA test (C. per- Commercial ELISA kits that detect both toxins A and
fringens Enterotoxin Test; Techlab, Blacksburg, VA) B in feces are recommended, but validation in dogs and
appears to be the most reliable in dogs. Another com- cats is needed.
mercial test, reverse passive latex agglutination
(RPLA Kit, Oxoid), is insensitive and nonspecific in
dogs and thus is not recommended. Use fresh feces Treatment
only and transport without delay to the laboratory Use metronidazole for treatment of suspected or con-
in prechilled diluent at 4∞C (freezing should be firmed C. difficile infections.
W0422-Ch069.qxd 11/12/05 10:43 AM Page 724
decreased serum cobalamin is common, especially in propria are too many. Infiltrates assessed to be
cats and Shar-Peis with IBD. minimal or mild by an inexperienced pathologist may
not be truly abnormal. Various grading systems have
Radiography and Ultrasonography been proposed, but these have not correlated well
with clinical disease activity.
In most cases, radiographic and ultrasonographic find-
ings are unremarkable and do not aid diagnosis. Some
• In some cases the inflammation is mostly lympho-
cytic; in others the infiltrate also contains a mixture
animals have a nonspecific finding of fluid- and gas- of other types of inflammatory cells (neutrophils,
distended bowel loops on plain abdominal radiography. eosinophils, macrophages). The cellular infiltrate is
Barium contrast radiography occasionally demonstrates usually confined to the mucosa but occasionally may
diffuse mucosal irregularity and ultrasonography may extend to the submucosa.
reveal intestinal thickening, but these are nonspecific
findings that merely suggest an infiltrative lesion. In
• Additional findings indicative of mucosal damage
include architectural distortion (e.g., atrophic or
selected cases, contrast radiography and ultrasonogra- fused villi), fibrosis, and epithelial abnormalities
phy can be helpful nonetheless, because they may (hyperplasia, degeneration, necrosis, erosion, ulcera-
discover an unexpected diagnosis other than IBD—for tion, glandular dilation, loss of goblet cells).
example, pancreatitis, hepatobiliary disease, or intesti-
nal tumors, polyps, granulomas, or malformations (e.g.,
• A severe infiltration of lymphocytes that extends
beyond the mucosa into the submucosa and muscu-
diverticulum or short colon). laris should raise the suspicion of early lymphoma
mimicking IBD, and further diagnostics should be
Endoscopic Examination recommended.
In animals with GI disease, the spectrum of clinical signs
usually suggests the most appropriate region of the GI
Evaluation for Dietary Hypersensitivity
tract for endoscopic examination. In IBD, however,
signs do not always correlate with the region of greatest Dietary hypersensitivity or food allergy is an immuno-
cellular infiltration, especially in cats. It is not uncom- logically mediated adverse reaction to a protein com-
mon to find significant involvement of the colon in cats ponent in food. A well-controlled dietary trial using a
that present with vomiting. Conversely, cats with hema- protein elimination diet is the basis for diagnosis of
tochezia or other colonic signs may have unexpected dietary hypersensitivity as a cause of IBD (for additional
gastroduodenal lesions. Therefore, it may be advisable information on diagnostic food trials, see Chapter 47).
in many cases to obtain biopsies from the stomach, The diet is changed to a well-defined, additive-free,
duodenum, jejunum (if possible), colon, and ileum highly digestible diet that contains a single source of
(if the ileocolic sphincter can be navigated during protein not found in the animal’s normal diet. Intake
colonoscopy). of all other foods or sources of antigen must be elimi-
Endoscopically, the mucosa in IBD may appear to be nated throughout the feeding trial, including table
normal or it may have any of the following abnormali- scraps, treats, and flavored medications such as vitamin
ties: erythema, petechiae, increased mucus, increased supplements. The goal is to feed a single protein source
friability, increased surface granularity, decreased visi- to which the animal is not yet sensitized. Although many
bility of the colonic submucosal vessels, thickened or commercial hypoallergenic diets are available (see the
increased folds, erosions or ulcers, or decreased disten- next section), home-prepared single-protein diets are
sibility. The mucosal lesions may only be apparent preferred for diagnostic testing purposes. Examples of
microscopically; thus, a normal endoscopic appearance novel protein sources not likely found in the animal’s
does not rule out IBD and multiple biopsies should regular diet might include turkey, duck, lamb, rabbit,
be taken even if there are no endoscopically visible venison, fish, or soybeans (tofu). Once dietary hyper-
abnormalities. sensitivity is confirmed with a home-prepared diet,
commercial hypoallergenic diets can be substituted for
Mucosal Histopathology more convenient long-term management.
A cooperative and patient owner is required for a suc-
The histopathologic lesion of lymphocytic-plasmacytic
cessful elimination diet trial. A minimum of 3 to 4 weeks
IBD is characterized by diffuse infiltration of the lamina
should be allowed for initial response to an elimination
propria with mature lymphocytes and plasma cells in
diet. If no improvement has occurred during this time,
association with mucosal damage. For definitive diag-
then dietary hypersensitivity is unlikely and medical
nosis of lymphocytic-plasmacytic IBD, there must be
therapy should be instituted. If some improvement
abnormal infiltration of lymphocytes and plasma cells,
has been observed, then the trial should continue as it
as well as evidence of mucosal damage.
may require 6 weeks or more before improvement is
• Pathologists may differ in their interpretation of complete.
endoscopic biopsies and in their definition of how If there is a substantial improvement with the elimi-
many lymphocytes and plasma cells within the lamina nation diet, then the animal can be rechallenged with
W0422-Ch069.qxd 11/12/05 10:43 AM Page 727
its original diet. Recurrence of clinical signs confirms effects of the diet on bowel motility, composition of the
dietary intolerance or hypersensitivity. In addition, once microflora, mucosal morphology and function, and
remission is restored with the controlled diet, the exposure to food-borne antigens or additives.
animal can then be challenged sequentially with indi-
vidual dietary components to identify the specific • The treatment of IBD associated with dietary hyper-
sensitivity is based on the controlled feeding of a
offenders. To do this, individual components of the
well-defined, additive-free, highly digestible diet that
original diet are added one at a time to the controlled
contains a single source of protein not found in the
diet while the animal is in remission. With each chal-
animal’s normal diet (i.e., a novel protein to which
lenge the animal is monitored for recurrence of signs
the animal is not yet sensitized). Home-prepared
for 7 to 10 days. If signs recur, then that substance is
diets (turkey, duck, lamb, rabbit, venison, white fish,
implicated as an offender.
or tofu) are most suitable for diagnostic testing
After several weeks to months of remission on the
purposes (see previous “Diagnosis” section); however,
controlled diet, some animals can be returned to their
if the home-prepared diet suggests diet-responsive
original diet and remain asymptomatic, but in most
disease, then a commercial “hypoallergenic” novel
cases, specially formulated or novel protein diets may
protein diet can be substituted and is more conve-
need to be continued indefinitely to prevent relapse. If
nient and balanced for long-term feeding. Many com-
there is no response to dietary management within 4 to
mercial diets that contain novel protein sources are
6 weeks, the animal can be fed a digestible commercial
now marketed for dietary hypersensitivity. A relapse
GI diet or returned to its original diet and medical
rate of approximately 15% to 20% is to be expected
therapy can be instituted.
when switching from a home-prepared to a commer-
cial hypoallergenic diet. For long-term feeding of a
Treatment home-prepared diet, recipes for balanced diets con-
Well-controlled therapeutic trials for chronic IBD in taining novel protein sources can found in veterinary
animals are lacking; thus, treatment is largely empirical nutrition text books or various reliable websites
and based on clinical experience. Because dietary under supervision of Diplomates of the American
hypersensitivity, parasites (see previous section), and College of Veterinary Nutrition.
bacterial enteropathogens (see previous section) may • An alternative approach is to use a diet containing
cause lymphocytic-plasmacytic IBD, it is appropriate hydrolyzed proteins (oligopeptides) that may be less
to first consider evaluation and treatment for these antigenic (e.g., Prescription Diet z/d, Hills; or HA
possibilities. Diet, Purina).
In most cases of lymphocytic-plasmacytic IBD, an • In cases in which hypoallergenic novel protein diets
underlying cause cannot be identified and the most have not been effective, other dietary adjustments
effective treatment is an anti-inflammatory regimen may be beneficial as an adjunct to medical therapy
of either corticosteroids or mesalamine (5-ASA deriva- for IBD. This includes fiber supplementation (psyl-
tive) combined with dietary modification (e.g., novel lium, bran, canned pumpkin) of the regular diet or
protein diet, hydrolyzed diet, or fiber-enriched diet). If switching to a commercial diet enriched with fer-
diet and anti-inflammatory drugs fail to control the mentable fiber (e.g., beet pulp) marketed for improv-
disease, metronidazole is added for its antibacterial and ing colonic function and ameliorating diarrhea in
immunomodulatory properties. Metronidazole can also animals with colitis. Fiber has many beneficial effects
be used as a single drug to induce or maintain remis- on colonic function and helps keep enteropathogens
sion in less severe cases. For refractory cases, a cytotoxic in check. Colonic bacteria metabolize fermentable
immunosuppressive agent such as azathioprine or chlor- fiber to short-chain fatty acids that nourish colonic
ambucil can be added to the corticosteroid regimen. epithelium and protect against mucosal injury.
Cyclosporine may also be beneficial in steroid-refractory • Modification of the intestinal bacterial flora is the
cases. Various drugs used to treat IBD and their sug- aim of probiotics (orally administered live bacterial
gested dosages are indicated in Table 69-7. cultures such as Lactobacillus) and prebiotics (benefi-
cial dietary carbohydrate substrates such as lactulose
Dietary Therapy and fructo-oligo-saccharides).
Various strategies for dietary modification have been • Adjustment of the levels of omega-6 and omega-3
fatty acids in the diet has been proposed to manage
used for treatment of chronic IBD, including novel
bowel inflammation through decreasing inflamma-
protein diets, hydrolyzed diets, fiber-enriched diets,
tory mediators, although evidence for this is lacking.
diets with adjusted omega-6 and omega-3 fatty acid
levels and diets with prebiotics and probiotics. In some
Cobalamin Therapy
animals with IBD, dietary modification produces com-
plete or partial resolution of the signs and sometimes Cobalamin (vitamin B12) is frequently depleted in
regression of the lesions. Potential explanations for a patients with chronic IBD, especially cats, and
beneficial response to dietary modification include the cobalamin deficiency can impair intestinal mucosal
W0422-Ch069.qxd 11/12/05 10:43 AM Page 728
Anti-inflammatory Drugs/Immunosuppressives
Prednisone* Many Tab: 5, 10, 20, 50 mg Dog: 1–2 mg/kg PO q24h
Cat: 2–3 mg/kg PO q24h
Budesonide Entocort (AstraZeneca) Cap: 3 mg Dog: 1–3 mg PO q24h
Cat: 1 mg PO q24h
Methylprednisolone acetate Depo-Medrol (Upjohn) Inj: 40 mg/ml Cat: 20 mg IM q2–4wk
Azathioprine† Imuran; Azasan (Salix) Tab: 25, 50, 75 mg Dog: 1–2 mg/kg PO q24–48h
Cat: 0.3–0.5 mg/kg PO q24–48h
Chlorambucil Leukeran (Glaxo) Tab: 2 mg 0.1–0.2 mg/kg PO q24–48h,
or 2–3 mg/m2 PO q24–48h,
or 15–20 mg/m2 PO once
every 3 weeks (cats)
Cyclosporine Atopica (Novartis) Cap: 10, 25, 50, 100 mg 5 mg/kg PO q24h
Colonic Anti-inflammatory Drugs
Sulfasalazine‡ Generic Tab: 500 mg Dog: 10–30 mg/kg PO q8–12h
Cat: 10–20 mg/kg PO q12–24h
Olsalazine Dipentum (Celltech) Cap: 250 mg Dog: 10–20 mg/kg PO q12h
Mesalamine Asacol (Procter & Gamble) Tab: 400 mg Dog: 10–20 mg/kg PO q8–12h
Pentasa (Shire) Tab: 250 mg
Anti-inflammatory Retention Enemas§
5-Aminosalicylate Rowasa (Solvay) Enema: 4 g/60 ml To be determined
Hydrocortisone Cortenema (Reid-Rowell) Enema: 100 mg/60 ml 20–60 ml rectally q24h
Antibiotics
Metronidazole Flagyl (Searle) or generic Tab: 250 mg, 500 mg 10–20 mg/kg PO q8–12h
Tylosin tartrate¶ Tylan Soluble (Elanco) Powder: 2270 mg/tsp Dog: 20–40 mg/kg PO q12h
Cat: 10–20 mg/kg PO q12h
Opioid Motility/Secretory Modifier
Loperamide Imodium AD Tab: 2 mg Dog: 0.1–0.2 mg/kg PO q8–12h
Liq: 0.2 mg/ml Cat: 0.1–0.3 mg/kg PO q12–24h
Adjunct Therapy
Cobalamin Generic Inj: 1000 mg/ml Dog: 250–1000 mg weekly
Cat: 250 mg weekly
Psyllium Metamucil (Procter & Gamble) Powder Dog: 1–3 tbsp/day with food
Cat: 1–3 tsp/day with food
*In some cats with severe colitis, prednisone dosage may need to be increased to 5 mg/kg/day, divided bid. In dogs, if steroidal side effects become a problem,
decrease dosage and combine with azathioprine, metronidazole, or both.
†
May cause myelotoxicity, so monitor the complete blood count; formulate as an oral suspension for accurate dosing of cats.
‡
Dosage may need to be increased to 25–50 mg/kg q8h to achieve effect in some dogs; may cause keratoconjunctivitis sicca in dogs and salicylate toxicosis in
cats.
§
Retention enemas for topical therapy of the distal colon may relieve signs of tenesmus and urgency in some animals with proctitis.
¶
Tylan Soluble can be mixed with dextrose or cornstarch. Tylosin powder is bitter-tasting and thus best tolerated when mixed with food.
Cap, capsules; Inj, injectable; Liq, elixir, suspension, or drops; Tab, tablets.
regeneration and cause mucosal atrophy, exacerbat- dogs and 2–4 mg/kg/day or a 5-mg total dose q12h for
ing diarrhea and making the patient refractory to cats) for initial treatment of lymphocytic-plasmacytic
the usual anti-inflammatory therapy. Thus, evaluate IBD. Clinical improvement using this dosage should be
serum cobalamin and treat with parenteral cobalamin noted within 1 to 2 weeks. After 2 weeks of remission,
(1000 mg/ml) when serum levels are decreased, espe- the dosage is tapered in 2- to 4-week increments to the
cially if <100 ng/L. Give injections weekly for at least 6 lowest effective alternate-day dosage.
weeks, then every other week for 6 weeks, and then
monthly. • In some cases dexamethasone seems to be more
effective than prednisolone with fewer side effects.
• For cats and small dogs: Give 250 mg SC, weekly • In cats that are too difficult to medicate orally,
• For medium dogs: Give 500 mg SC, weekly periodic injections of methylprednisolone acetate
• For large dogs: Give up to 1000 mg SC, weekly (20 mg IM or SC q2–4wk) may be substituted for oral
treatment.
Corticosteroids
• Budesonide (0.5–1-mg total dose/cat and 0.5–3-mg
Oral prednisone or prednisolone is the most consis- total dose/dog, PO q24–48h) is an alternative corti-
tently effective medical therapy (1–2 mg/kg/day for costeroid for refractory cases. Budesonide has high
W0422-Ch069.qxd 11/12/05 10:43 AM Page 729
receptor-binding affinity in the mucosa and under- • The advantages of olsalazine over sulfasalazine are
goes extensive first-pass metabolism in the liver. It that olsalazine contains only 5-ASA (without sulfa) so
achieves particularly high mucosal anti-inflammatory that side effects are fewer and that a greater per-
activity with less systemic side effects. It may be cost centage of the drug reaches the colon.
prohibitive for some owners. • Unfortunately, olsalazine is currently available only in
• Corticosteroid therapy may be discontinued on a trial 250-mg capsules, an inconvenient size for dosing
basis after 6 to 12 weeks of remission; however, con- most animals.
tinuous alternate-day therapy is often required to
prevent relapse. Polymer-Coated Mesalamine (Asacol)
• In refractory cases, metronidazole or mesalamine A pH-sensitive coating prevents release of 5-ASA until
(see the next sections) should be added to the pred- the drug reaches the site of inflammation in the colon.
nisolone regimen. If this fails to control the disease,
then the combination of azathioprine in dogs or chlor- Pentasa
ambucil in cats (see a later section) with pred-
nisolone may be more effective for achieving Encapsulation prevents release of 5-ASA until the drug
remission of the disease. reaches the site of inflammation in the colon.
disease (see Table 69-7). Besides treating refractory mental infiltration of some portion of the GI tract with
IBD, the addition of azathioprine enables use of a mature eosinophils, often accompanied by a peripheral
lower dose of corticosteroid to control the disease eosinophilia.
and thereby minimizes steroidal side effects.
• Azathioprine usually is given as a daily treatment until
remission occurs and then decreased to an alternate- Etiology
day treatment (alternating with every-other-day Food allergy and parasitism (e.g., visceral larva migrans)
prednisone) for maintenance. Because of its have been proposed as causes, but in most patients
myelosuppressive toxicity (leukopenia), periodically evidence for these is lacking and the disease must be
monitor the CBC of azathioprine-treated animals, considered idiopathic.
especially in the first 2 months, and use lower dosages
in cats (see Table 69-7). In cats, formulate azathio-
prine as an oral suspension to facilitate accurate and Clinical Signs
safe dosing. • One or more layers of the stomach, small intestine,
• Chlorambucil (0.1–0.2 mg/kg PO, or 2.0 mg/m2 PO, or colon may be affected, resulting in clinical syn-
q24–48h; alternatively, 15–20 mg/m2 PO, once every dromes of chronic vomiting (eosinophilic gastritis)
3 weeks) is an effective alternative to azathioprine (see Chapter 67), chronic small bowel-type diarrhea
that is well tolerated by most cats. (eosinophilic enteritis), chronic large bowel-type
diarrhea (eosinophilic colitis), or any combination of
Cyclosporine these. Weight loss is frequent.
Cyclosporine (Atopica, Novartis) (5 mg/kg PO q24h) • Diffuse infiltration of the intestinal tract with
is useful for treating corticosteroid-refractory IBD. eosinophils may result in malabsorption (watery diar-
Cyclosporine is a potent immunosuppressive drug that rhea and weight loss) or protein-losing enteropathy.
inhibits interleukin-2 and T cell recruitment. Transient • Diarrhea or vomitus may contain blood from mucosal
anorexia and vomiting are common side effects at the erosions or ulcers.
start of treatment but these resolve within 2 weeks. • Eosinophilic granulomas of the deeper layers of the
bowel wall occasionally produce segmental tumor-
Motility-Modifying Antidiarrheal Drugs like thickenings that can cause partial intestinal
obstruction.
Adjunctive use of motility-modifying drugs may provide
some symptomatic relief for animals with IBD (see
Table 69-5 for dosages). Diagnosis
• Opioid drugs such as loperamide (Imodium) and • The history may indicate dramatic responsiveness to
diphenoxylate (Lomotil) may aid control of diarrhea prior glucocorticoid therapy.
by acting on intestinal smooth muscle to inhibit • Palpation may reveal diffusely thickened intestinal
propulsive movements and by inhibiting mucosal loops or a tumor-like intestinal mass (eosinophilic
efflux of water and electrolytes. granuloma).
• Anticholinergic antispasmodics such as dicyclomine • Laboratory evaluation may reveal peripheral eosino-
(Bentyl) may be beneficial in colitis patients with philia (although not present in all cases), hypopro-
severe tenesmus and urgency associated with recto- teinemia, or impaired absorptive function tests.
colonic spasm. • Routine fecal flotation is indicated because para-
sitism can also cause eosinophilic inflammation; it is
Prognosis important to exclude occult whipworm or hookworm
infection in dogs by response to a therapeutic trial
• Monitor clinical response using a canine IBD activity of an anthelmintic such as fenbendazole (see Table
index and sequential evaluation of C-reactive protein 69-6).
as a serum marker of inflammation. • Barium GI radiography and abdominal ultrasono-
• Inform the owner that persistence or recurrence of graphy may be normal, may indicate thickening and
IBD is likely despite therapy; thus, a realistic expec- irregularity (mucosal filling defects) of bowel loops,
tation is the maintenance of remission or control of or may delineate sites of partial luminal obstruction
relapses rather than a permanent cure. caused by eosinophilic granulomas.
• The clinical course in basenjis, soft-coated wheaten • The diagnosis is based on demonstration of
terriers, and Shar-Peis is often progressive despite eosinophilic inflammation in intestinal biopsies. The
treatment. endoscopic appearance is similar to that described
for lymphocytic-plasmacytic IBD except that mucosal
Eosinophilic Gastroenteritis ulceration is more common in EGE. Occasionally,
Eosinophilic gastroenteritis (EGE) is a relatively uncom- lesions are deep in the submucosa and found only by
mon form of IBD that is characterized by diffuse or seg- full-thickness biopsy.
W0422-Ch069.qxd 11/12/05 10:43 AM Page 731
Etiology Diagnosis
The aggressive course and high mortality associated • The diseased segment of bowel may be palpable as a
with this syndrome are consistent with malignant neo- firm mass in the mid-abdomen. The adjacent intesti-
plasia involving eosinophils (see Chapter 22); thus, it is nal loops and mesentery may also be thickened and
very distinct from the benign EGE that is confined to regional lymph nodes may be enlarged.
the GI tract. • A routine CBC may reveal eosinophilia, neutrophilia,
or monocytosis. Panhypoproteinemia due to exces-
Clinical Signs sive enteric loss of protein may be found in some
animals.
• Vomiting, diarrhea (sometimes bloody), anorexia, • Barium contrast radiography of the ileum and colon
and weight loss are the most consistent clinical signs. may delineate a thickened or stenosed segment of
• Clinical deterioration is rapidly progressive and bowel and ultrasonography may identify an intestinal
the disease is eventually fatal. mass.
Diagnosis
• Definitive diagnosis of RGE requires biopsy by
colonoscopy or laparotomy. The key feature is
• Abdominal palpation may reveal intestinal thick- transmural granulomatous inflammation. Fibrosis
ening, hepatosplenomegaly, or mesenteric lymph- and aggregates of epithelioid cells, giant cells, and
adenopathy because of the disseminated visceral eosinophils often are found deep in the lesion. Deep
infiltration of eosinophils. ulceration is common.
