MKSAP For Students 5

MKSAP
FOR STUDENTS 5 (2011)

Front Matter
Ti tl e Page
MKSAP
for Students 5
Medical Knowledge Self-Assessment Program
Devel oped by
American College of Physicians
Clerkship Direct ors in Int ernal Medicine
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ISBN-13: 978-1-934465-54-7
ISBN-10: 1-934465-54-2
Acknowl edgments
MKSAP for Students 5 Edi tori al Board
Eyad Al -Hi hi , MD, MBA, FACP
Associat e Professor of Medicine
Chief, Division of General Int ernal & Hospit al Medicine
Direct or, Int ernal Medicine Ambulat ory Clerkship
Universit y of Missouri-Kansas Cit y School of Medicine
Medical Direct or, Medicine Clinics, Truman Med Cent er
Kansas Cit y, Missouri
Irene Al exandraki , MD, MPH, FACP
Assist ant Professor, Depart ment of Medicine
Medicine Clerkship Direct or
Universit y of Florida College of Medicine
Jacksonville, Florida
Mark Al l ee, MD, FACP
Associat e Professor, Depart ment of Medicine
Universit y of Oklahoma School of Medicine
Oklahoma Cit y, Oklahoma
Saad Al vi , MD, FACP
Assist ant Professor of Clinical Medicine
M3 Clerkship Direct or
Universit y of Illinois College of Medicine at Peoria
(UICOMP)
Peoria, Illinois
Al pesh Ami n, MD, MBA, FACP
Professor of Medicine
Universit y of California, Irvine
Orange, California
Li sa M. Antes, MD
Associat e Professor
Depart ment of Int ernal Medicine/Division of Nephrology
Inpat ient Int ernal Medicine Clerkship Co-Direct or
Carver College of Medicine/Universit y of Iowa Hospit als
and Clinics
Iowa Cit y, Iowa
Joel Appel , DO
Direct or Ambulat ory and St udent Programs
Wayne St at e Universit y School of Medicine
Chief Hemat ology/Oncology
Sinai-Grace Hospit al
Det roit Medical Cent er
Det roit , Michigan
Jonathan S. Appel baum, MD, FACP
Associat e Professor, Clinical Sciences
Direct or, Int ernal Medicine Educat ion
Florida St at e Universit y College of Medicine
Tallahassee, Florida
Scott Arnol d, MD, FACP
Universit y of Alabama School of Medicine
Tuscaloosa Campus
Tuscaloosa, Alabama
Emi l y Chi sm Barker, MD
Assist ant Professor of Medicine
Senior Associat e Program Direct or for Int ernal Medicine
Universit y of Texas Houst on Medical School
Houst on, Texas
Jenni fer Bi erman, MD, FACP
Primary Care Clerkship Direct or
Nort hwest ern Universit y Feinberg School of Medicine
Chicago, Illinois
Susan Crouch Brewer, MD, FACP
Assist ant Dean for Clinical Educat ion
Associat e Chair for St udent Programs
College of Medicine
Universit y of Tennessee Healt h Science Cent er
Memphis, Tennessee
Cynthi a A. Burns, MD, FACP
Assist ant Professor
Int ernal Medicine Clerkship Direct or
Depart ment of Int ernal Medicine
Sect ion on Endocrinology & Met abolism
Wake Forest Universit y School of Medicine
Winst on-Salem, Nort h Carolina
Mari a L. Cannarozzi , MD, FACP, FAAP
Associat e Professor of Int ernal Medicine & Pediat rics
Clerkship Direct or, Int ernal/Family Medicine
Universit y of Cent ral Florida College of Medicine
Orlando, Florida
Danel l e Cayea, MD, MS
Johns Hopkins Universit y School of Medicine
Balt imore, Maryland
J. Charl es, MD, FACP, FHM
Division Educat ion Coordinat or
Mayo Clinic Hospit al
Phoenix, Arizona
Bri an J. Costel l o, DO
Co-Clerkship Direct or Ambulat ory Medicine
Lehigh Valley Healt h Net work
Allent own, Pennsylvania
Cami l l a Curren, MD
Assist ant Clinical Professor of Int ernal Medicine
Ohio St at e Universit y Medical Cent er
Clinical Assist ant Professor of Pediat rics
Nat ionwide Childrens Hospit al
Assist ant Clerkship Direct or, Ambulat ory Medicine
Ohio St at e Universit y College of Medicine
Columbus, Ohio
Thomas M. DeFer, MD, FACP
Clerkship Direct or
Division of Medical Educat ion
Washingt on Universit y School of Medicine
St . Louis, Missouri
Stephani e A. Detterl i ne, MD, FACP
Associat e Program Direct or, Int ernal Medicine
Union Memorial Hospit al
Medicine Clerkship Sit e Direct or
Universit y of Maryland School of Medicine
Gurpreet Dhal i wal , MD
Sit e Direct or, Int ernal Medicine Clerkships
San Francisco VA Medical Cent er
Associat e Professor of Clinical Medicine
Universit y of California San Francisco
San Francisco, California
Gretchen Di emer, MD, FACP
Direct or of Undergraduat e Medical Educat ion
Clerkship Direct or Int ernal Medicine
Assist ant Program Direct or Int ernal Medicine
Thomas Jefferson Universit y
Philadelphia, Pennsylvania
Anne Eacker, MD, FACP
Medical Direct or, General Int ernal Medicine Cent er
Universit y of Washingt on
Seat t le, Washingt on
Mark J Fagan, MD, FACP
Clerkship Direct or
Depart ment of Medicine
Alpert Medical School of Brown Universit y
Providence, Rhode Island
Pamel a J. Fal l , MD, FACP, FASH
Sect ion of Nephrology, Hypert ension and Transplant at ion
Clerkship Direct or, Int ernal Medicine
Medical College of Georgia
August a, Georgia
L. Chri sti ne Faul k, MD
Medicine Clerkship Co-Direct or
Universit y of Kansas School of Medicine-Wichit a
Wichit a, Kansas
Sara B. Fazi o, MD, FACP
Associat e Professor, Harvard Medical School
Direct or, Core I Medicine Clerkship
Division of General Int ernal Medicine
Bet h Israel Deaconess Medical Cent er
Bost on, Massachuset t s
J. Mi chael Fi nl ey, DO, FACP, FACOI
Chief, Division of Rheumat ology
Associat e Dean for Graduat e Medical Educat ion
West ern Universit y College of Ost eopat hic Medicine
Pomona, California
Jose Franco, MD, AGAF
Professor of Medicine and Pediat rics
Direct or of Hepat ology
Medical College of Wisconsin
Milwaukee, Wisconsin
Eri ca Fri edman, MD, FACP
Associat e Dean
Associat e Professor of Medicine and Medical Educat ion
Mount Sinai School of Medicine
New York, New York
Peter Gl i atto, MD, FACP
Assist ant Professor of Medicine and Medical Educat ion
Co-Direct or, Medicine-Geriat rics Clerkship
Direct or, Medicine Subint ernship
New York, New York
Susan A. Gl od, MD
Associat e Clerkship Direct or, Int ernal Medicine
Penn St at e College of Medicine
Hershey, Pennsylvania
Gabri el l e R. Gol dberg, MD
Educat ion Direct or
The Hert zberg Palliat ive Care Inst it ut e
Depart ment of Geriat rics and Palliat ive Medicine
New York, New York
Eri c Goren, MD
Medicine Sub-Int ernship Course Co-Direct or
Assist ant Professor of Clinical Medicine
Universit y of Pennsylvania School of Medicine
Cyri l M. Grum, MD, FACP
Professor and Senior Associat e Chair
for Undergraduat e Medical Educat ion
Universit y of Michigan
Ann Arbor, Michigan
Heather Harrel l , MD, FACP
Direct or of Fourt h Year Programs
Gainesville, Florida
Dan A. Henry, MD, FACP
Direct or of Clinical Educat ion
Universit y of Connect icut School of Medicine
Farmingt on, Connect icut
Susan Thompson Hi ngl e, MD, FACP
Int ernal Medicine Residency Associat e Program Direct or
Sout hern Illinois Universit y School of Medicine
Springfield, Illinois
Wi l l i am Howel l , MBChB
Clinical Inst ruct or of Medicine
Universit y of Ut ah School of Medicine
Salt Lake Cit y, Ut ah
Eri c Hsi eh, MD
Direct or, Int ernal Medicine Clerkship
Senior Associat e Direct or, Int ernal Medicine Residency
Keck School of Medicine
Universit y of Sout hern California
Los Angeles, California
Hugh F. Hui zenga, MD, MPH
Clerkship Direct or-Inpat ient Medicine
Dart mout h Medical School
Hanover, New Hampshire
T.J. Hundl ey, MD, FACP
Universit y of Sout h Alabama College of Medicine
Mobile, Alabama
Nadi a J. Ismai l , MD, MPH, Med, FACP
Direct or, Int ernal Medicine Core Clerkship
Baylor College of Medicine
Houst on, Texas
Hari sh Iyer, MD, MRCP (UK)
Chief Medical Resident
Albert Einst ein Medical Cent er
Robert Jabl onover, MD
Assist ant Professor in Int ernal Medicine
Clerkship Direct or in Int ernal Medicine
George Washingt on Universit y School of Medicine
Washingt on, Dist rict of Columbia
Janet A. Jokel a, MD, MPH, FACP
Universit y of Illinois at Urbana-Champaign
Urbana, Illinois
Jason Kahn, MD, FACP
Int ernal Medicine Clerkship Sit e Direct or
St . Joseph Mercy Hospit al
Ann Arbor, Michigan
Chri stopher A. Kl i pstei n, MD
Universit y of Nort h Carolina School of Medicine
Chapel Hill, Nort h Carolina
Mary Ann Kuzma, MD, FACP
Drexel Universit y College of Medicine
Rosa Lee, MD
Medicine Clerkship Sit e Leader,
Mont efiore Medical Cent er
Albert Einst ein College of Medicine
Bronx, New York
Beth W. Li ston, MD, PhD, FACP
Assist ant Professor of Clinical Medicine/Pediat rics
Sub-int ernship Clerkship Direct or
The Ohio St at e Universit y College of Medicine
Columbus, Ohio
Mai A Mahmoud, MBBS, FACP
Weill Cornell Medical College in Qat ar
Doha, Qat ar
Li anne Marks, MD, PhD, FACP
Division Direct or, Int ernal Medicine
Scot t & Whit e Healt hcare
Assist ant Professor and Int ernal Medicine
Clerkship Direct or for 3rd Year Medical St udent s
Texas A&M College of Medicine
Round Rock, Texas
Kevi n M. McKown, MD
Associat e Professor and Head, Division of Rheumat ology
Co-Direct or M3 and M4 St udent Programs
Universit y of Wisconsin
School of Medicine & Public Healt h
Madison, Wisconsin
Laura Mei nke, MD
Sect ion of Pulmonary & Crit ical Care Medicine
Universit y of Arizona College of Medicine
Tucson, Arizona
James L. Mei sel , MD, FACP
Clerkship Direct or/Evans St udent Educat or
Bost on Universit y School of Medicine
Chad S. Mi l l er, MD, FACP
Associat e Program Direct or, Residency
Tulane Universit y Healt h Sciences Cent er
New Orleans, Louisiana
Ni na Mi ngi oni , MD FACP
Associat e Program Direct or, Int ernal Medicine
Clerkship Sit e Direct or, Int ernal Medicine
Albert Einst ein Medical Cent er
Al i ta Mi shra, MD, FACP
Clerkship Direct or, Depart ment of Medicine
Hospit alist , Inova Fairfax Hospit al
Clinical Assist ant Professor of Medicine
Virginia Commonwealt h Universit y School of Medicine
Inova Campus
Falls Church, Virginia
Archana Mi shra, MD, MS, FACP, FCCP
Associat e Clerkship Direct or
SUNY Buffalo School of Medicine and Biomedical Sciences
Buffalo, New York
Lynda Mi sra, DO, FACP, MA Ed
Direct or of St udent s - William Beaumont Hospit al
Oakland Universit y William Beaumont School of Medicine
Royal Oak, Michigan
Neha Mi ttal , MD
Year 4 Clerkship Direct or
Texas Tech Universit y Healt h Science Cent er
Lubbock, Texas
Justi n B. Moore, MD
Division Chief, Endocrinology
Wichit a, Kansas
Mark T. Munekata, MD, MPH, FACP
Associat e Clinical Professor of Medicine
Co-Direct or, Ambulat ory Int ernal Medicine Clerkship
David Geffen School of Medicine at UCLA
Medical Direct or, Ut ilizat ion Management
Direct or, Urgent Care Clinic
Harbor-UCLA Medical Cent er
Torrance, California
Marty Muntz, MD
Ambulat ory Medicine Clerkship Direct or
Medicine Subint ernship Direct or
Davi d G. Nayl or, MD
Assist ant Clerkship Direct or
Universit y of Kansas Medical Cent er
Kansas Cit y, Kansas
Adesoji E. Oderi nde, MD, MSCR, FACP
Associat e Program Direct or
Associat e Direct or St udent Educat ion
Morehouse School of Medicine
At lant a, Georgia
Thomas D. Pai nter MD
Inpat ient Int ernal Medicine Clerkship Direct or
Universit y of Pit t sburgh School of Medicine
Pit t sburgh, Pennsylvania
Carl os Pal aci o, MD, MPH, FACP
Associat e Professor of Medicine, Depart ment of Medicine
Clerkship Direct or
Universit y of Florida College of Medicine-Jacksonville
Robert I. Pargament, MD, FACP
York Hospit al
York, Pennsylvania
Al i sa Peet, MD
Temple Universit y School of Medicine
Roshi ni C. Pi nto-Powel l , MD
Dart mout h Medical School
Lebanon, New Hampshire
Suma Pokal a, MD, FACP
Texas A&M Healt h Sciences Cent er
Cent ral Texas Vet erans Healt h Care Syst em
Temple, Texas
Hari Raja, MD, FACP
Clerkship Direct or
UT Sout hwest ern Medical Cent er
Dallas, Texas
Templ e A. Ratcl i ffe, MD
Assist ant Clerkship Direct or
F. Edward Hebert School of Medicine
Uniformed Services Universit y of t he Healt h Sciences
Bet hesda, Maryland
Emran Rouf, MD, FACP
Scot t & Whit e Healt hcare
Texas A & M Healt h Science Cent er College of Medicine
Temple, Texas
Gary M. Rul l , MD, FACP
Associat e Professor of Clinical Int ernal Medicine
Doct oring Direct or
James L. Sebasti an, MD, FACP
Thomas K. Schul z, MD
Associat e Program Direct or,
Int ernal Medicine Residency Program
Wichit a, Kansas
Moni ca Ann Shaw, MD, FACP
Chief, Division of General Int ernal Medicine
Direct or, Int ernal Medicine Clerkships
Universit y of Louisville School of Medicine
Louisville, Kent ucky
Lei gh H. Si mmons, MD
Assist ant in Medicine
Associat e Medicine Clerkship Direct or
Massachuset t s General Hospit al
Harvard Medical School
Harol d M. Szerl i p, MD, FACP, FCCP, FASN
Professor and Vice-Chair, Depart ment of Medicine
Chief, Medical Service, UPH Hospit al
Tucson, Arizona
Heather Taranti no, MD
West Virginia Universit y School of Medicine
Charlest on Division
Charlest on, West Virginia
Robert L. Trowbri dge, MD, FACP
Tuft s Universit y School of Medicine
Maine Medical Cent er
Port land, Maine
John Varras, MD
Int erim Chair
Clerkship Direct or
Universit y of Nevada School of Medicine
Las Vegas, Nevada
T. Robert Vu, MD, FACP
Indiana Universit y School of Medicine
Indianapolis, Indiana
Joseph T. Wayne, MD, MPH, FACP
Albany Medical College
Albany, New York
Barry J. Wu, MD, FACP
Associat e Program Direct or of Int ernal Medicine
Hospit al of Saint Raphael
Clinical Professor of Medicine
Yale Universit y School of Medicine
New Haven, Connect icut
Parekha Yedl a, MBBS, FACP
Universit y of Alabama, Hunt sville Campus
Hunt sville, Alabama
MKSAP for Students 5 Contri butors
Arl i na Ahl uwal i a, MD, FACP
Medicine Clerkship Sit e Direct or, Palo Alt o VAHCS
St anford Universit y School of Medicine
Palo Alt o, California
Eri k K. Al exander, MD, FACP
Direct or, Medical St udent Educat ion
Brigham & Women's Hospit al
Irene Al exandraki , MD, MPH, FACP
Mark Al l ee, MD, FACP
Clerkship Direct or
Universit y of Oklahoma College of Medicine
Oklahoma Cit y, Oklahoma
Al pesh Ami n, MD, MBA, FACP
Universit y of California, Irvine
Orange, California
Joel Appel , DO
Direct or, Ambulat ory and Subint ernship Programs
Wayne St at e Universit y School of Medicine
Det roit , Michigan
Jonathan S. Appel baum, MD, FACP
Associat e Professor, Clinical Sciences Depart ment
Direct or, Int ernal Medicine Educat ion
Florida St at e Universit y College of Medicine
Tallahassee, Florida
MJ Barchman, MD, FACP, FASN
Sect ion of Nephrology and Hypert ension
Brody School of Medicine at East Carolina Universit y
Greenville, Nort h Carolina
Gonzal o Bearman, MD, MPH
Associat e Hospit al Epidemiologist
Virginia Commonwealt h Universit y
Richmond, Virginia
Seth Mark Berney, MD, FACP
Chief, Sect ion of Rheumat ology
Direct or, Cent er of Excellence for Art hrit is and
Rheumat ology
Louisiana St at e Universit y Healt h Sciences Cent er School of
Medicine in Shreveport
Shreveport , Louisiana
Jenni fer Bi erman, MD, FACP
Primary Care Clerkship Direct or
Nort hwest ern Universit y Feinberg School of Medicine
Chicago, Illinois
Cynthi a A. Burns, MD, FACP
Sect ion on Endocrinology & Met abolism
Wake Forest Universit y School of Medicine
Winst on Salem, Nort h Carolina
Danel l e Cayea, MD, MS
J. Charl es MD, FACP, FHM
Division Educat ion Coordinat or
Mayo Clinic Hospit al
Phoenix, Arizona
Amanda Cooper, MD
Universit y of Pit t sburgh Medical Cent er
Mark D. Corri ere, MD, FACP
Associat e Clerkship Direct or, Depart ment of Medicine
Bet hesda, Maryland
Gretchen Di emer, MD, FACP
Assist ant Professor of Int ernal Medicine
Clerkship Direct or Int ernal Medicine
Associat e Program Direct or Int ernal Medicine
Thomas Jefferson Universit y
Reed E. Drews, MD, FACP
Program Direct or, Hemat ology-Oncology Fellowship
D. Mi chael El ni cki , MD, FACP
Professor and Chief, Sect ion of General Int ernal Medicine,
UPMC Shadyside
Ambulat ory Clerkship Direct or
Universit y of Pit t sburgh
Mark J. Fagan, MD, FACP
Clerkship Direct or
Alpert Medical School of Brown Universit y
Providence, Rhode Island
Sara B. Fazi o, MD, FACP
Associat e Professor, Harvard Medical School
Direct or, Core I Medicine Clerkship
J. Mi chael Fi nl ey, DO, FACP, FACOI
Chief, Division of Rheumat ology
Associat e Dean for Graduat e Medical Educat ion
West ern Universit y College of Ost eopat hic Medicine
Pomona, California
Jane P. Gagl i ardi , MD, MHS
Assist ant Professor of Psychiat ry & Behavioral Sciences
Direct or of UME, Depart ment of Medicine
Medicine Clerkship and Subint ernship Direct or
Duke Universit y School of Medicine
Durham, Nort h Carolina
Peter Gl i atto, MD, FACP
Associat e Dean for Undergraduat e Medical Educat ion
and St udent Affairs
New York, New York
Eri c H. Green MD, MSc, FACP
Clinical Associat e Professor of Medicine
Associat e Program Direct or
Mercy Cat holic Medical Cent er
Darby, Pennsylvania
Heather Harrel l , MD, FACP
Direct or of Fourt h Year Programs
Gainesville, Florida
Warren Hershman, MD, MPH
Direct or of St udent Educat ion
Bost on Universit y School of Medicine
Susan Thompson Hi ngl e, MD, FACP
Int ernal Medicine Residency Associat e Program Direct or
Bryan Ho, MD
Assist ant Professor, Depart ment of Neurology
Neurology Clerkship Direct or
Tuft s Universit y School of Medicine
Mark D. Hol den, MD, FACP
Vice-Chair for Undergraduat e Educat ion
Universit y of Texas Medical Branch
Galvest on, Texas
Jeffrey Guy House, DO, FACP
Program Direct or Int ernal Medicine Residency
Universit y of Florida Healt h Science Cent er-Jacksonville
Eri c Hsi eh, MD
Senior Associat e Direct or, Int ernal Medicine Residency
Keck School of Medicine
Universit y of Sout hern California
Los Angeles, California
Robert Jabl onover, MD
Assist ant Professor in Int ernal Medicine
Clerkship Direct or in Int ernal Medicine
George Washingt on Universit y School of Medicine
Washingt on, Dist rict of Columbia
Saba Khan, MD
Fellow, Sect ion of Rheumat ology
Louisiana St at e Universit y Healt h Sciences Cent er
School of Medicine in Shreveport
Sarang Ki m, MD, FACP
Universit y of Medicine and Dent ist ry of New Jersey,
Robert Wood Johnson Medical School
New Brunswick, New Jersey
Val eri e J. Lang, MD, FACP
Direct or, Inpat ient Medicine Clerkship
Universit y of Rochest er School of Medicine & Dent ist ry
Hospit al Medicine Division
Rochest er, New York
Rosa Lee, MD
Clinical Assist ant Professor, Depart ment of Medicine
Albert Einst ein College of Medicine
Sit e Leader, Medicine Clerkship
Mont efiore Medical Cent er
Bronx, New York
Bruce Leff, MD, FACP
Co-Direct or, Basic Medicine Clerkship
Kyl e L. Loki tz, MD
Fellow, Sect ion of Rheumat ology
School of Medicine in Shreveport
Fred A. Lopez, MD, FACP
Richard Vial Professor and Vice Chair
Kevi n M. McKown, MD, FACP
Associat e Professor and Head, Division of Rheumat ology
Co-Direct or M3 and M4 St udent Programs
Universit y of Wisconsin
School of Medicine & Public Healt h
Madison, Wisconsin
Chad S. Mi l l er, MD, FACP
Direct or, St udent Programs
Associat e Program Direct or, Residency
Tulane Universit y Healt h Sciences Cent er
Katheri ne Ni ckerson, MD
Professor of Clinical Medicine
Vice Chair, Depart ment of Medicine
Clerkship Direct or, Int ernal Medicine
College of Physicians & Surgeons
Columbia Universit y
New York, New York
L. James Ni xon, MD
Vice Chair for Educat ion, Depart ment of Medicine
Universit y of Minnesot a Medical School
Minneapolis, Minnesot a
Isaac O. Opol e, MD, PhD, FACP
Assist ant Dean for St udent Affairs
Kansas Universit y Medical Cent er
Kansas Cit y, Kansas
Carl os Pal aci o, MD, MPH, FACP
Associat e Professor of Medicine, Depart ment of Medicine
Clerkship Direct or
Universit y of Florida College of Medicine-Jacksonville
Suma Pokal a, MD, FACP
Texas A&M Healt h Sciences Cent er
Cent ral Texas Vet erans Healt h Care Syst em
Temple, Texas
Nora L. Porter, MD, MPH, FACP
Co-direct or, Int ernal Medicine Clerkship
Saint Louis Universit y School of Medicine
Shal i ni Reddy, MD
Associat e Dean
St udent Programs and Professional Development
The Universit y of Chicago Prit zker School of Medicine
Chicago, Illinois
Kl ara J. Rosenqui st, MD
Clinical/Research Fellow
Division of Endocrinology, Diabet es and Hypert ension
Brigham & Women's Hospit al
Kathl een F. Ryan, MD, FACP
Mysti D. W. Schott, MD, FACP
Course Direct or, Advanced Clinical Evaluat ion Skills
Depart ment of Medicine, Division of General Medicine
& Office of Educat ional Programs
Universit y of Texas Healt h Science Cent er San Ant onio
San Ant onio, Texas
Amy Wi egner Shaheen, MD
Ambulat ory Medicine Clerkship Direct or
Universit y of Nort h Carolina School of Medicine
Chapel Hill, Nort h Carolina
Moni ca Ann Shaw, MD, FACP
Associat e Professor and Chief
Division of General Int ernal Medicine, Palliat ive
Medicine and Medical Educat ion
Universit y of Louisville
Louisville, Kent ucky
Patri ci a Short, MD, FACP
Associat e Clerkship Direct or
Madigan Army Medical Cent er
Tacoma, Washingt on
Karen Szauter, MD, FACP
Professor
Depart ment of Int ernal Medicine and Office of
Educat ional Development
Co-Direct or, Int ernal Medicine Clerkship
Universit y of Texas Medical Branch
Galvest on, Texas
Harol d M. Szerl i p, MD, FACP, FCCP, FASN
Professor and Vice-Chair, Depart ment of Medicine
Chief, Medical Service, UPH Hospit al
Tucson, Arizona
Gary Tabas, MD, FACP
Dari o M. Torre, MD, MPH, PhD, FACP
Associat e Program Direct or Int ernal Medicine Universit y
of Pit t sburgh-Shadyside
John Varras, MD
Int erim Chair
Clerkship Direct or
Universit y of Nevada School of Medicine
Las Vegas, Nevada
H. Dougl as Wal den, MD, MPH, FACP
Co-Direct or, Int ernal Medicine Clerkship
Saint Louis Universit y School of Medicine
John A. Wal ker, MD, FACP
Professor and Vice-Chair for Educat ion
Universit y of Medicine and Dent ist ry of New Jersey
Robert Wood Johnson Medical School
New Brunswick, New Jersey
Joseph T. Wayne, MD, MPH, FACP
Albany Medical College
Albany, New York
John Jason Whi te, MD, FASN
Sect ion of Nephrology, Hypert ension & Transplant at ion
Georgia Healt h Sciences Universit y
August a, Georgia
The American College of Physicians grat efully acknowledges t he cont ribut ions t o MKSAP for Students 5 of Scot t Hurd (product ion syst ems), Lisa Rockey (edit orial
product ion support ), Rosemarie Hout on (edit orial product ion support ) and t he Self-Assessment edit orial st aff. The College also wishes t o acknowledge t hat many ot her
persons, t oo numerous t o ment ion, have cont ribut ed t o t he product ion of t his product . Wit hout t heir dedicat ed effort s, t he publicat ion would not have been possible.