• Persistent, severe eosinophilia is a consistent CBC • Differentiate RGE from intestinal neoplasia and
finding in affected cats. infectious causes of granulomatous bowel lesions,
W0422-Ch069.qxd 11/12/05 10:43 AM Page 732
such as histoplasmosis (Chapter 20), pythiosis, and enrofloxacin, and recovery has persisted more than
mycobacteriosis (Chapter 19). Examine granuloma- 3 years after stopping the antibiotic.
tous lesions by special stains to detect fungi and • Anti-inflammatory and immunosuppressive therapy
acid-fast organisms. In cats, feline immunodeficiency (e.g., olsalazine or sulfasalazine, prednisone, azathio-
virus (Chapter 9) and feline infectious peritonitis prine, and metronidazole) in single-agent or
(Chapter 10) occasionally are associated with pyo- combination regimens, as described for lymphocytic-
granulomatous IBD. plasmacytic colitis, generally only provides temporary
palliation of the disease.
Treatment • In general, these dogs seem to have less diarrhea on
a highly digestible diet than on a high-fiber diet.
• Medical treatment of regional granulomatous colitis
is based on the use of anti-inflammatory and Neutrophilic (Suppurative) Enterocolitis
immunosuppressive agents such as olsalazine or
sulfasalazine, prednisone, azathioprine, and metro- Etiology
nidazole, as described for treatment of lymphocytic- • Bacterial enterocolitis (see under “Bacterial Infec-
plasmacytic IBD (see Table 69-7). tions of the Intestines”)
• If the degree of thickening and cicatrization of the • Idiopathic (i.e., neutrophilic IBD in the absence of
affected segment of bowel produces severe stenosis an identifiable infectious cause)
and obliteration of the lumen, surgical excision of
the lesion may be necessary, followed by medical Clinical Signs
therapy for 6 to 8 weeks or longer to prevent recur-
rence of the lesion at the surgical site. Always submit • Large bowel diarrhea that can be either acute or
chronic.
the excised lesion for histopathological evaluation.
Diagnosis
Histiocytic Ulcerative Colitis
• Colonoscopic biopsy shows infiltration of predomi-
• Histiocytic ulcerative colitis is a chronic idiopathic nantly neutrophils, with variable mucosal ulceration,
IBD of young boxer dogs characterized by infiltration necrosis, or crypt abscesses.
of the lamina propria and submucosa of the colon by • Diagnosis is based on tests to exclude bacterial
distinctive histiocytes engorged with deposits that enteropathogens (see under “Bacterial Infections of
stain positive with periodic acid-Schiff (PAS) stain. the Intestines”).
• In addition to boxers, there have been isolated case
reports of histiocytic colitis in a cat and a French Treatment
bulldog, but it is not known if this is the same disease
that occurs in boxers. Give antibiotics (e.g., enrofloxacin, trimethoprim-sulfa,
or tylosin) or regimens consisting of sulfasalazine,
Clinical Signs metronidazole, or anti-inflammatory or immunosup-
pressive drugs, as described for lymphocytic-plasmacytic
• Affected boxers generally develop severe, unrespon- IBD (see Table 69-7).
sive, bloody-mucoid large bowel diarrhea before 2
years of age.
• Severe weight loss and debilitation occur in dogs with
long-standing disease. FIBER RESPONSIVE DIARRHEA
(IRRITABLE BOWEL SYNDROME)
Diagnosis
The diagnosis is based on the known breed predisposi-
Etiology
tion and the presence of numerous PAS–positive histi- Fiber-responsive diarrhea is characterized by chronic,
ocytes in a colonoscopic biopsy. A mixture of other types non-inflammatory, mucoid large bowel diarrhea. The
of inflammatory cells is also found in the lesion, and condition has resemblances to irritable bowel syndrome
usually there is severe mucosal ulceration. (IBS) seen in people.
activity may be a consideration in animals that have accelerated loss of plasma proteins into the gut. Mech-
intermittent mucoid diarrhea but lack evidence of anisms of excessive enteric loss of protein include the
organic disease. following:
• Hematochezia is usually absent.
• Impaired intestinal lymphatic drainage (e.g.,
• Large breeds, especially those used as working dogs
lymphangiectasia) that results in extravasation of
(e.g., police dogs, Seeing Eye dogs, and sled dogs),
protein-rich lymph into the lumen
and temperamental or excitable dogs seem to be
predisposed.
• Disruption of the mucosal barrier (e.g., inflamma-
tion) that results in protein leakage from sites of
exudation, bleeding, or increased permeability
Diagnosis
The diagnosis is based on the complete absence of Etiology
abnormal findings on diagnostic evaluation, minimal Severe protein-losing enteropathy occurs most fre-
abnormalities on colonoscopic biopsy, and remission of quently in association with chronic enteropathies, such
clinical signs in response to modification of diet, par- as the following:
ticularly supplementation of fiber.
• Idiopathic canine intestinal lymphangiectasia
• By definition, IBS is a functional disorder. The diag- • Chronic inflammatory small bowel diseases (lympho-
nosis can be established only by normal colonoscopic cytic-plasmacytic enteritis, granulomatous enteritis,
biopsy and diligent exclusion of the other known eosinophilic enteritis, immunoproliferative enteropa-
causes of colonic disease, such as dietary, parasitic, thy of basenjis)
infectious, and chronic colitis (IBD). • Intestinal histoplasmosis
• At colonoscopy, the colon may appear to be hyper- • Intestinal lymphoma
motile or spastic. The mucosa appears normal except
for increased intraluminal mucus and an erythema- Intestinal Lymphangiectasia
tous response to insufflation.
Lymphangiectasia is a chronic protein-losing enteropa-
thy in dogs, characterized by marked dilation and dys-
Treatment function of the intestinal lymphatic network. Impaired
Dietary Modification intestinal lymph drainage is presumably caused by
obstruction to the normal lymphaticovenous flow. It
Supplement a digestible GI diet with added dietary fiber leads to stasis of chyle within dilated lacteals and lym-
in the form of psyllium (Metamucil) (1–5 tbsp/meal). phatics of the bowel wall and mesentery. Overdistended
This is sufficient to produce remission in many cases. lacteals release intestinal lymph into the gut lumen
Fiber may normalize colonic myoelectrical function and by rupture or extravasation, causing loss of the
have beneficial effects on fecal consistency, water constituents of chyle, including plasma proteins, lym-
content, and bulk. In addition, fermentable soluble phocytes, and lipid (chylomicrons).
fiber is fermented by colonic bacteria to short-chain
fatty acids that provide an energy source for colonic Clinical Signs
epithelium, protect against mucosal injury, and acidify
bowel contents, which may alter the bacterial flora. • The presenting signs of lymphangiectasia usually
are attributable to protein-losing enteropathy and
include dependent pitting edema of subcutis and
Medical Therapy limbs, fluid distention of the abdomen (ascites),
• If dietary fiber supplementation is unsuccessful, con- and respiratory distress (hydrothorax). These mani-
sider medication to alter motility such as opioid drugs festations of fluid transudation are the result of
such as loperamide (see Table 69-5 for dosages). hypoalbuminemia and reduced plasma colloidal
• Consider amitriptylin (Elavil) at 1 to 2 mg/kg PO osmotic pressure.
q12h. • Chronic intermittent or persistent diarrhea with a
• Light sedation during stressful times may be benefi- watery or semisolid consistency often is observed, but
cial in excessively nervous or excitable animals. not all patients have diarrhea.
• Progressive weight loss is common. Clinical signs
often develop insidiously.
Diagnosis Treatment
• Abdominal palpation may identify intestinal foreign • Intestinal obstructions are treated surgically. Give
bodies, intussusceptions (“sausage loop”), or gas- and close attention to supportive care, especially mainte-
fluid-distended loops of bowel proximal to the nance of fluid, electrolyte, and acid-base homeostasis
obstruction. before, during, and after surgery (for further infor-
• Radiography often confirms the presence of obstruc- mation on intestinal surgery, see Chapter 70).
tion and delineates the cause, especially when con- • Treatment includes management of complications
trast studies are used. such as necrosis or perforation of the bowel, peri-
• Radiographic findings suggesting obstruction include tonitis (see Chapter 76), and septic shock (see
gas or fluid distention (mechanical ileus) of the Chapter 156).
bowel, delayed transit of contrast material, fixation or
displacement of gut loops, luminal filling defects, and
foreign objects within the lumen. SUPPLEMENTAL READING
• Cats commonly ingest radiolucent linear intestinal
foreign bodies (e.g., thread, string, cloth, fishing line, Sherding RG: Diseases of the colon, rectum, and anus. In Tams TR
dental floss, and decorative tinsel) that cause aggre- (ed): Manual of Small Animal Gastroenterology, 2nd ed. Philadel-
phia: WB Saunders, 2003, pp 251–285.
gation and plication of the bowel and have a distinc- Sherding RG: Diseases of the small bowel. In Ettinger SJ (ed): Text-
tive radiographic pattern. book of Veterinary Internal Medicine, 3rd ed. Philadelphia: WB
• Laboratory findings often reflect fluid, electrolyte, Saunders, 1989, p 1323.
and acid-base derangements; these vary with location, Washabau RJ, Holt DE: Diseases of the large intestine. In Ettinger SJ
completeness, and duration of obstruction. (ed): Textbook of Veterinary Internal Medicine, 6th ed. St. Louis:
Elsevier, 2005, pp 1378–1407.
• Leukocytosis with a left shift or degenerative leukope-
nia accompanied by septic abdominal effusion
indicates intestinal ischemia or perforation with
peritonitis (see Chapter 76).
W0422-Ch070.qxd 11/10/05 5:39 PM Page 739
▼ Chapter
70 Surgery of the Intestines
Ronald M. Bright
Surgical therapy is indicated for structural disease of the • Attempt to correct electrolyte and water abnormali-
bowel. Most animals that require surgery of the small ties before surgery.
bowel are physiologically compromised. When obstruc- • Several factors may contribute to intestinal leakage
tion of the small bowel is proximal in location (high following resection and anastomosis. Dogs are at
obstruction), serious electrolyte and water abnormali- higher risk for leakage when there are two or
ties can place these patients at high risk. more of the following factors: hypoalbuminemia
Prophylactic antibiotics administered perioperatively (<2.5 g/dl), intestinal foreign body, peritonitis.
are indicated in small bowel surgery.
• Before surgery of the upper and middle small bowel, Surgical Procedure
give a first-generation cephalosporin such as cefa- Objectives
zolin (20 mg/kg) intravenously (IV) initially; repeat
IV 3 hours later. • Gain access to the lumen of the small bowel to
• Before surgery of the distal small bowel and large remove a foreign body.
intestine, give a second-generation cephalosporin • Help define a disease by acquiring a full-thickness
such as cefmetazole (15 mg/kg) IV or cefoxitin biopsy.
(30 mg/kg) IV; repeat IV 3 hours later. • Avoid contamination of the peritoneal cavity.
Equipment
ANATOMY • General surgical pack
• Babcock forceps
• The small intestine extends from the pylorus to the • Laparotomy sponges
cecum. • Doyen non-crushing intestinal clamps
• The duodenocolic ligament restricts the movement • #11 Bard-Parker blade
of the distal duodenum. • Fine-tip needle holders
• The jejunum is the major portion of the small bowel • Ewald thumb forceps
and is a very mobile structure.
• The major blood supply is from the cranial mesen- Technique
teric artery.
• A portion of the proximal duodenum is supplied by 1. Make a midline abdominal incision to allow access
the celiac artery and shares a source of blood with the to the small bowel.
right lobe of the pancreas via the pancreaticoduode- 2. Isolate the segment of bowel to be entered with
nal artery. moistened laparotomy sponges.
• The tunica of the small intestine includes the 3. Place a 3-0 stay suture at both ends of the proposed
mucosa, submucosa, muscularis, and serosa. enterotomy incision (Babcock forceps may be
• The submucosal layer provides blood vessels, lym- substituted).
phatics, and nerves. It is also the support or “holding” 4. Milk bowel contents away from the proposed
layer for sutures. enterotomy site; place non-crushing intestinal
forceps (or an assistant’s fingers) across the bowel
to minimize spillage.
5. Make a full-thickness stab incision into the lumen,
ENTEROTOMY using a #11 Bard-Parker scalpel blade. Place a
suction tip in the bowel lumen and remove its con-
Preoperative Considerations tents. Enlarge the incision as needed with Metzen-
• Give perioperative antibiotics, as previously described. baum scissors.
739
W0422-Ch070.qxd 11/10/05 5:39 PM Page 740
6. If removing a foreign body, perform the entero- • Diseases causing bowel necrosis (e.g., foreign body,
tomy over healthy bowel distal to the foreign body. volvulus, trauma)
7. If a biopsy is needed, excise a 2- to 3-mm strip of • Neoplasia
bowel parallel to the enterotomy incision. • Intussusception
8. Trim any everted mucosa with scissors. • Severe, focal infiltrative bowel disease (e.g., phy-
9. Close the enterotomy incision with 3-0 or 4-0 syn- comycosis pythiosis, zygomycosis)
thetic absorbable or monofilament non-absorbable
suture material on a swaged-on taper-point or Preoperative Considerations
taper-cut needle. A full-thickness, simple inter-
rupted or continuous appositional suture pattern is • Administer perioperative antibiotics starting 20 to 40
preferred. minutes before surgery, as described previously.
• Although controversy surrounds the choice of suture
▼ Key Point To minimize tissue trauma, avoid repeat- pattern for intestinal anastomosis, any of several tech-
edly grabbing the intestinal wall with thumb niques probably is acceptable in the hands of a com-
forceps. petent surgeon who follows sound intestinal surgery
principles.
10. Rinse the enterotomy site thoroughly with warm • It is probably best to use synthetic monofilament
saline. absorbable sutures. Polypropylene used in a continu-
11. Use omentum or a jejunal onlay patch to reinforce ous pattern has been associated with attaching to
the suture line. I prefer to use omentum, even in foreign bodies after being extruded into the lumen
relatively healthy tissue. of the bowel and was the cause of pyloric outflow
12. Some severely debilitated animals may benefit from obstruction in a dog following the formation of a
placement of a jejunostomy tube for postoperative granuloma around the suture.
enteral nutritional support. (See Chapter 3 for • I prefer the simple interrupted appositional (SIA)
nutritional support of critical patients.) suture pattern for intestinal (large or small) anasto-
13. Perform routine closure of the abdomen. moses. This non-crushing technique causes little
compromise of the blood supply of the intestinal seg-
Postoperative Care and Complications ments. (Disruption of vascularity is the most common
biologic cause of failure of an anastomosis.)
Short Term
• Monitor for signs of leakage peritonitis by abdominal ▼ Key Point Accurate and atraumatic placement of
palpation, body temperature measurements, and a sutures and gentle handling of the bowel gives the
complete blood count (CBC). best results. Failure of an anastomosis usually is
• Give food and water the day after surgery. due to poor surgical technique or a combination of
• Gradually taper off fluid and electrolyte therapy as the risk factors previously mentioned.
the animal returns to normal eating and drinking.
Equipment
• General surgery pack
SUBTOTAL COLECTOMY
• Babcock forceps
The primary indication for subtotal (90–95%) removal
• Laparotomy sponges
of the colon is for palliation of severe or recurrent
• Doyen non-crushing intestinal clamps
constipation (obstipation related to megacolon). Idio-
• #11 Bard-Parker blade
pathic megacolon in the cat (see Chapter 69) is the
most common disease for which surgery is indicated.
Technique
1. Make a caudal midline abdominal incision for access ▼ Key Point Meticulous handling and careful apposi-
to the colon. tion of tissue and a tension-free anastomosis are
2. Pack off the colon with laparotomy sponges at the critical for the success of subtotal colectomy.
proposed incision site.
3. Place stay sutures at both ends of the proposed colo-
tomy incision (Babcock forceps can be substituted). Preoperative Considerations
4. Milk the colonic contents away from the incision site • In cats, the ileocolic valve can be resected with few
and cross-clamp the bowel segment with Doyen postoperative problems. Reestablishing bowel conti-
clamps. nuity with an ileocolostomy versus a colocolostomy
5. Using a #11 Bard-Parker surgical blade, stab into the (when the ileocolic valve is preserved) is technically
lumen of the colon. Remove a full-thickness ellipti- easier. However, it is preferable to preserve the ileo-
cal piece of tissue with Metzenbaum scissors. colic valve. The postoperative convalescent period is
6. Close the colotomy incision side-to-side with 3-0 or 4- shorter and the likelihood of intractable diarrhea
0 synthetic absorbable suture (e.g., polydioxanone, secondary to small bowel bacterial overgrowth is
PDS) in a simple interrupted appositional pattern. A diminished.
non-absorbable suture (e.g., polypropylene) may be • Administer prophylactic antibiotics, as described
substituted. previously.
7. Gently irrigate the bowel immediately adjacent to the • Preoperative enemas are not necessary and, in fact,
colotomy incision with warm saline before removing can complicate the surgery because of potential
the laparotomy pad. Do not allow irrigation fluid to leakage of fluid from the colon.
enter the peritoneal cavity.
8. Cover the colotomy incision line with omentum.
9. Perform routine closure of the abdomen. Surgical Procedure
Objectives
Postoperative Care and Complications • Palliate signs of constipation or obstipation that are
Short Term associated with megacolon.
• Remove most of the colon with restoration of conti-
• Monitor closely for signs of leakage peritonitis for nuity by ileocolostomy or colocolostomy.
48 hours. • Promote movement of bowel contents from the small
• Abdominal pain, an unusually high fever, and a neu- bowel to the rectum.
trophilia with a left shift suggest a need for further • Prevent spillage of colonic contents.
diagnostic tests such as radiography and diagnostic
peritoneal lavage.
Equipment
Long Term • General surgery pack
• Balfour abdominal retractors
• Strictures occur rarely. • Laparotomy sponges
• Slow-leakage peritonitis may be masked by antibi- • Doyen non-crushing straight intestinal clamps
otics, or the infected area may be walled off, only to • Carmalt crushing forceps
be manifested later as an abscess.
Technique
Prognosis 1. Make a ventral midline abdominal incision, starting
• The prognosis is good if the colotomy is done to from midway between the xiphoid and umbilicus
remove a foreign body. and coursing caudally to the brim of the pelvis.
• If the biopsy suggests a non-neoplastic process, the 2. Exteriorize and carefully isolate the colon and distal
prognosis depends on the underlying disease (see small bowel from the rest of the abdominal viscera
Chapter 69). outside the abdominal cavity.
W0422-Ch070.qxd 11/10/05 5:39 PM Page 744
3. Isolate the appropriate colic vessels approximately Figure 70-4. Subtotal colectomy. Correction of luminal disparity
1 to 2 cm from the mesenteric side of the colon. of the bowel by partial closure of larger segment before anastomosis.
Ligate and divide these (Fig. 70-3).
4. If the ileocolic valve is being removed, ligate an rected by partial closure of the larger colonic
additional set of vessels (ileocecocolic artery and segment, using the same suture and pattern (Fig.
vein) (see Fig. 70-3). 70-4).
5. Caudally, ligate the caudal mesenteric artery and 12. Be careful to incorporate the serosa and to ensure
vein. accurate and gentle placement of all sutures. Place
6. Milk the fecal contents toward the center of the the sutures at 2- to 3-mm intervals.
segment of colon to be removed. 13. Gently irrigate the anastomotic site and adjacent 4
7. Place a non-crushing intestinal clamp across the to 5 cm of bowel with warm saline. Do not allow
distal colon approximately 1 cm cranial to the brim fluid to enter the peritoneal cavity.
of the pelvis; if the ileocolic valve is being preserved, 14. Place an omental patch over the site of anastomo-
place another clamp across the short 1-cm segment sis and gently tack it with one or two sutures below
of proximal colon remaining below the ileocolic the line of anastomosis.
valve. 15. Remove the laparotomy sponges and replace the
8. If the ileocolic valve is being resected, place a non- bowel in the abdominal cavity.
crushing clamp across the ileum just proximal to 16. Use new gloves and a sterile set of instruments for
the ileocolic valve. closure of the midline incision.
9. Use crushing forceps to clamp the colon approxi-
mately 1 cm to the inside of the previously placed Postoperative Care and Complications
non-crushing clamps. Transect the colon next to
the crushing forceps and the segment of bowel Short Term
being removed (i.e., the crushing forceps come out • Withhold food and liquids for 24 hours.
with the resected bowel segment). • Monitor closely for signs of leakage from the anasto-
10. Perform an end-to-end anastomosis using 4-0 mosis for 48 to 72 hours.
polypropylene or a monofilament synthetic • Some animals continue to have some tenesmus for 7
absorbable suture in a simple interrupted, full- to 10 days after surgery.
thickness, appositional suture pattern. • Loose stools and increased frequency of defecation
11. Correct any lumen disparity by longitudinally incis- occur but usually improve somewhat over a period of
ing the antimesenteric side of the bowel with the weeks to months.
smaller lumen. Lumen disparity can also be cor- • Continue intravenous fluids for 36 to 48 hours.
W0422-Ch070.qxd 11/10/05 5:39 PM Page 745
▼ Chapter
71 Diseases of the Liver and Biliary Tract
Susan E. Johnson / Robert G. Sherding
Nonspecific Signs
DIAGNOSTIC STRATEGY FOR LIVER DISEASE • Vomiting is a common sign of liver disease.
Hematemesis suggests gastroduodenal ulceration, a
The liver has many diverse functions related to hepatic
recognized complication of hepatobiliary disease.
blood flow; protein, carbohydrate, and fat metabolism;
detoxification and excretion of drugs and toxins; and
• Diarrhea occurs less frequently than vomiting and is
characteristically small-bowel diarrhea.
formation and elimination of bile. Consequently, the
clinical and laboratory abnormalities associated with
• Anorexia is a common but nonspecific sign of hepa-
tobiliary disease.
liver failure are diverse.
• Weight loss and stunted growth are nonspecific signs that
suggest chronic rather than acute hepatic disease.
Overview of the Diagnostic Strategy
• Clinical, laboratory, and imaging studies to identify Polyuria and Polydipsia
the presence of liver disease
• Characterization of the functional aspects of the
• Polyuria and polydipsia (PU/PD) may be important
presenting clinical signs in dogs with liver disease.
hepatic disease
The mechanism is multifactorial and includes psy-
• Determination of an etiologic or histologic diagnosis,
chogenic polydipsia, hypercortisolism, and renal con-
which usually requires a liver biopsy
centrating defects.
Acute versus Chronic Disease Signs of Abnormal Bilirubin Excretion
The clinical approach and management of patients with
hepatic disease is dictated largely by the acute versus
• Pigmented urine (bilirubinuria) and jaundice (icterus)
of the sclera, oral mucous membranes, and skin are
chronic nature of the hepatic disorder. Historical, phys-
classic signs of cholestatic liver disease. However, these
ical, laboratory, and radiographic findings may suggest
findings are not specific for hepatobiliary disease and
whether the hepatic disease is acute or chronic, but
can also be caused by hemolytic disorders.
hepatic biopsy often is required for definitive evalua-
tion. Classifying a disorder as acute or chronic has diag-
• Acholic (gray) feces occur secondary to severe cholesta-
sis (usually from common bile duct obstruction),
nostic, therapeutic, and prognostic implications.
which prevents bilirubin in the bile from entering the
• In acute hepatic failure, toxic or infectious causes are intestinal tract and imparting the normal brown color
common, and intensive supportive care is warranted to the feces.
to allow time for hepatic regeneration. The long-term
prognosis for recovery is favorable if the animal sur- Coagulopathy
vives the initial stages.
• Excessive bleeding (i.e., hemorrhages of the skin and
• Chronic hepatic disorders are more likely to be mucous membranes, melena, and hematuria) occa-
accompanied by irreversible changes (cirrhosis); sionally is associated with liver disease, especially if
thus, the long-term prognosis may not be favorable. hepatic damage is severe or is associated with
common bile duct obstruction.
Clinical Signs • Subclinical clotting abnormalities may become clini-
Clinical signs of liver disease include those typically asso- cally apparent after liver biopsy, surgery, and devel-
ciated with hepatic dysfunction, such as jaundice, opment of gastroduodenal ulcers.
hepatic encephalopathy (HE), ascites, and excessive • Potential mechanisms for bleeding include primary
bleeding, and nonspecific signs such as vomiting, diar- failure of the hepatocytes to synthesize clotting
rhea, anorexia, lethargy, and weight loss, which overlap factors, vitamin K deficiency, and disseminated
with signs of other body system disorders. intravascular coagulation (DIC) (see Chapter 23).
747
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biochemical tests identify elevated liver enzyme activity However, this test is not reliable in a clinical setting
or other evidence of hepatic dysfunction (e.g., hyper- because many non-hepatic factors affect urine uro-
bilirubinemia or hypoalbuminemia). Liver function bilinogen concentration, including altered intestinal
studies such as serum bile acid (SBA) concentrations flora, GI bleeding, intestinal absorption, renal excre-
are used to achieve the following: tion, urine pH, urine volume, and urine storage.
• Identify occult liver disease • Ammonium biurate crystals are commonly detected in
animals with portosystemic shunts.
• Assess liver function when there is increased
liver enzyme activity but normal serum bilirubin
▼ Key Point Suspect liver disease in any cat or dog
concentrations
with ammonium biurate crystalluria (except in dal-
• Determine whether significant hepatic dysfunction is
matians and bulldogs).
present to warrant performing a liver biopsy
• Monitor response to therapy
Liver Enzymes
Findings consistent with liver disease on routine lab- Evaluation of serum liver enzyme activity is used as a
oratory tests are described below. screening test to detect liver disease. Increases in liver
enzyme activity are not specific for the underlying
Complete Blood Count hepatic disorder. However, liver enzymes can be used to
• Mild to moderate anemia may occur secondary to liver categorize the underlying pathophysiologic mecha-
disease because of blood loss (e.g., gastroduodenal nism. Increases in liver enzyme activity may occur sec-
ulceration or coagulopathy) or may be associated ondary to hepatocellular injury and leakage (Fig. 71-1),
with normocytic-normochromic anemia of chronic or due to increased production stimulated by bile reten-
disease. tion (cholestasis) or drug induction (Fig. 71-2).
• Erythrocytic microcytosis is a common finding in dogs Many systemic diseases can secondarily affect the
and cats with portosystemic shunts. Decreased serum liver (reactive hepatopathy), causing increased liver
iron concentration, normal to increased serum fer- enzyme activity, but these are not necessarily associated
ritin concentration, and accumulation of stainable with clinical liver disease. For example, feline hyper-
iron in the liver suggests that microcytosis is associ- thyroidism is commonly associated with increased liver
ated with abnormal iron metabolism (impaired iron enzyme activity without significant hepatic dysfunction.
transport or sequestration of iron) rather than
absolute iron deficiency. Decreased availability of
iron for hemoglobin synthesis appears to occur
despite adequate tissue iron stores. ALT
AST
• Target cells and poikilocytosis (acanthocytes and ellipto-
cytes) may occur in dogs and cats with various types
of hepatic disease, due to altered red blood cell
(RBC) membranes.
Urinalysis
• Urine specific gravity may be isosthenuric or hypos-
thenuric if liver disease is associated with PU/PD.
• Bilirubinuria is a sensitive indicator of abnormal
bilirubin metabolism, and this finding precedes
hyperbilirubinemia and jaundice. Bilirubinuria
imparts a yellow-orange color to the urine. Bilirubin
crystals may form in the presence of bilirubinuria.
• Trace amounts of bilirubin may be found in con-
centrated urine of normal dogs (especially males).
• Bilirubinuria is always abnormal in cats and sug-
gests underlying hemolytic or hepatobiliary
disease.
• Urine urobilinogen is a colorless product of enteric bac-
terial degradation of bilirubin that is absorbed from
the gut. A small portion of urobilinogen escapes the Figure 71-1. With hepatocyte injury, leakage of alanine amino-
enterohepatic circulation and is excreted in the transferase (ALT) from the cytoplasm results in increased serum activ-
urine. The finding of urobilinogenuria indicates an ity. Aspartate aminotransferase (AST) is primarily associated with
mitochondria but is also present in the cytoplasm. Release of AST
intact enterohepatic circulation of bilirubin pig- from the mitochondria requires a severe insult. Thus, with hepatocyte
ments. The absence of urobilinogenuria in a jaun- injury, ALT is more readily released and its activity level will usually
diced animal suggests common bile duct obstruction. be higher than that of serum AST.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 750
Cholestasis Normal
ALP
GGT
Bile canaliculi
Figure 71-2. Impaired bile flow (cholesta-
sis) causes increased synthesis of alkaline phos-
phatase (ALP) and gamma-glutamyltransferase
Hepatocytes (GGT). ALP is a sensitive indicator of cholesta-
Bile canaliculi
sis in dogs but is less sensitive in cats (see text).
With cholestatic disorders, increased ALP activ-
ity precedes hyperbilirubinemia. ALP and GGT
lack specificity in differentiating between intra-
Bile ducts hepatic and extrahepatic cholestasis.
Bile ducts
Impaired flow
• Young growing animals or animals with severe bone • Anticonvulsant drug therapy is associated with
disease may have mild increases in ALP activity due enzyme induction of the liver isoenzyme of ALP
to the bone isoenzyme. in dogs (but not in cats) in the absence of obvious
• Cats generally have smaller increases in serum ALP hepatocellular injury. CIALP activity also may be
activity with hepatobiliary disease than do dogs owing increased in some dogs. Reported maximal increases
to a limited capacity for ALP production and a for induced serum ALP activity include those caused
shorter serum half-life (6 hours in cats versus 72 by phenobarbital (30 times normal), primidone (5
hours in dogs). Therefore, even small increases in times normal), and diphenylhydantoin (3 times
serum ALP activity (2–3 times normal) in cats suggest normal).
significant cholestasis.
• Exogenous or endogenous glucocorticoids are asso- Gamma-Glutamyltransferase
ciated with hepatic production of a novel isoenzyme
of ALP, corticosteroid-induced ALP (CIALP), in dogs This membrane-associated enzyme is present in many
but not in cats. The CIALP isoenzyme can be distin- tissues. Increased serum gamma-glutamyltransferase
guished from the liver isoenzyme (LALP) by lev- (GGT) activity usually reflects cholestasis and increased
amisole inhibition using an automated analyzer. production by hepatocytes (see Fig. 71-2).
Increased CIALP activity is a consistent finding in • Increased GGT activity parallels increased ALP activ-
dogs with spontaneous hyperadrenocorticism and ity in dogs, including increases associated with excess
absence of this isoenzyme is uncommon in this corticosteroids.
disorder. • Anticonvulsant therapy causes mild (2–3 times
normal) increases in serum GGT activity in dogs.
▼ Key Point Hypercortisolism caused by glucocorti- • In cats, serum GGT is more sensitive for detecting
coid therapy or hyperadrenocorticism (Cushing’s hepatobiliary disease than ALP. Serum GGT activity
disease) is the most common pathologic cause of exceeds serum ALP activity in most hepatobiliary dis-
increased serum ALP activity in dogs; it is usually eases; an exception is hepatic lipidosis, in which GGT
attributed to an increase in CIALP. activity may be normal or mildly increased despite a
moderate to severe elevation of serum ALP.
Systemic
Postprandial Serum Bile Acid Concentration
Enterohepatic
Liver circulation circulation Postprandial serum bile acid (PPSBA) concentration is
synthesis
an endogenous challenge test of liver function. Whether
PPSBA concentration is a more useful diagnostic test
than FSBA concentration remains unclear. In dogs,
Portosystemic similar information is provided by either test in most
shunt hepatobiliary disorders. Notable exceptions include
dogs with portosystemic shunts or cirrhosis, because with
Intestinal Renal these disorders, FSBA can be in the normal range. In
B clearance clearance
cats, the diagnostic efficacy of PPSBA exceeds that of
Figure 71-3. A, Bile acids are synthesized in the liver, secreted into FSBA for all hepatic disorders, including portosystemic
the biliary system, and stored in the gallbladder during fasting. With shunts. For best diagnostic utility, paired FSBA and 2-
ingestion of a meal, cholecystokinin release stimulates gallbladder
contraction and entry of bile acids into the intestinal tract. Bile acids
hour PPSBA is recommended. To perform the PPSBA
are efficiently reabsorbed in the distal ileum and carried in the portal concentration test, take the following steps:
blood back to the liver, thus completing the enterohepatic circulation.
In the healthy animal, the liver removes 90% to 95% of bile acids from • Obtain a serum sample for FSBA concentration, and
the portal circulation during the first pass of the enterohepatic cir- then feed at least 2 teaspoons of food to small dogs
culation. This allows only small amounts of bile acids to escape to the and cats (<5 kg) and at least 2 tablespoons to larger
systemic circulation. Normal serum concentrations are therefore low patients.
(fasting < 15 mmol/L, postprandial < 25 mmol/L). B, Hepatocellular
dysfunction or cholestasis interferes with hepatic uptake, storage, and
• To ensure gallbladder contraction, feed a diet high
secretion of bile acids. Thus, impaired extraction of bile acids from in fat (e.g., Hill’s Pet Prescription Diet p/d and Hill’s
the portal blood results in increased serum bile acid concentrations. Pet Prescription Diet c/d for cats). For encephalo-
With portosystemic shunting, bile acids in the portal blood are pathic animals in which a high-protein diet is con-
diverted directly into the systemic circulation. traindicated, substitute a protein-restricted diet and
add a few milliliters of corn oil per feeding.
temic shunting, in which bile acids are diverted • Obtain a second serum sample 2 hours after feeding.
directly into the systemic circulation (see Fig. 71-3B). • Results: In normal dogs and cats, PPSBA concentra-
• Serial evaluation of SBA concentration to monitor tions are <25 mmol/L and peak 2 hours after a meal.
liver function may not have merit unless the SBA con- A liver biopsy may be indicated when concentrations
centration returns to normal. This is because there are >30 mmol/L.
are wide fluctuations in SBA concentration in a given • On occasion, FSBA is higher than PPSBA. This prob-
patient with liver disease within a 24-hour period ably occurs because of sporadic gallbladder contrac-
(although all values are abnormal). tion during fasting, which releases bile into the
• Dogs and cats receiving the oral synthetic bile acid, intestinal tract, resulting in increased SBAs.
ursodiol, may have an increase in SBA concentration
because of the absorption of the drug and reflection Urine Bile Acids
of its presence in the serum. Recently, urine bile acids (UBAs) have been investi-
• Interference in bile acid measurement can occur gated as a diagnostic tool in dogs and cats. Normally
with hemolysis or lipemia. only small amounts of bile acids are present in the
W0422-Ch071.qxd 11/12/05 10:43 AM Page 754
urine. Liver disease and increased SBA result in total dose of 3 g), either as a dilute solution by
increased excretion of bile acids in the urine. Potential stomach tube or as a powder in a gelatin capsule.
advantages of UBA over a random FSBA are that UBA • Take a heparinized blood sample before and 30
may reflect an average value over time, ease of sample minutes (stomach tube method) or 45 minutes
collection, and lack of interference from oral ursodiol (capsule method) after administering the ammo-
administration. nium chloride. Vomiting may occur but does not
invalidate the test.
• UBAs are normalized with urine creatinine (Cr), and • In normal dogs, there is no increase in blood
values are expressed as UBA/Cr (mmol/mg) ¥ 100.
ammonia concentration or a mild increase (<2 times
Values greater than 7.3 are abnormal in dogs. Values
greater than baseline). In dogs with portosystemic
greater than 4.4 are abnormal in cats.
shunting, results are consistently abnormal (up to 10
• Timing of urine collection to the 4- to 8-hour post-
times baseline values).
prandial period may improve diagnostic perfor-
mance, particularly in dogs with congenital • The ATT and paired FSBA and PPSBA tests have equal
sensitivity in detecting portosystemic shunting. Con-
portosystemic shunting where sensitivity of UBA
sequently, the SBA testing has largely replaced blood
(taken 4 to 8 hours after eating) was 100% compared
ammonia and ATT. Paired FSBA and PPSBA provide
with 84% for FSBA and 98% for PPSBA.
a better screening test because it detects a broader
• The role of UBA in the evaluation of hepatobiliary
range of hepatobiliary disorders, and bile acids are
function awaits further clinical evaluation.
stable, permitting routine laboratory analysis.
Blood Ammonia Concentration Protein C
Ammonia is metabolized by the liver, and normal Protein C, an anticoagulant protein synthesized in the
plasma concentrations are low. Measurement of liver, has been investigated as a clinical marker of liver
ammonia is technically difficult, and appropriate disease. Preliminary results show decreased protein C
sample handling requires heparinized blood samples to concentrations in 100% of dogs with liver failure, 98%
be stored immediately on ice, cold-centrifuged, and of dogs with portosystemic shunt, and 30% of dogs with
assayed as soon as possible. hepatic microvascular dysplasia. The role of protein C
• Measurement of blood ammonia concentration pri- in the detection of liver disease awaits further clinical
marily is indicated to document HE. However, studies.
normal values do not exclude this diagnosis, because
other toxins can contribute to the encephalopathy. Parameters of Hemostasis
• Portosystemic shunting (congenital or acquired) is The liver plays a central role in the coagulation and fi-
the most common mechanism of hyperammonemia, brinolytic systems. The liver is responsible for synthesis
but severe, diffuse hepatic disease (especially acute of all coagulation factors except factor 8, von Wille-
hepatic necrosis) also increases blood ammonia con- brand factor. Fibrinogen, antithrombin, and protein C
centrations. are all synthesized in the liver and can be decreased with
• Blood ammonia values have poor sensitivity in detect- hepatic dysfunction. Activated coagulation factors and
ing other types of hepatobiliary disease without por- fibrinolytic enzymes are also cleared by the liver.
tosystemic shunting.
• Blood ammonia concentration is not a suitable • Mechanisms of excessive bleeding associated with
screening test for congenital portosystemic shunt in hepatobiliary disease include primary failure of hepa-
young Irish wolfhounds since a transient metabolic tocytes to synthesize clotting factors, DIC, and
hyperammonemia unassociated with liver disease vitamin K deficiency. Vitamin K deficiency in hepa-
occurs in this breed. tobiliary disease is usually caused by malabsorption of
• Congenital urea cycle enzyme deficiency is a rare vitamin K secondary to complete bile duct obstruc-
cause of hyperammonemia. tion. However, a vitamin K–responsive coagulopathy
may sometimes be detected in dogs and cats with
severe hepatic insufficiency, possibly due to marked
Ammonia Tolerance Test
intrahepatic cholestasis causing vitamin K malab-
This is a more sensitive test than blood ammonia con- sorption or the inability of the liver to reactivate
centration for documenting portosystemic shunting. vitamin K from its inactive (epoxide) form.
However, the ammonia tolerance test (ATT) is con- • Clinical evidence of bleeding secondary to hepato-
traindicated if resting ammonia levels are already biliary disease is uncommon; however, the frequency
increased, because no further diagnostic information of abnormal coagulation tests is much higher.
will be obtained and performing an ATT can cause signs
of HE. Note: The ATT is not recommended for use in cats. Coagulation Tests
• The test is performed in a fasted dog by giving • Measure prothrombin time (PT) to evaluate the
100 mg/kg of ammonium chloride (do not exceed a extrinsic coagulation system and activated partial
W0422-Ch071.qxd 11/12/05 10:43 AM Page 755
thromboplastin time (APTT) to evaluate the intrinsic If hepatic neoplasia is suspected, take thoracic films
coagulation system. These tests can be abnormal in to evaluate for pulmonary metastases.
the presence of liver disease. Activated coagulation
time also can be used as a rapid screening test for Ultrasonography
abnormalities of the intrinsic coagulation system. For Ultrasonography can be used to image the liver non-
further discussion of these tests, see Chapter 23. invasively, especially when abdominal effusion pre-
• The PIVKA (proteins induced by vitamin K absence) cludes survey radiographic evaluation. A normal
clotting time is a more sensitive test than PT or APTT ultrasonographic appearance of the liver does not elim-
to detect bleeding tendencies in dogs and cats with inate the possibility of significant hepatic pathology;
liver disease. Normalization of PIVKA clotting time however, ultrasonography is diagnostically useful to
may occur after treatment with vitamin K1. achieve the following:
• The combination of prolonged PT and APTT, low
plasma fibrinogen, increased fibrin degradation • Detect focal parenchymal abnormalities such as
products, fragmented RBCs, and thrombocytopenia masses, abscesses, cysts, and regenerative nodules.
suggests DIC (see Chapter 23). The ultrasonographic appearance of these focal
lesions often is similar, and biopsy is required for
Thrombocytopenia and Platelet Dysfunction differentiation.
• Thrombocytopenia may occur secondary to splenic • Document that a palpable mass is associated with the
liver.
sequestration of platelets associated with portal
hypertension or consumption of platelets from DIC. • Investigate disorders of the biliary tract and gallblad-
der, such as biliary obstruction, cholelithiasis, or gall-
• Platelet function defects also have been documented
bladder mucocele.
in dogs with liver disease, which may account for
clinical bleeding tendencies in the presence of • Detect vascular lesions such as portosystemic shunts,
hepatic arteriovenous fistulas, and hepatic venous
normal coagulation tests and platelet numbers. Use
congestion.
mucosal bleeding time to detect platelet function
abnormalities. • Obtain percutaneous liver biopsies (see below).
• Identify abnormalities in other abdominal organs
Blood Gas Analysis that may be a cause or effect of liver disease (e.g., pan-
creas, spleen, kidneys, bladder, GI tract, adrenal
Various acid-base imbalances may occur secondary to glands, and lymph nodes). For example, urate or uric
liver disease, including respiratory alkalosis, metabolic acid urolithiasis may be detected in animals with por-
alkalosis, metabolic acidosis, and mixed acid-base tosystemic shunts, the primary tumor may be ident-
disturbances. ified in animals with hepatic metastases, and
identification of adrenal gland enlargement may aid
Abdominal Fluid Analysis the diagnosis of steroid hepatopathy.
• Ascitic fluid that accumulates secondary to liver dis-
ease and hypoalbuminemia is usually a transudate. With Angiography
hepatic venous congestion from vena caval obstruc- Angiography is useful to diagnose vascular disorders
tion or cardiac causes, the fluid typically is a modified involving the liver, such as congenital and acquired por-
transudate with protein concentration > 2.5 g/dl. tosystemic shunts, hepatic arteriovenous fistulas, and
• Rupture of the biliary tract is associated with bile peri- vena caval obstruction causing hepatic venous obstruc-
tonitis. Grossly, the abdominal fluid appears yellow or tion (see under “Congenital Portosystemic Shunt”).
green. Chemical tests for bilirubin are positive, and
concentrations of bilirubin are higher in abdominal Liver Cytology
fluid than in serum. Cytologic examination reveals
a mixed inflammatory infiltrate and bile-laden Fine-needle aspiration (FNA) of the liver for cytology is
macrophages. Bacteria may be seen if bile peritonitis commonly performed because it is easy and safe, does
is complicated by sepsis. not require sedation or anesthesia, and provides rapid
preliminary information. However, the diagnostic accu-
Diagnostic Imaging racy of cytology versus histopathology of the liver is con-
troversial. Studies suggest a lack of correlation exists as
Survey Radiography much as 50% of the time. Cytology of impression smears
Abdominal radiographs are useful to evaluate for the of liver biopsy tissue correlates better than samples
following: obtained by fine-needle aspirate.
• Changes in liver size (hepatomegaly, microhepatica) • Cytology of the liver is most useful if the pathologic
• Altered tissue characteristics such as mineralized process is diffuse and architectural relationships
hepatic densities (choleliths) and radiolucencies (which can be obtained only by histopathology) are
(abscesses) not essential to the diagnosis. Examples include vac-
• Presence of abdominal effusion uolar hepatopathies such as feline hepatic lipidosis,
W0422-Ch071.qxd 11/12/05 10:43 AM Page 756
diffuse hepatic neoplasia, and liver disease associated hepatic biliary tract. Biopsies also are obtained under
with infectious agents such as histoplasmosis. direct visualization.