Foreword
Dear St udent :
As t he nat ional organizat ion for int ernal medicine specialist s and subspecialist s, t he American College of Physicians is commit t ed t o providing t he highest qualit y educat ional
mat erials and resources t hroughout t he cont inuum of t raining and pract ice in int ernal medicine. Early in t hat cont inuum are t he clinical clerkships in int ernal medicine for
st udent s during t heir t hird and fourt h years of medical school. Recognizing t he crit ical import ance of t hese clerkships for all st udent s - whet her or not t hey plan t o ent er t he
specialt y of int ernal medicine - t he College has been collaborat ing wit h t he Clerkship Direct ors in Int ernal Medicine t o develop and produce t wo publicat ions specifically
t arget ed t o medical st udent s on t heir int ernal medicine clerkships.
This publicat ion, MKSAP for Students, now in it s 5
th
edit ion, employs an int eract ive, case-based model of t opic-based quest ions (wit h accompanying answers and crit iques) t o
t each st udent s about t he major clinical problems in int ernal medicine. The companion publicat ion, Internal Medicine Essentials for Medical Students, nicely complement s
MKSAP for Students, providing a concise t ext t hat can be read from cover t o cover during an int ernal medicine clerkship. Bot h MKSAP for Students and Internal Medicine
Essentials are modeled aft er t he much larger Medical Knowledge Self-Assessment Program (MKSAP), which has served for t he past 43 years (and t hrough 15 edit ions) as t he
gold st andard for resident s preparing for t he cert ifying examinat ion in int ernal medicine and for pract icing physicians who wish t o refresh, updat e, and assess t heir knowledge.
Int ernal medicine is an excit ing and int ellect ually st imulat ing specialt y. We hope t hat MKSAP for Students will reinforce t hat feeling for you, enriching your clinical
experiences and serving as a useful companion as you learn t he fundament al concept s of t he specialt y and apply t hem in clinical set t ings. Remember, t he knowledge we gain is
not just abst ract learning - it provides t he foundat ion for t he care of our pat ient s, who deserve only t he best !
Best of luck t o you in your st udies and in your fut ure career.
Steven E. Wei nberger, MD, FACP
Executive Vice President and Chief Operating Officer
Preface
Welcome t o t he newest edit ion of MKSAP for Students. The fift h edit ion of t his popular series cont ains over 450 compl etel y new mult iple-choice quest ions, updat ed
references, more color phot ographs and ECG t racings t han ever before. MKSAP for Students is int ended primarily for t hird-year st udent s part icipat ing in t heir required
int ernal medicine clerkship. Ot her audiences include fourt h-year st udent s on an advanced medicine clerkship; second-year st udent s involved in problem-based learning; and
physician assist ant st udent s.
MKSAP for Students 5 is support ed by it s companion t ext book, Internal Medicine Essentials for Students. Aut hors who cont ribut ed t o t he Essentials t ext book also wrot e
quest ions for MKSAP for Students. Addit ional quest ions were writ t en by int ernal medicine clerkship direct ors. Like Essentials, MKSAP for Students 5 is organized int o 11
chapt ers t hat correspond t o t he t radit ional subspecialt y disciplines of int ernal medicine and general int ernal medicine. The edit ors and aut hors have made every effort t o
ensure t hat all quest ions in MKSAP for Students are associat ed wit h relevant cont ent in t he t ext book t hat can direct ly answer t he quest ion. This allows a one-t o-one
correspondence bet ween t he t ext book and t he self-assessment quest ions.
As in previous issues, t he quest ions are format t ed as clinical vignet t es t hat resemble t he t ypes of quest ions you will encount er at t he end of t he clerkship subject examinat ion
and t he int ernal medicine component of t he USMLE licensing examinat ion. Each quest ion has a det ailed answer crit ique t hat ident ifies t he correct answer and explains why
t hat answer is correct and t he ot her opt ions are incorrect , an educat ional object ive, and a short bibliography. Succinct "Key Point s" summarize t he import ant "t ake-home
messages" for each quest ion. We ant icipat e t hat reviewing t he "Key Point s" will be an efficient way t o prepare for upcoming examinat ions. We recommend t hat st udent s
read t he clinical vignet t e, select an answer, and t hen read t he associat ed answer crit ique. Each quest ion has been specifically reviewed by at least t hree clerkship direct ors t o
ensure t hat it meet s t he learning needs of st udent s part icipat ing in t he medicine clerkship.
New t o t his edit ion is a cat egorizat ion scheme for t he self-assessment quest ions. All quest ions are cat egorized as eit her Advanced (A) or Basic (B) by t he MKSAP for Students
Edit orial Board, which consist s ent irely of clerkship direct ors. Advanced quest ions are difficult and assess knowledge expect ed of an honors-level st udent or beginning first -
year int ernal medicine resident . Basic quest ions assess knowledge expect ed of all t hird-year st udent s complet ing t he basic int ernal medicine clerkship. It is our expect at ion
t hat clerkship st udent s will be able t o answer most of t he Basic quest ions and approximat ely half of t he Advanced quest ions. We hope t hat t his new syst em will provide
st udent s wit h a bet t er measure of t heir knowledge acquisit ion.
The fift h edit ion of MKSAP for Students would have been impossible wit hout t he valuable and ent irely volunt ary cont ribut ions of many people, some of whom are named in
t he Acknowledgment s sect ion. Ot hers, not specifically named, were represent at ives of a wide spect rum of const it uencies and organizat ions, such as t he Clerkship Direct ors in
Int ernal Medicine and various commit t ees wit hin t he American College of Physicians, including t he Educat ion and Publicat ion Commit t ee and t he Council of St udent
Members.
As in t he past , we hope t o receive more excellent feedback from st udent s t o improve fut ure edit ions. Thank you for making MKSAP for Students such a success!
Pat rick C. Alguire, MD, FACP
Editor-in-Chief
Senior Vice President for Medical Education
Note: The drug dosage schedules cont ained in t his publicat ion are, we believe, accurat e and in accordance wit h current st andards. However, please ensure t hat t he
recommended dosages concur wit h informat ion provided in t he product informat ion mat erial, especially for new, infrequent ly used, or highly t oxic drugs.
Contents
Acknowl edgmentsiii
Forewordxi
Prefacexiii
Cardiovascular Medicine Quest ions1
Cardiovascular Medicine Answers and Crit iques17
Endocrinology and Met abolism Quest ions39
Endocrinology and Met abolism Answers and Crit iques46
Gast roent erology and Hepat ology Quest ions61
Gast roent erology and Hepat ology Answers and Crit iques73
General Int ernal Medicine Quest ions91
General Int ernal Medicine Answers and Crit iques107
Hemat ology Quest ions139
Hemat ology Answers and Crit iques147
Infect ious Disease Medicine Quest ions161
Infect ious Disease Medicine Answers and Crit iques172
Nephrology Quest ions193
Nephrology Answers and Crit iques201
Neurology Quest ions215
Neurology Answers and Crit iques222
Oncology Quest ions235
Oncology Answers and Crit iques241
Pulmonary Medicine Quest ions253
Pulmonary Medicine Answers and Crit iques262
Rheumat ology Quest ions279
Rheumat ology Answers and Crit iques288
Normal Laboratory Val ues305
Col or Pl ates
Errataht t p://www.acponline.org/acp_press/essent ials/errat a.ht ml
Secti on 1. Cardi ovascul ar Medi ci ne
Questi ons
Item 1 [Basic]
A 66-year-old man is evaluat ed in t he emergency depart ment for left -sided chest pain t hat began at rest , last ed for 15 minut es, and has since resolved. A similar episode
occurred at rest yest erday. Pert inent medical hist ory includes hypert ension and t ype 2 diabet es mellit us. Current medicat ions are amlodipine, glyburide, and aspirin.
On physical examinat ion, blood pressure is 125/65 mm Hg, heart rat e is 70/min, and respirat ory rat e is 12/min. Est imat ed cent ral venous pressure is 6 cm H
2
O, carot id
upst roke is normal, t here are no cardiac murmurs, and t he lung fields are clear.
Laborat ory findings include an elevat ed serum t roponin I level. Elect rocardiogram is shown. Chest radiograph is normal.
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s?
(A) Chronic st able angina
(B) Non-ST-elevat ion myocardial infarct ion
(C) ST-elevat ion myocardial infarct ion
(D) Unst able angina
Item 2 [Basic]
A 63-year-old woman is admit t ed t o t he hospit al wit h pleurit ic chest pain, diaphoresis, and dyspnea of 1 hour's durat ion. The pain is not affect ed by food, ant acids, or
exert ion. It may be worse when supine and wit h deep breat hing. She has a 10-year hist ory of hypert ension and hyperlipidemia. Her medicat ions are chlort halidone and
lovast at in.
On physical examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 145/90 mm Hg (bot h arms), heart rat e is 108/min, and respirat ion rat e is 22/min. Cardiovascular
examinat ion reveals a regular rhyt hm and a biphasic, scrat chy sound best heard at t he lower left st ernal border. No murmur, S
3
, or S
4
is heard. The lungs are clear t o
auscult at ion. The jugular venous pressure is normal and no peripheral edema is not ed.
The elect rocardiogram shows sinus t achycardia wit h diffuse ST elevat ion. Troponin level and chest radiograph findings are normal.
(A) Acut e myocardial infarct ion
(B) Acut e pericardit is
(C) Aort ic dissect ion
(D) Pulmonary embolism
Item 3 [Basic]
A 78-year-old man is evaluat ed in t he emergency depart ment for new-onset chest pain. He describes a crushing pain t hat is locat ed in t he left subst ernal area and has been
present for 10 hours. He has had no prior episodes of chest pain. His medical hist ory is not able for hypert ension and hyperlipidemia. Current medicat ions are aspirin,
hydrochlorot hiazide, and at orvast at in.
On physical examinat ion, blood pressure is 100/70 mm Hg in bot h arms, pulse is 100/min, and respirat ion rat e is 16/min. There is no jugular venous dist ent ion and no cardiac
murmurs or rubs. The lungs are clear.
Laborat ory result s are not able for elevat ed levels of serum creat ine kinase and t roponin I. The init ial elect rocardiogram is shown. Chest radiograph is normal.
Whi ch of the fol l owi ng i s the best management for thi s pati ent?
(A) Chest CT wit h cont rast
(B) Echocardiogram
(C) Percut aneous coronary int ervent ion
(D) Thrombolyt ic t herapy
Item 4 [Basic]
A 50-year-old man is evaluat ed for a 2-hour episode of epigast ric discomfort and dyspnea during exercise t hat is relieved by rest . He is now pain free. The pat ient st at es a
similar episode occurred on t hree previous occasions, but he did not seek medical advice. He has been using ant acids for t he past 6 weeks wit h part ial relief. He report s no
fever, chills, nausea, vomit ing, diaphoresis, or post prandial abdominal pain. He has a 15-year hist ory of hypert ension and hyperlipidemia; his only medicat ion is
chlort halidone.
On physical examinat ion, he is afebrile, blood pressure is 150/85 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 14/min. BMI is 28. Est imat ed cent ral venous pressure is
normal. Cardiac examinat ion reveals a regular rhyt hm. The S
2
is normal, and an S
4
is heard at t he apex; no murmurs or ot her ext racardiac sounds are heard. The lungs are
clear t o auscult at ion. The abdomen is not t ender t o palpat ion.
Complet e blood count and t roponin level are normal as are t he elect rocardiogram and chest radiograph.
(A) Acut e pericardit is
(B) Aort ic dissect ion
(C) Ischemic heart disease
(D) Pept ic ulcer disease
Item 5 [Advanced]
A 52-year-old woman is evaluat ed in t he emergency depart ment for ongoing subst ernal chest pressure associat ed wit h nausea, diaphoresis, and light headedness. Her sympt oms
began 3 hours ago. She has hypert ension and hypercholest erolemia. Her medicat ions are hydrochlorot hiazide, pravast at in, and aspirin.
On physical examinat ion, her blood pressure is 84/62 mm Hg, pulse is 68/min, and respirat ion rat e is 20/min. Cardiac auscult at ion reveals dist ant heart sounds wit h an S
4
. The
lungs are clear bilat erally; est imat ed cent ral venous pressure is elevat ed at 11 cm H
2
O.
Elect rocardiogram wit h right -sided precordial leads is shown. (Leads V
1
t hrough V
6
are recorded from t he right side of t he chest .)
Whi ch of the fol l owi ng shoul d be gi ven next i n the treatment of thi s pati ent?
(A) Dobut amine int ravenously
(B) Met oprolol int ravenously
(C) Nit roglycerin sublingually
(D) 0.9% saline int ravenous bolus
Item 6 [Basic]
A 58-year-old woman is evaluat ed in t he emergency depart ment for subst ernal chest pain of 18 hours' durat ion. She describes t he pain as a t ight ening t hat is not associat ed
wit h eat ing or exert ion and t hat radiat es t o t he neck. The pain is not accompanied by dyspnea, nausea, or diaphoresis and is not associat ed wit h exert ion. She also report s
sympt oms of occasional heart burn and acid regurgit at ion. She had a similar episode of subst ernal chest pain 1 mont h ago, and an exercise st ress t est t hat achieved 90% her
predict ed maximal heart rat e showed no ischemia. The pat ient 's medical hist ory is ot herwise unremarkable.
On physical examinat ion, t emperat ure is 37.2C (99.0F), blood pressure is 130/74 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 16/min; BMI is 32. The
cardiopulmonary examinat ion is normal. Elect rocardiography shows nonspecific ST-segment and T-wave abnormalit ies, which are unchanged from several previous
examinat ions.
Whi ch of the fol l owi ng i s the most appropri ate management for thi s pati ent?
(A) Ambulat ory esophageal pH monit oring
(B) Coronary angiography
(C) Esophagogast roduodenoscopy
(D) Oral prot on pump inhibit or t herapy
(E) Repeat exercise st ress t est
Item 7 [Advanced]
A 22-year-old man is evaluat ed during t he mont h of June in t he emergency depart ment for int ermit t ent palpit at ions and dizziness for t he past week. He has not experienced
chest pain, dyspnea, or ort hopnea. He has no prior medical hist ory and is healt hy and act ive. He report s being ill 6 t o 8 weeks ago wit h fever, fat igue, myalgia, and a gradually
expanding, flat , eryt hemat ous rash on his abdomen measuring a minimum of 5 cm at widest point . He works as a forest er in Massachuset t s and has not t raveled out of t he
area recent ly.
On physical examinat ion, his t emperat ure is normal, blood pressure is 120/70 mm Hg, and pulse is 45/min. There are cannon waves in t he jugular pulsat ion. There is no rash,
and result s of cardiac and pulmonary auscult at ion are normal.
The elect rocardiogram is shown.
(A) First -degree at riovent ricular block
(B) Mobit z t ype I at riovent ricular block
(C) Mobit z t ype II at riovent ricular block
(D) Third-degree at riovent ricular heart block
Item 8 [Basic]
A 46-year-old man is evaluat ed for an 8-year hist ory of episodic chest pain associat ed wit h dyspnea, t achycardia, diaphoresis, and dizziness t hat occurs several t imes each
week. The sympt oms develop suddenly, are oft en so severe t hat he feels t hat he is going t o die, and improve significant ly wit hin 20 t o 30 minut es. The pat ient does not
know what precipit at es t hese episodes or whet her anyt hing makes t he sympt oms bet t er or worse.
Previous medical evaluat ions have been unremarkable. St udies have included elect rocardiographic exercise st ress t est ing, 24-hour elect rocardiographic monit oring,
echocardiography, cardiac cat het erizat ion, and upper endoscopy. The pat ient t akes no medicat ions. Findings on physical examinat ion are unremarkable. Medical records
reveal t hat during t hese episodes, hypert ension or t achycardia have never been document ed.
(A) Acut e coronary syndrome
(B) Panic disorder
(C) Pheochromocyt oma
(D) Pneumot horax
(E) Pulmonary embolism
Item 9 [Basic]
A 65-year-old woman is hospit alized for chest pain secondary t o an acut e coronary syndrome. Her immediat e t reat ment consist s of met oprolol, heparin, nit roglycerin, and
aspirin, which result s in immediat e relief of her chest discomfort . A rhyt hm st rip is shown.
Whi ch of the fol l owi ng i s the most l i kel y el ectrocardi ographi c di agnosi s?
(B) Mobit z t ype I second-degree at riovent ricular block
(C) Mobit z t ype II second-degree at riovent ricular block
(D) Third-degree at riovent ricular block (complet e heart block)
Item 10 [Advanced]
A 65-year-old man is evaluat ed during a rout ine follow-up examinat ion for coronary art ery disease. He was diagnosed wit h a myocardial infarct ion 5 years ago, and was st art ed
on aspirin, met oprolol, at orvast at in, lisinopril, and sublingual nit roglycerin. He was asympt omat ic unt il 3 mont hs ago, when he not ed exert ional angina aft er walking t wo
blocks. He now uses sublingual nit roglycerin on a daily basis. He has not had any episodes of pain at rest or prolonged chest pain t hat were not relieved by sublingual
nit roglycerin.
On physical examinat ion, blood pressure is 146/94 mm Hg and heart rat e is 87/min. Carot id upst rokes are normal wit h no bruit s. Cardiac examinat ion is normal. The lungs
are clear.
His elect rocardiogram is unchanged since t he last visit , wit h no evidence of acut e changes.
In addi ti on to addi ng a l ong-acti ng ni trate, whi ch of the fol l owi ng i s the most appropri ate management for thi s pati ent?
(A) Add ranolazine
(C) Exercise t readmill st ress t est ing
(D) Increase met oprolol
Item 11 [Advanced]
A 48-year-old woman is evaluat ed in t he emergency depart ment 3 hours aft er t he sudden onset of cent ral ant erior chest pain and dyspnea. There is const ant chest pressure,
t ight ness, and dyspnea. She is not on any medicat ions.
On physical examinat ion, t he pat ient is afebrile. Blood pressure is 144/76 mm Hg bilat erally, pulse is 118/min, and respirat ion rat e is 18/min. Est imat ed cent ral venous
pressure is 15 cm H
2
O. There are no murmurs, rubs, or gallops on cardiac auscult at ion. Her lungs are clear. There is mild pedal and lower leg edema t hat is more pronounced
on t he right side.
The elect rocardiogram shows ST-segment depression in t he lat eral leads. The chest radiograph is normal. Handheld echocardiography shows a small, hyperdynamic left
vent ricle wit h normal regional wall mot ion.