• In cats, primary liver diseases such as lymphoma and
• Laparoscopy is a useful alternative to ultrasound-
cholangitis may be accompanied by hepatic vacuolar
guided needle biopsy when the liver is small.
changes. These cats may be misdiagnosed as idio-
pathic hepatic lipidosis if cytology only reflects the • It is preferable to ultrasound-guided biopsy when
excess bleeding is anticipated and to laparotomy
vacuolated hepatocytes.
when delayed wound healing (hypoalbuminemia) is
• For focal lesions, accuracy is improved when the fine-
anticipated.
needle aspirate is guided by ultrasound.
• Poor correlation of cytology with histopathology • Laparoscopy requires heavy sedation or anesthesia
and is subject to equipment availability and clinician
occurs in primary inflammatory liver diseases,
expertise.
although it may be better for detection of suppura-
tive inflammation than for lymphocytic-plasmacytic
Laparotomy
inflammation.
Laparotomy is indicated for liver biopsy when a surgi-
Liver Biopsy cally correctable disease is suspected, such as extrahep-
atic biliary tract obstruction or a single, large hepatic
Liver biopsy often is required to definitively character- mass (see Chapter 72 for a description of the procedure
ize the nature and severity of hepatic disease, to differ- for surgical biopsy).
entiate acute from chronic disorders, and to assess
response to therapy. Selection of the best procedure for • Laparotomy makes it possible to obtain large samples
obtaining a liver biopsy depends on numerous factors, of liver tissue and monitor for post-biopsy bleeding.
including liver size, presence of coagulopathy, diffuse • Disadvantages include the need for general anesthe-
versus focal hepatic lesions, presence of biliary tract sia, the relatively high risk of complications, and the
obstruction, presence of other intra-abdominal abnor- risk of delayed wound healing in hypoalbuminemic
malities, likelihood of surgical resection of a mass, tol- patients.
erance of general anesthesia, available equipment, and Biopsy Analysis
expertise of the clinician.
• To prepare biopsy tissue for histopathology, place
▼ Key Point Perform a hemostasis screen prior to samples in 10% buffered formalin and allow them to
liver biopsy to detect coagulopathy. After the fix for 24 hours. The volume of fixative should be 20
biopsy is performed, monitor for bleeding from the times the volume of biopsy tissue.
biopsy site. • To prepare needle biopsy samples, gently remove
liver tissue from the biopsy needle and place it on
Biopsy Methods tissue paper; fold the paper and place it in a forma-
lin jar.
Ultrasound-Guided Needle Biopsy • Perform routine light microscopy on liver tissue
This technique is the most common percutaneous stained with hematoxylin and eosin (H&E).
method used for liver biopsy. However, it is dependent • Additional stains may be requested, including
on the availability of equipment and clinician expertise. trichrome for fibrous connective tissue, periodic acid-
Schiff (PAS) for glycogen, rhodanine or rubeanic
• With ultrasound-guided biopsy, it is possible to obtain acid for copper, Prussian blue for iron, Congo red for
tissue from focal lesions (whether superficial or deep amyloid, oil red O for fat, and silver or acid-fast stains
within the hepatic parenchyma), avoid structures for infectious organisms.
adjacent to the liver, and monitor post-biopsy • Submit fresh liver tissue for bacterial and fungal
bleeding. culture as indicated.
• Ultrasound-guided biopsy may be difficult if the liver • Perform quantitative copper analysis on fresh hepatic
is small or the ultrasonographer lacks experience. tissue.
• Because needle biopsy specimens are smaller than • Place samples for electron microscopy in chilled,
wedge biopsies, they may not be representative of buffered 2.5% glutaraldehyde.
underlying liver pathology. In one study, the mor-
phologic diagnosis made by needle biopsy correlated
with the definitive diagnosis obtained by wedge PRINCIPLES OF TREATMENT
biopsy in only 48% of dogs and cats. FOR LIVER DISEASE
Laparoscopy Objectives
Laparoscopy provides direct visualization of the liver • Whenever possible, identify and eliminate the incit-
and adjacent structures such as the pancreas and extra- ing or predisposing causes of liver disease. Identifi-
W0422-Ch071.qxd 11/12/05 10:43 AM Page 757
cation of the underlying cause of hepatobiliary Avoid drugs that fit the following descriptions:
disease can provide insight into specific therapy, the
likelihood and nature of potential complications, and • Are known to depend primarily on the liver for inac-
the prognosis for recovery. (Therapy for individual tivation or excretion
hepatobiliary disorders is discussed later under spe- • Are potential hepatotoxins, such as phenobarbital
cific diseases.) • May worsen signs of hepatic failure, such as methionine-
containing products, tranquilizers, sedatives, and
• Prevent or manage complications of liver failure,
diuretics (may exacerbate HE) and nonsteroidal anti-
including HE, ascites, GI ulceration, coagulopathy,
infection, and endotoxemia. inflammatory drugs (NSAIDs) and corticosteroids
(may cause GI bleeding and exacerbate HE)
• In patients in which hepatic regeneration and recov-
ery are possible, supportive care allows time for this
to occur. In other cases, clinical manifestations of Supportive Therapy for Liver Disease
hepatic failure may be minimized for variable periods. Supportive measures for patients with liver disease are
summarized in Table 71-1.
Consider Drug Metabolism
The liver is a major site of drug metabolism, and liver Restore Fluid, Electrolyte, and Acid-Base Balance
disease may alter drug metabolism. In many cases, • Maintain normal fluid balance to support hepatic
hepatic disease is associated with decreased hepatic blood flow and microcirculation and prevent com-
clearance of a drug, with subsequent potential toxicity. plications such as HE, DIC, shock, and renal failure.
The composition of the fluid to be given is influenced
▼ Key Point Prior to administering any drug to a by the patient’s electrolyte and acid-base status and
patient with hepatic disease, consider whether the the presence or potential for hypoglycemia (see
drug is metabolized or excreted by the liver, is Table 71-1 for guidelines; also see Chapter 5).
potentially hepatotoxic, or may exacerbate signs of • Avoid alkalinizing agents (e.g., lactate in lactated
liver failure. Ringer’s solution and sodium bicarbonate) when HE
Fluid Therapy
Maintain hydration Use a balanced polyionic solution such as lactated Ringer’s solution or Plasma-Lyte 148 IV.a Use
0.45% NaCl in patients with ascites or edema.
Prevent hypokalemia Add 20–30 mEq KCl to each liter of maintenance fluid. Monitor serum potassium daily and
adjust as necessary.
Maintain acid-base balance Avoid alkalosis in HE by using 0.45% or 0.90% saline for IV fluid therapy. Give NaHCO3 or
acetate-containing fluids (Plasma-Lyte) rather than lactated fluids for treatment of severe
metabolic acidosis. Avoid lactate-containing fluids in cats with severe hepatic lipidosis.
Prevent or control hypoglycemia To treat hypoglycemia, give 50% dextrose (0.5–1 ml/kg) IV to effect. To maintain
normoglycemia, add dextrose to fluids to achieve a 2.5–5.0% solution.
Nutritional Support
Maintain caloric intake Provide 40–60 kcal/kg/day of good-quality diet.
Provide adequate vitamins and Add B vitamins to fluids of anorexic cats. For long-term therapy, give an oral vitamin-mineral
minerals (especially B vitamin) supplement.
Give vitamin K1 (0.5–1.5 mg/kg IM or SC q12h for three treatments, then weekly as needed) in
biliary obstruction or severe cholestatic liver disease (dogs and cats).
Modify diet to control complications See specific complications (e.g., HE and ascites).
Control HE
Modify diet Give NPO in initial stages of HE. For long-term management, provide a reduced-protein (dairy or
vegetable source protein preferred; avoid red meat protein), easily digested, high-carbohydrate
diet. Recommend moderate protein restriction of 15–20% dry matter (dogs) or 30–35% dry
matter (cats). Increase dietary soluble fiber (psyllium 1–3 tsp/day).
Prevent formation and absorption In hepatic coma, give a warm-water cleansing enema initially (10–20 ml/kg) until fluid is clear,
of enteric toxins followed by retention enema (5–10 ml/kg q8–12h) containing lactulose (30% lactulose with
70% water) and neomycin solution (22 mg/kg) and held for 20–30 minutes or povidone iodine
solution (diluted 1 : 10 with water, 50–200 ml total) and flushed out within 10 minutes.
For follow-up oral therapy, give neomycinb (22 mg/kg q8–12h PO), metronidazole (7.5 mg/kg
q12h PO), or amoxicillin (22 mg/kg q12h PO) combined with lactulosec (0.25–0.5 ml/kg q8–12h
PO) or lactitol (0.5–0.75 g/kg q12h PO) to achieve two or three soft stools per day; if diarrhea
occurs, reduce dose.
Control gastrointestinal hemorrhage Correct coagulopathy. Treat Gl parasites and treat gastric ulcer (famotidine or nizatidine or
omeprazoled combined with sucralfatee). Avoid drugs that exacerbate Gl hemorrhage (e.g., aspirin
and other NSAIDs or glucocorticoids).
Table continued on following page
W0422-Ch071.qxd 11/12/05 10:43 AM Page 758
a
May be given SC if animal is mildly dehydrated and is not vomiting.
b
Neomycin has been associated with rare ototoxicity and nephrotoxicity; its use should be restricted to acute management of HE.
c
Crystalline lactulose (powder) is also available commercially (Kristalose, Bertek Pharmaceuticals) as 10- or 20-g packets (syrup concentration is 10 g/15 ml).
d
Partially metabolized by the liver; use a reduced dose in animals with liver failure. Inhibits hepatic P-450 enzymes.
e
Beware of drug-associated constipation, which may worsen HE.
f
Avoid bromide in cats due to cough and asthma-like side effects.
g
Can be used in dogs and cats with congenital PSS, but avoid in animals with acquired liver disease.
h
Start at the low end of the dose range due to impaired hepatic metabolism.
i
Dose may be doubled if there is no effect in 4–7 days.
j
GD Searle & Co., Chicago, IL.
k
Partially metabolized by liver. Use a reduced dosage (7.5 mg/kg q12h PO) in animals with liver failure.
DDAVP, desmopressin acetate; DIC, disseminated intravascular coagulation; GI, gastrointestinal; HE, hepatic encephalopathy; NPO, nothing per os; NSAIDs,
nonsteroidal anti-inflammatory drugs; vWD, von Willebrand disease.
Adapted from Johnson SE: Liver and biliary tract. In Anderson NV (ed): Veterinary Gastroenterology, 2nd ed. Philadelphia: Lea & Febiger, 1992, p 504.
is present or impending, because alkalosis augments • Supply the bulk of the calories by carbohydrates,
the entry of ammonia into the CNS and can exacer- which provide an easily assimilated source of non-
bate signs of HE. protein calories.
• Avoid high-protein diets that may exacerbate signs of
Give Nutritional Support HE. Indiscriminate protein restriction is discouraged,
however, because adequate protein intake is impor-
Nutritional support is important for promoting hepatic
tant for normal hepatic regeneration and to coun-
regeneration and maintenance of body weight.
teract hypoproteinemia.
• Modify the diet as needed to control complications • When voluntary food intake is lacking, provide other
of hepatic disease, such as HE, hypoproteinemia, and methods of nutritional support, such as feeding
ascites (see Table 71-1). through a gastrostomy tube (see Chapter 3).
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S-adenosylmethionine Denosyl SD4 20 mg/kg PO q24h (D&C) Intermediary metabolite: indirect Don’t break enteric-coated tablets. Use
(SAMe) (Nutramax Labs): glutathione precursor (antioxidant), only foil-wrapped products. Food
90 and 225 mg tab choleretic (cats), detoxification. decreases absorption. No side effects are
Supports membrane function. noted. Can be used in acetaminophen
toxicity. Expensive.
Acetylcysteine 10% or 20% Dilute at least 1 : 4 with Glutathione precursor. Antidote for acetaminophen toxicity.
solution saline. Give 140 mg/kg May have protective effects for other
IV through 0.25-mm filter drug-induced (carprofen, potentiated
over 20–30 min, then sulfas, methimazole, diazepam) or toxin-
70 mg/kg PO or IV q6h induced liver injury. Safe. May cause
W0422-Ch071.qxd 11/12/05 10:43 AM Page 760
for seven treatments (D&C) nausea and vomiting when given orally.
Section 6 / Digestive System
Milk thistle (Silybin) Marin (Nutramax 6–100 mg total dose PO q24h Antioxidant, anti-inflammatory, Silybin has low bioavailability;
Labs: silybin, per package insert (D); antifibrotic. Protects against Amanita improved when complexed with
vitamin E, zinc)* 9–18 mg total dose PO q24h mushroom toxicity (experimental) in phosphatidylcholine (Marin, Sil-phos).
9-, 24-, or 70-mg (C) dogs. Other products have variable potency
tab; Sil-phos and absorption.
(Indea Labs)
Vitamin E (alpha- Many available 50–400 IU PO q24h (D&C) Membrane-associated antioxidant. Natural Vitamin E (d-a tocopherol) has
tocopherol) Protects liver against oxidative injury. greater bioavailability than synthetic
(d,l) form. In severe cholestasis, use
water-soluble form.
Ursodiol Actigall (Ciba): 15 mg/kg PO q24h (D&C) Hydrophilic bile acid. Shifts bile acid Used in cholestatic disorders;
300-mg caps pool to less toxic hydrophilic bile acids. contraindicated in biliary obstruction.
Choleretic in dogs (cats unknown). Side effects are rare (vomiting).
Protects hepatocyte membranes. Expensive.
Modulates immune response.
L-carnitine Many available 250 mg PO q24h (C) Essential cofactor for transport of fatty May improve fatty acid oxidation in
acids into mitochondria for oxidation. obese cats undergoing weight loss but
will not prevent hepatic lipidosis. Used
in ancillary treatment of hepatic
lipidosis.
Zinc Zinc acetate: To decrease Cu Induces intestinal metallothionein, Many zinc products are available
Galzin (Gate absorption: 100-mg which preferentially binds Cu and (acetate, sulfate, gluconate). Avoid zinc
Pharmaceuticals); elemental zinc PO decreases absorption. Zinc has methionine if impending HE. Calculate
many others q12h for 2–3 months, antioxidant and antifibrotic effects; dose on elemental zinc content. Monitor
available then 50 mg PO q12h supports cell membrane function and blood zinc levels: Ideal = 200–400 mg/dl;
(D). For zinc immune response. avoid >800 mg/dl (hemolysis). Do not give
supplementation in concurrently with Cu chelator (will be
chronic liver disease: chelated). Nausea, vomiting, decreased
1–2 mg/kg PO q12h (D) appetite (less with zinc acetate).
Vitamin C (ascorbic Many available 100–500 mg PO q24h (D&C) Free radical scavenger; functions in Avoid in Cu-associated hepatopathy.
acid) converting vitamin E back to active
form. Acts as pro-oxidant in the
presence of high iron, Cu levels.
net mail-order sites, yet for many of these products Idiosyncratic Hepatotoxins
there is a lack of safety and efficacy data.
These hepatotoxins cause hepatic injury at therapeutic
• Lack of a regulatory mechanism for nutraceuticals is
doses in only a few individuals in the exposed popula-
not justification for ignoring the potential therapeu-
tion. These reactions are unpredictable and infrequent;
tic benefits of some of these products. However, most
most individuals treated with the drug do not have a
of these drugs have not been studied adequately in
reaction, even at high doses. Affected individuals
spontaneous hepatobiliary diseases of dogs and cats
appear to be unusually susceptible, possibly because
to prove efficacy.
they generate a unique toxic intermediate metabolite.
An immunologic response may or may not be involved.
Within susceptible individuals, toxicity may be more
ACUTE HEPATIC FAILURE pronounced at higher doses. Because of the unpre-
dictable nature of the reaction, they can be difficult to
Acute hepatic failure occurs when a sudden severe recognize clinically.
insult to the liver compromises at least 70% to 80% of
functional hepatic tissue. The clinical manifestations • If an idiosyncratic reaction occurs, the drug must be
and laboratory findings associated with acute hepatic discontinued or it could result in the death of the
failure reflect general liver failure and are not specific patient.
for the underlying cause of injury. • Examples include halothane and methoxyflurane,
carprofen and other NSAIDs, lomustine, mebenda-
zole, oxibendazole, potentiated sulfonamides, and
Etiology methimazole.
Causes of acute hepatic injury in dogs and cats include • Drugs that have been incriminated as potential hepa-
hepatotoxins, infectious or parasitic agents, systemic or totoxins include analgesics, anticonvulsants, and
metabolic disorders, or miscellaneous causes of liver antimicrobials (see Table 71-3). Specific clinical
injury (Table 71-3). In many cases, a specific cause details regarding known drug reactions in dogs and
cannot be identified. cats are summarized in Table 71-4.
Analgesics
Acetaminophen Canine Initial toxicity is Centrilobular Dose-related Dose-related injury (doses exceeding 200 mg/kg
(Tylenol, and feline cyanosis and necrosis and in dogs and 120 mg/kg in cats). Treatment: N-
McNeil) methemoglobinemia. congestion, acetylcysteine (140 mg/kg IV or PO initially, then
Acute hepatic vacuolar 70 mg/kg IV or PO q6h for 36 hours) and ascorbic
failurea occurs in hepatopathy acid (30 mg/kg q6h for 36 hours). SAMe (20 mg/kg
dogs but is less likely and bile stasis PO q24h) can also serve as a glutathione source.
in cats. Cimetidine (5–10 mg/kg IV q8–12h for at least 3 days)
inhibits hepatic P-450 enzymes and prevents further
conversion of acetaminophen to toxic product.
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Carprofen (Rimadyl, Canine Acute hepatic Hepatocellular Idiosyncratic Evaluate liver and kidney function prior to starting
Pfizer) failurea within 5–30 necrosis, treatment. Concurrent renal tubular necrosis and
days after starting ballooning glucosuria may occur. Rapid recovery in Labradors
drug. Labrador degeneration, after stopping drug and giving supportive care. A 50%
retrievers may be cholestasis mortality rate in non-Labrador breeds. Whether dogs
at increased risk. with carprofen hepatotoxicity can be safely switched
to another NSAID without experiencing a hepatic
reaction is unknown.
Anticonvulsants
Phenobarbital Canine Chronic liver disease Hepatocellular Dose- related? Phenobarbital causes chronic hepatic disease and
and cirrhosis. hypertrophy cirrhosis when given at high doses (serum
Anorexia, lethargy, and vacuolar concentrations >40 mg/ml) or for long periods
weight loss, sedation, hepatopathy (months to years). Dogs with phenobarbital
PU/PD, icterus, (early); bridging hepatotoxicity may improve when dosage is decreased
ascites, portal fibrosis, to therapeutic range as determined by serum
encephalopathy. ≠ nodular phenobarbital levels or when potassium bromide
ALP, ≠ ALT, ≠ regeneration, therapy is substituted for phenobarbital. Incidence of
GGT, ≠ total biliary hyperplasia, chronic hepatic disease from long-term anticonvulsant
bilirubin, ≠ SBA, mild inflammatory therapy is approximately 6–14%. Hepatocutaneous
hypoalbuminemia, infiltrates syndrome has also been described in dogs on
hypocholesterolemia, long-term phenobarbital therapy.
coagulopathy.
Diazepam Feline Acute hepatic Diffuse hepatic necrosis Idiosyncratic Most cats with hepatotoxicity die within 15 days of initial
failurea within 4–13 administration of drug. In cats treated with oral
days of starting oral diazepam, monitor baseline liver enzymes before and
drug administration. within 5 days after starting therapy; if enzymes are
increased, discontinue drug and give supportive therapy.
Antimicrobials
Ketoconazole Canine Asymptomatic with Not characterized Idiosyncraticb May be dose-related phenomenon: >40 mg/kg/day in
(Nizoral, Janssen and feline ≠ ALT, ≠ ALP, or dogs. In humans, asymptomatic serum enzyme
Pharmaceuticals) rarely acute hepatic elevations are considered harmless and enzymes usually
failure.a return to normal despite continued therapy. Therapy
should be discontinued if ≠ ALT >3 times normal or if
clinical signs or jaundice occur. Recovery is usually
uneventful.
Chapter 71 / Diseases of the Liver and Biliary Tract
Itraconazole Canine Asymptomatic with Not characterized Dose- related? Hepatotoxicity most likely at higher doses. Therapy
(Sporanox, and feline ≠ ALT or anorexia. should be stopped if ≠ ALT >3 times normal or if
Janssen anorexia occurs. When appetite returns, can reinstitute
763
Steroids
Section 6 / Digestive System
Glucocorticoids Canine Chronic hepatopathy, Centrilobular Dose-related Lesions reversible after treatment is discontinued. Does
(various types) but hepatic failure vacuolization but considerable not occur in cats.
rare. Signs indicative due to glycogen individual
of hypercortisolism accumulation variation
(e.g., PU/PD,
polyphagia,
hepatomegaly, and
lethargy). ≠ ALP,
usually with induction
of steroid isoenzyme
of ALP. Mild ≠ ALT;
normal total bilirubin.
SBA within normal
limits or mildly ≠
(<60 mmol/L).
Stanozolol Feline Increased ALT and Hepatic lipidosis Dose-related Most cats recover after discontinuing stanozolol and
(Winstrol-V, hyperbilirubinemia; after supportive care.
Pharmacia and anorexia.
Upjohn)
Miscellaneous
Methimazole Feline Acute hepatic Necrosis and Idiosyncratic Clinical signs resolve within 7 days of stopping therapy.
(Tapazole, Lilly) failurea within 2 cholestasis Biochemical resolution by 45 days.
months of starting
therapy.
Lomustine Canine Chronic liver disease Hepatocellular Idiosyncratic Median time to detection of hepatic disease from
(CCNU) with decreased vacuolization, last dose of CCNU was 11 weeks (range of 2–49
(CeeNu, Bristol- appetite, weight loss, mild to moderate weeks). Cumulative drug doses and number of
Meyers Squibb) PU/PD, vomiting, periportal doses tends to be higher in dogs that develop
ascites and ≠ ALT, inflammation, hepatotoxicity than in those that do not. Majority
≠ ALP, fibrosis, of affected dogs die of progressive chronic liver
hypoalbuminemia. hemosiderin- disease.
laden Kupffer
cells
a
Typical manifestations of acute hepatic failure include anorexia, depression, vomiting, and jaundice accompanied by ≠ ALT, ≠ ALP, and ≠ serum bilirubin.
b
For drug reaction accompanied by clinical signs and hyperbilirubinemia.
c
Includes trimethoprim-sulfadiazine, trimethoprim-sulfamethoxazole, and ormetoprim-sulfadimethoxine.
ALP, alkaline phosphatase; ALT, alanine aminotransferase; GGT, gamma-glutamyltransferase; NSAID, nonsteroidal anti-inflammatory drug; PSS, portosystemic shunt; PU/PD, polyuria/polydipsia; SAMe,
S-adenosylmethionine; SBA, serum bile acid.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 765
period it is difficult to differentiate hepatic damage or cal intervention may provide both diagnostic and
jaundice caused by the hypoxic effects of anesthesia and therapeutic benefit.
surgery from other potential causes, such as toxic injury
induced by anesthetic agents (e.g., halothane or History
methoxyflurane) and other drugs, postoperative infec- Attempt to document recent or potential exposure to
tions, endotoxemia, or a combination of these factors. any drug, toxin, or infectious disease, especially those
listed in Table 71-3.
Acute Pancreatitis
Pancreatitis in dogs and cats often is characterized by • Suspect a drug- or toxin-induced cause of acute
hepatic failure when clinical and biochemical evi-
increased serum concentrations of liver enzymes result-
dence of acute hepatic dysfunction is associated with
ing from secondary hepatic injury from released
recent exposure to a potential hepatotoxin.
enzymes and inflammatory cytokines (see Chapter 73).
Hepatic lesions usually resolve with resolution of the • Consider toxin-induced injury even in the absence of
known exposure to toxins, because potential hepato-
pancreatitis and require no special treatment. Less
toxins can be present in contaminated dog food (afla-
commonly, jaundice results from partial to complete
toxins), pond water (cyanobacteria, or “blue-green
obstruction of the common bile duct associated with
algae”), and many other unobserved sources.
peripancreatic inflammation, pancreatic abscess, or pan-
creatic healing by fibrosis. Surgical intervention to • Although numerous drugs have been incriminated
(see Tables 71-3 and 71-4), remember that an idio-
relieve biliary obstruction is indicated in animals with
syncratic reaction can occur with any drug. With most
pancreatic abscess or if jaundice persists after resolution
drug- and toxin-induced disorders, the diagnosis is
of acute pancreatitis, which usually indicates pancreatic
presumptive and cannot be proved.
fibrosis as a cause of biliary obstruction (see Chapter 73).
• To confirm the diagnosis, discontinue the drug and
observe for clinical improvement, which usually occurs
Extrahepatic Bacterial Infections
within several weeks, even after chronic drug adminis-
Septicemia and endotoxemia associated with infections tration. Recurrence of hepatic damage after a chal-
such as pneumonia, pyometra, peritonitis, and abscesses lenge dose of the same drug (or inadvertent re-
can cause jaundice, mild to moderate increases in liver exposure) supports the diagnosis of drug-induced
enzyme activity (especially ALP), and increased SBA hepatotoxicity. Note: This is not recommended as a diag-
concentration. Liver biopsy reveals intrahepatic nostic procedure because it is potentially dangerous,
cholestasis without significant necrosis or inflammation. especially with a drug that causes hepatic necrosis.
The hepatic injury resolves when the infection is con- • Determine if there is a history of recent surgical or
trolled. anesthetic procedures that may be associated with
drug- or hypoxia-related hepatic damage.
Clinical Signs • Evaluate the animal’s vaccination status for infectious
Clinical signs of acute hepatic failure often are non- diseases that can involve the liver, such as leptospiro-
specific and overlap signs of disorders of other body sis and infectious canine hepatitis.
systems. Clinical signs reflect general hepatic dysfunc- • Determine if there are any subtle chronic signs of
tion rather than the specific underlying cause. Signs of illness that suggest that the underlying liver disease
extrahepatic or multisystemic disease often provide may be chronic rather than acute and that the
important diagnostic clues when hepatic injury occurs current illness may be exacerbation or decompensa-
secondary to acute pancreatitis, hemolytic disease, sep- tion of chronic liver disease.
ticemia or endotoxemia, and many infectious diseases.
Physical Examination
• Acute onset of anorexia, lethargy, vomiting, and diar-
rhea are the most common presenting signs of acute Physical findings often reflect general hepatic dysfunc-
hepatic failure. tion rather than the specific etiology (see previous
• Other potential findings include PU/PD, jaundice, discussion of physical examination findings under
excessive bleeding, and HE. “Diagnostic Strategy for Liver Disease”).
Bacterial cultures
Liver, gallbladder, bile Bacterial cholangiohepatitis, cholecystitis, hepatic abscess
Blood, urine, infected tissues Extrahepatic infections and sepsis
Serologic tests (antibody titers) Leptospirosis
Mycoses (histoplasmosis, coccidioidomycosis, blastomycosis)
Toxoplasmosis
Feline infectious peritonitis
Bartonellosis
Other infectious diseases
Microfilaria exam Heartworm disease
Heartworm antigen or antibody tests Heartworm disease
Fecal sedimentation (formalin-ether technique) Liver fluke infection
Serum amylase and lipase Acute pancreatitis in dogs
Serum pancreatic lipase immunoreactivity Pancreatitis in cats and dogs
Serum T4 Feline hyperthyroidism
Coombs’ test Immune hemolytic anemia
Lymph node aspiration cytology Mycoses
Lymphoma
Hepatic fine-needle aspiration cytology Infectious agents (e.g., mycoses)
Neoplasia (e.g., lymphoma)
Feline hepatic lipidosis
Hepatic abscess (ultrasound guided)
Abdominocentesis Ruptured biliary tract
Feline infectious peritonitis
Neoplasia
Thoracic radiography Mycoses
Toxoplasmosis
Heartworm disease
Metastatic neoplasia
Diaphragmatic hernia
Abdominal radiography Hepatic abscesses
Emphysematous cholecystitis
Cholelithiasis
Pancreatitis
Abdominal ultrasonography Focal and diffuse hepatic parenchymal abnormalities
Biliary or gallbladder disease
Portosystemic shunt(s)
Hepatic arteriovenous fistulas
Pancreatic disease
Diaphragmatic hernia
Angiography
Portogram Portosystemic shunt(s)
Portal vein obstruction
Hepatic venography Obstruction of caudal vena cava and hepatic veins
Celiac arteriography Hepatic arteriovenous fistulas
Nuclear imaging
Portal scintigraphy Portosystemic shunting
Modified from Johnson SE: Diseases of the liver. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, vol. 2, 4th ed. Philadelphia: WB
Saunders, 1995, p 1316.
this book, including leptospirosis (see Chapter 19), tered throughout the liver, or microabscesses that are
ehrlichiosis and rickettsial diseases (Chapter 17), toxo- only detected histologically.
plasmosis (see Chapter 21), systemic mycoses (see
Chapter 20), FIP virus (see Chapter 10), and infectious Etiology
canine hepatitis virus (see Chapter 16).
• Potential sources of bacteria include hematogenous
spread, translocation of intestinal bacteria into the
Hepatic Abscess portal blood, ascension via bile ducts, penetrating
Hepatic abscesses from bacterial infection of the liver abdominal and caudal thoracic wounds, and direct
occur uncommonly in dogs and cats. Abscesses may extension from local suppurative diseases. Umbilical
form as a solitary large mass, multiple small masses scat- infections are the most common cause of hepatic
W0422-Ch071.qxd 11/12/05 10:43 AM Page 768
Viral
Infectious canine hepatitis Canine adenovirus I Chapter 16
Systemic neonatal herpesvirus Canine herpesvirus Chapter 16
Canine acidophil cell hepatitis Unknown Chapter 16
Feline infectious peritonitis Feline coronavirus Chapter 10
Feline systemic hemorrhagic-like febrile disease Feline calicivirus (virulent strains) Chapter 11
Bacterial
Leptospirosis Leptospira interrogans sensu strictu Chapter 19
Acute hepatic failure Serovars icterohaemorrhagiae, canicola, autumnalis, pomona,
bratislava, bataviae, hardjo, and Leptospira kirshneri serovar
grippotyphosa
Chronic hepatitis Serovars grippotyphosa and australis
Tyzzer’s disease Bacillus piliformis Chapter 69
Nocardiosis Nocardia species Chapter 19
Actinomycosis Actinomyces species Chapter 19
Tuberculosis Mycobacterium tuberculosis, M. bovis, M. avium Chapter 19
Salmonellosis Salmonella typhimurium Chapter 69
Brucellosis Brucella canis Chapter 19
Bartonellosis (dogs) Bartonella henselae, B. clarridgeiae Chapter 19
Hepatic abscess Gram-negative bacteria (especially Escherichia coli), anaerobes,
mixed infections common, Staphylococcus species (puppies)
Cholangitis/cholangiohepatitis Gram-negative bacteria (especially Escherichia coli), anaerobes
Cholecystitis Gram-negative bacteria (especially Escherichia coli), Campylobacter
jejuni, Clostridium species
Yersiniosis Yersinia pestis Chapter 19
Tularemia Francisella tularensis Chapter 19
Fungal
Histoplasmosis Histoplasma capsulatum Chapter 20
Blastomycosis Blastomyces dermatitidis Chapter 20
Coccidioidomycosis Coccidioides immitis Chapter 20
Aspergillosis Aspergillus terreus Chapter 20
Others
Protozoal
Toxoplasmosis Toxoplasma gondii Chapter 21
Babesiosis Babesia canis, B. gibsoni Chapters 21 & 22
Cytauxzoonosis Cytauxzoon felis Chapters 21 & 22
Hepatozoonosis Hepatozoon canis Chapter 21
Leishmaniasis Leishmania species Chapter 21
Encephalitozoonosis Encephalitozoon cuniculi Chapter 21
Rickettsial
Ehrlichiosis Ehrlichia species Chapter 17
Rocky Mountain spotted fever Rickettsia rickettsii Chapter 17
Algal
Protothecosis Prototheca species Chapter 69
Parasitic
Canine schistosomiasis Heterobilharzia americana
Visceral larval migrans Toxocara canis
Liver flukes Platynosomum concinnum (feline)
Amphimerus pseudofelineus (feline)
Canine hepatic capillariasis Capillaria hepatica
Canine hepatic alveolar echinococcosis Echinococcus multilocularis
abscesses in puppies (Staphylococcus) and kittens patient to abscess formation, because small numbers
(Streptococcus). of anaerobes (e.g., Clostridium spp.) normally are
• Escherichia coli and anaerobic bacteria are most com- present in the liver and can proliferate under these
monly identified; mixed bacterial infections are conditions.
common. • Systemic diseases that are associated with immuno-
• Hypoxia of hepatic tissue caused by hepatic neopla- suppression (e.g., feline leukemia virus and feline
sia, liver lobe torsion, or trauma may predispose the immunodeficiency virus) or that predispose the
W0422-Ch071.qxd 11/12/05 10:43 AM Page 769
patient to infection (e.g., diabetes mellitus) may pre- Liver Fluke Infection
dispose the patient to hepatic abscesses.
• Systemic infections (urinary tract infection, pneumo- Liver fluke infection is uncommon in cats and rare in
nia), pancreatitis, gallbladder rupture, and previous dogs. Infection usually is asymptomatic but may cause
surgical liver biopsy have also been associated with clinical biliary tract disease when associated with
hepatic abscesses. marked biliary fibrosis, cholangitis, cholangiohepatitis,
or extrahepatic bile duct obstruction. Cholangiocarci-
noma has been reported in cats chronically infected
Clinical Signs with Platynosomum concinnum.
• Signs are attributed to sepsis, inflammation, and
hepatic dysfunction and include anorexia, lethargy, Etiology
fever, vomiting, and diarrhea.
• Rupture of a hepatic abscess leads rapidly to peri- • P. concinnum (Platynosomum fastosum) is the most
tonitis, septic shock, and death. important liver fluke in cats and is found in tropical
and subtropical geographic areas, including Hawaii,
Florida, and the Caribbean. In endemic areas, the
Diagnosis
prevalence of infection is high.
• Physical examination findings are often vague but • Other liver flukes that have been identified in cats
may include depression, fever, hepatomegaly, abdom- include Amphimerus pseudofelineus (Opisthorchis pseudo-
inal tenderness, and abdominal effusion. felineus), Opisthorchis tenuicollis, Opisthorchis sinensis,
• Potential laboratory findings include neutrophilia and Metorchis conjunctus (Metorchis complexus).
with a left shift (or neutropenia and degenerative left • Liver flukes require two intermediate hosts for their
shift if rupture occurs), thrombocytopenia, markedly life cycle. Adult flukes reside in the gallbladder and
increased ALT and ALP activity (although they may bile ducts. Embryonated eggs are shed in the feces
be in the normal range), hyperglobulinemia, hyper- and ingested by a snail, the first intermediate host for
bilirubinemia, hypoglycemia, and septic suppurative all liver flukes. The house gecko, skink, lizard, and
abdominal effusion. Increased ALT and ALP activity Bufo toad are second intermediate hosts for P. concin-
occur in less than 50% of cats with hepatic abscesses. num; fish are second intermediate hosts for the other
• Radiolucent areas may be seen on abdominal radi- species of flukes.
ographs when gas-producing organisms are involved.
Ultrasonography may reveal one or more parenchy- Clinical Signs
mal abscess cavities. They appear as poorly echogenic
lesions that may be round, oval, or irregular in shape. • Most infected cats are asymptomatic for liver fluke
Ultrasound-guided FNA for cytology and culture may infection.
be diagnostic. • Liver fluke infection occasionally is associated with
• Diagnosis often is established at exploratory laparo- anorexia, weight loss, diarrhea, vomiting, jaundice,
tomy to determine the cause of septic peritonitis. hepatomegaly, abdominal distention, and death.
• Perform aerobic and anaerobic cultures of abdomi-
nal effusion, blood, and hepatic tissue. Diagnosis
Treatment
• Operculated fluke eggs can be identified in feces by
a formalin-ether technique (a sedimentation proce-
• Treatment of large, unifocal hepatic abscesses dure). Routine methods for flotation do not consis-
requires surgical excision of the affected liver lobe tently identify eggs. With complete bile duct
(see Chapter 72). obstruction, no eggs will be passed in the feces. Eggs
• Ultrasound-guided percutaneous abscess drainage may be identified on cytologic examination of the
has been advocated for medical management of bile.
single lesions. No complications were observed in • Other laboratory findings are inconsistent and often
one series of cases. unremarkable. Eosinophilia, hyperbilirubinemia, and
• Initiate broad-spectrum antibiotics such as intra- increased serum ALP and ALT activity are sometimes
venous penicillin combined with an aminoglycoside detected.
(e.g., gentamicin or amikacin) while awaiting culture • A possible relationship between positive feline
results. Monitor renal function during aminoglyco- immunodeficiency virus status and infection with A.
side therapy, and base further therapy on results of pseudofelineus has been suggested.
sensitivity testing. Give long-term antibiotic therapy • At laparotomy or necropsy, the bile ducts and gall-
(but not aminoglycosides) for at least 6 to 8 weeks. bladder may be distended and thick walled and may
• The mortality rate was high (79%) in a recent series contain inspissated bile and small (<12 mm long)
of cats with hepatic abscesses as compared with dogs adult flukes. The liver frequently is enlarged. In many
(50%). cases, no visible abnormalities are present.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 770
• Serum ALP, ALT, and AST activities; FSBA and PPSBA Treatment
concentrations; and total serum bilirubin concentra-
tion usually are increased. Increases in liver enzymes Because of lack of information regarding the underly-
precede increases in total bilirubin and bile acids. ing cause, treatment is primarily supportive. The great-
est success has been with aggressive nutritional support.
▼ Key Point Serum ALP activity is generally higher in During initial stabilization, correct dehydration, elec-
cats with lipidosis than with other hepatic diseases. trolyte imbalances, coagulopathies and any complica-
Serum GGT activity, which usually parallels or tions of liver failure. A nasogastric tube can be placed
exceeds serum ALP activity in most feline hepatic for short-term nutritional support. CliniCare (Abbott
diseases, is normal or only mildly increased in Veterinary Diets) can be used initially through the naso-
hepatic lipidosis. gastric tube while stabilizing the patient prior to anes-
thesia for a longer-term feeding tube (gastrostomy or
• Other potential findings include hypokalemia, hyper- esophagostomy tube).
ammonemia, hypoalbuminemia, and decreased
BUN. Many affected cats have abnormal coagulation Initial Fluid Therapy
tests, especially PIVKA values and hypofibrinogene-
mia. In one study, PIVKA values improved in 50% of • Use intravenous fluid therapy with a balanced elec-
the cats treated with vitamin K1, suggesting acquired trolyte solution supplemented with potassium chlo-
vitamin K deficiency. ride in the initial stages of treatment (see Table 71-1).
• Consider serum pancreatic lipase immunoreactivity Hepatic lactate metabolism may be impaired in cats
to evaluate for concurrent pancreatitis. with hepatic lipidosis; thus, avoid lactated Ringer’s
• Consider serum cobalamin (B12) levels if an underly- solution.
ing intestinal disorder suspected. • If hypokalemia persists despite supplementation,
evaluate serum magnesium concentration to see
Radiography and Ultrasonography if hypomagnesemia is the cause of refractory
• Radiographically, the liver is normal to increased in hypokalemia.
size.
• Ultrasonographic findings include hepatomegaly ▼ Key Point Avoid dextrose supplementation unless
and diffuse hyperechogenicity of the liver. Ascites is hypoglycemia is documented, because glucose
rare. Evaluate for concurrent pancreatitis or other may promote hepatic lipid accumulation if caloric
disorders causing secondary hepatic lipidosis. needs are not being adequately met.
short-term management and are preferable to force- Response to Treatment and Prognosis
feeding. Techniques for placement of indwelling
feeding tubes are described in Chapter 3. • With aggressive nutritional and supportive care,
• Feed Maximum Calorie (Iams), Prescription Diet a/d approximately 60% to 85% of cats with lipidosis
(Hill’s Pet Nutrition), or other complete and bal- respond within 3 to 6 weeks. Biochemical improve-
anced feline diet that can be delivered through a tube ment (decreases in bilirubin, ALP, and ALT) is
in small feedings. usually seen within 1 to 2 weeks of initiating tube
• Initially, give one-fourth to one-half of the daily feeding. Normalization may take several weeks. Do
dietary caloric requirement through the tube, not remove the tube until the cat is eating on its own
divided into 4 to 6 feedings per day. Gradually for at least a week.
increase the total amount fed over 3 to 4 days until • Recurrence is rare and there is no evidence of resid-
maintenance requirements are achieved. ual hepatic damage.
• Use a restricted-protein diet only if hyperammone- • The earlier treatment is initiated, the better the
mia or overt signs of HE occur. prognosis.
Treatment
Vacuolar Hepatopathy in Hyperlipidemic
Miniature Schnauzers
▼ Key Point Steroid hepatopathy does not require Idiopathic hyperlipoproteinemia in miniature schnau-
any specific therapy for the liver. zers is an inborn error of lipoprotein metabolism
characterized by fasting hypertriglyceridemia and
• Steroid hepatopathy is reversible after withdrawal of hypercholesterolemia. A partial decrease in lipoprotein
exogenous glucocorticoids or treatment of sponta- lipase activity has been described in lipemic compared
neous hyperadrenocorticism. with non-lipemic miniature schnauzers. Other breeds
• The length of time required for complete resolution (such as Shetland sheepdogs) may also be affected.
is unpredictable, varying from weeks to months.
• Affected dogs typically develop a marked vacuolar
hepatopathy. Vacuoles contain both fat and glycogen.
Vacuolar Hepatopathy in Scottish Terriers • Rarely, they may develop a nodular liver with stromal
Scottish terriers with diffuse vacuolar hepatopathy collapse and clinical evidence of hepatic insufficiency
similar to steroid hepatopathy have been recently or severe sludging of bile and cholelithiasis.
described. Increased levels of adrenal steroids (espe-
cially progesterone and 17-OH progesterone) have
Clinical Signs
been documented. Progesterones, which are precursors Clinical findings in hyperlipidemic miniature schnau-
of glucocorticoids, have intrinsic glucocorticoid activity zers are referable to the lipemia and not hepatic
and can promote hepatic glycogen accumulation. dysfunction.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 775
• Signs include lethargy, abdominal pain, decreased nobarbital hepatotoxicity (see under “Phenobarbital-
appetite, hepatomegaly, and seizures. Associated Hepatic Disease”).
• Recurrent acute pancreatitis is common and many
dogs will eventually develop diabetes mellitus. Pathogenesis
The dermatologic lesions are similar to necrolytic
Diagnosis
migratory erythema in humans, which is usually associ-
• Laboratory findings include moderate to marked ated with hyperglucagonemia and hypoaminoacidemia
increases in ALP and GGT activity. The cortico- secondary to a glucagon-secreting pancreatic tumor.
steroid-induced isoenzyme of ALP typically predomi- Hyperglucagonemia is believed to cause severe
nates. Increased ALT activity is variable. SBAs are hypoaminoacidemia by stimulating hepatic utilization
typically normal or mildly increased. Associations of amino acids during gluconeogenesis, resulting in a
with increased urine protein-to-creatinine ratio and metabolic or nutritional imbalance affecting the skin.
microalbuminuria have also recently been described. Intravenous amino acid infusions can reverse the skin
• Abdominal ultrasonography of the liver reveals lesions in humans.
hepatomegaly and diffuse increase in echogenicity.
• Cytology and biopsy are consistent with vacuolar • Plasma glucagon levels are increased and most
hepatopathy. plasma amino acids are decreased in dogs with SND
that have an underlying pancreatic endocrine tumor.
Dermatologic signs resolve if the tumor can be com-
Treatment pletely resected.
Manage hyperlipidemia with a low-fat, high-fiber diet • Plasma glucagon levels are reported to be normal or
and possibly lipid-lowering drugs. General liver support only mildly increased in dogs with SND and hep-
with hepatoprotectants such as antioxidants and urso- atopathy. However, most of these dogs have severe
diol may be warranted (see Table 71-2). Avoid the use hypoaminoacidemia and some have responded to
of corticosteroids. dietary supplementation with egg yolks, which are a
rich source of amino acids. The plasma amino acid
Superficial Necrolytic Dermatitis levels in dogs with SND and hepatopathy are signifi-
cantly lower than in normal dogs or dogs with acute
(Hepatocutaneous Syndrome) or chronic liver disease, suggesting that the patho-
Superficial necrolytic dermatitis (SND), also called genesis is not simply related to hepatic dysfunction.
hepatocutaneous syndrome, necrolytic migratory ery- Hyperglucagonemia may still play a central role in
thema, or metabolic epidermal necrosis, is a crusting, dogs with hepatopathy because glucagon exists in
ulcerative dermatopathy that appears to be a complica- numerous immunoreactive fractions and the assay for
tion of hepatic or endocrine pancreatic disease in dogs this hormone may be insensitive to some glucagon
and cats. species.