Whi ch of the fol l owi ng tests shoul d be performed next?
(A) CT pulmonary angiography
(C) Radionuclide perfusion imaging
(D) Transesophageal echocardiography
Item 12 [Basic]
A 68-year-old woman is evaluat ed for chest pain of 3 mont hs' durat ion. She describes t he pain as a left -sided burning t hat occurs bot h at rest and when she exercises. It last s
for about 10 minut es, and is relieved by eat ing and by rest . She has hypert ension, for which she t akes hydrochlorot hiazide. She has ast hma, for which she t akes inhaled
cort icost eroids and inhaled albut erol as needed. If she pret reat s herself wit h t he inhaled bronchodilat or, she can walk long dist ances at a brisk pace wit hout dyspnea. She
cont inues t o smoke cigaret t es and has smoked 1 pack per day for 40 years.
On physical examinat ion, she is afebrile. Blood pressure is 138/84 mm Hg, pulse is 64/min, and respirat ion rat e is 18/min. Cardiopulmonary examinat ion is normal. The
result s of an elect rocardiogram are normal.
Whi ch of the fol l owi ng i s the most appropri ate di agnosti c test for thi s pati ent?
(A) Adenosine nuclear perfusion st ress t est
(C) Dobut amine st ress echocardiography
(D) Exercise st ress t est
Item 13 [Basic]
A 54-year-old man is evaluat ed for 2 days of fat igue and dyspnea on exert ion. He denies chest pain and light headedness. He has no ot her medical problems, and his only
medicat ion is aspirin.
On physical examinat ion, his blood pressure is 123/65 mm Hg and his pulse is 100/min. Cardiac examinat ion reveals a normal S
1
and S
2
and no murmurs or gallops. Lungs are
clear t o auscult at ion.
The elect rocardiogram is shown.
(A) At rial fibrillat ion
(B) At rial flut t er
(C) Sinoat rial node dysfunct ion
(D) Vent ricular t achycardia
Item 14 [Basic]
A 75-year-old man wit h chronic st able angina is evaluat ed during a rout ine appoint ment . He had a myocardial infarct ion 5 years ago t reat ed medically and has had no
complicat ions. He only get s chest pain wit h significant exert ion, t ypically occurring less t han once a week. The pain is relieved by one sublingual nit roglycerin t ablet or
rest ing. He report s no short ness of breat h or edema. Medicat ions are lisinopril, carvedilol, simvast at in, aspirin, and nit roglycerin, as needed.
On examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 118/70 mm Hg, pulse rat e is 60/min, and respirat ion rat e is 14/min. BMI is 22. Cardiovascular examinat ion
reveals normal heart sounds wit hout murmurs, gallops, or rubs. Lungs are clear t o auscult at ion. The remainder of t he examinat ion is normal.
Tot al cholest erol 140 mg/dL (3.6 mmol/L)
Triglycerides 100 mg/dL (1.1 mmol/L)
HDL cholest erol 44 mg/dL (1.1 mmol/L)
LDL cholest erol 76 mg/dL (2.0 mmol/L)
Whi ch of the fol l owi ng i s the best management for thi s pati ent?
(A) Add clopidogrel
(B) Add ranolazine
(C) Coronary angiography
(D) No changes
Item 15 [Basic]
A 43-year-old man is evaluat ed in t he emergency depart ment for dyspnea. He has no prior personal or family hist ory of cardiovascular disease, diabet es mellit us, or
hypert ension. On physical examinat ion, t he lungs are clear. Cardiovascular examinat ion is unremarkable wit h t he except ion of a rapid heart rat e.
The chest radiograph is normal. The elect rocardiogram is shown.
(C) Sinus t achycardia
Item 16 [Basic]
A 48-year-old man is evaluat ed aft er a coworker had a myocardial infarct ion; he is worried about having a heart at t ack. He report s no episodes of chest pain or short ness of
breat h. He jogs on a t readmill 30 minut es a day four t imes a week. He does not smoke. He has hypert ension for which he t akes hydrochlorot hiazide. Family hist ory is
negat ive for coronary art ery disease.
On physical examinat ion his vit al signs are normal. The cardiopulmonary examinat ion is normal, as is t he remainder of t he physical examinat ion.
The most recent lipid panel shows: t ot al cholest erol 208 mg/dL (5.4 mmol/L), HDL cholest erol 70 mg/dL (1.8 mmol/L), and LDL cholest erol 114 mg/dL (3.0 mmol/L).
The pat ient 's Framingham Risk Score for a major cardiac event is calculat ed as 4% over t he next 10 years.
Whi ch of the fol l owi ng i s the best di agnosti c test for thi s pati ent?
(A) Coronary angiography
(B) Coronary calcium scoring
(C) CT angiography
(D) Exercise st ress t est
(E) No addit ional t est ing
Item 17 [Advanced]
A 26-year-old nurse is evaluat ed in t he emergency depart ment aft er an episode of syncope. While working in t he int ensive care unit , she developed t achycardia and t hen lost
consciousness. She has had brief episodes of rapid palpit at ions in t he past but no prior syncope.
Physical examinat ion is unremarkable and t he pat ient is in sinus rhyt hm. The chest radiograph is unremarkable. The elect rocardiogram is shown.
(A) Accelerat ed idiovent ricular t achycardia
(C) At riovent ricular reent rant t achycardia
(D) Mult ifocal at rial t achycardia
Item 18 [Basic]
A 62-year-old man wit h coronary art ery disease is evaluat ed for angina. He was diagnosed wit h coronary art ery disease 4 years ago. Medical t herapy was st art ed wit h aspirin,
met oprolol, isosorbide mononit rat e, pravast at in, and sublingual nit roglycerin. He was asympt omat ic unt il 8 mont hs ago, when he not ed exert ional angina; his dosages of
met oprolol and isosorbide mononit rat e were increased and long-act ing dilt iazem was added, result ing in cont rol of his sympt oms. Over t he past 2 mont hs, however, he has
had gradually increasing sympt oms, and current ly he requires daily nit roglycerin for angina relief during exercise. He has not had any episodes of angina at rest .
On physical examinat ion, blood pressure is 100/60 mm Hg and heart rat e is 48/min. Carot id upst roke is normal wit h no bruit s. Cardiac examinat ion reveals no murmurs, and
t he lungs are clear.
An elect rocardiogram shows no acut e ischemic changes.
Whi ch of the fol l owi ng shoul d be the next step i n thi s pati ent's management?
(A) Coronary angiography
(B) Exercise t readmill st ress t est ing
(C) Increase met oprolol
(D) Int ravenous heparin and nit roglycerin
Item 19 [Basic]
A 62-year old man wit h a hist ory of a myocardial infarct ion 1 year ago is evaluat ed in t he emergency depart ment for sudden episodes of dyspnea and weakness. He is
diaphoret ic, cool, clammy, and pale; cannon waves are not ed in t he jugular pulsat ions. An elect rocardiogram t aken at t he beginning of a t ypical episode is shown.
(A) At rial fibrillat ion wit h left bundle branch block
(B) At rial fibrillat ion wit h preexcit at ion (Wolf-Parkinson-Whit e syndrome)
(C) Supravent ricular t achycardia wit h right bundle branch block
Item 20 [Basic]
A 54-year-old woman is evaluat ed in t he emergency depart ment for jaw and shoulder pain t hat has occurred int ermit t ent ly for t he past week. The sympt oms occur wit h
act ivit y and are relieved by rest . Medical and family hist ory is unremarkable. She is not t aking any medicat ions.
Physical examinat ion shows a blood pressure of 150/68 mm Hg and a pulse of 90/min. There is no jugular venous dist ent ion and carot id upst rokes are normal. There are no
cardiac murmurs and t he lung fields are clear. Ext remit ies show no edema and peripheral pulses are normal bilat erally. The t roponin I level is elevat ed.
Elect rocardiogram shows 1.0-mm ST-segment depression in leads V
1
t hrough V
4
wit h T-wave inversions.
The pat ient is given aspirin, int ravenous nit roglycerin, low-molecular-weight heparin, clopidogrel, and at orvast at in.
Whi ch of the fol l owi ng i s the most appropri ate addi ti onal i mmedi ate treatment for thi s pati ent?
(A) Int ra-aort ic balloon pump
(B) Met oprolol
(C) Verapamil
(D) Warfarin
Item 21 [Advanced]
A 72-year-old man is evaluat ed in t he emergency depart ment for dyspnea. One week ago, an episode of severe chest pain and dyspnea awoke him from sleep. Over t he next
several days his dyspnea st abilized. On t he morning of admission, t he pat ient not ed a sudden increase in dyspnea. His medical hist ory is significant for hypert ension and
hyperlipidemia. He has no hist ory of heart murmur. He current ly t akes simvast at in, aspirin, and lisinopril.
On physical examinat ion, t he pat ient is sit t ing up wit h labored breat hing. Blood pressure is 86/52 mm Hg, pulse is regular at 110/min, and respirat ion rat e is 24/min. Oxygen
sat urat ion is 92% on 6 L of oxygen. Jugular veins are dist ended t o t he angle of t he jaw while sit t ing upright . Cardiac examinat ion reveals a grade 3/6 holosyst olic murmur at
t he cardiac apex radiat ing t oward t he left axilla. Bibasilar crackles are present .
An elect rocardiogram is shown. A chest radiograph shows pulmonary vascular congest ion.
(A) Acut e mit ral regurgit at ion
(B) Left vent ricular aneurysm
(C) Pulmonary embolism
(D) Vent ricular free wall rupt ure
Item 22 [Advanced]
A 62-year-old woman is brought t o t he emergency depart ment for chest pain t hat has been present for 5 hours. Medical hist ory is not able for t ype 2 diabet es mellit us,
hyperlipidemia, and hypert ension. Medicat ions are glyburide, lisinopril, at orvast at in, and aspirin.
On physical examinat ion, blood pressure is 160/80 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 16/min. Cardiac examinat ion shows no murmurs, ext ra sounds, or rubs.
The lungs are clear. Neurologic examinat ion is normal.
The elect rocardiogram shows 2-mm ST-segment elevat ion in leads II, III, and aVF.
A coronary cat het erizat ion laborat ory is not available, and t he nearest hospit al wit h percut aneous int ervent ion capabilit y is 3 hours away.
Whi ch of the fol l owi ng i s the best management opti on for thi s pati ent?
(A) Aggressive medical t herapy wit hout reperfusion at t empt
(B) Immediat e t hrombolyt ic t herapy
(C) Transfer for coronary art ery bypass graft surgery
(D) Transfer for percut aneous coronary int ervent ion
Item 23 [Basic]
A 65-year-old man is evaluat ed before beginning an exercise program. He is asympt omat ic and his only medical problem is chronic hypert ension t hat is well cont rolled on
hydrochlorot hiazide. He t akes no ot her medicat ions.
On physical examinat ion, blood pressure is 138/76 mm Hg, and pulse is 80/min and regular. Physical examinat ion is normal, except for a soft S
1
. His elect rocardiogram is
shown.
Whi ch of the fol l owi ng best descri bes the el ectrocardi ographi c fi ndi ngs?
(B) Second-degree at riovent ricular block
(C) Third-degree (complet e) at riovent ricular block
(D) Vent ricular preexcit at ion (Wolff-Parkinson-Whit e) syndrome
Item 24 [Advanced]
A 56-year-old man is evaluat ed in t he emergency depart ment for chest discomfort t hat began 3 hours ago. He describes t he pain, which is well localized t o t he left chest , as
pressure. He denies prior episodes. Medical hist ory is not able for t ype 2 diabet es mellit us and hyperlipidemia. Medicat ions are aspirin, met formin, and at orvast at in.
On physical examinat ion, he is diaphoret ic. Blood pressure is 95/60 mm Hg and heart rat e is 110/min. There is jugular venous dist ent ion, wit h an est imat ed cent ral venous
pressure of 14 cm H
2
O. An S
3
is heard on cardiac auscult at ion, but no murmurs are present . The lung fields are clear and t here is no peripheral edema.
The elect rocardiogram shows sinus t achycardia, 2-mm ST-segment elevat ion in leads II, III, and aVF, and 0.5-mm ST-segment elevat ion in lead V
1
. The chest radiograph is
normal.
Whi ch of the fol l owi ng i s the most l i kel y cause of hypotensi on i n thi s pati ent?
(A) Increased vagal t one
(B) Pericardial t amponade
(C) Right vent ricular infarct ion
(D) Vent ricular sept al defect
Item 25 [Basic]
An 85-year-old woman is admit t ed t o t he coronary care unit following successful t hrombolyt ic t herapy for an acut e ant erosept al ST-elevat ion myocardial infarct ion. Blood
pressure is 120/70 mm Hg and heart rat e is 90/min. There is no jugular venous dist ent ion and no cardiac murmurs. The lung fields are clear. Medicat ions st art ed in t he hospit al
are aspirin, low-molecular-weight heparin, int ravenous nit roglycerin, and met oprolol.
On hospit al day 3, t he pat ient experiences acut e onset of respirat ory dist ress and her syst olic blood pressure falls t o 80 mm Hg. Her oxygen sat urat ion remains at 80% despit e
t he administ rat ion of 100% oxygen by face mask. On physical examinat ion, blood pressure is 96/40 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 28/min. Findings
include jugular venous dist ent ion, crackles t hroughout bot h lung fields, and a grade 4/6 syst olic murmur associat ed wit h a t hrill.
(A) Aort ic dissect ion
(B) Pericardial t amponade
Item 26 [Advanced]
A 77-year-old woman is admit t ed t o t he hospit al for int ermit t ent dizziness over t he past few days. She has hypert ension, hyperlipidemia, and paroxysmal at rial fibrillat ion
wit h a hist ory of rapid vent ricular response. Medicat ions are met oprolol, hydrochlorot hiazide, pravast at in, lisinopril, aspirin, and warfarin.
On physical examinat ion, blood pressure is 137/88 mm Hg and pulse is 52/min. Est imat ed cent ral venous pressure is 7 cm H
2
O. Cardiac auscult at ion reveals bradycardia wit h
regular S
1
and S
2
, as well as an S
4
. The lungs are clear t o auscult at ion.
On t elemet ry, she has sinus bradycardia wit h rat es bet ween 40/min and 50/min, wit h t wo sympt omat ic sinus pauses of 3 t o 5 seconds each.
(A) Mobit z I at riovent ricular block
(B) Mobit z II at riovent ricular block
(C) Third-degree at riovent ricular block
(D) Sinoat rial node dysfunct ion
Item 27 [Advanced]
A 70-year-old man is evaluat ed in t he emergency depart ment for bradycardia t hat was det ect ed in t he nursing home and is found t o have second-degree at riovent ricular block.
The pat ient has Alzheimer dement ia. His medicat ions are donepezil (dosage recent ly increased); memant ine (recent ly st art ed); vit amin E; and t razodone for agit at ion.
Whi ch of the pati ent's medi cati ons i s l i kel y to expl ai n the bradycardi a?
(A) Donepezil
(B) Memant ine
(C) Trazodone
(D) Vit amin E
Item 28 [Basic]
A 67-year-old man is brought t o t he emergency depart ment aft er he lost consciousness. His wife report s he had been experiencing palpit at ions and light headedness earlier in
t he day. He has hypert ension, dyslipidemia, and chronic obst ruct ive pulmonary disease. His medicat ions are lisinopril, hydrochlorot hiazide, pravast at in, and a flut icasone-
salmet erol inhaler.
On physical examinat ion, t he pat ient is awake but confused and in respirat ory dist ress. He is afebrile, blood pressure is 80/45 mm Hg, pulse rat e is 167/min, and respirat ion
rat e is 24/min and labored. Oxygen sat urat ion is 86% on ambient air. The cardiac rhyt hm is irregular, and bibasilar crackles are present on pulmonary examinat ion.
An elect rocardiogram shows at rial fibrillat ion.
Whi ch of the fol l owi ng i s the most appropri ate i mmedi ate management for thi s pati ent?
(A) Bedside echocardiography
(B) CT pulmonary angiography
(C) Coronary angiography
(D) Elect rical cardioversion
Item 29 [Basic]
A 62-year-old-woman is evaluat ed for a 6-mont h hist ory of difficult y falling asleep and an unexplained 4.5-kg (10 lb) weight loss. She is act ive and rides her bicycle 5 miles a
day. She does not drink alcohol, smoke cigaret t es, or use recreat ional drugs. She has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, she is afebrile, blood pressure is 125/75 mm Hg, pulse rat e is 108/min, and respirat ion rat e is 14/min. On cardiac examinat ion, a regular rhyt hm
wit hout murmurs or ext ra cardiac sounds is heard. The remainder of t he physical examinat ion is normal.
A met abolic profile and complet e blood count are normal.
An elect rocardiogram shows only sinus t achycardia.
(A) Administ er adenosine int ravenously
(B) Measure serum t hyroid-st imulat ing hormone level (TSH)
(C) Obt ain an exercise st ress t est
(D) Radiofrequency ablat ion of t he sinoat rial node
Item 30 [Advanced]
A 79-year-old man is evaluat ed in t he emergency depart ment for a 1-week hist ory of dyspnea and weakness. He has had several such episodes over t he past 5 years but has
never sought medical at t ent ion. He report s t hat 1 year ago, he had a 10-minut e episode of left arm weakness t hat resolved spont aneously. He was never evaluat ed for t his
problem. He has hypert ension t reat ed wit h lisinopril and hydrochlorot hiazide.
On physical examinat ion, blood pressure is 135/80 mm Hg and heart rat e is 143/min. Ot her t han a rapid heart rat e, t he cardiopulmonary examinat ion is normal, as is t he
remainder of t he physical examinat ion.
Elect rocardiogram shows at rial fibrillat ion wit h a rapid vent ricular rat e wit hout evidence of ischemic changes. Cardiac enzyme values are normal. Following t he administ rat ion
of met oprolol, he convert s t o sinus rhyt hm, wit h a heart rat e of 74/min.
Whi ch of the fol l owi ng i s the most appropri ate l ong-term treatment for thi s pati ent?
(A) Amiodarone
(B) Low-molecular-weight heparin followed by warfarin
(C) Met oprolol
(D) Met oprolol and warfarin
Item 31 [Basic]
A 28-year-old man is evaluat ed for a pre-employment physical examinat ion and elect rocardiogram before ent ering t he police academy. He has no medical problems, describes
no worrisome sympt oms, and does not t ake any medicat ions. He does not smoke cigaret t es, has one alcoholic drink or less each week, and rarely consumes caffeine. He runs
4 miles a day 3 days a week and bikes 25 t o 50 miles on t he weekends. His parent s are bot h alive and in good healt h as are his t wo older brot hers.
On physical examinat ion, vit al signs are normal. The cardiopulmonary examinat ion is normal as is t he remainder of t he examinat ion.
The rest ing 12-lead elect rocardiogram shows 3 unifocal premat ure vent ricular cont ract ions.
Whi ch of the fol l owi ng i s the best management pl an for thi s pati ent?
(A) Begin amiodarone
(B) Begin met oprolol
(C) Exercise st ress t est
(D) No furt her invest igat ion or t herapy
(E) Order 24-hour ambulat ory elect rocardiography
Item 32 [Advanced]
A 55-year-old man is evaluat ed for fat igue, dyspnea wit h modest exert ion, occasional light headedness, and palpit at ions. He has a hist ory of ischemic cardiomyopat hy
following a large ant erolat eral myocardial infarct ion 6 weeks ago. He does not have chest pain, and a post discharge adenosine st ress t est wit h nuclear imaging demonst rat ed
no inducible ischemia. His medicat ions are lisinopril, carvedilol, furosemide, spironolact one, digoxin, and aspirin.
On physical examinat ion, he is afebrile, blood pressure is 130/83 mm Hg, pulse rat e is 50/min, and respirat ion rat e is 12/min. He has no jugular venous dist ension. S
1
and S
2
are soft , and S
3
and S
4
are present . A grade 2/6 holosyst olic murmur at t he cardiac apex is present . The lungs are clear. No peripheral edema is not ed.
An elect rocardiogram shows an episode of nonsust ained vent ricular t achycardia. Echocardiography shows diminished ant erior wall mot ion wit h an eject ion fract ion of 25%.
Whi ch of the fol l owi ng i s the most appropri ate treatment for thi s pati ent?
(A) Amiodarone
(B) Flecainide
(C) Procainamide
(D) Implant able cardiovert er-defibrillat or (ICD)
Item 33 [Advanced]
A 67-year-old man present ed t o t he emergency depart ment 2 days ago wit h an acut e ST-elevat ion myocardial infarct ion. During t he init ial evaluat ion, he became
unresponsive due t o vent ricular fibrillat ion. He was successfully resuscit at ed and t aken t o t he cardiac cat het erizat ion lab, where a 100% occlusion of his proximal left ant erior
descending art ery was st ent ed. His post infarct ion course was not able for mild heart failure, which has now resolved. He is now st able on aspirin, met oprolol, at orvast at in,
clopidogrel, and lisinopril.
On physical examinat ion, blood pressure is 115/72 mm Hg, pulse is 65/min, and respirat ion rat e is 12/min. There is no jugular venous dist ent ion, crackles, murmur, or S
3
. The
elect rocardiogram shows ST-segment changes consist ent wit h a resolving ant erior myocardial infarct ion but is ot herwise unremarkable. Transt horacic echocardiogram reveals
mild hypokinesis of t he ant erior wall and a left vent ricular eject ion fract ion of 42%.
Whi ch of the fol l owi ng i s the best management opti on at thi s ti me?
(A) Add amiodarone
(B) Cont inue medical management
(C) Implant able cardiovert er-defibrillat or placement
(D) Pacemaker placement
Item 34 [Advanced]
An 18-year-old woman is evaluat ed for recurrent syncope. She has experienced four syncopal episodes in her lifet ime, all of which occurred during act ivit y. Episodes have no
prodrome, and she has had no dizziness. She is healt hy and act ive, wit hout cardiopulmonary complaint s, and t akes no medicat ions. Her mat ernal cousin drowned at age 10
years, and her mot her has been evaluat ed for recurrent episodes of loss of consciousness.
On physical examinat ion, blood pressure is 112/65 mm Hg, and pulse is 67/min and regular. The cardiopulmonary and general physical examinat ions are normal. An
echocardiogram examinat ion is normal. An elect rocardiogram is ordered.
Whi ch of the fol l owi ng el ectrocardi ographi c fi ndi ngs i s most l i kel y to provi de a di agnosi s?
(A) Left bundle branch block
(B) Long PR int erval
(C) Long QT int erval
(D) Right bundle branch block
Item 35 [Basic]
A 50-year-man wit h a 6-mont h hist ory of New York Heart Associat ion class IV heart failure secondary t o idiopat hic dilat ed cardiomyopat hy is evaluat ed following a recent
hospit alizat ion for worsening heart failure sympt oms. The pat ient is adherent t o his medicat ions and his fluid and sodium rest rict ions. His medicat ions are lisinopril,
carvedilol, spironolact one, and furosemide.
On physical examinat ion, vit al signs are normal. He has no jugular venous dist ent ion. The cardiac rhyt hm is regular. Cardiac auscult at ion reveals an S3 and holosyst olic
murmur at t he cardiac apex. The chest is clear, and no peripheral edema is not ed.
In t he hospit al, no evidence of ischemia, infect ion, arrhyt hmia, or t hyroid disease was present . An echocardiogram demonst rat ed global hypokinesis of t he left vent ricle,
moderat e mit ral regurgit at ion, and an eject ion fract ion of 25%
Whi ch of the fol l owi ng medi cati ons shoul d be i ni ti ated for thi s pati ent?
(A) Digoxin
(B) Met olazone
(C) Valsart an
(D) Warfarin
Item 36 [Basic]
A 35-year-old woman is evaluat ed for progressive dyspnea 3 weeks aft er delivery of her first child. The pregnancy and delivery were uncomplicat ed. She has no hist ory of
cardiovascular disease.
On physical examinat ion, blood pressure is 110/70 mm Hg in bot h arms, heart rat e is 105/min and regular, and respirat ory rat e is 28/min. The est imat ed cent ral venous
pressure is 10 cm H
2
O and t here are no carot id bruit s. The apical impulse is displaced and diffuse. There is a grade 2/6 holosyst olic murmur at t he apex. Third and fourt h heart
sounds are present . There is dullness t o percussion at t he post erior lung bases bilat erally, and t here are crackles ext ending up half of t he lung fields. Lower ext remit y pulses are
normal and wit hout delay. Pedal edema is present .
The elect rocardiogram demonst rat es sinus t achycardia. There are no ST-segment or T-wave changes. The chest radiograph demonst rat es bilat eral pleural effusions and
int erst it ial infilt rat es. The aort ic cont our is unremarkable.
Whi ch of the fol l owi ng i s the most l i kel y cause of the pati ent's current symptoms?
(B) Aort ic dissect ion
(C) Coarct at ion of t he aort a
(D) Heart failure
Item 37 [Advanced]
A 65-year-old man is evaluat ed for 2 mont hs of cent ral chest pain wit h exert ion and relief wit h rest , exert ional dyspnea, ort hopnea, and lower-ext remit y edema. The chest
discomfort is increasing in frequency and severit y. He has a 25-year hist ory of hypert ension and a 44-year hist ory of smoking. His only medicat ion is hydrochlorot hiazide.
On physical examinat ion, blood pressure is 118/80 mm Hg, pulse is 95/min, and respirat ion rat e is 16/min. There is jugular venous dist ent ion. Cardiac examinat ion reveals a
regular rhyt hm. S
1
and S
2
are normal, and an S
3
and S
4
are present . Crackles are heard at bot h lung bases. There is edema at t he ankles. Laborat ory st udies show a normal
serum t roponin T level. Elect rocardiogram is normal. Echocardiogram shows an eject ion fract ion of 40%, global hypokinesis, and left vent ricular hypert rophy.
Whi ch of the fol l owi ng i s the most appropri ate di agnosti c test?
(A) Cardiac angiography
(B) Nuclear medicine st ress t est
(C) Radionuclide vent riculography
(D) St andard exercise st ress t est
Item 38 [Basic]
A 40-year-old woman is evaluat ed for 2 mont hs of progressive dyspnea on exert ion, ort hopnea, and lower ext remit y edema. She denies chest discomfort and has no ot her
medical problems and t akes no medicat ions. She does not smoke cigaret t es and rarely drinks alcohol. There is no family hist ory of heart disease.
On physical examinat ion, she is afebrile. Blood pressure is 120/80 mm Hg and pulse is 80/min. Est imat ed cent ral venous pressure is 10 cm H
2
O. The lungs are clear. Cardiac
examinat ion reveals a regular rhyt hm, an S
3
, and no murmurs. There is ankle edema. Chest radiograph shows vascular congest ion. Elect rocardiogram is normal. Init ial
laborat ory evaluat ion reveals a normal hemoglobin level and met abolic profile, including t hyroid st udies.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al di agnosti c test?
(A) B-t ype nat riuret ic pept ide level
(B) Echocardiography
(C) Radionuclide vent riculography
(D) St ress t est
Item 39 [Basic]
A 70-year-old woman is evaluat ed for a 1-mont h hist ory of dyspnea on exert ion and fat igue. She can st ill perform act ivit ies of daily living, including vacuuming, grocery
shopping, and ascending t wo flight s of st airs carrying laundry. She has a hist ory of hypert ension. Her medicat ions are lisinopril and hydrochlorot hiazide.
On physical examinat ion, blood pressure is 110/80 mm Hg and pulse is 70/min. Jugular veins are not dist ended. S
1
and S
2
are normal, and t here is no S
3
or murmur. The
pulmonary examinat ion is normal and t here is no edema. Laborat ory st udies show normal hemoglobin and t hyroid-st imulat ing hormone levels. Elect rocardiogram shows low
volt age and left axis deviat ion. Echocardiogram shows a left vent ricular eject ion fract ion of 45% and global hypokinesis. Chest radiograph is normal.
Whi ch of the fol l owi ng i s the most appropri ate addi ti onal treatment?
(A) Amlodipine
(B) Carvedilol
(C) Digoxin
(D) Losart an
(E) Spironolact one
Item 40 [Basic]
A 60-year-old woman is diagnosed wit h heart failure due t o nonischemic cardiomyopat hy. Her eject ion fract ion is 40%. She current ly has mild short ness of breat h wit h
moderat e exert ion but no ort hopnea or light headedness. She has a hist ory of hypert ension t reat ed wit h hydrochlorot hiazide and met oprolol.
On physical examinat ion, she is afebrile. Blood pressure is 120/80 mm Hg and pulse is 65/min. The jugular veins are not dist ended, and t he lungs are clear. Cardiac
examinat ion discloses a regular rat e and rhyt hm wit h no S
3
or murmurs. There is no edema.
Whi ch of the fol l owi ng agents shoul d be added to her regi men?
(A) Digoxin
(B) Eplerenone
(C) Hydralazine and a nit rat e
(D) Lisinopril
Item 41 [Basic]
A 60-year-old woman is evaluat ed for dyspnea wit h mild act ivit y (ascending less t han one flight of st airs, walking less t han one block on level ground) t hat has been st able for
t he past year. She has a hist ory of nonischemic cardiomyopat hy (most recent left vent ricular eject ion fract ion, 20%). Her current medicat ions are lisinopril, carvedilol,
digoxin, and furosemide. She had an implant able cardiovert er-defibrillat or placed 1 year ago.
On physical examinat ion, blood pressure is 115/75 mm Hg and pulse rat e is 70/min. Jugular veins are not dist ended, and t he lungs are clear. Cardiac examinat ion discloses a
regular rhyt hm, no murmurs, normal S
1
and S
2
, and no S
3
. There is no edema. Laborat ory st udies show normal serum creat inine and pot assium levels.
Whi ch of the fol l owi ng i s the most appropri ate addi ti on to thi s pati ent's treatment?
(A) Losart an
(B) Met olazone
(C) Nifedipine
(D) Spironolact one
Item 42 [Basic]
An 81-year-old woman wit h aort ic st enosis is evaluat ed for increased short ness of breat h and exercise int olerance. She was asympt omat ic unt il 2 weeks ago when she not ed
increased short ness of breat h wit h exert ion. She report s no chest pain, ort hopnea, paroxysmal noct urnal dyspnea, or palpit at ions. She has had no fever, chills, or recent
procedures t hat might increase t he risk for infect ive endocardit is. She has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, she is afebrile, blood pressure is 116/72 mm Hg, pulse rat e is irregularly irregular at 112/min, and respirat ion rat e is 12/min. No jugular venous
dist ent ion is present . Cardiac auscult at ion reveals an irregular rhyt hm wit h a grade 3/6 crescendo-decrescendo syst olic murmur loudest at t he second left int ercost al space wit h
radiat ion t o t he carot id art eries. Bibasilar pulmonary crackles are present , as is 1+ bilat eral lower ext remit y edema.
Whi ch of the fol l owi ng i s most l i kel y responsi bl e for the new symptoms?
(B) Infect ive endocardit is
(C) Development of mit ral st enosis
(D) Development of mit ral regurgit at ion
Item 43 [Basic]
A 54-year-old man is evaluat ed for increased short ness of breat h of 3 weeks' durat ion. He has dyspnea on exert ion, ort hopnea, and occasional paroxysmal noct urnal dyspnea.
He report s no chest pain, fever, or chills. He had an aort ic bioprost het ic valve replacement for bicuspid valve aort ic st enosis 15 years ago. He t akes no medicat ions.
On physical examinat ion, he is afebrile, blood pressure is 140/50 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 14/min. The carot id pulse is hyperdynamic. The S
2
is
diminished. Cardiac auscult at ion reveals a grade 2/6 diast olic murmur, heard loudest at t he t hird left int ercost al space. A few scat t ered crackles can be heard at t he lung bases.
No peripheral edema is present .
(A) Aort ic regurgit at ion
(B) At rial sept al defect
(C) Coarct at ion of t he aort a
(D) Mit ral st enosis
(E) Vent ricular sept al defect
Item 44 [Basic]
A 65-year-old woman is evaluat ed as a new pat ient during a rout ine office visit . She is healt hy and act ive and swims laps t hree or four t imes per week. She does not smoke and
she t akes no medicat ions.
On physical examinat ion, blood pressure is 118/60 mm Hg. There are no carot id bruit s. There is a normal S
1
and a physiologically split S
2
. There is a grade 2/6 midsyst olic
murmur t hat does not radiat e and is heard best at t he second right int ercost al space. The rest of t he physical examinat ion is unrevealing.
Whi ch of the fol l owi ng i s the most appropri ate management?
(A) Ant ibiot ic endocardit is prophylaxis
(B) Transt horacic echocardiography
(C) Treadmill st ress echocardiography
(D) No furt her int ervent ion
Item 45 [Advanced]
A 30-year-old woman is evaluat ed in t he emergency depart ment for short ness of breat h, palpit at ions, and pedal edema. She is gravida 1, para 0, and she is 30 weeks pregnant .
She has not received prenat al care unt il t his point .
On physical examinat ion, t he pat ient is sit t ing upright t o breat he. Blood pressure is 112/80 mm Hg, and pulse is 96/min. There is jugular venous dist ent ion t o her jaw line
while sit t ing upright . Cardiac auscult at ion demonst rat es an irregularly irregular rhyt hm, a loud P
2
, and an opening snap followed by a low-pit ched diast olic murmur heard best
at t he cardiac apex. Bibasilar crackles are present .
(A) Acut e aort ic regurgit at ion
(C) Mit ral st enosis
(D) Tricuspid regurgit at ion
Item 46 [Advanced]
An 18-year-old woman is evaluat ed during a rout ine examinat ion prior t o ent ering college. She has had no major medical problems and t here is no family hist ory of
cardiovascular disease.
On physical examinat ion, blood pressure is 110/60 mm Hg and pulse is 70/min. S
1
and S
2
are normal and t here is an S
4
present . There is a harsh grade 2/6 midsyst olic murmur
heard best at t he lower left st ernal border. The murmur does not radiat e t o t he carot id art eries. A Valsalva maneuver increases t he int ensit y of t he murmur; moving from a
st anding posit ion t o a squat t ing posit ion decreases t he int ensit y. Rapid upst rokes of t he carot id pulses are present . Blood pressures in t he upper and lower ext remit ies are
equal.
(A) Aort ic coarct at ion
(B) Bicuspid aort ic valve
(C) Hypert rophic cardiomyopat hy
Item 47 [Basic]
A 25-year-old asympt omat ic man is evaluat ed during a rout ine examinat ion. His blood pressure is 150/40 mm Hg and his heart rat e is 90/min. Est imat ed cent ral venous
pressure is normal. The carot id upst roke is brisk and collapses quickly. The apical impulse is displaced. A grade 3/6 high-pit ched decrescendo diast olic murmur is heard at t he
second right int ercost al space wit h radiat ion down t he left st ernal border. The murmur is heard best wit h t he pat ient leaning forward and in end-expirat ion. There is evidence
of nailbed pulsat ion. Femoral pulsat ions are full and collapse quickly. There is no change in t he murmur wit h inspirat ion.
(A) Aort ic valve regurgit at ion
(B) Mit ral valve st enosis
(C) Pat ent duct us art eriosus
(D) Tricuspid regurgit at ion
Item 48 [Basic]
A 35-year-old woman is evaluat ed during a rout ine examinat ion. She has no cardiovascular risk fact ors and no family hist ory of cardiovascular disease. She is not current ly on
any medicat ions.
On physical examinat ion, vit al signs are normal. There is a midsyst olic click and a grade 2/6 lat e syst olic murmur at t he cardiac apex t hat radiat es t oward t he left axilla.
Following squat -t o-st and maneuvers, t he midsyst olic click moves closer t o t he S
1
, and murmur durat ion and int ensit y are increased. Carot id upst rokes are normal. The rest of
t he examinat ion is unremarkable.
(A) Aort ic st enosis
(B) Coarct at ion of t he aort a
(C) Hypert rophic cardiomyopat hy
(D) Mit ral valve prolapse
Item 49 [Advanced]
A 43-year-old man is evaluat ed during a rout ine examinat ion. He has a hist ory of a cardiac murmur diagnosed during childhood. He exercises regularly wit hout rest rict ion t o
act ivit y and has no hist ory of syncope, palpit at ions, or edema. He t akes no medicat ions.
On physical examinat ion, blood pressure is 120/64 mm Hg, pulse is 80/min and regular, and respirat ion rat e is 16/min. Cardiac examinat ion reveals a normal S
1
and a
physiologically split S
2
. There is a grade 2/6 decrescendo diast olic murmur at t he upper left st ernal border. Dist al pulses are brisk. There is no pedal edema.
A t ranst horacic echocardiogram demonst rat es normal vent ricular size and funct ion, wit h eject ion fract ion of 60% t o 65%. There is a bicuspid aort ic valve wit h moderat e
regurgit at ion. Pulmonary pressure est imat es are in t he normal range.
Whi ch of the fol l owi ng i s the most appropri ate management opti on for thi s pati ent?
(A) Ant ibiot ic endocardit is prophylaxis
(B) Aort ic valve replacement
(C) Begin met oprolol
(D) Clinical follow-up in 1 year
Answers and Cri ti ques
Item 1 Answer: B
Educati onal Objecti ve: Diagnose non-ST-elevation myocardial infarction.
The most likely diagnosis is a non-ST-elevat ion myocardial infarct ion (NSTEMI). This pat ient has had chest pain at rest , an elevat ed serum t roponin I level, and an
elect rocardiogram t hat shows ST-segment depression t hat is part icularly prominent in leads V
2
t hrough V
6
. These feat ures indicat e a NSTEMI.
In an acut e coronary syndrome, obst ruct ion t o coronary blood flow result s in eit her t ransient or prolonged episodes of severe myocardial ischemia. ST-elevat ion myocardial
infarct ion (STEMI) is diagnosed in pat ient s wit h a clinical present at ion consist ent wit h acut e myocardial infarct ion t oget her wit h elect rocardiographic evidence of ST-
segment elevat ion. Alt hough most pat ient s wit h STEMI ult imat ely develop Q waves on elect rocardiogram, some exhibit diagnost ic ST-segment elevat ion and cardiac enzyme
elevat ions wit hout Q waves.
Pat ient s who present wit h ischemic chest pain but wit hout diagnost ic ST-segment elevat ion are cat egorized as having unst able angina or NSTEMI. These t wo condit ions are
closely relat ed and have similar pat hophysiology and clinical present at ions, but t hey differ in t he severit y of t he myocardial ischemia. Pat ient s wit h eit her condit ion t ypically
present wit h angina at rest ; however, some pat ient s describe a pat t ern of new-onset or increasing angina. In NSTEMI, ischemia is severe and result s in a det ect able release of
biomarkers of myocardial injury hours aft er t he onset of ischemic chest pain, most commonly cardiac t roponin I, t roponin T, and t he MB isoenzyme of creat ine kinase. In
unst able angina, t here is no det ect able increase in t hese enzymes.
Chronic st able angina refers t o a coronary art ery syndrome t hat is charact erized by chest discomfort t hat occurs predict ably and reproducibly at a cert ain level of exert ion
and is relieved wit h rest or nit roglycerin. Ischemic pain t hat occurs wit h rest is not compat ible wit h t he diagnosis of chronic st able angina, and t he presence of posit ive serum
biomarkers for myocardial necrosis also excludes t his diagnosis.
Key Poi nt
Non-ST-elevat ion myocardial infarct ion is charact erized by chest pain at rest , absence of ST-elevat ion on t he elect rocardiogram, and elevat ed biomarkers of myocardial
injury.
Bi bl i ography
Hillis LD, Lange RA. Opt imal management of acut e coronary syndromes. N Engl J Med. 2009;360(21):2237-2240. [PMID: 19458369]
Item 2 Answer: B
Educati onal Objecti ve: Diagnose acute pericarditis
The most likely diagnosis is acut e pericardit is. Chest pain from acut e pericardit is is sharp and pleurit ic and worsened by assuming a supine posit ion. Acut e pericardit is is
diagnosed by t he presence of at least t wo of t he t hree classic feat ures: (1) pleurit ic chest pain; (2) frict ion rub; and (3) diffuse concordant ST-segment elevat ion on
elect rocardiography, oft en wit h depression of t he PR segment . The classic pericardial frict ion rub has t hree component s (not all component s may be heard) relat ed t o cardiac
mot ion and occurs during at rial syst ole, vent ricular cont ract ion, and rapid vent ricular filling. The sound of t he rub can be squeaky, scrat chy, and high-pit ched.
Pat ient s wit h an acut e aort ic dissect ion present wit h t he abrupt onset of severe pain in t he t horax. Blood pressure is variable. Pain described as "ripping" or "t earing" occurs in
only about 50% of pat ient s. The physical finding of a pulse deficit is uncommon. At least one t hird of pat ient s have no elect rocardiographic abnormalit y, and at least 40% of
pat ient s lack widening of t he mediast inum on plain chest radiograph. However, pleurit ic chest pain, pericardial frict ion rub, and diffuse ST elevat ions are not compat ible wit h
aort ic dissect ion.
The pain of an acut e myocardial infarct ion is usually ret rost ernal in locat ion, may radiat e t o t he shoulders or arms, and may be associat ed wit h nausea and vomit ing,
diaphoresis, or short ness of breat h. Alt hough t he init ial elect rocardiogram is nondiagnost ic in up t o 50% of pat ient s, compat ible changes would include focal ST elevat ions
wit h reciprocal ST depression associat ed wit h elevat ion of cardiac biomarkers such as t roponin.
Pat ient s wit h pulmonary embolism may present wit h t he classic sympt oms of dyspnea, chest pain, hemopt ysis, or syncope, but t he present at ion is oft en more subt le. At
t imes, only nonspecific respirat ory or hemodynamic manifest at ions may occur. Pulmonary embolism is not associat ed wit h a pericardial frict ion rub or diffuse ST-segment
changes.
Key Poi nt
Diagnosis of acut e pericardit is is made by t he presence of at least t wo of t he t hree classic feat ures: (1) pleurit ic chest pain; (2) frict ion rub; and (3) diffuse concordant ST-
segment elevat ion on elect rocardiography.
Bi bl i ography
Lee TH, Goldman L. Evaluat ion of t he pat ient wit h acut e chest pain. N Engl J Med. 2000;20;342(16):1187-95. [PMID: 10770985]
Item 3 Answer: C
Educati onal Objecti ve: Treat a patient with ST-elevation myocardial infarction with percutaneous coronary intervention.
The best management for t his pat ient is percut aneous coronary int ervent ion (PCI). This pat ient is present ing wit h an ST-elevat ion inferior wall myocardial infarct ion
(STEMI). The diagnosis is based upon t he presence of chest pain, elevat ed cardiac biomarkers, and ST-segment elevat ions in t he inferior leads (II, III, and aVF). Reperfusion
st rat egies for STEMI pat ient s include eit her t hrombolyt ic t herapy or PCI. Percut aneous angioplast y and st ent placement is t he preferred t herapy for most pat ient s wit h
STEMI because it is associat ed wit h a lower 30-day mort alit y rat e compared t o t hrombolyt ic t herapy. PCI is also indicat ed in pat ient s wit h a cont raindicat ion t o
t hrombolyt ic t herapy and in pat ient s wit h cardiogenic shock. Cont raindicat ions t o t hrombolyt ic t herapy include prior int racerebral hemorrhage, ischemic st roke wit hin 3
mont hs, suspect ed aort ic dissect ion, or act ive bleeding. PCI is most effect ive if complet ed wit hin 12 hours of t he onset of chest pain; t he earlier t he int ervent ion, t he bet t er
t he out come.
A chest CT can be a useful diagnost ic t ool in pat ient s being evaluat ed for chest pain if t here is a high clinical suspicion for an aort ic dissect ion. This pat ient does not have any
charact erist ics of ascending aort ic dissect ionback pain, unequal blood pressures or pulses, or a widened mediast inum on chest radiograph. Given t hese fact ors, t he possibilit y
of an acut e aort ic dissect ion is ext remely low, and furt her imaging wit h a chest CT would likely furt her delay t reat ment for t he STEMI.
An echocardiogram is occasionally useful in t he management of pat ient s present ing wit h chest pain and a nondiagnost ic elect rocardiogram (ECG). A focal wall mot ion
abnormalit y suggest s a cardiac basis t o t he sympt oms. In t his pat ient present ing wit h a markedly abnormal ECG wit h ST-segment elevat ion and elevat ed cardiac biomarkers,
echocardiography would not add t o t he management .
Key Poi nt
Percut aneous angioplast y and st ent placement is t he preferred t herapy for most pat ient s wit h ST-elevat ion myocardial infarct ion.
Bi bl i ography
Item 4 Answer: C
Educati onal Objecti ve: Diagnose angina pectoris.