• Alternatively, up-regulation of hepatic amino acid uti-
Etiology lization in a hypercatabolic state has also been
hypothesized in dogs with SND and hepatopathy.
The etiology and pathogenesis of this syndrome are Contributing factors may include hormonal imbal-
poorly understood. In dogs it is most commonly associ- ances (glucocorticoids, thyroid supplementation,
ated with hepatopathy but has also been described with increased adrenergic stimulation), phenobarbital
glucagon-producing pancreatic endocrine tumors or therapy causing chronic hepatic microsomal enzyme
glucagon-producing hepatic tumors. The syndrome has induction, and age-related changes in hepatocellular
also been reported in one cat with a pancreatic carci- membrane stability (increased hepatocyte respon-
noma and two cats with hepatopathy. Many dogs with siveness to adrenergic stimulation and enhanced
SND develop diabetes mellitus in the late stages of the amino acid utilization for gluconeogenesis). Aging
disease. has also been associated with alterations in hepatic
The hepatopathy is usually of unknown origin, sensitivity to glucagon.
although liver disease associated with anticonvulsant • Other nutritional deficiencies such as zinc, biotin, or
therapy and potential exposure to mycotoxins has been essential fatty acids have also been proposed.
suggested. In a recent report, chronic phenobarbital
therapy was associated with SND in 44% of cases. Bio-
chemical evaluation, liver function testing, ultrasono- Signalment and Clinical Signs
graphic appearance of the liver, and hepatic biopsy • SND is a disease of older dogs (mean age of 10 years),
indicate that the hepatopathy of dogs with phenobar- especially males. Shetland sheepdogs, West Highland
bital-related SND is distinctly different from the typical white terriers, cocker spaniels, Scottish terriers may
hepatic dysfunction and cirrhosis seen in dogs with phe- be at increased risk.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 776
0.5 mg/kg or the lowest effective dose for alternate- • Give vitamin E at a dosage of 50 to 400 IU PO q24h.
day maintenance. Absorption of fat-soluble vitamins may be decreased
• Although prednisone must be converted by the liver in chronic cholestatic hepatobiliary disorders. In this
to its active metabolite, prednisolone, either drug can setting, a water-soluble form of vitamin E may be
probably be used, based on the observation that preferable.
humans with liver disease can still rapidly convert
prednisone to prednisolone.
Prognosis
• Potential side effects of glucocorticoid therapy
include sodium and water retention (exacerbation of The response to treatment of idiopathic chronic hepati-
ascites), GI bleeding and catabolic effects (exacerba- tis is variable, which is expected because it probably
tion of HE), iatrogenic Cushing’s disease, and sec- represents a heterogeneous group of diseases.
ondary infections.
• Monitor serum biochemistries every 1 to 2 weeks in
• Some dogs eventually can be taken off medication
and remain in remission, but more often therapy
the initial stages of treatment.
must be continued indefinitely.
• Consider a follow-up liver biopsy, 2 to 3 months after
• Other dogs fail to respond, especially those that have
starting therapy, to confirm remission of the disease.
advanced disease and cirrhosis (the treatment of cir-
Azathioprine rhosis and its complications is discussed elsewhere in
this chapter).
Azathioprine is an antimetabolite with anti-inflamma-
tory and immune-modulating effects. When pred-
nisolone alone is ineffective or side effects become
Hepatic Copper Accumulation
objectionable, consider combination therapy using and Chronic Hepatitis
azathioprine and prednisolone (at a lower dose if side Copper accumulation in the liver can be associated with
effects are a problem). significant hepatic injury resulting in acute hepatitis,
• Give azathioprine (Imuran, Burroughs Wellcome) at chronic hepatitis, and cirrhosis. It is one of the few
a dosage of 1 to 2 mg/kg PO q24h for induction well-documented causes of chronic hepatitis in the
therapy. For maintenance, give the same dose once dog. The severity of hepatic injury is related to the
every other day while giving prednisolone on the amount of accumulated copper. Hepatic copper
alternate days. concentration in normal dogs is less than 400 mg/g
• Because azathioprine may cause bone marrow (ppm) dry weight.
suppression (neutropenia and thrombocytopenia), • An inherited metabolic defect in biliary copper
monitor periodically with a CBC. Other less common excretion causes chronic hepatitis in Bedlington
side effects include GI toxicity, pancreatitis, and terriers. Copper concentrations range from 850 to
hepatotoxicity. 12,000 mg/g dry weight in affected Bedlingtons.
• Hepatic damage in Bedlington terriers does not con-
Ursodiol sistently occur until the copper concentration
Ursodiol (Actigall) is a synthetic bile acid that has been exceeds 2000 mg/g dry weight. The concentration at
useful in the treatment of humans with chronic hepati- which abnormal hepatic copper contributes to
tis. Its use in conjunction with anti-inflammatory hepatic damage in other breeds is unknown and may
therapy in dogs with chronic hepatitis appears vary among breeds.
promising. • Copper accumulation in the liver may be a cause or
an effect of chronic hepatitis. Because copper nor-
• Ursodiol, a hydrophilic bile acid, is believed to be mally is excreted in the bile, hepatic copper accu-
beneficial by expanding the bile acid pool and mulation can also occur secondary to any cholestatic
displacing potentially hepatotoxic hydrophobic hepatobiliary disorder (such as idiopathic chronic
bile acids that may accumulate in cholestasis. It hepatitis) that impairs bile flow.
also has membrane-stabilizing, cytoprotective, and • Whether secondary copper accumulation can further
immunomodulatory effects on liver cells and pro- contribute to hepatic injury is unclear, but this is an
motes choleresis (see Table 71-2). important question with therapeutic implications.
• Ursodiol appears to be well tolerated in dogs when • Other breeds of dogs occasionally are diagnosed with
used at a dosage of 15 mg/kg PO q24h. chronic hepatitis and cirrhosis accompanied by
increased hepatic copper concentrations. At this
Antioxidants advanced stage of disease, it is difficult to know
• Free radicals may be generated in chronic hepatitis, whether copper accumulation is a cause or an effect
and they may contribute to hepatic injury. Antioxi- of the chronic hepatitis. As a general rule, the higher
dants, such as vitamin E, are important to scavenge the copper content, the more likely it is to be a
free radicals and prevent oxidative injury. primary problem.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 780
develops, the liver decreases in size and there is a • For treating an acute hemolytic crisis, trientine
mixture of fine and coarse nodules. hydrochloride (but not penicillamine) may be effec-
• Histologically, H&E-stained hepatic tissue reveals tive in chelating copper in the circulation.
dark granules in hepatocyte cytoplasm. In the early • There may be other protective effects of penicil-
stages, centrilobular hepatocytes are most affected, lamine besides depletion of hepatic copper, because
but later the distribution is diffuse. many Bedlington terriers on long-term therapy do
• Histochemical stains for copper, such as rhodanine not develop hepatic failure despite continued ele-
and rubeanic acid, are positive. These stains correlate vated copper levels and ongoing hepatic damage.
well with quantitative copper analysis when values Penicillamine may induce hepatic metallothionein,
exceed 850 mg/g dry weight. which binds and sequesters copper in a non-toxic
• Associated histologic hepatic damage is variable. In form. Additional effects that may be beneficial
the most mildly affected animals, only centrilobular include anti-inflammatory, antifibrotic activity, and
copper granules are detected. This progresses to immunomodulating effects.
focal hepatitis, lesions of chronic hepatitis, and even-
tually cirrhosis. Zinc Therapy
Use oral zinc therapy when hepatic copper concentra-
Hepatic Copper Analysis tions are >400, but <1500 mg/g dry weight to prevent
Perform quantitative copper analysis on fresh hepatic intestinal copper absorption and hepatic copper accu-
tissue. Copper analyses are available to veterinarians mulation. Preliminary information in Bedlington terri-
through the veterinary diagnostic laboratories of Michi- ers and West Highland white terriers suggests it may also
gan State University and Colorado State University. deplete hepatic copper concentrations (see Table 71-9).
Affected dogs have hepatic copper concentrations of
850 to 12,000 mg/g dry weight. Dietary Therapy
Low copper diets are of little value once hepatic copper
DNA Testing accumulation has occurred (see Table 71-9) but may be
• DNA testing is available (www.vetgen.com) that iden- helpful in the early stages to decrease intestinal copper
tifies a linked marker located in the chromosome absorption.
close to the as-yet-unidentified causative gene.
• Carrier, affected, or unaffected dogs can be charac- Vitamin E Therapy
terized with 90% accuracy. Administer vitamin E to all dogs with hepatic copper
• DNA-screened carriers or normal dogs should have accumulation (see Table 71-9). Hepatic injury associ-
annual liver enzyme evaluations. Increases in liver ated with hepatic copper overload in Bedlington terri-
enzyme activity should merit further evaluation of the ers appears to involve free radical damage to hepatic
liver. mitochondria. Vitamin E therapy protects against
copper-induced hepatic damage experimentally.
Treatment
Specific measures to control hepatic copper accumula- Prognosis
tion are summarized in Table 71-9. Base the choice of • Dogs with mild to moderate acute hepatic failure
therapy for an individual patient on the severity of exist- usually respond to supportive care.
ing hepatic damage. • If this disease is detected before severe hepatic failure
occurs, many dogs can live out their lives with peni-
▼ Key Point Lifelong therapy is necessary because cillamine therapy.
copper reaccumulates if treatment is stopped. • The prognosis is poor if there is fulminant hepatic
failure or chronic end-stage cirrhosis and failure.
Management of the acute hepatic crisis also involves
symptomatic and supportive care to control electrolyte, Prevention
acid-base, and fluid imbalances and HE (see Table 71-
1). Treatment of hemolytic anemia may require a blood
• Treatment of affected dogs with minimal hepatic
injury is recommended in the hope of preventing
transfusion. acute hepatitis or progression to cirrhosis.
Chelator Therapy
• Zinc therapy is a promising and less expensive alter-
native to penicillamine in this setting.
• Treat affected dogs with copper accumulation • Bedlington terriers used in breeding programs can
(>1500 mg/g dry weight) and chronic hepatitis with a be certified free of disease through either the Canine
copper chelator such as penicillamine or trientine Liver Registry at Purdue University or the Liver Reg-
hydrochloride, which promotes urinary copper istry of the Orthopedic Foundation for Animals in
excretion (see Table 71-9). Columbia, Missouri.
782
Chelate Systemic Cu
Penicillamine Cuprimine: 125- 15 mg/kg q12h Anorexia and vomitingb are common; Causes systemic Cu chelation and urinary excretion.
(Cuprimine, and 250-mg caps PO given on an dermatologic drug eruption or autoimmune- Indicated when hepatic Cu >1500 mg/g. Takes
MSD; Depen, Depen: 250-mg tabs empty stomach to like excretion. Indicated when vesicular months to years to produce significant decrease
Wallace) improve absorption; do lesions of mucocutaneous junctions;c in hepatic Cu concentration (900 mg/g/year)d,
not give concurrently reversible renal disease.c but may produce subjective clinical
with any medication, improvement after a few weeks. May have
including Zinca or protective effect in liver beyond chelation:
vitamin and mineral induces hepatic metallothionein, which binds
supplements. and sequesters Cu in non-toxic form? Not
effective for treatment of Cu-associated hemolysis.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 782
Trientine 250-mg caps 15 mg/kg q12h PO. None noted as yet. Use as an alternative to penicillamine if vomiting
Section 6 / Digestive System
dihydrochloridee Give 1 hour before occurs. May be useful for treatment of hemolysis
(Syprine, MSD) meals; do not give by chelating Cu in blood. More expensive than
concurrently penicillamine.
with any medication,
including zinca
or vitamin/mineral
supplement.
Decrease Intestinal Cu Absorption
Zinc acetate, Many available 100-mg elemental zinc Vomiting,f zinc-induced hemolysis at Induces intestinal metallothionein, which
sulfate, or PO q12h for 2–3 plasma levels >800 mg/dl. preferentially binds Cu and decreases
gluconate to months, then 50 mg absorption. Takes 3–6 months. Monitor
obtain PO q12h for plasma zinc every 2–3 months. Ideal level
therapeutic zinc maintenance. Separate is 200–400 mg/dl. Do not give concurrently
administration with Cu chelators. Use when hepatic Cu is
from meals by increased but is <1500 mg/g dry weight.
>1 hour.
Decrease Cu Intake
Cu-restricted diet Prescription Low Cu diet may slow further Cu accumulation
Diet l/d (Hill’s) but won’t decopper the liver. Most commercial
Homemade diets diets have abundant Cu. Avoid mineral
supplements, liver, shell fish, organ meats,
chocolate, nuts, mushrooms, cereals.
Antioxidant Therapyg
Vitamin E Many available 100–400 IU/day, PO. None noted as yet. Oxidative damage occurs in Cu-associated
liver disease. Vitamin E protects the liver
against oxidant damage.
a
Penicillamine and trientine will chelate zinc (and decrease its absorption) when given concurrently.
b
Often resolves after several weeks; start at a reduced dose and increase to maintenance after a few days. Giving with food will decrease absorption, but a small amount of milk, cheese, or bread given con-
currently may decrease vomiting.
c
Rare complications; renal compromise more likely with Depen?
d
In Bedlington terriers; more rapid response in Doberman pinschers and other breeds.
e
Availability limited; may require a special order direct from manufacturer.
f
Zinc acetate may be less irritating to the stomach than other formulations. To minimize vomiting, open capsule and mix contents with small amount of tuna or hamburger.
g
Although vitamin C has antioxidant effects, it should be avoided in dogs with Cu accumulation because it increases Cu’s oxidative damage to the liver.
Cu, copper.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 783
hepatitis on liver biopsy (probably due to other • Rhodanine and rubeanic acid stains usually are posi-
reversible causes). These findings suggest that there tive for copper, especially in centrilobular regions.
is a relationship among copper storage, hepatocellu- Stains for hepatic iron also are usually positive.
lar damage and hepatitis in Doberman pinschers. • Quantitative copper analysis reveals mild to moderate
• An immune-mediated mechanism of disease in copper accumulation (650–4000 mg/g dry weight).
affected Dobermans is supported by the finding of
up-regulation of major histocompatibility complex
class II antigens in hepatocytes. Treatment
Optimal treatment has not been established.
Signalment and Clinical Signs • Institute, as needed, symptomatic and supportive
• Middle-aged females are predominantly affected. therapy for complications of hepatic failure, includ-
• Clinical signs may be mild or absent when the disease ing correction of fluid, electrolyte, and acid-base
is fortuitously diagnosed in the early stages. However, balance and treatment of ascites, HE, and coagu-
most dogs are diagnosed in the advanced stages of lopathies (see Table 71-1 and “Principles of Treat-
hepatic failure. ment for Liver Disease”).
• Signs include anorexia, weight loss, lethargy, PU/PD, • Therapy with anti-inflammatory or immunosuppres-
vomiting, diarrhea, ascites, and jaundice. sive drugs such as prednisolone with or without aza-
• Evidence of excessive bleeding (gingival bleeding, thioprine may be given, as described previously for
epistaxis, and melena) may be found. idiopathic chronic hepatitis. The efficacy of this treat-
• Signs of HE often predominate in the terminal stages. ment remains to be determined, but generally the
response is poor, possibly because most dogs are pre-
sented in advanced stages of liver failure. Doberman
Diagnosis
pinschers with subclinical hepatitis treated with low
Suspect chronic hepatitis in any Doberman pinscher doses of prednisolone (0.1–0.5 mg/kg/day) did not
(especially female) with clinical and biochemical evi- show any significant improvement.
dence of hepatic disease. Definitive diagnosis requires • Consider penicillamine therapy, especially when sub-
liver biopsy. clinical hepatitis is diagnosed. Five female Doberman
pinschers with persistent subclinical hepatitis and
• Common physical examination findings include increased hepatic copper concentrations were treated
ascites, jaundice, weight loss, and encephalopathy.
Splenomegaly (associated with portal hypertension) with penicillamine (200 mg PO q12h for 4 months).
is common. The liver is small and not palpable. Mean liver copper concentrations decreased from
1036 to 407 mg/g dry weight and improvement in liver
• Laboratory findings frequently include increased
histopathology was noted. Whether histopathologic
ALP and ALT activity, hyperbilirubinemia, bilirubin-
uria, hypoalbuminemia, increased SBA levels, and improvement was related to copper-chelating or anti-
hyperammonemia. Coagulopathy and thrombocy- inflammatory effects of penicillamine could not be
topenia are common in the advanced stages. Con- ascertained.
sider concurrent von Willebrand disease in affected • Consider ursodiol therapy in this cholestatic disorder
dogs with a bleeding disorder, because of its preva- (see Table 71-2). Vitamin E may also provide a bene-
lence in this breed (see Chapter 23). ficial antioxidant effect.
• Radiographic and ultrasonographic findings of
microhepatica and ascites are consistent with chronic Prognosis
liver disease and cirrhosis.
• When Doberman hepatitis is diagnosed in the
advanced stages, treatment usually is unsuccessful.
Liver Biopsy and Copper Analysis Most dogs die within weeks to months.
• Liver biopsy and histopathologic evaluation are nec- • The prognosis may be more favorable if the disease
essary to confirm the diagnosis. is detected in the subclinical stage, but the optimal
• Grossly, the liver is small with micronodular or therapeutic regimen remains to be determined.
macronodular cirrhosis.
• Histologically, the earliest lesion is inflammation and
Copper-Associated Hepatitis in Dalmatians
fibrosis around the small hepatic vein branches. As
the disease progresses, fibrous tissue septa radiate Chronic hepatitis and cirrhosis associated with hepatic
from hepatic vein branches to the portal areas. In the copper accumulation has been reported in dalmatians.
late stage of the disease, lymphoplasmacytic inflam- Cholestasis is not a prominent biochemical or histologic
mation occurs around larger hepatic veins and portal feature until later in the disease, suggesting that hepatic
tracts. Fibrosis and architectural distortion consistent copper accumulation is more likely to be caused by a
with cirrhosis are present. familial metabolic disorder than to be secondary to
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altered hepatic biliary copper excretion. Two of the have a short duration of clinical illness prior to pre-
dogs were related. sentation of usually 2 weeks or less.
• Ascites is the most consistent presenting complaint.
Clinical Signs Other nonspecific signs of liver disease include
depression, mild jaundice, melena, dehydration, sub-
Most dogs presented initially with acute GI signs
cutaneous edema, and coma.
(anorexia, vomiting, diarrhea).
Diagnosis Diagnosis
• Biochemical findings revealed markedly increased ▼ Key Point Ascites and profound hypoalbuminemia
ALT activity (average 10.8 times above normal range) (mean of 1.7 g/dl) are consistent findings.
and moderately increased ALP activity (average 5.5
times above normal range). • Laboratory findings include mild anemia and mild to
• Hyperbilirubinemia and hypoalbuminemia were moderate increases in serum liver enzyme activity
seen with advanced disease. Glucosuria (in the (although some dogs have normal values).
absence of hyperglycemia) and proteinuria were • The total serum bilirubin concentration is normal or
identified in some dogs. mildly increased, suggesting that cholestasis is not a
• Liver biopsy revealed hepatocellular degeneration, key feature of the disorder. FSBA and PPSBA con-
necrosis, and inflammation (predominantly lympho- centrations are increased.
cytes or neutrophils). The mean hepatic copper con- • Ascitic fluid analysis is consistent with a transudate or
centration was 3197 mg/g dry weight (range of 754– modified transudate.
8390 mg/g dry weight). • Radiographic findings include microhepatica and
ascites. Ultrasonography often shows a diffuse
Treatment and Prognosis increase in echogenicity, although some dogs have a
• Rapid progression of the disease was characteristic. normal-appearing liver.
• Copper chelator therapy may be beneficial if diag- • Liver biopsy reveals chronic periportal hepatitis (lym-
nosed before advanced liver disease occurs (see Table phocytes, plasma cells, and lesser numbers of neu-
71-9). trophils), portal fibrosis, and micronodular or
macronodular cirrhosis.
Copper-Associated Hepatitis in Skye Terriers • Hepatic copper accumulation is not a consistent
feature (200–550 mg/g dry weight).
Chronic hepatitis and cirrhosis associated with hepatic
copper accumulation (range of 358–2257 mg/g dry Treatment
weight) has been described in genetically related Skye
terriers. Treatment for cocker spaniels with chronic hepatitis
consists of general supportive therapy for the compli-
• In the early stages, copper accumulation is absent, cations of liver failure (see “Principles of Treatment for
and biopsy findings indicate hepatocellular degener- Liver Disease” and Table 71-1).
ation with cholestasis and mild inflammation.
• Chronic lesions are associated with intracanalicular • Corticosteroid therapy may be beneficial.
cholestasis, chronic hepatitis, and cirrhosis. • The prognosis is poor and most dogs die within a
• Skye terrier hepatitis is speculated to be a result of month of diagnosis. Early diagnosis appears to be the
disturbed bile secretion with secondary accumulation key to long-term survival.
of copper.
Lobular Dissecting Hepatitis
Chronic Hepatitis in Cocker Spaniels Lobular dissecting hepatitis is a distinctive histologic
American and English cocker spaniels have an form of chronic hepatitis that occurs in young dogs.
increased incidence of chronic hepatitis. The cause is The median age of 21 affected dogs was 11 months, with
unknown. Hepatic copper accumulation does not 54% of dogs being 7 months or younger. It has been
appear to be a consistent feature. Accumulation of suggested that this is a specific reaction pattern of the
alpha-1-antitrypsin in hepatocytes, a well-recognized liver in neonatal and juvenile dogs to a wide variety of
cause of cirrhosis in man, may be important in the hepatic insults. Standard poodles may be at increased
pathogenesis. risk for this form of chronic hepatitis.
Diagnosis Etiology
An attempt should be made to identify other causes of • The mechanism of phenobarbital-induced injury is
chronic hepatic disease (see Table 71-8). Diagnosis not known, but higher doses, higher blood levels
requires liver biopsy. (>40 mg/ml), and long duration appear to be impor-
tant factors.