Sympt oms of ischemic heart disease are fairly predict able for an individual pat ient , but great het erogeneit y exist s bet ween pat ient s. Pat ient s may have a difficult t ime
describing t he pain and may use words such as discomfort , pressure, or heaviness. Alt hough t he locat ion of t he pain is classically subst ernal, it may be difficult for pat ient s t o
localize t he pain; t hey may indicat e t he ent ire chest or upper abdomen is involved. Sharp pain, well-localized pain, and back pain are infrequent ly associat ed wit h ischemic
heart disease. Ischemic cardiac pain has a predict able relat ion t o exercise and relief wit h rest or nit roglycerin. In some pat ient s, exert ional dyspnea may be t he only
manifest at ion of cardiac ischemia (angina equivalent ). A normal elect rocardiogram at rest does not exclude ischemic heart disease nor does a normal t roponin level.
The pain of acut e pericardit is is oft en pleurit ic, may radiat e t o t he t op of t he shoulder, and is oft en worse when t he pat ient is supine. Fever and a pericardial frict ion rub are
usually evident . Charact erist ic elect rocardiographic changes include diffuse ST elevat ions and PR depression.
The classic present at ion of aort ic dissect ion consist s of sudden-onset severe chest pain radiat ing t o t he back. Ot her findings may include a blood pressure different ial bet ween
t he right and left arms, murmur of aort ic regurgit at ion, and a widened mediast inum on chest x-ray. Aort ic dissect ion should always be considered in t he different ial diagnosis
of acut e chest pain, but t his pat ient 's pain is not consist ent wit h t his diagnosis.
Most pat ient s wit h pept ic ulcer disease do not have pain at diagnosis; ulcers are usually det ect ed during an evaluat ion for pot ent ial ulcer-relat ed complicat ions such as overt or
obscure bleeding. When sympt oms are present , t hey include dyspepsia or a nonspecific, gnawing epigast ric pain. Ot her present at ions include bleeding, perforat ion (somet imes
wit h penet rat ion int o adjacent organs), and gast ric out let obst ruct ion. Finally, discomfort caused by a duodenal ulcer is not t ypically relieved by rest , worsened by exert ion, or
accompanied by short ness of breat h.
Key Poi nt
Ischemic cardiac pain has a predicable relat ion t o exercise and relief wit h rest or nit roglycerin.
Bi bl i ography
Lee TH, Goldman L. Evaluat ion of t he pat ient wit h acut e chest pain. N Engl J Med. 2000;342(16):1187-95. [PMID: 10770985]
Item 5 Answer: D
Educati onal Objecti ve: Treat right ventricular myocardial infarction with normal saline infusion.
Volume expansion wit h normal saline is t he primary support ive t reat ment for t he hemodynamic abnormalit ies of a right vent ricular myocardial infarct ion. The physical
examinat ion findings of hypot ension, clear lung fields, and elevat ed est imat ed cent ral venous pressure represent t he classic t riad of right vent ricular myocardial infarct ion.
However, t he most predict ive finding is ST-segment elevat ion on right -sided elect rocardiographic lead V
4
R. Therefore, all pat ient s wit h an inferior ST-elevat ion myocardial
infarct ion (STEMI) should have a right -sided elect rocardiogram performed at t he t ime of present at ion. This pat ient 's elect rocardiogram shows ST-segment elevat ion in
front al inferior leads II, III, and aVF, and 1-mm ST-segment elevat ion in right -sided precordial lead V
4
R. These findings indicat e inferior and right vent ricular injury in t he
set t ing of an inferior STEMI, likely relat ed t o a right coronary art ery occlusion.
In t he set t ing of right vent ricular myocardial infarct ion, right vent ricular cont ract ilit y is reduced, result ing in higher right vent ricular diast olic pressure, lower right vent ricular
syst olic pressure, and reduced preload or filling of t he left vent ricle. Volume expansion improves t he hemodynamic abnormalit ies of right vent ricular myocardial infarct ion
because t he gradient of pressure from t he right at rium t o t he left at rium maint ains filling of t he left vent ricle. In addit ion t o reperfusion t herapy for STEMI, t he acut e
t reat ment of right vent ricular myocardial infarct ion is support ive.
Inot ropic support , specifically using int ravenous dobut amine, is appropriat e t reat ment in pat ient s wit h right vent ricular myocardial infarct ion whose hypot ension is not
correct ed aft er 1 L of saline infusion. However, volume expansion should be t ried before giving inot ropic agent s. By increasing cardiac cont ract ilit y, inot ropic agent s increase
myocardial oxygen demand and pot ent ially ext end t he infarct ion.
Bradycardia, pot ent ially caused by increased vagal act ivit y or sinoat rial node ischemia, exacerbat es t he hemodynamic abnormalit ies of right vent ricular myocardial infarct ion,
so -blocker t herapy wit h met oprolol is cont raindicat ed in t his pat ient .
Nit roglycerin is cont raindicat ed in pat ient s wit h hypot ension and pat ient s wit h t he pot ent ial for hypot ension, part icularly right vent ricular myocardial infarct ion. In right
vent ricular infarct ion, nit rat e-induced venodilat ion impairs right vent ricular filling and t hereby cardiac out put .
Key Poi nt
Volume expansion is t he primary support ive t reat ment for t he hemodynamic abnormalit ies of a right vent ricular myocardial infarct ion.
Bi bl i ography
Reynolds HR, Hochman JS. Cardiogenic shock: current concept s and improving out comes. Circulat ion. 2008;117(5):686-697. [PMID: 18250279]
Item 6 Answer: D
Educati onal Objecti ve: Manage noncardiac chest pain caused by gastroesophageal reflux disease with an oral proton pump inhibitor.
The most appropriat e management for t his pat ient is empiric t reat ment wit h a prot on pump inhibit or. Esophageal disease is t he most common cause of noncardiac chest
pain. Gast roesophageal reflux disease (GERD) is caused by reflux of gast ric cont ent s int o t he esophagus. Sympt oms of GERD can mimic cardiac ischemia, wit h subst ernal
squeezing or burning t hat may radiat e widely, including t o t he back, neck, jaw, or arms. Chest pain due t o GERD may last minut es t o hours and can resolve spont aneously or
wit h ant acids. Most pat ient s wit h GERD-induced chest pain also have t ypical reflux sympt oms, including regurgit at ion and heart burn. The recommended approach in pat ient s
wit h suspect ed esophageal chest pain is t o rule out cardiac ischemia and t hen t reat t he pat ient empirically wit h a prot on pump inhibit or.
Ambulat ory esophageal pH monit oring can be used if t he pat ient 's condit ion does not respond t o empiric t herapy or if t he pat ient has at ypical sympt oms.
Esophagogast roduodenoscopy is indicat ed in pat ient s wit h long-st anding reflux disease t o screen for Barret t esophagus and in pat ient s wit h such alarm sympt oms as anemia,
weight loss, or dysphagia, but not as t he init ial screening t est for GERD.
This pat ient 's previous normal st ress t est makes cardiac disease very unlikely and a repeat exercise st ress t est or coronary angiography is unlikely t o provide addit ional
diagnost ic informat ion. Because ischemic heart disease has been ruled out , it is reasonable in t his pat ient t o at t empt empiric acid suppression t herapy wit h a prot on pump
inhibit or. A complet e response t o empiric t herapy is considered diagnost ic of GERD.
Key Poi nt
Empiric prot on pump inhibit or t herapy is t he first st ep in t he management of esophageal noncardiac chest pain.
Bi bl i ography
Fass R. Evaluat ion and diagnosis of noncardiac chest pain. Dis Mon. 2008;54(9):627-641. [PMID: 18725005]
Item 7 Answer: D
Educati onal Objecti ve: Diagnose third-degree atrioventricular heart block.
This pat ient most likely has t hird-degree (complet e) at riovent ricular heart block due t o Lyme cardit is. The presence of t he charact erist ic skin rash (eryt hema migrans) wit h
or wit hout a hist ory of t ick bit e in an endemic region, has a probabilit y great er t han 80% of being caused by Borrelia burgdorferi infect ion. Lyme cardit is is manifest ed by
acut e-onset , high-grade at riovent ricular conduct ion defect s t hat may occasionally be associat ed wit h myocardit is.
At riovent ricular block is classified as first , second, or t hird degree. First -degree block is charact erized by prolongat ion of t he PR int erval t o great er t han 0.2 sec and usually is
not associat ed wit h alt erat ions in heart rat e. There are t wo t ypes of second-degree block, bot h recognized elect rocardiographically by t he presence of a P wave t hat is not
followed by a vent ricular complex. Mobit z t ype I block (Wenckebach block) manifest s as progressive prolongat ion of t he PR int erval unt il t here is a dropped beat , whereas
Mobit z t ype II block manifest s as a dropped beat wit hout progressive PR-int erval prolongat ion. Mobit z t ype I block usually does not progress t o complet e heart block, but
Mobit z t ype II block, which is usually associat ed wit h a bundle branch block, t ypically progresses t o t hird-degree block. Second-degree block may be associat ed wit h
bradycardia, depending upon t he frequency of blocked at rial impulses. Third-degree block is t he complet e absence of conduct ion of at rial impulses t o t he vent ricle and is t he
most common cause of marked bradycardia; vent ricular rat es are usually 30-50/min. Pat ient s wit h at riovent ricular block may be asympt omat ic or have severe bradycardia-
relat ed sympt oms (weakness, presyncope, syncope) and vent ricular arrhyt hmias.
Key Poi nt
Third-degree block is t he complet e absence of conduct ion of at rial impulses t o t he vent ricle and is t he most common cause of marked bradycardia.
Bi bl i ography
Barold SS. At riovent ricular block revisit ed. Compr Ther. 2002;28(1):74-78. [PMID: 11894446]
Item 8 Answer: B
Educati onal Objecti ve: Diagnose panic disorder.
This pat ient 's present at ion is charact erist ic of panic disorder. Panic disorder is charact erized by recurrent , unexpect ed panic at t acks t hat feat ure t he abrupt onset of numerous
somat ic sympt oms, such as palpit at ions, sweat ing, t remulousness, dyspnea, chest pain, nausea, dizziness, and numbness. Sympt oms t ypically peak wit hin 10 minut es of onset ,
and at t acks usually last from 15 t o 60 minut es. The most appropriat e t reat ment for panic disorder is cognit ive-behavioral t herapy and a select ive serot onin reupt ake
inhibit or, such as paroxet ine.
Because t he sympt oms of panic disorder are primarily physical, most pat ient s wit h t his disorder present t o t heir primary care physicians or t o emergency depart ment s for
evaluat ion. Pat ient s wit h panic disorder are evaluat ed, on average, by 10 clinicians before t he diagnosis is est ablished. The alarming nat ure of t heir sympt oms prompt s
pat ient s wit h panic disorder t o seek medical at t ent ion; consequent ly, t hey have very high healt h care ut ilizat ion rat es.
The clinical manifest at ions of pheochromocyt omas are variable, wit h hypert ension (episodic or sust ained) observed in more t han 90% of pat ient s. Ot her major sympt oms
include diaphoresis, pallor, palpit at ions, and headaches; t he classic t riad of sudden severe headache, diaphoresis, and palpit at ions is highly suggest ive of pheochromocyt oma.
Ot her manifest at ions include hyperglycemia, weight loss, arrhyt hmias (at rial and vent ricular fibrillat ion), and cat echolamine-induced cardiomyopat hy. The absence of
hypert ension and t he long durat ion of sympt oms make t his diagnosis unlikely.
The diagnosis of acut e coronary syndrome is unlikely in a pat ient wit h recurrent , self-limit ed at t acks and previous normal result s of coronary angiography. The current
nat ure of t he sympt oms and normal physical examinat ion findings are not compat ible wit h t he diagnosis of pneumot horax. Sympt oms t hat resolve aft er 20 minut es or recur
frequent ly over many years are not compat ible wit h t he diagnosis of pulmonary embolism.
Key Poi nt
Panic disorder is charact erized by recurrent , unexpect ed panic at t acks t hat feat ure t he abrupt onset of numerous somat ic sympt oms such as palpit at ions, sweat ing,
t remulousness, dyspnea, chest pain, nausea, dizziness, and numbness.
Bi bl i ography
Culpepper L. Ident ifying and t reat ing panic disorder in primary care. J Clin Psychiat ry. 2004;65(suppl 5):19-23. [PMID: 15078114]
Item 9 Answer: B
Educati onal Objecti ve: Diagnose Mobitz type I second-degree atrioventricular block.
This pat ient has evidence for Mobit z t ype I second-degree at riovent ricular (AV) block. Second-degree heart block is charact erized by int ermit t ent nonconduct ion of P waves
and subsequent "dropped" vent ricular beat s. Second-degree heart block is divided int o t ypes, Mobit z I and Mobit z II. Mobit z t ype I second-degree heart block is charact erized
by progressive prolongat ion of t he PR int erval unt il a dropped beat occurs. Mobit z t ype I block can occur in t he absence of heart disease, including in at hlet es and older
adult s; in pat ient s wit h underlying heart disease, including acut e ischemia; and in pat ient s who are t aking drugs t hat block t he AV node, such as -blockers (met oprolol),
calcium channel blockers, and digoxin. This t ype of heart block is charact erist ically t ransient and usually requires no specific t reat ment ; however, some pat ient s may develop
excessively slow heart rat es and experience sympt oms relat ed t o decreased cerebral or coronary perfusion. If t reat ment is necessary, it begins by ident ifying and correct ing
reversible causes of slowed conduct ion, such as myocardial ischemia, increased vagal t one (for example, from pain or vomit ing), and discont inuat ion of drugs t hat depress AV
conduct ion.
Mobit z t ype II second-degree AV block is charact erized by a regularly dropped beat (for example, a nonconduct ed P wave every second or t hird beat ) wit hout progressive
prolongat ion of t he PR int erval. It is oft en associat ed wit h evidence of addit ional disease in t he conduct ion syst em, such as bundle branch block or bifascicular or t rifascicular
block. Mobit z t ype II second-degree block suddenly and unpredict ably progresses t o complet e heart block and is usually t reat ed wit h a pacemaker.
First -degree AV block is recognized, elect rocardiographically, as a prolongat ion of t he PR int erval t o great er t han 0.2 sec. All P waves are conduct ed. First -degree block
requires no specific t reat ment .
Third-degree AV block, or complet e heart block, refers t o a lack of AV conduct ion, charact erized by lack of conduct ion of all at rial impulses t o t he vent ricles.
Key Poi nt
Mobit z t ype I second-degree at riovent ricular block is charact erized by progressive prolongat ion of t he PR int erval unt il a dropped beat occurs.
Bi bl i ography
Da Cost a D, Brady WJ, Edhouse J. Bradycardias and at riovent ricular conduct ion block. BMJ. 2002;324:535-538. [PMID: 11872557]
Item 10 Answer: D
Educati onal Objecti ve: Treat chronic stable angina with worsening symptoms with increased dosage of a -blocker.
The most appropriat e management at t his point is t o increase t he pat ient 's dose of met oprolol. Medical t herapy for chronic st able coronary art ery disease (CAD) includes
bot h ant ianginal and vascular-prot ect ive agent s. Ant ianginal t herapy includes -blockers, calcium channel blockers, and nit rat es. Vascular-prot ect ive t herapy includes aspirin,
angiot ensin-convert ing enzyme (ACE) inhibit ors, and st at ins. This pat ient is already on a -blocker, aspirin, a st at in, and an ACE inhibit or. Swit ching t o a long-act ing nit rat e
will help relieve his angina sympt oms. However, his rest ing heart rat e of 87/min and high blood pressure suggest a subopt imal dose of -blocker, and t he pat ient 's dosage of
met oprolol should be increased. The -blocker dose should be t it rat ed t o achieve a rest ing heart rat e of approximat ely 55 t o 60/min and approximat ely 75% of t he heart rat e
t hat produces angina wit h exert ion. The pat ient should be reevaluat ed in a few weeks t o assess t he response t o t herapy.
Ranolazine is a novel ant ianginal agent t hat is approved for t he t reat ment of chronic st able angina. It should only be used, however, in addit ion t o baseline t herapy wit h a -
blocker, a calcium channel blocker, and a long-act ing nit rat e. Given t hat t his pat ient was on subopt imal doses of met oprolol and is just being st art ed on a long-act ing nit rat e,
t he addit ion of ranolazine would be premat ure.
Coronary angiography would not be indicat ed at t his t ime because t he pat ient is not receiving maximal medical t herapy. In t he set t ing of cont inued angina despit e maximal
medical t herapy, coronary angiography could be considered.
Exercise t readmill st ress t est ing would not provide useful informat ion in t his set t ing. It would only confirm t he high pret est probabilit y t hat t his pat ient has underlying CAD
as a cause for t he current sympt oms.
Key Poi nt
In t he t reat ment of chronic st able angina, t he -blocker dose should be t it rat ed t o achieve a rest ing heart rat e of approximat ely 55 t o 60/min and approximat ely 75% of t he
heart rat e t hat produces angina wit h exert ion.
Bi bl i ography
Jawad E, Arora R. Chronic st able angina pect oris. Dis Mon. 2008;54(9):671-689. [PMID: 18725007]
Item 11 Answer: A
Educati onal Objecti ve: Diagnose pulmonary embolism with CT pulmonary angiography.
This pat ient 's sympt oms of chest pain and dyspnea in combinat ion wit h t he physical findings of asymmet ric leg edema, elevat ed cent ral venous pressure, t achypnea, and
t achycardia suggest t he possibilit y of pulmonary embolism. The most appropriat e diagnost ic t est t o perform next is CT pulmonary angiography t o look for pulmonary
emboli.
A normal echocardiogram bet ween episodes of chest pain does not rule out unst able angina because wall mot ion ret urns t o normal bet ween ischemic episodes. However, t his
pat ient had no wall mot ion abnormalit ies during her ongoing chest pain, making acut e myocardial ischemia very unlikely. Because an acut e coronary syndrome is highly
unlikely, coronary angiography is not indicat ed as t he next diagnost ic t est .
A rest ing radionuclide perfusion st udy can be helpful in t he diagnosis of coronary ischemia when t he elect rocardiogram is nondiagnost ic but does not provide addit ive
informat ion t o t hat already obt ained by echocardiography.
Transesophageal echocardiography is not sensit ive for det ect ion of pulmonary emboli but may be useful in acut e chest pain if aort ic dissect ion is suspect ed. Ascending aort ic
dissect ion is oft en associat ed wit h acut e aort ic regurgit at ion, myocardial ischemia, cardiac t amponade or hemopericardium, and hemot horax or exsanguinat ion. Considerable
(>20 mm Hg) variat ion in syst olic blood pressure in t he arms may be present . Descending t horacic aort ic aneurysm is more commonly associat ed wit h splanchnic ischemia,
renal insufficiency, lower ext remit y ischemia, or focal neurologic deficit due t o spinal cord ischemia. This woman has no physical findings t o suggest t his diagnosis.
Key Poi nt
Normal wall mot ion on echocardiography during chest pain excludes coronary ischemia or infarct ion.
Bi bl i ography
Chunilal SD, Eikelboom JW, At t ia J, et al. Does t his pat ient have pulmonary embolism? JAMA. 2003;290(21):2849-2858. [PMID: 14657070]
Item 12 Answer: D
Educati onal Objecti ve: Evaluate suspected coronary artery disease using an exercise stress test.
The most appropriat e diagnost ic t est for t his pat ient is an exercise st ress t est . This 68-year-old woman has cardiac risk fact ors of smoking and hypert ension, wit h an
int ermediat e Framingham risk score (18% likelihood of a coronary event in 10 years). (A t ool t o calculat e t he Framingham risk score can be accessed at
www.acponline.org/acp_press/essent ials/calculat or.ht m.) In addit ion, she has at ypical chest pain, so furt her evaluat ion is appropriat e. An exercise st ress t est is recommended
in pat ient s wit h int ermediat e probabilit y of coronary art ery disease wit h a normal baseline elect rocardiogram (ECG) who are able t o exercise because it provides informat ion
about exercise t olerance and hemodynamic response t o exercise.
An adenosine nuclear perfusion st ress t est is cont raindicat ed in pat ient s wit h significant bronchospast ic disease and hence is not t he correct choice for a pat ient wit h ast hma.
Furt hermore, exercise st ress t est ing is preferred over pharmacologic st ress t est ing because of t he addit ional physiologic informat ion on exercise t olerance and t he blood
pressure and heart rat e response t o exercise.
Coronary angiography would only be appropriat e if t he pat ient were present ing wit h an acut e coronary syndrome or aft er an abnormal st ress t est t o det ermine if t here is an
indicat ion for revascularizat ion.
Dobut amine st ress echocardiography is an appropriat e choice in pat ient s who are unable t o exercise and are not hypert ensive at rest . This pat ient is able t o exercise, so
t readmill t est ing is t he more appropriat e choice.
Key Poi nt
Exercise elect rocardiographic st ress t est ing is t he primary approach t o t he diagnosis of coronary art ery disease in pat ient s who can exercise and have a normal rest ing
elect rocardiogram.
Bi bl i ography
Wilson JM. Diagnosis and t reat ment of acquired coronary art ery disease in adult s. Post grad Med J. 2009;85(1005):364-365. [PMID: 19581247]
Item 13 Answer: B
Educati onal Objecti ve: Diagnose atrial flutter.
The most likely diagnosis for t his pat ient is at rial flut t er. The presence on t he elect rocardiogram of mult iple P waves in a "sawt oot h" pat t ern, t ypically wit h 2:1 vent ricular
conduct ion, charact erizes at rial flut t er and eliminat es at rial fibrillat ion as a diagnost ic considerat ion. Elect rocardiographically, at rial fibrillat ion is charact erized by an absence
of discernible P waves, which are replaced by fibrillat ory waves t hat vary in amplit ude, shape, and t iming. The vent ricular response is grossly irregular and oft en rapid, except
when t here is concomit ant at riovent ricular block.
Sinoat rial node dysfunct ion (sick sinus syndrome) is a frequent cause of pacemaker implant at ion. It consist s of sympt omat ic sinus bradycardia and t he t achycardia-bradycardia
syndrome (alt ernat ing at rial t achyarrhyt hmias and bradycardia). In pat ient s wit h "t achy-brady" syndrome, bradycardia usually occurs aft er t erminat ion of t he t achycardia;
at rial fibrillat ion is t he most common t achyarrhyt hmia observed in t his group of pat ient s. The pat ient does not fulfill t he diagnost ic crit eria for sinus node dysfunct ion.
Vent ricular t achycardia is charact erized by wide-complex QRS morphology (QRS >0.12 sec) and a vent ricular rat e t hat is great er t han 100/min. In vent ricular t achycardia, t he
vent ricular rat e t ypically ranges from 140/min t o 250/min. The pat ient does not have a wide-complex t achycardia and, t herefore, does not have vent ricular t achycardia.