• Liver enzymes are typically increased.
• Hypoalbuminemia and increased SBA concentra- • Prior therapy with phenytoin or primidone may
tions are common. increase the risk of hepatotoxicity.
• The lesion is characterized histologically by lobular • Hepatotoxicity has not been described in association
hepatitis; inflammation (lymphocytes, plasma cells, with short-term injectable (IV or IM) doses.
macrophages, and neutrophils) is scattered through-
out the hepatic lobule rather than concentrated Clinical Signs
in periportal regions. Bands of collagen and reticulin • Clinical signs are those of chronic hepatic disease and
fibers dissect around single or small groups of hepa- include anorexia, lethargy, weight loss, weakness,
tocytes and disrupt hepatic lobular architecture. PU/PD, coagulopathy, and jaundice. Signs of over-
Copper stains are negative or moderately positive, dosage (sedation and ataxia) are consistent findings
consistent with secondary copper accumulation. The in dogs with phenobarbital hepatotoxicity. Ascites
liver is shrunken, pale to tan, with an almost smooth and HE are most likely with advanced hepatic disease.
surface and occasional hyperplastic nodules. Multiple • When impaired hepatic inactivation of phenobarbi-
acquired portosystemic shunts are present. tal causes increased blood levels, seizure frequency
may decrease.
Treatment • An increased frequency of seizures may be related to
the development of HE.
Optimal treatment has not been determined, but
general measures for management of chronic liver Diagnosis
failure are appropriate (see Table 71-1).
Suspect phenobarbital-induced hepatopathy in any dog
with a history of chronic phenobarbital therapy and
Acidophil Cell Hepatitis clinical and biochemical evidence of hepatic injury.
Acidophil cell hepatitis has been described in Great
Britain and is caused by an unidentified transmissible
Laboratory Evaluation
agent that is probably viral but distinct from canine
adenovirus type 1 (see Chapter 16). ▼ Key Point To detect early evidence of hepatic
damage, routinely monitor liver enzymes (serum
• It is characterized by acute or chronic hepatitis with ALP and ALT), total serum bilirubin, cholesterol,
slow progression to cirrhosis. Acidophils, which are a albumin, and phenobarbital levels at least every 6
consistent histologic feature of the disease, represent months in all dogs on chronic phenobarbital
dying hepatocytes. therapy.
• Signs usually are typical of chronic liver failure.
• Specific treatment has not been described, but • Mild reversible increases in serum ALP and ALT activ-
general measures for management of chronic liver ity (usually <5 times upper normal limit) are common
failure are appropriate. in dogs treated with phenobarbital related to micro-
somal enzyme induction rather than hepatocyte
injury. The increased ALP is usually attributable to
induction of the liver isoenzyme, but sometimes it
PHENOBARBITAL-ASSOCIATED results from increased CIALP.
HEPATIC DISEASE • Elevations in ALT and ALP activity greater than 5
times the upper limit of normal or any elevation in
Long-term phenobarbital therapy for control of AST may be an indicator of hepatotoxicity.
seizures has been associated with chronic hepatic • Increased SBA, hyperbilirubinemia, hypoalbumine-
disease and cirrhosis in dogs (see Table 71-4). Most dogs mia, and hypocholesterolemia are better indicators
have been treated with phenobarbital for months to of significant hepatic damage.
years before the liver disease is apparent. Chronic phe-
nobarbital therapy also is rarely associated with SND Radiography and Ultrasonography
(hepatocutaneous syndrome) in dogs (see previous dis-
cussion in this chapter), which is distinct from the char- ▼ Key Point Dogs on phenobarbital without hepatic
acteristic phenobarbital-associated chronic hepatic injury often have an incidental finding of
disease and cirrhosis described in this section. hepatomegaly.
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• Hemostatic abnormalities may reflect DIC, impaired properties as well as anti-inflammatory activity; however,
hepatic synthesis of coagulation factors, or vitamin K weigh the benefits of corticosteroids with the risks of
deficiency due to cholestasis (least likely). potential adverse effects, such as GI ulceration and
bleeding, increased body catabolism that may exacer-
Radiography and Ultrasonography bate HE, and sodium retention that may exacerbate
ascites and edema.
▼ Key Point Microhepatica is common in dogs with
cirrhosis, whereas most cats with biliary cirrhosis Colchicine
have hepatomegaly due to marked biliary hyper-
plasia. Colchicine (0.025–0.03 mg/kg PO q24h) is an antifi-
brotic drug used to treat humans with cirrhosis. It acts
Ultrasonography findings include microhepatica, irreg- as a microtubule inhibitor, stimulant of collagenase
ular hepatic margins, focal lesions representing activity, and inhibitor of collagen deposition. Its benefit
regenerative nodules, and increased parenchymal in dogs with cirrhosis is unproven. The major side
echogenicity associated with increased fibrous tissue. effects in dogs are nausea, vomiting, and diarrhea. In
Splenomegaly and secondary acquired portosystemic humans, other side effects include bone marrow toxic-
shunts also may be detected. ity and myoneuropathy.
Liver Biopsy
CONGENITAL PORTOSYSTEMIC SHUNTS
Definitive diagnosis of cirrhosis requires liver biopsy.
• Laparotomy or laparoscopy provides a better appre- Portosystemic shunts (PSSs) are vascular communica-
ciation for the gross nodularity of the liver than tions between the portal and the systemic venous
can be ascertained from blind percutaneous needle systems that allow portal blood to access the systemic cir-
biopsy. culation without first passing through the liver. Clinical
• Microscopic features include fibrosis, regenerative signs of HE result from inadequate hepatic clearance of
nodules, and disruption of normal hepatic enterically derived toxins such as ammonia, mercap-
architecture. tans, short-chain fatty acids, GABA, and endogenous
• Concurrent inflammation may be detected, espe- benzodiazepines. Decreased hepatic blood flow and
cially when the inciting cause of cirrhosis is chronic lack of hepatotrophic factors result in hepatic atrophy.
inflammation.
Etiology
Treatment PSS in dogs and cats can be a congenital malformation
Because cirrhosis is essentially irreversible, treatment is or develop secondary to portal hypertension.
mainly supportive, emphasizing measures that control
the various complications of severe generalized liver Single Congenital Portosystemic Shunts
failure, such as ascites, encephalopathy, gastric ulcers, Single PSSs are most common and occur as a congeni-
coagulopathies, and infection (see Table 71-1 and tal developmental malformation. Single shunts are not
“Principles of Treatment for Liver Disease”). associated with portal hypertension. Single PSSs can be
If a probable cause or category of injury can be deter- further categorized as intrahepatic or extrahepatic.
mined, specific treatment directed at preventing
further injury may slow progression of cirrhosis. If an Single Intrahepatic Shunts
underlying cause can be determined (or is suspected),
refer to the appropriate section of this chapter for spe-
• Single intrahepatic shunts provide a communication
between the portal vein and the caudal vena cava,
cific details regarding treatment. For example, adjust
often via the left hepatic vein. This results from
the drug regimen of dogs receiving phenobarbital (see
failure of the fetal ductus venosus to close.
under “Phenobarbital-Associated Hepatic Disease”).
• This type of shunt is most frequent in large-breed
dogs.
Penicillamine
Use a chelating agent such as penicillamine to treat Single Extrahepatic Shunts
dogs with copper-positive biopsies (see Table 71-9).
Penicillamine also has antifibrotic properties.
• Single extrahepatic shunts usually connect the portal
vein or one of its tributaries (left gastric or splenic
vein) with the caudal vena cava cranial to the phreni-
Anti-inflammatory Therapy coabdominal veins. Less frequently, the anomalous
Treat dogs with histologic features of chronic hepatitis vessel will enter the azygous vein.
with anti-inflammatory drugs (see under “Idiopathic • This type of shunt is most frequent in small-breed
Chronic Hepatitis”). Prednisolone has antifibrotic dogs and cats.
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more anatomic detail with less radiation exposure guishable from those seen in animals with hepatic
than transcolonic portal scintigraphy. microvascular dysplasia, primary hypoplasia of the
• Positive-contrast portography is the procedure of choice portal veins, or portal vein obstruction or after exper-
to accurately characterize the type and location of a imental surgical creation of a PSS.
PSS. Techniques include splenoportography, mesen- • Microscopic CNS abnormalities include polymicro-
teric (or jejunal) portography, and cranial mesenteric cavitation of the brain stem and cerebellum and an
or celiac arterial portography. An operative mesen- increased number of astrocytes in the cerebral
teric portogram is preferred because it allows evalua- cortex.
tion of the entire portal vein, does not require special
equipment, and results in few complications. Treatment
Surgery
Technique for Mesenteric Portography
• The treatment of choice for dogs and cats with a
1. Place the animal under general anesthesia (see single PSS is surgical attenuation or complete ligation
Chapter 2 for anesthesia of the patient with liver of the shunt (see Chapter 72). Although complete
disease). shunt ligation is preferred for improved long-term
2. Isolate a loop of jejunum through a ventral midline outcome, concurrent hypoplasia of the portal system
incision. (whether as a primary vascular disorder or secondary
3. Place two ligatures around a jejunal vein, and place to prolonged portosystemic shunting), may increase
an over-the-needle catheter (Abbocath, Abbott) intrahepatic vascular resistance and predispose the
within the vessel. Tie the ligatures and secure the patient to portal hypertension. Consequently, atten-
catheter to the vessel. uate the shunt to the maximum degree that can be
4. Temporarily close the abdominal incision. tolerated without causing portal hypertension.
5. Inject a water-soluble contrast agent (Conray, • Highly successful alternative approaches for gradual
Mallinckrodt, or Iohexol, Winthrop) as a bolus (2 progressive closure of the shunt use surgically placed
ml/kg) into the catheter. ameroid constrictors or cellophane bands around the
6. If a rapid film changer is not available, take a lateral shunt or intravascular thrombogenic coils within the
and ventrodorsal radiograph as the final milliliter is lumen of the shunt (see Chapter 72). Theoretical
injected. advantages of slow attenuation of the shunt (over
days to weeks) include reduced risk of postoperative
Interpretation portal hypertension and neurologic dysfunction and
• If a single PSS is identified, it should be further char- decreased surgical and anesthetic time.
acterized as intrahepatic or extrahepatic, because this
has important surgical ramifications (see Chapter ▼ Key Point Gradual occlusion of the shunt should
72). allow time for hepatic regeneration, expansion of
• If multiple extrahepatic PSSs are identified, portal the portal vascular system, and accommodation of
pressure determination and gross and microscopic portal blood flow without portal hypertension.
findings of the liver are used to distinguish between
congenital and acquired causes (see the next Medical Therapy
section). Medical management of dogs and cats with PSS is pal-
• Failure to visualize the intrahepatic portal system is liative and is directed primarily at control of HE with a
not a reliable indicator of vascular atresia but may moderately protein-restricted diet supplemented with
correlate with a greater occurrence of postoperative soluble fiber, lactulose, and neomycin (see Table 71-1).
complications after complete or partial shunt
ligation. • The short-term response to therapy for HE is often
dramatic, and the animal usually is clinically normal
even prior to surgical shunt ligation.
Liver Biopsy
• If surgical shunt correction is not feasible or is
• The liver is grossly small but otherwise fairly normal declined by the owner, long-term medical manage-
in appearance. ment may control clinical signs for as long as 2 to 3
• In some animals, biopsy findings are unremarkable. years. However, medical management of PSS does not
• Liver biopsy lesions can be subtle but most consis- reverse the progressive hepatic atrophy and alter-
tently reveal hepatocyte atrophy with small or absent ations in carbohydrate, lipid, and protein metabo-
portal veins. Varying degrees of arteriolar hyperpla- lism.
sia, lipogranulomas, and biliary hyperplasia may be • Acute decompensation of encephalopathy requires
seen. Hepatocellular vacuolization is sometimes fluid therapy for correction of dehydration, correc-
noted and may be severe. These biopsy findings tion of electrolyte and acid-base imbalances, and
reflect decreased portal blood flow and are indistin- maintenance of blood glucose levels (see Table 71-1).
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Liver Biopsy
Signalment
A wedge biopsy of the liver is preferred over a
• Yorkshire terriers and Cairn terriers are most com- needle biopsy because the vascular lesions are subtle
monly affected. However, HMD has been diagnosed
and a wedge biopsy provides more hepatic lobules for
in many other small breeds of dogs, such as Maltese,
evaluation.
dachshund, poodle, Shih Tzu, Lhasa apso, cocker
spaniel, and WHWTs. • Grossly, the liver is normal in size and color com-
• Domestic shorthair cats are at increased risk for pared with the small liver seen with congenital PSS.
HMD. • The histologic features of HMD are typical for inad-
• Dogs with HMD tend to be older at presentation than equate portal vein flow and include small or absent
dogs with congenital PSS. portal veins, hepatic arteriolar hyperplasia, and
W0422-Ch071.qxd 11/12/05 10:43 AM Page 794
hepatic lipogranulomas. These findings are similar to portal hypertension and subsequent portosystemic
those seen in dogs with congenital PSS, primary shunting. Thus, we advocate retaining the clinical dis-
hypoplasia of the portal vein, portal vein obstruction, tinction between HMD and PPVH until definitive
or after experimental surgical creation of a PSS. clarification is available.
▼ Key Point Biopsy more than one lobe in HMD Signalment and Clinical Signs
because the histologic lesions can vary among
liver lobes, with some lobes appearing very abnor- The mean age is about 2 years. Medium- or large-breed
mal and others appearing normal. dogs appear to be at increased risk. In one study, one
unrelated and three related Doberman pinschers were
Treatment and Prognosis reported. Related cocker spaniels have also been
described.
• No treatment is indicated for animals whose symp-
toms are subclinical. • Common clinical signs include lethargy, weight loss
• If clinical signs of HE are present, they can often be or stunted growth, intermittent vomiting and
successfully managed with a moderately protein- diarrhea, ascites, and polydipsia. Neurologic signs
restricted diet. Additional therapy with lactulose and of hepatoencephalopathy may occur but are
antibiotics is sometimes warranted (see Table 71-1). inconsistent.
• Follow-up in 11 dogs for a mean period of 15 months • The duration of clinical signs may range from a few
(range of 1 week to 4.5 years) indicated a good clin- weeks to a year. Most dogs have persistent signs for
ical response to dietary therapy alone. Repeated SBA 2 to 3 months.
concentrations remained unchanged. How often
dogs that are asymptomatic for HMD progress and ▼ Key Point Clinical signs of PPVH are similar to
develop clinical signs is unknown. those seen in dogs with single congenital PSSs,
• Anecdotal reports suggest some severely affected except that ascites is common in PPVH and rare in
dogs may develop a progressive hepatopathy with dogs with congenital PSS.
portal hypertension and multiple extrahepatic PSSs,
similar to primary hypoplasia of the portal veins (see Diagnosis
below).
Laboratory Evaluation
• Laboratory findings are consistent with hepatic dys-
PRIMARY PORTAL VEIN HYPOPLASIA function and portosystemic shunting and include
microcytosis, hypoalbuminemia, decreased BUN, and
Primary portal vein hypoplasia (PPVH) is a congenital mild increases in ALP and ALT (2–4 times normal).
abnormality of portal vascular development seen in • A pattern of normal to mildly increased FSBA con-
young medium- to large-breed dogs. Small intrahepatic centrations accompanied by markedly increased
portal venules are predominantly affected, although PPSBA values is consistent with portosystemic
hypoplasia of the extrahepatic portal vein may occur in shunting.
30% of dogs. Underdevelopment of the portal system • Hyperammonemia and an abnormal ATT are also
leads to obstruction to portal blood flow resulting consistent features.
in portal hypertension and development of multiple • Ascitic fluid is typically a transudate.
extrahepatic PSSs.
• Dogs described in the literature with idiopathic non- Radiography and Ultrasonography
cirrhotic portal hypertension have clinical and pathologic • Survey abdominal radiographs reveal microhepatica
findings that resemble portal vein hypoplasia, and and poor intra-abdominal contrast.
these are now considered the same disorder. • Microhepatica and abdominal effusion are common
• In addition to the vascular changes, variable amounts findings on ultrasonography. Liver echotexture is
of fibrosis may be present in portal areas, leading to variable. Multiple extrahepatic PSSs appear as
the suggestion that hepatoportal fibrosis of young dogs enlarged tortuous vessels caudal to the liver.
is a variant of portal vein hypoplasia. Splenomegaly may also be detected.
• It has also been proposed that HMD (discussed in the • Ultrasonography can also provide important infor-
previous section) is a milder variant of PPVH and that mation regarding other disorders associated with
the term HMD should be abandoned. Although his- portal hypertension, multiple PSSs, and ascites. With
tologic features are similar, the clinical presentations chronic end-stage liver disease, the liver may be
of HMD and PPVH are distinctly different. HMD is small and hyperechoic with multiple regenerative
not typically associated with portal hypertension (or nodules. Congenital hepatic arteriovenous fistulas
even clinical signs in many cases), whereas the clini- appear as tortuous, anechoic tubular structures in the
cal features of PPVH are primarily related to marked liver.
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Laparotomy and Contrast Portography • Consider colchicine (0.025 mg/kg PO q24h) and
ursodiol (15 mg/kg PO q24h) to prevent progressive
Multiple PSSs can be confirmed by contrast portogra- hepatic fibrosis.
phy or at exploratory laparotomy (or necropsy). Multi-
ple PSSs usually appear as multiple tortuous vessels that
communicate with the caudal vena cava in the area of ▼ Key Point Surgical ligation of multiple acquired
the left kidney. PSSs is contraindicated. Ligation may result in fatal
portal hypertension because shunts form as a pro-
• The portal pressure can be measured to document tective compensatory response to portal hyperten-
portal hypertension (normal portal pressure is 6 to sion. Also, do not perform caudal vena caval
13 cm of water). banding.
• Patency of the portal vein should be verified (by
mesenteric portography or at surgery) since portal
vein obstruction could cause similar clinical and radi-
ographic features. With PPVH, the extrahepatic HEPATIC ARTERIOVENOUS FISTULA
portion of the portal vein is patent but may be under-
developed. Intrahepatic arteriovenous (AV) fistulas are vascular
• Congenital hepatic arteriovenous fistulas can be communications between the hepatic artery and the
diagnosed by celiac arteriography or exploratory portal vein that result in portal hypertension, ascites,
laparotomy. and secondary PSSs. They occur rarely in dogs and cats.
Specific treatment for PPVH is not available. Initiate • Other causes of ascites to be differentiated include
symptomatic therapy to control the consequences of hypoproteinemia and right-sided congestive heart
portal hypertension and portosystemic shunting, such failure and other causes of portal hypertension and
as ascites and HE (see Table 71-1 and “Principles of multiple PSSs, such as PPVH (see the preceding
Treatment for Liver Disease”). The long-term progno- section and Table 71-10).
sis is variable, but some dogs can live for years on • Auscultate the abdominal wall over the area of the
medical management. Owners should be discouraged liver for a continuous murmur (bruit) caused by
from electing euthanasia for affected dogs until medical runoff of arterial blood into the portal system.
management has been tried.
• Avoid indiscriminate dietary protein restriction since Laboratory Evaluation
it can worsen hypoalbuminemia and promote ascites • Laboratory abnormalities are similar to those seen
formation. Although ascites is a common presenting in congenital PSS and PPVH and include hypo-
sign, it may resolve over time and diuretics can be proteinemia, normal or mildly increased serum
discontinued. liver enzyme activity, and abnormal liver function
• Use H2 receptor blockers indefinitely because perfo- tests including FSBA, PPSBA, blood ammonia, and
rated duodenal ulcer is a potential cause of death in ATT.
PPVH (see Table 71-1). • Ascitic fluid typically is a transudate.
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• If needle biopsy only describes vacuolated hepato- FELINE INFLAMMATORY LIVER DISEASE
cytes, the clinician may be misled to search for causes
of metabolic disease, such as hyperadrenocorticism. Inflammatory diseases of the liver are the second most
common type of feline liver disease, after hepatic lipi-
• A wedge biopsy may be necessary to differentiate
dosis. The cause, pathogenesis, natural history, and
nodular hyperplasia from hepatocellular carcinoma
and hepatoma. optimal treatment of inflammatory liver disease in cats
are largely unknown. Various terms have been used to
• No treatment is required.
describe these disorders, such as cholangitis or cholan-
giohepatitis complex, suppurative cholangiohepatitis,
non-suppurative cholangiohepatitis, lymphoplasmacytic
HEPATIC CYSTS cholangiohepatitis, lymphocytic cholangitis, progressive
lymphocytic cholangitis, lymphocytic portal hepatitis,
Single or multiple diffuse hepatic cysts occasionally are sclerosing cholangitis, and biliary cirrhosis.
identified in the liver of dogs and cats, usually as inci-
dental findings at necropsy but occasionally in the live • Recently, the World Small Animal Veterinary Associ-
ation (WSAVA) Liver Diseases and Pathology
animal.
Standardization Research Group developed a classi-
fication system with the goal of worldwide standard-
Etiology ization of terminology for histologic evaluation of
Hepatic cysts can be congenital or acquired, although liver diseases in dogs and cats.
the distinction is often difficult to make. In general, • The term cholangitis is preferred over cholangiohepati-
acquired cysts are usually solitary and congenital cysts tis because the inflammation primarily originates in
are often multiple. the bile ducts, and extension beyond the limiting
plate into the hepatic parenchyma (cholangiohepati-
• Congenital polycystic disease of the liver and kidneys tis) is not always a feature. Cholangitis is further
has been reported in Cairn terriers and WHWTs. divided into neutrophilic (acute or chronic) or lym-
• Polycystic renal disease in cats has been associated phocytic cholangitis. This classification scheme will
with cystic dilation of the intrahepatic bile ducts (see be used for the purposes of the following discussion.
Chapter 77).
• Acquired cysts may represent benign bile duct ade- Neutrophilic Cholangitis
nomas or biliary cystadenomas or may occur sec-
Neutrophilic cholangitis (also called suppurative cholangitis)
ondary to trauma.
is the most common form of cholangitis in cats.
• Peliosis hepatis, a vasculoproliferative disorder char-
acterized by cystic, blood-filled spaces in the liver, is • Histologically, the lesion is characterized by neu-
a rare disease in dogs and cats. Infection with Bar- trophilic inflammation within the walls or lumen of
tonella henselae was confirmed by polymerase chain bile ducts. The neutrophilic inflammation may
reaction of liver tissue in a dog with peliosis hepatis. disrupt the limiting plate and extend into the
W0422-Ch071.qxd 11/12/05 10:43 AM Page 800
hepatic parenchyma, causing necrosis of periportal sure and predispose the patient to reflux of duode-
hepatocytes. nal juice into the pancreatic and biliary systems. Since
• Chronic neutrophilic cholangitis (previously referred the normal bacterial count in the proximal small
to as lymphoplasmacytic or non-suppurative cholan- intestine is higher in cats than in dogs, it may be more
gitis or cholangiohepatitis) is characterized by a likely to induce pathology in cats.
mixed inflammatory response (neutrophils plus • Congenital biliary tract malformations or biliary
lymphocytes and plasma cells). Other features of reconstructive surgery may also predispose the
chronicity include marked biliary hyperplasia, con- patient to ascending bacterial infection.
centric periductal fibrosis, and bridging portal • Concurrent extrahepatic biliary tract abnormalities
fibrosis. include cholecystitis and sludged bile or choleliths,
which may cause bile duct obstruction.
▼ Key Point Chronic neutrophilic cholangitis may • Cats with cholangitis may develop secondary hepatic
progress to biliary cirrhosis. As opposed to the lipidosis, possibly related to anorexia and weight loss.
small liver in dogs with end-stage cirrhosis, cats
with biliary cirrhosis typically have hepatomegaly Clinical Signs
because of profound biliary hyperplasia.
• Acute neutrophilic cholangitis causes acute onset of
vomiting, anorexia, lethargy, and weight loss.
Etiology
• Chronic neutrophilic cholangitis causes intermittent or
persistent vomiting, anorexia, lethargy, and weight
▼ Key Point Acute neutrophilic cholangitis is most
loss lasting weeks to years. Signs of HE, ascites, and
likely caused by ascending bacterial infection from
excessive bleeding are uncommon unless chronic
the intestine into the biliary tract.
neutrophilic cholangitis has progressed to biliary
cirrhosis.
• Bacterial organisms isolated from bile or liver tissue
are primarily gram-negative and anaerobic enteric
bacteria such as E. coli (most common), Staphylococ- Diagnosis
cus, alpha-hemolytic Streptococcus, Bacillus, Actinomyces, Suspect neutrophilic cholangitis in any cat with non-
Bacteroides, and Clostridia. hemolytic jaundice, especially if accompanied by fever
• Chronic bacterial infections elsewhere in the body (although not all cases are febrile). Definitive diagnosis
(sinusitis, splenic abscess, pyelonephritis) and sep- requires liver biopsy to distinguish this disease from
ticemia may also be associated with neutrophilic other hepatic disorders, such as hepatic lipidosis,
cholangitis. hepatic FIP, and neoplasia.
• Chronic neutrophilic cholangitis may represent a
persistent bacterial infection, or the lesion may have History and Physical Examination
been initiated by bacteria but an immune-mediated
response may result in a chronic self-perpetuating • Cats with acute neutrophilic cholangitis typically have
an acute clinical presentation of short duration
disorder. Other possible causes of neutrophilic
(<5 days). Young cats appear to be at increased risk.
cholangitis may include viral, toxin-induced, or drug-
A history of antibiotic-responsive illness is common.
induced disease.
• Infectious agents infrequently associated with lesions • In contrast, cats with chronic neutrophilic cholangi-
tis are usually middle age or older.
of cholangitis in cats include liver flukes (see previ-
ous discussion in this chapter), Toxoplasma-like organ- • Physical examination findings include fever, jaun-
dice, abdominal pain, hepatomegaly, and dehydra-
isms, and Hepatozoon canis.
tion. Fever and abdominal pain are more likely with
acute cholangitis.
Clinical Associations and Predispositions
▼ Key Point Ascites may be present if chronic neu-
▼ Key Point Neutrophilic cholangitis in cats is com-
trophilic cholangitis has progressed to cirrhosis.
monly associated with IBD and chronic subclinical
pancreatitis (“triaditis”).
Laboratory Evaluation
• In cats, the pancreatic and bile ducts join into a • For both acute and chronic disease, liver enzyme ele-
common channel prior to opening into the duode- vations are variable. Although cholangitis is typically
num at the sphincter of Oddi. Underlying IBD may considered a cholestatic disorder, the ALP may be
be the key feature that predisposes to both cholangi- normal, especially in the acute form. This may occur
tis and pancreatitis. Inflammation of the duodenal because ALP is an induced enzyme with a lag period
mucosa could alter the normal function of the before it increases in the serum.
sphincter of Oddi. IBD commonly causes vomiting in • Increased ALT is a more consistent finding and prob-
cats, and vomiting could raise the intraduodenal pres- ably indicates inflammation is extending beyond the
W0422-Ch071.qxd 11/12/05 10:43 AM Page 801
portal area and limiting plate, resulting in hepato- culture of liver tissue (or bile obtained by cholecys-
cellular necrosis (cholangiohepatitis). tocentesis).
• Hyperbilirubinemia and bilirubinuria are common • Cytologic evaluation of impression smears of bile or
in both the acute and the chronic forms of cholan- liver tissue has been recommended since bacteria are
gitis. FSBAs and PPSBAs are consistently increased. more easily detected cytologically than histopatho-
logically.
▼ Key Point Neutrophilia with a left shift is most fre-
quent in cats with the acute form of neutrophilic Treatment
cholangitis, whereas hyperglobulinemia is a fre-
quent finding in cats with the chronic form. General Supportive Care
• Treat neutrophilic cholangitis with fluid therapy,
• Cats with chronic neutrophilic cholangitis frequently nutritional support, and supplementation of potas-
have a mild nonregenerative anemia. A coagulopathy sium and B vitamins (see Table 71-1).
may occur secondary to vitamin K malabsorption,
hepatocyte failure, or DIC. Hypoalbuminemia,
• Give vitamin K1 (0.5–1.5 mg/kg SC or IM q12h for
three doses) if hemostasis evaluation suggests vitamin
decreased BUN, and hyperammonemia suggest K deficiency.
advanced disease.
• Avoid dietary protein restriction unless overt signs of
• Consider evaluating serum cobalamin level (B12) and HE are present. If concurrent IBD is suspected,
feline pancreatic lipase immunoreactivity because of dietary modifications may include commercial GI or
the association of neutrophilic cholangitis with IBD novel protein diets (see Chapter 69).
and pancreatitis (see Chapters 69 and 73).
• In endemic tropical locations, rule out liver flukes by Antibiotics
fecal exams or a therapeutic trial of praziquantel.
▼ Key Point Antibiotics are the primary therapy for
Radiography and Ultrasonography acute neutrophilic cholangitis. They are also used
• Abdominal radiographs may reveal a liver that is in the initial therapy of chronic neutrophilic cholan-
normal or increased in size. Radiopaque choleliths gitis prior to initiating glucocorticoid therapy, in
may also be detected. order to eliminate any bacterial component.
• Ultrasonographically, cats with neutrophilic cholan-
gitis have no detectable parenchymal abnormalities, If possible, base the choice of antibiotic on culture
a diffuse hepatic hypoechogenicity, or a coarse or and sensitivity testing results; otherwise, consider the
nodular liver texture. This helps differentiate cholan- following recommendations: Continue antibiotics for a
gitis from lipidosis, which causes hyperechogenicity minimum of 6 to 8 weeks. In some cats with persistent
of the liver. elevation of serum bilirubin and liver enzymes, con-
• Ultrasonography is also useful to evaluate for con- tinue antibiotic therapy for 3 to 6 months.
current abnormalities of the biliary tract and pan-
creas, such as common bile duct obstruction, • For initial treatment, consider ampicillin (20–
40 mg/kg PO, IV, IM or SC q8h), amoxicillin (10–
cholelithiasis, sludging of bile, cholecystitis, and
20 mg/kg PO, IV, or SC q8–12h), amoxicillin-clavulanate
pancreatitis.
(62.5 mg/cat PO q12h), or a cephalosporin. Combine
one of these with metronidazole (7–10 mg/kg PO
Liver Biopsy
q12h) for broader spectrum against anaerobes, as well
Definitive diagnosis requires liver biopsy to distinguish as modulation of cell-mediated immunity and treat-
neutrophilic cholangitis from other hepatic disorders, ment of concurrent IBD.
such as hepatic lipidosis, hepatic FIP, and neoplasia. • For refractory cases, use enrofloxacin (2.5 mg/kg
PO, IM, or IV q12h) or a 1-week course of an
• If concurrent biliary obstruction occurs, obtain a liver aminoglycoside.
biopsy specimen and aerobic and anaerobic bile cul-
tures at laparotomy during surgical relief of the
obstruction (see Chapter 72). Duodenal and pancre-
Prednisolone
atic biopsies are also indicated. At laparotomy, the • Prednisolone is recommended for treatment of cats
gallbladder and common bile duct frequently are with chronic neutrophilic cholangitis because of its
thickened, firm, and distended. Inspissated bile and anti-inflammatory and immunosuppressive proper-
choleliths may be present. ties. However, efficacy of corticosteroids for treat-
• In the absence of obstruction, ultrasound-guided ment of chronic neutrophilic cholangitis has never
liver biopsy is adequate for diagnosis in most cats. been proven.
Laparoscopic liver biopsy provides larger tissue • Give prednisolone, 2 to 4 mg/kg q24h (once daily or
samples than those obtained with ultrasound guid- divided), until clinical remission, then taper over 6 to
ance. Perform an aerobic and anaerobic bacterial 8 weeks to 1 to 2 mg/kg once every other day.
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Prognosis
Cats with acute neurophilic cholangitis may have a com- CHOLECYSTITIS
plete recovery after treatment with antibiotics. However,
some of these cats progress to the chronic form. Cholecystitis, or inflammation of the gallbladder, is a
clinical problem that occurs uncommonly in both dogs
▼ Key Point Many cats with chronic neutrophilic and cats. Cholecystitis may be associated with cho-
cholangitis continue to have smoldering disease langitis, cholangiohepatitis, gallbladder mucocele,
requiring continued treatment for months or years. cholelithiasis, and choledocholithiasis. Acute necrotic
cholecystitis in dogs frequently is complicated by
Cats with neutrophilic cholangitis that survive less rupture of the gallbladder and septic bile peritonitis.
than 1 year commonly have concurrent diseases that
probably contribute to their death. Etiology
Lymphocytic Cholangitis • Bacteria appear to play an important role in chole-
cystitis. An enteric origin of bacteria seems most
Lymphocytic cholangitis (also called progressive lymphocytic likely, because isolates are usually aerobic gram-
cholangitis or cholangiohepatitis) is believed to be a distinct negative bacteria (especially E. coli, but also Klebsiella,
form of cholangitis in the cat. It appears to be rare in Pseudomonas, and Salmonella spp.) or anaerobes
the United States but has been well described in (Clostridium spp.). Intestinal bacteria may be refluxed
W0422-Ch071.qxd 11/12/05 10:43 AM Page 803
into the gallbladder, or they may be blood-borne • If cholecystitis is complicated by rupture of the gall-
from the hepatic circulation. bladder or biliary tract, abdominal fluid analysis is
• Campylobacter jejuni bacteremia and acute cholecysti- consistent with septic bile peritonitis. For a general
tis have been documented in dogs. Although the GI discussion of peritonitis, see Chapter 76.
tract was suspected to be the source of the bacteria,
diarrhea was not a presenting clinical sign. Radiography and Ultrasonography
• Gas-producing organisms, such as E. coli and Clostrid-
• Potential radiographic findings include cholecys-
ium, can cause emphysema of the gallbladder wall. tolithiasis, emphysema of the gallbladder wall, and, if
Emphysematous cholecystitis is recognized most fre- perforation occurs, abdominal effusion.
quently in diabetic dogs.
• Ultrasonographic findings include distension of the
• Cholelithiasis can predispose the patient to chole- gallbladder and cystic duct, increased echogenicity or
cystitis by obstructing the cystic duct, causing gall- hypoechoic thickening of the gallbladder wall, chole-
bladder overdistension and stasis, which enables cystoliths, and increased echogenicity of gallbladder
proliferation of anaerobic organisms. bile with or without bile sludge. Small amounts of
• Anatomic malformations of the gallbladder, biliary abdominal effusion not evident on survey radi-
obstruction from any cause, and biliary surgery also ographs may also be identified.
predispose the patient to biliary infections.
• Ultrasonographic-guided percutaneous cholecysto-
centesis has been recommended to obtain bile for
Clinical Signs cytology and culture (aerobic and anaerobic).
• Signs include anorexia, lethargy, fever, abdominal pain, Perform blood cultures to isolate bacteria associated
hepatomegaly, vomiting, diarrhea, and jaundice. with bacteremia and acute cholecystitis. Culture for
• Acute rupture of the gallbladder with septic bile peri- C. jejuni requires selective culture techniques.
tonitis causes abdominal distension, collapse, and
septic shock (see also Chapter 76). Surgery
• Signs may be acute or chronic and persistent or • Findings at exploratory surgery include thickening,
episodic. necrosis, and rupture of the gallbladder, localized or
generalized peritonitis, and calculi or inspissated bile
Diagnosis in the gallbladder, cystic duct, or bile duct. Previous
gallbladder rupture may be associated with omental
Differentiate cholecystitis from other cholestatic hepa- or hepatic adhesions.
tobiliary disorders that have fever, inflammation, and • Obtain aerobic and anaerobic cultures of the gall-
similar clinical findings, such as acute pancreatitis or bladder mucosa and bile.
pancreatic abscess, cholangiohepatitis, cholelithiasis, • Histologic examination of the gallbladder reveals vary-
hepatic abscess, and septicemia or endotoxemia. ing degrees of necrosis, inflammation, and fibrosis.
• Common postoperative complications include vom- compounds can induce lesions of gallbladder cystic
iting, diarrhea, anorexia, hypoproteinemia, and mucosal hyperplasia in dogs.
hypokalemia. • Acute pancreatitis may be a concurrent finding or a
postoperative complication of gallbladder mucocele
Prognosis surgery.
• Increased recognition of gallbladder mucoceles in
• Death usually is attributed to sepsis and peritonitis. dogs may suggest a role for nutritional or environ-
• If the animal survives the immediate postoperative mental factors, or it may be the result of increased
period, the long-term prognosis is good and the use of abdominal ultrasonography.
recurrence of biliary or hepatic disease is unlikely.
Clinical Signs
GALLBLADDER MUCOCELE • Common clinical signs include anorexia, lethargy,
vomiting, icterus, diarrhea, weight loss, PU/PD,
Gallbladder mucocele is an abnormal accumulation of abdominal discomfort, and abdominal distention.
mucus in the gallbladder lumen accompanied by cystic • Some dogs with gallbladder mucocele are clinically
mucosal hyperplasia of the gallbladder mucosa. (and biochemically) normal.
• Dogs with gallbladder mucoceles can be asympto- Diagnosis
matic early in the course of disease. Clinical and bio-
chemical abnormalities occur when mucoceles are History and Physical Exam
complicated by secondary bacterial infection, extra- • Gallbladder mucocele appears to be more likely in
hepatic biliary obstruction, or marked distention of older (>10 years) small to medium-sized dogs. No
the gallbladder leading to ischemic necrosis, gall- sex predilection is apparent. Cocker spaniels and
bladder rupture, and bile peritonitis. Shetland sheepdogs appear to be at increased risk.
• Signs are usually acute to subacute and less than 3
▼ Key Point Gallbladder rupture is a common life- weeks in duration.
threatening complication of mucocele. • Physical examination findings include depression,
weakness, lethargy, abdominal pain, icterus, fever,
• The incidence of gallbladder mucocele appears to be hepatomegaly, tachypnea, and tachycardia. Most dogs
increasing, and it is one of the most common causes with gallbladder rupture have abdominal pain.
of extrahepatic biliary tract disease in dogs. • Physical examination may be unremarkable.
Etiology Laboratory Evaluation
The cause of gallbladder mucocele formation in dogs is • Hematologic findings often include leukocytosis
unknown. (mature neutrophilia or neutrophilic with left shift)
• In humans, gallbladder mucoceles form secondary to and monocytosis.
functional or mechanical biliary obstruction associ- • Increased liver enzyme activity (ALP, ALT, AST, and
ated with cholecystitis, cholangitis, or cholelithiasis. GGT) and hyperbilirubinemia are common bio-
• In dogs, it is not clear whether gallbladder mucoce- chemical features. Other less consistent findings
les are a primary gallbladder disorder or whether include hypercholesterolemia, hyperglobulinemia,
biliary obstruction leads to increased mucus secre- hypoalbuminemia, and azotemia.
tion. However, predisposing disorders causing • Values for serum ALP and ALT, total bilirubin, and
mechanical biliary obstruction (infiltrative disease of WBC count are higher in dogs with gallbladder muco-
cystic duct, cholelithiasis) are not typically identified. cele and secondary rupture than in dogs without
A primary motility disorder of the gallbladder with rupture. In one study, all dogs with high venous
delayed gallbladder emptying could potentially lactate concentrations had a ruptured gallbladder.
predispose the patient to functional gallbladder
obstruction. ▼ Key Point Biochemical findings may be normal in
• A primary bacterial or inflammatory disorder of the some dogs with early gallbladder mucocele
gallbladder and biliary tract appear unlikely, since formation detected ultrasonographically.
aerobic and anaerobic cultures are frequently nega-
tive and gallbladder inflammation is inconsistent Ultrasonography
and, if present, occurs in association with gallbladder
wall necrosis. ▼ Key Point The ultrasonographic appearance of a
• Dogs with hyperadrenocorticism (or receiving corti- gallbladder mucocele is characteristic. The gall-
costeroids) appear to be at increased risk for bladder bile is echogenic and organized in a stel-
mucocele formation. Experimentally, progestational late or finely striated, “kiwi fruit” pattern.
W0422-Ch071.qxd 11/12/05 10:43 AM Page 805
▼ Key Point Because the majority of choleliths do not Table 71-12. CAUSES OF EXTRAHEPATIC
cause clinical signs, surgical removal may not BILIARY OBSTRUCTION
always be warranted.
Cholelithiasis
Inspissated (sludged) bile
Laparotomy Gallbladder mucocele
Cholangitis and cholecystitis
Perform exploratory laparotomy for definitive diagno- Acute pancreatitis, pancreatic abscess, pancreatic fibrosis
sis and treatment of cholelithiasis (see Chapter 72). Biliary, hepatic, pancreatic or duodenal neoplasia
Pigment choleliths usually are greenish-brown to black Biliary stricture
Biliary hematoma
and may be single or multiple. Perform the follow- Liver flukes
ing diagnostic and therapeutic procedures during Diaphragmatic hernia with entrapment of the gallbladder
exploratory laparotomy:
• Evaluate the patency of the gallbladder and bile
ducts.
• Remove choleliths for chemical analysis and bacter- Etiology
ial culture.
• Identify and repair secondary biliary rupture. Biliary obstruction can be a complication of primary
• Collect samples of affected tissue (liver, gallbladder) biliary tract disorders such as gallbladder mucocele,
and bile for aerobic and anaerobic bacterial culture cholelithiasis, or biliary tumors or can be caused by
and biopsy. extrahepatic disorders such as pancreatic fibrosis and
pancreatic or duodenal masses (Table 71-12).
Histopathologic Evaluation
Clinical Signs
Histopathologic changes in the gallbladder, bile ducts,
and liver may be absent with uncomplicated cholelithi- • Signs of biliary obstruction include anorexia, vomit-
asis. However, mild cholangitis (cholangiohepatitis) ing, jaundice, weight loss, abdominal pain, diarrhea,
and cholecystitis are common. acholic feces, and excessive bleeding.
• Diarrhea and steatorrhea are characterized by tan-
colored feces and are attributed to failure to secrete
Treatment and Prognosis bile acids, which results in malabsorption of fat and
• Institute supportive therapy to correct fluid, elec- fat-soluble vitamins such as vitamin K.
trolyte, and acid-base imbalances prior to surgery. • With prolonged extrahepatic biliary obstruction,
Feed a well-balanced diet. vitamin K malabsorption and the subsequent
• If a coagulopathy is detected, give vitamin K1 for 24 decreased synthesis of vitamin K–dependent factors
to 48 hours prior to surgery (see Table 71-1). results in a coagulopathy.
• Administer systemic antibiotics in animals with • With complete biliary obstruction, the feces may
inflammatory biliary tract disease and cholelithiasis. become clay colored (acholic) because of a lack of
Ideally, base the choice of antibiotic on culture and bile pigments.
sensitivity testing of bile and hepatic tissue obtained
at surgery. See the discussion of antibiotic therapy of Diagnosis
biliary infections under “Neutrophilic Cholangitis.” The diagnostic strategy is to identify that biliary obstruc-
• Management of complications of cholelithiasis, such tion is present and then to identify the underlying cause
as biliary obstruction or rupture, is discussed in the of obstruction.
next sections. Surgery of the biliary tract is discussed
in Chapter 72. Physical Examination
• Little is known about the likelihood of recurrence of
cholelithiasis in dogs and cats, but if the underlying • Findings include jaundice and hepatomegaly due to
mechanism of cholelith formation is not reversed, bile engorgement of the liver.
recurrence is possible. • A firm, distended gallbladder occasionally is pal-
pated.
• Other findings are dependent on the underlying
cause of obstruction, such as palpation of an abdom-
EXTRAHEPATIC BILIARY OBSTRUCTION inal mass (pancreatic or biliary neoplasia) and
abdominal pain (acute pancreatitis, peritonitis).
Extrahepatic biliary obstruction of the common bile • Fever may suggest bacterial cholecystitis or cholan-
duct or large hepatic ducts interrupts bile flow into the giohepatitis, biliary rupture with peritonitis, pancre-
intestine. atitis, or pancreatic abscess.
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Radiography Treatment
Abdominal radiography is frequently non-diagnostic. Surgery
• Occasionally, a large, fluid-filled gallbladder can be Specific therapy requires surgery to correct the under-
seen superimposed over the liver. The liver may be lying cause of obstruction (see Chapter 72).
normal to increased in size. Chronic biliary obstruc- • Prior to surgery, stabilize the patient with fluid
tion in dogs may lead to biliary cirrhosis and therapy. Give vitamin K1 parenterally for 24 to 48