Key Poi nt
At rial flut t er is t ypically a narrow-complex t achycardia charact erized by mult iple regular at rial cont ract ions (flut t er waves) creat ing a "sawt oot h" baseline pat t ern prior t o t he
QRS complex.
Bi bl i ography
Sawhney NS, Anousheh R, Chen WC, Feld GK. Diagnosis and management of t ypical at rial flut t er. Cardiol Clin. 2009;27(1):55-67, viii. [PMID: 19111764]
Item 14 Answer: D
Educati onal Objecti ve: Treat chronic stable angina with appropriate medical therapy.
The most appropriat e t reat ment of t his pat ient would be t o cont inue his current medical management . Medical t herapy for chronic coronary art ery disease (CAD) can be
classified as ant ianginal or vascular prot ect ive. Ant ianginal medicat ions include -blockers, calcium channel blockers, nit rat es, and ranolazine. -Blockers reduce mort alit y by
approximat ely 20%. Pat ient s wit h chronic st able angina can be t reat ed wit h calcium channel blockers if t hey are unable t o t olerat e -blockers, or calcium channel blockers
can be added t o -blocker t herapy for difficult -t o-cont rol sympt oms. All pat ient s wit h chronic st able angina should carry eit her a sublingual or a spray form of nit roglycerin
for emergency use. Ranolazine should only be considered in pat ient s who remain sympt omat ic despit e opt imal doses of -blockers, calcium channel blockers, and nit rat es.
Vascular-prot ect ive medicat ions include aspirin, clopidogrel, angiot ensin-convert ing enzyme (ACE) inhibit ors, and st at ins. Aspirin reduces t he risk of st roke, myocardial
infarct ion, sudden deat h, and vascular deat h by 33%. Alt hough clopidogrel is beneficial in pat ient s wit h acut e coronary syndromes, it has small clinical benefit in pat ient s wit h
chronic st able angina and is associat ed wit h an increased risk of bleeding. ACE inhibit ors reduce cardiovascular mort alit y by 17% t o 23%. St at ins reduce fut ure cardiovascular
event s by approximat ely 25% t o 30%. Current guidelines specify an LDL cholest erol t arget level of less t han 100 mg/dL (2.6 mmol/L) for pat ient s wit h coronary art ery
disease. This pat ient is receiving st andard t herapy for chronic st able angina wit h aspirin, -blocker (carvedilol), ACE inhibit or (lisinopril), a st at in (simvast at in), and
nit roglycerin. His blood pressure is well cont rolled, pulse rat e is appropriat ely reduced, and t he lipid profile is at t arget . His sympt oms are infrequent and st able; no change in
his medical t herapy is needed.
Coronary angiography is reserved for pat ient s wit h acut e coronary sympt oms, angina increasing in severit y, markedly abnormal st ress t est s, sudden cardiac deat h, or
diagnost ic difficult ies and is not indicat ed in t his clinically st able pat ient . Because t his pat ient 's sympt oms are well cont rolled wit h t he current t herapy, it is not necessary t o
add ranolazine.
Key Poi nt
Most pat ient s wit h chronic st able angina are t reat ed wit h aspirin, a -blocker, an ACE inhibit or, nit roglycerin, and a st at in.
Bi bl i ography
Pfist erer ME, Zellweger MJ, Gersh BJ. Management of st able coronary art ery disease. Lancet . 2010;375(9716):763-72. [PMID: 20189028]
Item 15 Answer: A
Educati onal Objecti ve: Diagnose atrial fibrillation.
The elect rocardiogram is charact erist ic for at rial fibrillat ion, showing a rapid, irregularly irregular rhyt hm wit h no discernible P waves and at rial fibrillat ory waves at a rat e
bet ween 350 and 600 beat s/min. The fibrillat ory waves vary in amplit ude, morphology, and int ervals, creat ing a rough, irregular baseline bet ween t he QRS complexes. The
pat ient 's evaluat ion should minimally include a t ranst horacic echocardiogram t o exclude occult valve or ot her st ruct ural heart disease and also t o assess t he size of t he left
at rial appendage; in addit ion, t hyroid st udies should be performed t o exclude hypert hyroidism.
At rial flut t er is recognized by it s saw-t oot h pat t ern of flut t er waves, most not iceable in t he inferior leads II, III, and aVF; flut t er waves are dist inct ly different from t he small,
chaot ic fibrillat ion waves t hat are charact erist ic of at rial fibrillat ion.
Sinus t achycardia is a regular rhyt hm associat ed wit h P waves prior t o each QRS complex. In each lead, t he P-wave morphology and PR int erval remain const ant in shape and
durat ion. The absence of well-defined P waves in t his elect rocardiogram rules out sinus t achycardia.
Vent ricular t achycardia is charact erized by wide-complex QRS morphology (QRS >0.12 sec) and a vent ricular rat e ranging from 140-250/min. This pat ient 's QRS complexes
are narrow, excluding vent ricular t achycardia as a diagnosis.
Key Poi nt
At rial fibrillat ion is charact erized elect rocardiographically by an irregularly irregular rhyt hm wit h no discernible P waves and at rial fibrillat ion waves creat ing an irregular
baseline.
Bi bl i ography
Zimet baum P. At rial fibrillat ion. Ann Int ern Med. 2010;153(11):ITC61. [PMID: 21135291]
Item 16 Answer: E
Educati onal Objecti ve: Avoid screening for asymptomatic coronary artery disease.
No addit ional t est ing for coronary art ery disease (CAD) is t he best management opt ion for t his pat ient . He is at low risk for CAD, and he is asympt omat ic. In addit ion, he
only has a 4% probabilit y of a major coronary event over t he next 10 years (www.acponline.org/acp_press/essent ials/calculat or.ht m). The American College of
Cardiology/American Heart Associat ion, American College of Physicians, and U.S. Prevent ive Services Task Force all agree t hat t here is lit t le evidence t o support rout ine
t est ing for CAD in adult s who are low risk and asympt omat ic. Screening for CAD in adult s who are asympt omat ic is not recommended because t he probabilit y of a false-
posit ive t est is much great er t han t he probabilit y of a t rue posit ive t est . For pat ient s wit h an int ermediat e probabilit y of CAD, noninvasive st ress t est ing wit h an exercise
st ress t est provides t he most useful informat ion.
Coronary angiography should be reserved for pat ient s wit h chronic CAD who have lifest yle-limit ing angina despit e medical t herapy, markedly posit ive result s on noninvasive
st ress t est ing, successful resuscit at ion from sudden cardiac deat h, or document ed vent ricular t achycardia. Coronary angiography can also be considered in pat ient s wit h
nonspecific chest pain t o complet ely exclude CAD as a cause for t he current sympt oms if t hey have had recurrent hospit alizat ions. Coronary calcium t est ing may be
considered in asympt omat ic persons wit h a 10% t o 20% Framingham 10-year risk cat egory (int ermediat e risk) and in young persons wit h a st rong family hist ory of
premat ure cardiovascular disease. The diagnost ic accuracy of CT angiography t o det ect obst ruct ive CAD is approximat ely 90%. Because CT angiography provides no
funct ional informat ion (t hat is, t he ext ent of ischemia), a markedly abnormal st udy is followed by referral t o coronary angiography or st ress t est ing t o det ermine t he
ischemic burden. Recent consensus guidelines suggest t hat t he benefit s of CT angiography are great est in sympt omat ic pat ient s wit h an int ermediat e pret est probabilit y of
CAD.
Key Poi nt
There is lit t le evidence t o support rout ine t est ing for coronary art ery disease in adult s who are low risk and asympt omat ic.
Bi bl i ography
Snow V, Barry P, Fihn SD, Gibbons RJ, Owens DK, Williams SV, Weiss KB, Mot t ur-Pilson C; ACP; ACC Chronic St able Angina Panel. Evaluat ion of primary care pat ient s
wit h chronic st able angina: guidelines from t he American College of Physicians. Ann Int ern Med. 2004;141 (1):57-64. [PMID: 15238371]
Item 17 Answer: C
Educati onal Objecti ve: Diagnose atrioventricular reentrant tachycardia (Wolff-Parkinson-White syndrome).
The most likely diagnosis is at riovent ricular reent rant t achycardia. The pat ient present s wit h a hist ory of t achycardia and recent syncope. The elect rocardiogram shows a
short PR int erval and t he presence of a delt a wave, which signifies preexcit at ion. These feat ures, t oget her wit h t achycardia, make t he diagnosis of Wolff-Parkinson-Whit e
syndrome, a t ype of at riovent ricular reent rant t achycardia.
There are no clinical feat ures t o suggest idiovent ricular t achycardia or slow vent ricular t achycardia, which is demonst rat ed elect rocardiographically as a wide QRS complex
and a heart rat e bet ween 60/min and 100/min. At rial flut t er is recognized by t he charact erist ic negat ive sawt oot h deflect ions in ECG leads II, III, and aVF, wit h a posit ive
deflect ion in V
1
, findings t hat are not present in t his pat ient 's elect rocardiogram. Mult ifocal at rial t achycardia charact erist ically occurs in t he set t ing of chronic lung disease
and is manifest ed by t hree or more P-wave configurat ions on t he elect rocardiogram wit h associat ed t achycardia.
Key Poi nt
The combinat ion of a short PR int erval and a delt a wave plus t achycardia confirms t he diagnosis of Wolff-Parkinson-Whit e syndrome, a t ype of at riovent ricular t achycardia.
Bi bl i ography
Lee KW, Badhwar N, Scheinman MM. Supravent ricular t achycardia-part I. Curr Probl Cardiol. 2008;33(9):467-546. [PMID: 18707990]
Item 18 Answer: A
Educati onal Objecti ve: Evaluate progressive chronic angina pectoris with coronary angiography.
Coronary angiography is t he most appropriat e opt ion in t his pat ient wit h cont inued anginal sympt oms despit e opt imal medical t herapy. Compared wit h opt imal medical
t herapy, a st rat egy of coronary angiography and revascularizat ion provides no benefit in pat ient s wit h chronic st able angina. This pat ient , however, remains highly
sympt omat ic despit e opt imal medical t herapy, and t herefore may benefit from coronary angiography and revascularizat ion. Coronary revascularizat ion is beneficial in
pat ient s wit h chronic st able angina and t he following condit ions: angina pect oris refract ory t o medical t herapy; a large area of ischemic myocardium and high-risk crit eria on
st ress t est ing; high-risk coronary anat omy, including left main coronary art ery st enosis or t hree-vessel disease; and significant coronary art ery disease wit h reduced left
vent ricular syst olic funct ion. In appropriat ely select ed pat ient s, revascularizat ion, eit her a percut aneous coronary int ervent ion or coronary art ery bypass graft ing surgery, has
been shown t o reduce angina, increase longevit y, and improve left vent ricular performance.
Exercise t readmill st ress t est ing would not be useful for t his pat ient 's management as it would only confirm t he known diagnosis of coronary art ery disease. Result s of an
exercise st ress t est would not influence t herapeut ic decisions.
-Blockers, such as met oprolol, reduce myocardial oxygen demand by reducing heart rat e and cont ract ilit y, t hereby reducing myocardial oxygen consumpt ion. However, t his
pat ient 's heart rat e is already reduced t o 48/min and his blood pressure is under excellent cont rol. Increasing t he dose of met oprolol in t hese circumst ances is unlikely t o
produce furt her benefit and may not be t olerat ed because of unaccept ably low pulse rat e and blood pressure.
For pat ient s wit h unst able angina, admission t o t he coronary care unit and int ravenous heparin and nit roglycerin would be beneficial. This pat ient has chronic st able angina,
charact erized by progressive exert ional angina for 2 mont hs wit hout episodes of pain while at rest or prolonged episodes of pain.
Key Poi nt
Coronary angiography is indicat ed in pat ient s wit h chronic st able angina who experience lifest yle-limit ing angina despit e opt imal medical t herapy.
Bi bl i ography
Jawad E, Arora R. Chronic st able angina pect oris. Dis Mon. 2008;54(9):671-689. [PMID: 18725007]
Item 19 Answer: D
Educati onal Objecti ve: Diagnose ventricular tachycardia.
The most likely diagnosis is vent ricular t achycardia. The elect rocardiogram demonst rat es sinus rhyt hm t hat is suddenly int errupt ed by t he onset of vent ricular t achycardia.
Vent ricular t achyarrhyt hmias consist of vent ricular t achycardia, vent ricular fibrillat ion, and t orsades de point es (a special subset of polymorphic vent ricular t achycardia).
Vent ricular t achyarrhyt hmias are charact erized by wide QRS complex morphology (QRS >0.12 sec) and vent ricular rat es great er t han 100/min. In vent ricular t achycardia, t he
vent ricular rat e t ypically ranges from 140 t o 250/min; in t orsades de point es, t he vent ricular rat e ranges from 200 t o 300/min; and in vent ricular fibrillat ion, t he rat e is
t ypically above 300/min.
At rial fibrillat ion is charact erized by an irregularly irregular rhyt hm, an irregular baseline (at rial fibrillat ory waves), and t he absence of P waves, which is inconsist ent wit h t his
pat ient 's elect rocardiographic findings.
Supravent ricular t achycardia wit h a wide QRS complex, usually due t o coexist ing bundle branch block or preexcit at ion (Wolff-Parkinson-Whit e syndrome), can mimic
vent ricular t achycardia. Different iat ing vent ricular t achycardia from supravent ricular t achycardia wit h aberrant conduct ion is import ant because t he t reat ment differs
markedly. Vent ricular t achycardia is more common t han supravent ricular t achycardia wit h aberrancy, part icularly in pat ient s wit h st ruct ural heart disease. A key point is t hat
any wide QRS t achycardia should be considered t o be vent ricular t achycardia unt il proven ot herwise. The most import ant different iat ing point is t he hist ory of ischemic heart
disease. In t he presence of known st ruct ural heart disease, especially a prior myocardial infarct ion, t he diagnosis of vent ricular t achycardia is almost cert ain. The presence of
cannon waves (large a waves) in t he jugular venous pulsat ions and varying int ensit y of t he first heart sound support t he diagnosis of at riovent ricular dissociat ion caused by
eit her vent ricular t achyarrhyt hmias or heart block.
Key Poi nt
A wide QRS t achycardia in t he presence of known st ruct ural heart disease, especially a prior myocardial infarct ion, is almost cert ainly vent ricular t achycardia.
Bi bl i ography
Srivat hsan K, Ng DW, Mookadam F. Vent ricular t achycardia and vent ricular fibrillat ion. Expert Rev Cardiovasc Ther. 2009;7(7):801-809. [PMID: 19589116]
Item 20 Answer: B
Educati onal Objecti ve: Treat non-ST-elevation myocardial infarction with a -blocker.
The most appropriat e addit ional t reat ment for t his pat ient is met oprolol. This pat ient 's elevat ed t roponin I level and ST-segment depression and T-wave inversions on
elect rocardiogram are indicat ive of a non-ST-elevat ion myocardial infarct ion (NSTEMI). Early int ravenous -blocker t herapy reduces infarct size, decreases t he frequency of
recurrent myocardial ischemia, and improves short - and long-t erm survival. -Blockers diminish myocardial oxygen demand by reducing heart rat e, syst emic art erial pressure,
and myocardial cont ract ilit y; in addit ion, prolongat ion of diast ole augment s perfusion t o t he injured myocardium. -Blocker t herapy can be used in left vent ricular
dysfunct ion if heart failure st at us is st able.
An int ra-aort ic balloon pump is indicat ed for an acut e coronary syndrome wit h cardiogenic shock t hat is unresponsive t o medical t herapy, acut e mit ral regurgit at ion
secondary t o papillary muscle dysfunct ion, vent ricular sept al rupt ure, or refract ory angina. The int ra-aort ic balloon pump reduces aft erload during vent ricular syst ole and
increases coronary perfusion during diast ole. Pat ient s wit h refract ory cardiogenic shock who are t reat ed wit h an int ra-aort ic balloon pump have a lower in-hospit al mort alit y
rat e t han pat ient s who are not t reat ed. This pat ient has no indicat ion for an int ra-aort ic balloon pump.
Calcium channel blockers, such as verapamil, are also effect ive ant ianginal medicat ions, but dat a are conflict ing as t o whet her calcium channel blockers reduce mort alit y in
pat ient s wit h NSTEMI. Therefore, -blockers are first -line t herapy for unst able angina and NSTEMI unless cont raindicat ions are present . Wit h ongoing ischemia despit e -
blocker t herapy, a calcium channel blocker can be added. However, t here is no indicat ion for st art ing verapamil rat her t han met oprolol at t his t ime.
There is no role for t he rout ine use of warfarin in t he t reat ment of acut e coronary syndrome, including NSTEMI. Warfarin is not associat ed wit h improved pat ient out come
as compared t o t reat ment wit hout warfarin. Warfarin may be considered in pat ient s at increased risk for t hromboembolism, such as t hose wit h at rial fibrillat ion.
Key Poi nt
In pat ient s wit h myocardial infarct ion, early int ravenous -blocker t herapy reduces infarct size, decreases t he frequency of recurrent myocardial ischemia, and improves
short - and long-t erm survival.
Bi bl i ography
Item 21 Answer: A
Educati onal Objecti ve: Diagnose acute severe mitral regurgitation due to papillary muscle rupture.
The most likely diagnosis is acut e mit ral valve regurgit at ion due t o papillary muscle rupt ure. The clinical hist ory of chest pain and dyspnea a week ago and t he
elect rocardiographic findings of Q waves in leads II, III, and aVF st rongly suggest an acut e inferior wall myocardial infarct ion. The presence of a new syst olic murmur and
respirat ory dist ress several days aft er an acut e myocardial infarct ion indicat es t he possibilit y of eit her a vent ricular sept al rupt ure or mit ral regurgit at ion. Papillary muscle
rupt ure generally present s several days aft er t he infarct event . Severe mit ral regurgit at ion complicat ing an acut e myocardial infarct is more common wit h inferior versus
ant erior infarct s and should be suspect ed in pat ient s wit h pulmonary edema and respirat ory dist ress in t hat set t ing. The murmur of mit ral regurgit at ion may not be prominent
because of t he acut ely elevat ed left at rial pressure and relat ively lower t ransmit ral syst olic pressure gradient . Echocardiography is diagnost ic, and early clinical recognit ion
wit h aggressive support (int ra-aort ic balloon pump, aft erload reduct ion if blood pressure allows) is essent ial, providing a bridge t o surgical repair.
A left vent ricular aneurysm may result in lat e-appearing complicat ions of acut e myocardial infarct ion. A vent ricular aneurysm may be associat ed wit h int ract able vent ricular
t achyarrhyt hmias, syst emic emboli, or heart failure. It is not associat ed wit h a new holosyst olic murmur.
Pulmonary embolism can complicat e acut e myocardial infarct ion and should be considered in any pat ient wit h new-onset pleurit ic chest pain, dyspnea, and hypot ension.
However, pulmonary embolism is not associat ed wit h a new holosyst olic murmur.
Vent ricular free wall rupt ure t ypically leads t o pericardial t amponade manifest ing as sudden hypot ension and deat h. Vent ricular free wall rupt ure t ypically occurs 1 t o 4 days
aft er acut e myocardial infarct ion. Pat ient s usually present wit h cardiovascular collapse, t amponade, or pulseless elect rical act ivit y.
Key Poi nt
The presence of a new syst olic murmur and respirat ory dist ress several days aft er an acut e myocardial infarct ion indicat es t he possibilit y of eit her a vent ricular sept al rupt ure
or mit ral regurgit at ion.
Bi bl i ography
Topalian S, Ginsberg F, Parrillo JE. Cardiogenic shock. Crit Care Med. 2008;36:S66-S74. [PMID: 18158480]
Item 22 Answer: B
Educati onal Objecti ve: Treat ST-elevation myocardial infarction with thrombolytic therapy.
The best management opt ion for t his pat ient is immediat e t hrombolyt ic t herapy. The pat ient is experiencing an acut e inferior wall ST-elevat ion myocardial infarct ion
(STEMI). The diagnosis is est ablished by t he presence of chest pain and ST-segment elevat ions in leads II, III, and aVF. The t reat ment for an acut e STEMI is eit her
revascularizat ion or t hrombolyt ic t herapy. The pat ient has no cont raindicat ions for t hrombolyt ic t herapy. She is current ly hemodynamically st able wit hout cardiogenic
shock. The t reat ment of choice is percut aneous coronary int ervent ion (PCI) provided t hat it can be done immediat ely or in less t han 60 minut es if t ransfer t o anot her
hospit al is necessary. Since t he nearest hospit al wit h PCI capabilit y is 3 hours away, immediat e t hrombolyt ic t herapy is t he most appropriat e t reat ment for t his pat ient .
Thrombolyt ic agent s are an alt ernat ive t o primary PCI in suit able candidat es wit h STEMI. By lysing t he clot t hat is limit ing blood flow t o t he myocardium, t hrombolyt ics
rest ore perfusion t o t he ischemic area, reduce infarct size, and improve survival. Thrombolyt ics should be administ ered wit hin 12 hours aft er t he onset of chest pain; t he
earlier t he administ rat ion, t he bet t er t he out come.
Aggressive medical t herapy would not be t he correct opt ion for t his pat ient given t he elect rocardiographic findings, her relat ively young age, and t he abilit y t o t reat her wit h
a t hrombolyt ic agent .
Transfer for coronary art ery bypass graft surgery would not be t he correct opt ion given t hat t he pat ient 's coronary anat omy has not yet been defined and t here would be an
unaccept able delay if she were t ransferred for coronary angiography. Most pat ient s present ing wit h a STEMI can be t reat ed effect ively wit h percut aneous coronary
int ervent ion or t hrombolyt ic t herapy. Bypass surgery in t he set t ing of an acut e infarct ion is t herefore rarely performed. Bypass surgery may be preferred in pat ient s who
have a large amount of myocardium at ischemic risk owing t o proximal left main disease or mult ivessel disease, especially if t he left vent ricular eject ion fract ion is reduced.
However, t his is predicat ed by first performing coronary angiography and knowing t he coronary anat omy.
Key Poi nt
Thrombolyt ic agent s are an alt ernat ive t o primary percut aneous coronary int ervent ion in suit able candidat es wit h ST-elevat ion myocardial infarct ion and should be
administ ered wit hin 12 hours aft er t he onset of chest pain.
Bi bl i ography
Item 23 Answer: A
Educati onal Objecti ve: Diagnose first-degree atrioventricular block.
This elect rocardiogram shows first -degree at riovent ricular block and is ot herwise unremarkable. First -degree at riovent ricular block is diagnosed when t he PR int erval is great er
t han 0.20 sec. It is oft en associat ed wit h a soft S
1
. The presence of first -degree heart block suggest s at riovent ricular nodal disease but rarely requires t herapy. First -degree
at riovent ricular block is also associat ed wit h acut e reversible condit ions, including inferior myocardial infarct ion, rheumat ic fever, and digit alis int oxicat ion. Addit ionally, any
medicat ion t hat slows conduct ion t hrough t he at riovent ricular node (for example, dilt iazem) can pot ent ially produce a first -degree at riovent ricular block.
Second-degree at riovent ricular block is est ablished when not all beat s are conduct ed from t he at ria t o t he vent ricles ("dropped beat s"). It is recognized in t he t racing by t he
presence of isolat ed P waves t hat are not followed by a QRS complex.
Third-degree (complet e) at riovent ricular heart block is charact erized by complet e absence of conduct ion from t he at ria t o t he vent ricles; t he P waves and t he QRS complexes
are complet ely independent of each ot her. Careful analysis will show t hat t he P wave rat e and t he QRS rat e are different and t hat t he PR int erval is different for every QRS
complex.
The elect rocardiographic diagnosis of vent ricular preexcit at ion is based on a short PR int erval (<0.11 sec), prolonged QRS durat ion, and slurred onset of t he QRS (delt a wave)
complex. None of t hese findings are present .
Key Poi nt
First -degree at riovent ricular block is diagnosed when t he PR int erval is great er t han 0.20 sec.
Bi bl i ography
Ufberg JW, Clark JS. Bradydysrhyt hmias and at riovent ricular conduct ion blocks. Emerg Med Clin Nort h Am. 2006;24(1):1-9, v. [PMID: 16308110]
Item 24 Answer: C
Educati onal Objecti ve: Diagnose right ventricular infarction complicating an inferior wall ST-elevation myocardial infarction.
The most likely cause of hypot ension in t his pat ient is right vent ricular infarct ion. Right vent ricular infarct ion occurs in approximat ely 20% of pat ient s wit h an inferior wall
ST-elevat ion myocardial infarct ion (STEMI). This diagnosis should be considered in pat ient s wit h t he clinical t riad of hypot ension, clear lung fields, and jugular venous
dist ent ion. The diagnosis can be made using a right -sided elect rocardiogram, on which ST-segment elevat ion in leads V
3
R and V
4
R will be seen. Treat ment for right vent ricular
infarct ion consist s of rapid rest orat ion of blood flow t o t he right vent ricle wit h eit her t hrombolyt ic t herapy or primary percut aneous coronary int ervent ion, aggressive
volume loading wit h int ravenous normal saline t o increase filling of t he right vent ricle, and dopamine or dobut amine if hypot ension persist s.
Increased vagal t one can cause bradycardia and decreased right vent ricular preload, result ing in hypot ension early in t he course of a myocardial infarct ion. Alt hough increased
vagal t one is commonly associat ed wit h inferior wall myocardial infarct ion, t he pat ient 's t achycardia suggest s an alt ernat ive diagnosis.
Pericardial t amponade from rupt ure of t he left vent ricular free wall usually leads t o sudden hypot ension and deat h. Free wall rupt ure is second only t o heart failure as t he most
common cause of deat h for pat ient s who die in hospit als aft er myocardial infarct ion. Vent ricular free wall rupt ure t ypically occurs 1 t o 4 days aft er acut e myocardial
infarct ion. It would be unlikely for pericardial t amponade t o be present upon init ial present at ion unless t he pat ient had chest pain for several days prior t o t he
hospit alizat ion.
A vent ricular sept al defect manifest s as a new syst olic murmur, hypot ension, and respirat ory dist ress 1 t o 3 days following t he onset of a myocardial infarct ion. It would be
exceedingly uncommon for a pat ient t o present init ially wit h a vent ricular sept al defect unless sympt oms of chest pain were present for several days.
Key Poi nt
In t he set t ing of an inferior wall ST-elevat ion myocardial infarct ion, t he clinical t riad of hypot ension, clear lung fields, and jugular venous dist ent ion suggest s a right
vent ricular infarct ion.
Bi bl i ography
Reynolds HR, Hochman JS. Cardiogenic shock: current concept s and improving out comes. Circulat ion. 2008;117(5):686-697. [PMID: 18250279]
Item 25 Answer: D
Educati onal Objecti ve: Diagnose ventricular septal defect following ST-elevation myocardial infarction.
The most likely diagnosis is a vent ricular sept al defect . Mechanical complicat ions occur in roughly 0.1% of pat ient s wit h ST-elevat ion myocardial infarct ion (STEMI) and
usually occur 2 t o 7 days aft er infarct ion. Lat e complicat ions following STEMI include cardiogenic shock, vent ricular sept al defect , mit ral regurgit at ion, free wall rupt ure, and
left vent ricular t hrombus. This pat ient 's progressive hypot ension, respirat ory dist ress, and new syst olic murmur and t hrill suggest eit her ischemic mit ral regurgit at ion or a
vent ricular sept al defect . Following echocardiography t o confirm t he diagnosis, t his pat ient should undergo emergent surgery t o repair t he defect or valve.
Pat ient s wit h aort ic dissect ion t ypically present wit h severe, sharp, t earing chest pain. The pain may radiat e widely and be associat ed wit h syncope, syst emic ischemia (relat ed
t o impaired blood flow t o an organ or limb), or heart failure (aort ic valve disrupt ion, t amponade). Ascending aort ic dissect ion is oft en associat ed wit h acut e aort ic
regurgit at ion (diast olic murmur at t he base of t he heart ), myocardial ischemia, cardiac t amponade or hemopericardium, and hemot horax or exsanguinat ion. A new syst olic
murmur and t hrill are not compat ible wit h aort ic dissect ion.
Pericardial t amponade may occur following an STEMI from hemorrhagic pericardit is or free wall rupt ure. Pericardial t amponade from rupt ure of t he left vent ricular free wall
usually leads t o sudden hypot ension and deat h. Vent ricular free wall rupt ure t ypically occurs 1 t o 4 days aft er acut e myocardial infarct ion. Pat ient s usually present wit h
cardiovascular collapse, t amponade, or pulseless elect rical act ivit y. It is not associat ed wit h a new, loud syst olic murmur or palpable t hrill.
A massive pulmonary embolism may produce cardiovascular collapse and hypoxemia but cannot explain t he new syst olic murmur or left -sided heart failure.
Key Poi nt
A vent ricular sept al defect following an ST-elevat ion myocardial infarct ion result s in respirat ory dist ress, hypot ension, a new syst olic murmur, and a palpable t hrill.
Bi bl i ography
Poulsen SH, Praest holm M, Munk K, Wierup P, Egeblad H, Nielsen-Kudsk JE. Vent ricular sept al rupt ure complicat ing acut e myocardial infarct ion: clinical charact erist ics and
cont emporary out come. Ann Thorac Surg. 2008;85(5):1591-1596. [PMID: 18442545]
Item 26 Answer: D
Educati onal Objecti ve: Diagnose sinoatrial node dysfunction.
This pat ient has sympt omat ic sinoat rial node dysfunct ion (also called sick sinus syndrome). Sinoat rial node dysfunct ion comprises a collect ion of pat hologic findings t hat
result in bradycardia. These include sinus arrest , sinus exit block, and sinus bradycardia. This pat ient has sinus bradycardia and sinus arrest . Approximat ely 50% of pat ient s
wit h sinoat rial node dysfunct ion also have associat ed supravent ricular t achycardia, most oft en at rial fibrillat ion or at rial flut t er. The t achycardia-bradycardia syndrome is
charact erized by rapid vent ricular conduct ion during episodes of at rial fibrillat ion, but rest ing bradycardia bet ween episodes. Sympt omat ic sinus node dysfunct ion is an
indicat ion for pacemaker placement , even if t he bradycardia occurs as a consequence of drug t herapy, if t here is no accept able alt ernat ive.
At riovent ricular nodal block is classified as first , second, or t hird degree. First -degree block is defined by prolongat ion of t he PR int erval t o great er t han 0.2 sec and usually is
not associat ed wit h alt erat ions in heart rat e. There are t wo t ypes of second-degree block, bot h recognized elect rocardiographically by t he presence of a P wave t hat is not
followed by a vent ricular complex. Mobit z t ype I block (Wenckebach block) manifest s as progressive prolongat ion of t he PR int erval unt il t here is a dropped beat , whereas
Mobit z t ype II block manifest s as a dropped beat wit hout progressive PR-int erval prolongat ion. Mobit z t ype I block usually does not progress t o complet e heart block, but
Mobit z t ype II block, which is usually associat ed wit h a bundle branch block, t ypically progresses t o t hird-degree block. Second-degree block may be associat ed wit h
bradycardia, depending upon t he frequency of blocked at rial impulses. Third-degree block is t he complet e absence of conduct ion of at rial impulses t o t he vent ricle and is t he
most common cause of marked bradycardia; vent ricular rat es are usually 30-50/min. This pat ient has no evidence of at riovent ricular block.
Key Poi nt
Sinoat rial node dysfunct ion comprises a collect ion of pat hologic findings (sinus arrest , sinus exit block, and sinus bradycardia) t hat result in bradycardia.
Bi bl i ography
Ufberg JW, Clark JS. Bradydysrhyt hmias and at riovent ricular conduct ion blocks. Emerg Med Clin Nort h Am. 2006;24(1):1-9, v. [PMID: 16308110]
Item 27 Answer: A
Educati onal Objecti ve: Diagnose heart block due to donepezil.
The medicat ion most likely responsible for t he pat ient 's heart block is donepezil. Donepezil inhibit s acet ylcholinest erase. It s act ivit y occurs preferent ially in t he cent ral
nervous syst em, but mild peripheral cholinergic side effect s are common. These effect s include increased vagal t one, bradycardia, and, occasionally, at riovent ricular block. In
t his pat ient , t his side effect became manifest when t he dosage of donepezil was increased. In pat ient s wit h preexist ing heart block, cholinest erase inhibit ors should be used
wit h caut ion.
Memant ine inhibit s t he glut amat ergic N-met hyl-D-aspart at e recept or on cent ral neurons. The side effect s of memant ine include hallucinat ions, confusion, rest lessness,
anxiet y, dizziness, headache, fat igue, and const ipat ion.
Trazodone does not commonly cause slowing of cardiac conduct ion, alt hough it may be associat ed wit h palpit at ions and vent ricular ect opy. Vit amin E at a high dose can
cause loose st ools and may inhibit vit amin K carboxylase, but it is not associat ed wit h cardiac side effect s.
Key Poi nt
Donepezil, an acet ylcholinest erase inhibit or, may cause mild peripheral cholinergic side effect s, including increased vagal t one, bradycardia, and at riovent ricular block.
Bi bl i ography
Feldman H, Gaut hier S, Hecker J, et al. A 24-week, randomized, double-blind st udy of donepezil in moderat e t o severe Alzheimer's disease. Neurology. 2001;57:613-620.
[PMID: 11524468]
Item 28 Answer: D
Educati onal Objecti ve: Treat an unstable patient with a cardiac arrhythmia with electrical cardioversion.
Elect rical cardioversion is indicat ed for an unst able pat ient wit h any arrhyt hmia, ot her t han sinus t achycardia, including at rial fibrillat ion wit h a rapid vent ricular rat e. This
pat ient has persist ent t achycardia, worsening ment al st at us, hypoxia, and hypot ension consist ent wit h significant hemodynamic inst abilit y. Immediat e cardioversion is oft en
t he safest choice even in hemodynamically st able pat ient s, part icularly in t hose wit h wide complex t achycardia. Aft er t erminat ion of t he arrhyt hmia, t he elect rocardiogram
can provide clues regarding t he presence of previous myocardial infarct ion, left vent ricular hypert rophy, or long QT syndrome, and an echocardiogram provides evaluat ion
for st ruct ural heart disease and assessment of left vent ricular funct ion. Exercise t est ing can screen for significant coronary art ery disease and provoke exercise-associat ed
t achycardias. In newly diagnosed cardiomyopat hy, cardiac cat het erizat ion is oft en necessary t o evaluat e for coronary art ery disease as t he cause of myocardial dysfunct ion.
CT pulmonary angiography can evaluat e t he pat ient for pulmonary emboli; however, none of t hese st udies are indicat ed unt il t he pat ient 's cardiac rhyt hm is st abilized wit h
immediat e cardioversion.
Key Poi nt
Elect rical cardioversion is indicat ed in hemodynamically unst able pat ient s wit h an arrhyt hmia.
Bi bl i ography
Item 29 Answer: B
Educati onal Objecti ve: Identify hyperthyroidism as the cause of sinus tachycardia.
Measuring t he TSH level is an appropriat e first st ep t o det ermine t he underlying cause of t he sinus t achycardia. Sinus t achycardia originat es from t he sinoat rial node and is
defined as a rat e of great er t han 100/min. Common causes of sinus t achycardia include normal response t o exercise and sit uat ions associat ed wit h increased cat echolamine
release (fear, pain, anxiet y, alcohol wit hdrawal) as well as fever, hypovolemia, sepsis, heart failure, pulmonary embolism, and hypoxia. Hypert hyroidism is a relat ively
common cause of sinus t achycardia. Ot her clues suggest ing hypert hyroidism in t his pat ient include difficult y sleeping and unexplained weight loss. In pat ient s wit h
hypert hyroidism, t reat ment wit h a -blocker may provide some sympt omat ic relief unt il t he underlying t hyroid disease is t reat ed.
Adenosine bolus inject ion is highly effect ive at t erminat ing at riovent ricular (AV) nodal reent rant t achycardia and providing diagnost ic informat ion in unclear cases such as
revealing flut t er waves during adenosine-induced AV block or revealing an underlying at rial t achycardia. Adenosine has no role in managing pat ient s wit h sinus t achycardia.
An exercise st ress t est is used t o diagnose coronary art ery disease. This pat ient is asympt omat ic, has good exercise t olerance, and has no ot her signs or sympt oms of coronary
art ery disease. Therefore, an exercise st ress t est is not warrant ed.
Sinoat rial ablat ion is indicat ed for pat ient s wit h at rial t achycardia t hat uses part of t he sinoat rial node as a reent ry circuit . Sinoat rial node ablat ion is rarely used t o t reat
inappropriat e sinus t achycardia. This is a condit ion charact erized by an elevat ed rest ing sinus rat e in t he absence of a recognized cause and an exaggerat ed rat e response t o
exercise. Most pat ient s wit h inappropriat e sinus t achycardia respond t o -blockers or nondihydropyridine calcium channel blockers, but some refract ory cases are t reat ed wit h
sinoat rial node ablat ion.
Key Poi nt
Det ermining t he underlying cause of sinus t achycardia is necessary t o guide appropriat e t reat ment .
Bi bl i ography
DeVoe JE, Judkins DZ, Woods L. Clinical inquiries. What is t he best approach t o t he evaluat ion of rest ing t achycardia in an adult ? J Fam Pract . 2007;56(1):59-61. [PMID:
1721790]
Item 30 Answer: D
Educati onal Objecti ve: Treat atrial fibrillation with metoprolol and warfarin.
This pat ient is best t reat ed wit h met oprolol and warfarin. There are t wo st rat egies in t he t reat ment of persist ent or paroxysmal at rial fibrillat ion: cont rolling t he vent ricular
response rat e t o at rial fibrillat ion (rat e cont rol) and using ant iarrhyt hmic drugs t o maint ain sinus rhyt hm (rhyt hm cont rol). There is no survival advant age associat ed wit h
eit her of t hese st rat egies, but for older pat ient s (age >70 years), rat e cont rol is associat ed wit h improved qualit y-of-life scores. More hospit alizat ions and adverse drug
react ions occur in pat ient s receiving rhyt hm cont rol compared wit h rat e cont rol. This elderly pat ient would be at significant risk of drug side effect s from ant iarrhyt hmic
t herapy. Therefore, t his pat ient should receive medicat ion t o cont rol t he vent ricular rat e, such as met oprolol, and not an ant iarrhyt hmic agent , such as amiodarone. The use
of ant icoagulat ion for st roke prevent ion is not affect ed by choice of approach.
In pat ient s wit h nonvalvular at rial fibrillat ion, warfarin wit h a t arget INR of 2.0 t o 3.0 has been shown t o decrease st roke risk by an average of 62%, compared wit h a 19%
decrease wit h aspirin t herapy. To det ermine whet her t he risk of st roke is high enough t o warrant chronic ant icoagulat ion, risk st rat ificat ion scores have been developed. The
CHADS
2
risk score for assessing t he risk of st roke associat ed wit h at rial fibrillat ion has been validat ed in a large populat ion. Point s are scored for t he presence of t he
following specific risk fact ors for st roke: Congest ive heart failure, Hypert ension, Age >75 years, Diabet es, and St roke or t ransient ischemic at t ack (TIA). Pat ient s are given 2
point s for a hist ory of st roke or TIA (t he st rongest risk fact or) and 1 point for all ot her risk fact ors. The risk of st roke is lowest in pat ient s wit h a CHADS
2
score of 0
(1.2%). The risk is 18% for a CHADS
2
score of 6 (maximum score). Pat ient s wit h a CHADS
2
score of 3 or great er and pat ient s wit h a hist ory of TIA or st roke are at high
risk and should be considered for chronic ant icoagulat ion wit h warfarin. This pat ient 's 10-minut e episode of arm weakness is very suggest ive of TIA, placing him in t he
highest risk cat egory for st roke. Pat ient s wit h a CHADS
2
score of 1 or 2 should be assessed on an individual basis for aspirin versus warfarin t herapy.
Not all pat ient s wit h newly diagnosed at rial fibrillat ion require acut e ant icoagulat ion wit h heparin. Asympt omat ic pat ient s wit h good rat e cont rol who require long-t erm
ant icoagulat ion wit h aspirin or warfarin can have t his t herapy init iat ed as an out pat ient .
Key Poi nt
Most pat ient s wit h at rial fibrillat ion are t reat ed wit h a combinat ion of rat e cont rol and long-t erm ant icoagulat ion.
Bi bl i ography
Item 31 Answer: D
Educati onal Objecti ve: Manage benign premature ventricular contractions.
The most appropriat e management for t his pat ient is no addit ional invest igat ion or t herapy. He is very act ive and has no sympt oms associat ed wit h t he premat ure
vent ricular cont ract ions (PVCs). Physical examinat ion is normal and no findings suggest st ruct ural heart disease. Finally, t he family hist ory includes no worrisome feat ures t o
suggest premat ure or sudden cardiac deat h syndromes. PVCs oft en are not associat ed wit h sympt oms, alt hough t hey can cause palpit at ions or a sensat ion t hat t he heart has
st opped, owing t o t he post -PVC compensat ory pause. PVCs at rest in t he set t ing of a st ruct urally normal heart appear t o be associat ed wit h lit t le t o no increased risk of
cardiovascular event s, part icularly in pat ient s younger t han 30 years. Repet it ive or complex ect opy in t he set t ing of heart disease is associat ed wit h increased mort alit y risk,
alt hough t he risk is due t o t he underlying pat hophysiologic subst rat e, and suppression of ambient vent ricular arrhyt hmias does not reduce mort alit y. Some pat ient s have
bot hersome sympt oms associat ed wit h PVCs. If sympt oms can be clearly correlat ed wit h PVCs, t reat ment may be appropriat e, alt hough many pat ient s respond well t o simple
reassurance. First -line t herapy is almost always a -blocker such as met oprolol or a calcium channel blocker such as verapamil. However, ant iarrhyt hmic drug t herapy is
associat ed wit h side-effect s, so t reat ment cannot be undert aken wit hout a discussion of it s risks and benefit s. Addit ional invest igat ion in t his asympt omat ic young and healt hy
pat ient is unlikely t o change his management . Therefore, echocardiography, arrhyt hmia monit oring, and exercise st ress t est ing is not indicat ed.
Key Poi nt
Premat ure vent ricular cont ract ions at rest in t he set t ing of a st ruct urally normal heart appear t o be associat ed wit h lit t le t o no increased risk of cardiovascular event s,
part icularly in pat ient s younger t han 30 years.
Bi bl i ography
Ng GA. Treat ing pat ient s wit h vent ricular ect opic beat s. Heart . 2006;92 (11):1707-12. [PMID: 17041126]
Item 32 Answer: D
Educati onal Objecti ve: Treat patients at risk for sudden death with an implantable cardioverter-defibrillator.
The most appropriat e t reat ment for t his pat ient is an ICD. Sust ained vent ricular t achycardia (VT) occurs most commonly in pat ient s wit h previous myocardial infarct ion,
and it is t he scar formed by t he infarct ion t hat provides t he anat omic subst rat e for reent ry. Areas of fibrosis int erspersed wit h viable myocardial t issue are present in t he
border zone of dense scar t issue and impart t he required conduct ion delay crit ical t o t he est ablishment of reent ry circuit s. Sympt oms depend on t he underlying st at e of t he
pat ient , and some pat ient s can be asympt omat ic, part icularly if t he VT rat e is slow. In general, medical t herapy (amiodarone, procainamide, flecainide) does not improve
survival in pat ient s wit h VT and st ruct ural heart disease; t hus, most pat ient s are candidat es for ICD placement . Large clinical t rials have demonst rat ed ICD t herapy improves
survival rat es in pat ient s wit h hemodynamically unst able VT aft er cardiac arrest who have ischemic or nonischemic cardiomyopat hy and eject ion fract ions less t han 35%. In
pat ient s wit h left vent ricular dysfunct ion in t he absence of VT, ICD implant at ion has also been shown t o improve survival. The primary eligibilit y crit erion for ICD
implant at ion for primary prevent ion of sudden cardiac deat h in t he set t ing of heart failure is left vent ricular eject ion fract ion less t han 35%, regardless of t he presence or
absence of coronary disease or t he occurrence of arrhyt hmia.
Key Poi nt
The primary eligibilit y crit erion for implant able cardiovert er-defibrillat or implant at ion for primary prevent ion of sudden cardiac deat h in t he set t ing of heart failure is left
vent ricular eject ion fract ion less t han 35%.
Bi bl i ography
Cevik C, Nugent K, Perez-Verdia A, Fish RD. Prophylact ic implant at ion of cardiovert er defibrillat ors in idiopat hic nonischemic cardiomyopat hy for t he primary prevent ion
of deat h: a narrat ive review. Clin Cardiol. 2010;33(5):254-60. [PMID: 20513063]
Item 33 Answer: B
Educati onal Objecti ve: Manage a patient with ventricular fibrillation arrest in the setting of acute myocardial infarction.
The best opt ion for t he pat ient at t his t ime is t o cont inue medical management . Vent ricular t achyarrhyt hmias are common in t he set t ing of acut e myocardial infarct ion,
occurring in up t o 20% of pat ient s. Despit e a sixfold increase in in-hospit al mort alit y, t he overall mort alit y at 1 year is not increased in pat ient s wit h vent ricular fibrillat ion
t hat occurs early in t his set t ing. Therefore, unlike sudden cardiac deat h occurring in ot her set t ings, cardiac arrest occurring wit hin t he first 48 hours of t ransmural acut e
myocardial infarct ion does not require defibrillat or placement .
Primary vent ricular fibrillat ion should be dist inguished from vent ricular fibrillat ion t hat occurs lat er in t he course, usually as a result of heart failure. Before t he advent of t he
implant able cardiovert er-defibrillat or, vent ricular fibrillat ion occurring lat e in t he hospit al course was associat ed wit h an 85% 1-year mort alit y rat e. All pat ient s, even t hose
who have not suffered arrhyt hmia during myocardial infarct ion, should be reevaluat ed aft er myocardial infarct ion by t ranst horacic echocardiogram t o furt her st rat ify risk. If
t he eject ion fract ion is found t o be reduced (<35%), t he pat ient may be a candidat e for defibrillat or placement .
Amiodarone has not been shown t o improve overall mort alit y following myocardial infarct ion. In t he general populat ion of cardiac arrest survivors, amiodarone does not
improve mort alit y.
Implant able cardiovert er-defibrillat or placement is not indicat ed for pat ient s who experience vent ricular arrhyt hmias less t han 48 hours aft er an acut e ST-elevat ion
myocardial infarct ion. Implant able cardiovert er-defibrillat ors have demonst rat ed a mort alit y benefit for essent ially all ot her groups of cardiac arrest survivors.
The t ypical indicat ions for a pacemaker include sympt omat ic sinoat rial node dysfunct ion (sinus bradycardia, int ra-at rial block, exit block) and sympt omat ic bradycardia due
t o advanced second- or t hird-degree heart block. This asympt omat ic man wit h no evidence of bradycardia or advanced heart block on his elect rocardiogram has no indicat ion
for a pacemaker. Pacemaker placement does not prevent sudden deat h due t o vent ricular t achyarrhyt hmias.
Key Poi nt
Cardiac arrest occurring wit hin t he first 48 hours of an acut e, t ransmural myocardial infarct ion does not require secondary prevent ion t herapy ot her t han st andard post -
myocardial infarct ion care.
Bi bl i ography
Kusumot o F. A comprehensive approach t o management of vent ricular arrhyt hmias. Cardiol Clin. 2008;26(3):481-496, vii. [PMID: 18538192]
Item 34 Answer: C
Educati onal Objecti ve: Diagnose familial long QT syndrome.
This pat ient most likely has long QT syndrome (LQTS). Cardiac event s in pat ient s wit h LQTS include syncope and cardiac arrest due t o t orsade de point es vent ricular
t achycardia. LQTS may be eit her congenit al or acquired. This pat ient probably has congenit al LQTS, suggest ed by recurrent syncope t riggered by act ivit y and a family hist ory
of early sudden deat h (cousin drowning). Her mot her is probably affect ed as well. Risk fact ors for acquired LQTS include female sex, hypokalemia, hypomagnesemia,
st ruct ural heart disease, previous QT-int erval prolongat ion, and a hist ory of drug-induced arrhyt hmia. (An ext ensive list of offending agent s can be found at
www.azcert .org/medical-pros/drug-list s/drug-list s.cfm.) Ot her cardiac causes of syncope and sudden deat h in young pat ient s include hypert rophic cardiomyopat hy and
arrhyt hmogenic right vent ricular dysplasia.
Left bundle branch block (LBBB) and right bundle branch block (RBBB) are elect rocardiographic pat t erns t hat increase in frequency wit h age. LBBB most oft en occurs in
pat ient s wit h underlying heart disease. In older pat ient s, LBBB is associat ed wit h increased mort alit y. In younger pat ient s, however, LBBB is not associat ed wit h syncope or
sudden deat h and t he prognosis is generally excellent . RBBB is similarly associat ed wit h increased mort alit y in older pat ient s wit h underlying heart disease. When RBBB is not
associat ed wit h underlying cardiac disease, pat ient out comes are generally excellent , and RBBB is an unlikely cause of t his pat ient 's sympt oms.
First -degree at riovent ricular block is charact erized by prolongat ion of t he PR int erval t o longer t han 0.2 sec; it usually is not associat ed wit h alt erat ions in heart rat e and has
no associat ion wit h syncope or sudden deat h.
Key Poi nt
Cardiac event s in pat ient s wit h long QT syndrome include syncope and cardiac arrest due t o t orsade de point es vent ricular t achycardia.
Bi bl i ography
Goldenberg I, Zareba W, Moss AJ. Long QT syndrome. Curr Probl Cardiol. 2008;33(11):629-694. [PMID: 18835466]
Item 35 Answer: A
Educati onal Objecti ve: Treat New York Heart Association class IV heart failure with digoxin.
Digoxin is t he most appropriat e t herapy t o init iat e in t his pat ient . The role of digoxin in t reat ing heart failure pat ient s in sinus rhyt hm is primarily for sympt om cont rol
rat her t han improving survival. Treat ment wit h digoxin has not been shown t o affect mort alit y but has been shown t o reduce hospit alizat ions. Digoxin can be added t o ot her
t herapy in pat ient s wit h New York Heart Associat ion class III or IV heart failure for sympt om cont rol. Maint aining lower serum concent rat ions of digoxin is as effect ive as
maint aining higher concent rat ions, and pot ent ial t oxicit ies are avoided. Higher digoxin levels (1.2 ng/mL [1.5 nmol/L] versus 0.5-0.8 ng/mL [0.6-1.0 nmol/L]) appear t o be
associat ed wit h higher mort alit y in pat ient s wit h syst olic heart failure. The primary reason t o use an angiot ensin recept or blocer (ARB) inst ead of an angiot ensin-convert ing
enzyme (ACE) inhibit or, such as lisinopril, is t o avoid t he side effect of cough. Combined t reat ment wit h an ACE inhibit or and an ARB is generally not recommended,
because concurrent t herapy is significant ly associat ed wit h increased risk of medicat ion nonadherence and adverse effect s, including worsening renal funct ion and
sympt omat ic hypot ension, whereas t he addit ional benefit of using t hese t wo medicat ions t oget her is not well est ablished. ACE inhibit ors are current ly preferred over ARBs
for most pat ient s, because t here is more clinical experience wit h t hese agent s.
There is no role for t he rout ine ant icoagulat ion of heart failure pat ient s wit h warfarin (or aspirin) because t here is no apparent benefit and an increased risk of bleeding. Major
guidelines generally agree t hat warfarin should be considered in a pat ient wit h a heart failure and a previous t hrombot ic event (for example, st roke or pulmonary embolism)
and in pat ient s wit h an underlying at rial fibrillat ion heart rhyt hm.
Key Poi nt
Digoxin alleviat es sympt oms and decreases hospit alizat ions, but it provides no survival benefit in pat ient s wit h heart failure.
Bi bl i ography
Goldberg LR. Heart failure. Ann Int ern Med. 2010;152(11):ITC61-15; quiz ITC616. [PMID: 20513825]
Item 36 Answer: D
Educati onal Objecti ve: Diagnose heart failure due to peripartum cardiomyopathy.
This pat ient most likely has heart failure due t o peripart um cardiomyopat hy. Peripart um cardiomyopat hy is defined as heart failure wit h a left vent ricular eject ion fract ion
less t han 45% t hat is diagnosed bet ween 3 mont hs before and 6 mont hs aft er delivery in t he absence of an ident ifiable cause. It is usually diagnosed during t he first mont h
post part um. This pat ient has clinical feat ures consist ent wit h heart failure (progressive dyspnea), evidence of left vent ricular dysfunct ion (t achycardia, elevat ed cent ral
venous pressure, S
3
and S
4
, displaced and diffuse apical impulse, mit ral regurgit ant murmur, pulmonary crackles), and confirmat ory chest radiography (pleural effusions and
int erst it ial infilt rat es).
Acut e myocardial infarct ion may occur during pregnancy and in t he post part um period. It may be relat ed t o at herosclerot ic coronary art ery disease or coronary art ery
dissect ion and vasculit is and carries a high risk of mat ernal mort alit y and morbidit y. This pat ient 's present at ion, however, does not suggest an acut e coronary syndrome, given
t he absence of chest pain or elect rocardiographic changes.
Aort ic dissect ion may occur in t he peripart um or post part um period and is a part icular concern in pat ient s wit h aort opat hy relat ed t o Marfan syndrome, familial t horacic
aort ic aneurysmal disease, or bicuspid aort ic valve-relat ed aort opat hy. However, t he current present at ion does not suggest aort ic dissect ion given t he absence of chest pain,
t he presence of equal and normal blood pressures in t he upper ext remit ies, and t he presence of normal lower ext remit y pulses. Addit ionally, aort ic dissect ion is usually
associat ed wit h an abnormal chest radiograph (widened mediast inum, abnormal aort ic cont our), and t he absence of t hese findings argues st rongly against t he diagnosis. Aort ic
dissect ion cannot explain t he pat ient 's findings of a dilat ed left vent ricle and signs of heart failure.
Coarct at ion of t he aort a may rarely present init ially as hypert ension during pregnancy. However, t he pat ient 's current physical examinat ion findings of easily palpable lower
ext remit y pulses wit hout delay and t he absence of hypert ension argue against coarct at ion. In addit ion, rib not ching is not report ed on t he chest radiograph.
Key Poi nt
The presence of elevat ed cent ral venous pressure, pulmonary crackles, vent ricular gallops (S
3
or S
4
), any cardiac murmur, and lower ext remit y edema all increase t he
likelihood of heart failure.
Bi bl i ography
Item 37 Answer: A
Educati onal Objecti ve: Evaluate a patient with new-onset heart failure with cardiac angiography.
The most appropriat e diagnost ic t est for t his pat ient is a cardiac angiography. This pat ient has t ypical angina (subst ernal chest pain precipit at ed by exert ion and relieved by
rest ) and new-onset heart failure, as evidenced by sympt oms (exert ional dyspnea and ort hopnea), examinat ion findings (elevat ed jugular venous pressure, pulmonary crackles,
and an S
3
and S
4
), and echocardiogram wit h a subnormal eject ion fract ion. Definit ive t est ing for coronary art ery disease (CAD) by cardiac cat het erizat ion is warrant ed. The
primary aim of an evaluat ion for CAD is t o ident ify possible t arget s for revascularizat ion (percut aneous or surgical) wit h t he goals of reducing angina, improving syst olic
funct ion, reducing t he risk of heart failure progression, and improving survival.
For pat ient s wit h an int ermediat e likelihood of CAD who have no feat ures of unst able angina, st ress t est ing is t he preferred approach when assessing for CAD. An exercise
st ress t est is recommended in a pat ient wit h an int ermediat e probabilit y of disease and a normal rest ing elect rocardiogram (ECG). A nuclear medicine st ress t est is helpful if
t he rest ing ECG is abnormal. In t his pat ient , however, t he pret est probabilit y for CAD is high based on his age, sex, and t he presence of t ypical anginal sympt oms. Because a
negat ive result on st ress t est ing in a pat ient wit h a high pret est probabilit y of CAD would have a high likelihood of being a false negat ive, cat het erizat ion would st ill be needed
for a definit ive diagnosis, as well as for planning t herapy.
A radionuclide vent riculogram can be useful in confirming t he eject ion fract ion if clarificat ion is needed. In t his pat ient , however, t he eject ion fract ion value is provided by
t he echocardiogram. Furt hermore, a radionuclide vent riculogram would not assist in det ermining t he cause of t he new-onset heart failure.
Key Poi nt
Pat ient s wit h new-onset heart failure and angina should be evaluat ed wit h cardiac cat het erizat ion and angiography if t hey are possible candidat es for revascularizat ion.
Bi bl i ography
Item 38 Answer: B
Educati onal Objecti ve: Evaluate new-onset heart failure with echocardiography.
An echocardiogram should be obt ained in all pat ient s wit h newly diagnosed or suspect ed heart failure t o det ermine whet her t he heart failure is syst olic or diast olic and whet her
t here are any st ruct ural or funct ional abnormalit ies t hat may be causing t he heart failure (such as regional wall abnormalit ies, pericardial disease, or valvular abnormalit y). All
of t hese issues may have a significant impact on management and prognosis.
B-t ype nat riuret ic pept ide (BNP) is a hormone synt hesized by t he cardiac vent ricles in response t o increased wall st ress due t o pressure or volume overload. BNP assays have
become a useful t ool in t he diagnosis of acut e heart failure and different iat ing it from noncardiac causes of dyspnea. A pat ient wit h a BNP concent rat ion below 100 pg/mL is
unlikely t o have acut e heart failure, whereas a pat ient wit h a concent rat ion higher t han 500 pg/mL has a high likelihood of having heart failure. BNP level will likely be
elevat ed in t his pat ient , confirming t he presence of volume overload. The physical examinat ion, hist ory, and chest radiograph concordant ly suggest volume overload and
heart failure, and a BNP level confirming t his would not be helpful.
A radionuclide vent riculogram would accurat ely assess vent ricular eject ion fract ion but would not provide ot her cardiac st ruct ural or funct ional informat ion t hat may impact
management . A radionuclide vent riculogram, t herefore, is not t he most appropriat e next t est .
Ischemia is a major cause of left vent ricular dysfunct ion. Given t he pot ent ial significant benefit s of revascularizat ion in appropriat e candidat es, including improved
vent ricular funct ion and reduced morbidit y and mort alit y, diligent evaluat ion for coronary art ery disease should be undert aken for most pat ient s wit h heart failure. A st ress
t est would be appropriat e in t his pat ient if t here were a higher clinical suspicion for coronary disease or ischemia causing new-onset heart failure. However, given t he lack of
anginal sympt oms, t he pat ient 's relat ively young age, and lack of risk fact ors, clinical suspicion at t his point is low. Finally, and import ant ly, an exercise st ress t est is
cont raindicat ed in a pat ient wit h decompensat ed heart failure, such as t his pat ient .
Key Poi nt
An echocardiogram should be obt ained in all pat ient s wit h newly diagnosed or suspect ed heart failure.
Bi bl i ography
Abraham J, Abraham TP. The role of echocardiography in hemodynamic assessment in heart failure. Heart Fail Clin. 2009;5(2):191-208. [PMID: 19249688]
Item 39 Answer: B
Educati onal Objecti ve: Treat New York Heart Association class I or II systolic heart failure with a -blocker.
Treat ment wit h an angiot ensin-convert ing enzyme (ACE) inhibit or (such as lisinopril) and a -blocker (such as carvedilol) is indicat ed for all pat ient s wit h syst olic heart
failure regardless of sympt oms or funct ional st at us, including asympt omat ic or very funct ional pat ient s. The combinat ion of t hese t wo classes of medicat ions has addit ive
benefit s wit h regard t o morbidit y and mort alit y in syst olic heart failure. This pat ient is already t aking an ACE inhibit or, so a -blocker such as carvedilol should be added. -
Blockers should not be init iat ed or increased during decompensat ed st at es, such as volume overload or hypot ension, because t he t ransient decline in cardiac out put may worsen
a decompensat ed st at e.
Amlodipine is t he only calcium channel blocker demonst rat ed t o have a neut ral (rat her t han det riment al) effect on morbidit y and mort alit y in heart failure. Thus, it is an
accept able agent t o use for angina or hypert ension t hat is not adequat ely cont rolled wit h ACE inhibit ors or -blockers. However, t his pat ient has neit her angina nor
uncont rolled hypert ension, and amlodipine is not indicat ed.
Digoxin is indicat ed for pat ient s wit h moderat ely t o severely sympt omat ic heart failure (New York Heart Associat ion [NYHA] class III-IV) or for rat e cont rol in pat ient s
wit h at rial fibrillat ion. Digoxin improves sympt oms and reduces hospit alizat ions, but it does not affect survival. Spironolact one is indicat ed only for t reat ment of NYHA class
III or IV heart failure; in t his set t ing, it s use is associat ed wit h a 30% reduct ion in mort alit y. This pat ient , however, is only minimally sympt omat ic (NYHA class II);
t reat ment wit h eit her digoxin or spironolact one is not indicat ed.
There are current ly no robust dat a t o support addit ion of an angiot ensin recept or blocker (ARB), such as losart an, t o ACE inhibit or t herapy for t reat ment of syst olic heart
failure. No definit ive improvement in survival has been demonst rat ed using t he combinat ion of t hese t wo agent s. ARBs are current ly recommended only for pat ient s who are
int olerant of ACE inhibit ors, primarily owing t o ACE inhibit or-induced cough.
Key Poi nt
Treat ment wit h an angiot ensin-convert ing enzyme inhibit or and a -blocker is indicat ed for all pat ient s wit h syst olic heart failure regardless of sympt oms or funct ional
st at us, including asympt omat ic or very funct ional pat ient s.
Bi bl i ography
Item 40 Answer: D
Educati onal Objecti ve: Treat a patient with heart failure with a -blocker and an angiotensin-converting enzyme inhibitor.
This pat ient should be st art ed on lisinopril in addit ion t o met oprolol. Angiot ensin-convert ing enzyme (ACE) inhibit ors, such as lisinopril, are indicat ed for t reat ment of all
New York Heart Associat ion (NYHA) funct ional classes of syst olic heart failure, including asympt omat ic (NYHA class I) pat ient s. ACE inhibit ors reduce mort alit y and
morbidit y in asympt omat ic and sympt omat ic pat ient s and delay t he onset of clinical heart failure in pat ient s wit h asympt omat ic left vent ricular dysfunct ion. Overall, ACE
inhibit or t herapy reduces mort alit y by about 20%, risk for myocardial infarct ion by about 20%, and hospit alizat ion for heart failure by 30% t o 40%.
For pat ient s int olerant of ACE inhibit ors owing t o hyperkalemia or renal insufficiency, t he combinat ion of hydralazine and a nit rat e is a suit able alt ernat ive, wit h
hemodynamic effect s of vasodilat ion and aft erload reduct ion. Treat ment wit h t his combinat ion is also associat ed wit h a reduct ion in mort alit y, alt hough t o a lesser degree
t han is seen wit h ACE inhibit ors, and t his combinat ion does not have t he same posit ive impact on qualit y of life as an ACE inhibit or.
The role of digoxin in t reat ing heart failure pat ient s in sinus rhyt hm is primarily for sympt om cont rol rat her t han improving survival. Treat ment wit h digoxin has not been
shown t o affect mort alit y but has been shown t o reduce hospit alizat ions. Digoxin can be added t o ot her t herapy in pat ient s wit h NYHA class III or IV heart failure for
sympt om cont rol. Maint aining lower serum concent rat ions of digoxin is as effect ive as maint aining higher concent rat ions, and pot ent ial t oxicit ies are avoided.
Eplerenone is a select ive aldost erone blocker t hat is current ly approved for t reat ment of hypert ension and for left vent ricular dysfunct ion aft er myocardial infarct ion.
Eplerenone is a suit able alt ernat ive t o spironolact one in t reat ment of severe heart failure (NYHA class III or IV) if gynecomast ia develops as a side effect of spironolact one
t reat ment .
This pat ient has NYHA class II heart failure (sympt oms wit h moderat e exert ion) and does not meet t he crit eria for t reat ment wit h digoxin or an aldost erone agonist .
Key Poi nt
Angiot ensin-convert ing enzyme inhibit ors are indicat ed for t reat ment of all New York Heart Associat ion (NYHA) funct ional classes of syst olic heart failure, including
asympt omat ic (NYHA class I) pat ient s.
Bi bl i ography
Goldberg LR. Heart failure. Ann Int ern Med. 2010;152(11):ITC61-15; quiz, ITC616. [PMID: 20513825]
Item 41 Answer: D
Educati onal Objecti ve: Treat a patient with New York Heart Association functional class III or IV heart failure with spironolactone.
The most appropriat e addit ion t o t his pat ient 's t reat ment is spironolact one. She has sympt oms consist ent wit h New York Heart Associat ion (NYHA) class III funct ional
st at us (sympt oms develop wit h mild act ivit y), and she does not appear volume-overloaded on examinat ion (normal cent ral venous pressure and no S
3
, pulmonary crackles, or
edema). Spironolact one is indicat ed for t reat ment of severe (NYHA funct ional class III or IV) syst olic heart failure in addit ion t o st andard t herapy wit h an angiot ensin-
convert ing enzyme (ACE) inhibit or, -blocker, and diuret ic as needed. Spironolact one furt her blocks t he act ions of aldost erone, which is not complet ely suppressed by
chronic ACE inhibit or t herapy; aldost erone has adverse effect s of sodium ret ent ion, pot assium wast ing, and myocardial fibrosis. The addit ion of spironolact one is associat ed
wit h a 30% relat ive reduct ion in mort alit y.
Serum creat inine and pot assium levels should be serially monit ored in pat ient s t aking spironolact one. Cont raindicat ions t o spironolact one t herapy include a serum creat inine
level great er t han 2.5 mg/dL (221 mol/L) in men or 2.0 mg/dL (176.8 mol/L) in women or a pot assium level great er t han 5 meq/L (5 mmol/L).
It is generally not recommended t o add angiot ensin recept or blocker t herapy, such as losart an, t o ACE inhibit or t herapy because t he risk of adverse side effect s, such as
hyperkalemia and hypot ension, is increased.
The addit ion of met olazone t o loop diuret ic t herapy can be useful t o increase diuret ic effect iveness. However, t his pat ient appears euvolemic on her current diuret ic regimen,
so enhanced diuresis is not needed.
First -generat ion calcium channel blockers (such as nifedipine) have been shown t o increase t he risk of heart failure decompensat ion and hospit alizat ion. Amlodipine and
felodipine are t he only calcium channel blockers wit h demonst rat ed neut ral effect s on mort alit y in pat ient s wit h heart failure. These agent s can be used in pat ient s wit h heart
failure for t he management of hypert ension or angina not adequat ely cont rolled wit h ot her agent s such as ACE inhibit ors or -blockers.
Key Poi nt
Angiot ensin-convert ing enzyme inhibit ors, -blockers, and spironolact one reduce mort alit y in pat ient s wit h New York Heart Associat ion class III or IV heart failure.
Bi bl i ography
Item 42 Answer: A
Educati onal Objecti ve: Diagnose atrial fibrillation as the cause of clinical deterioration in a patient with aortic stenosis.
New-onset at rial fibrillat ion is t he most likely cause of t he pat ient 's new sympt oms. Aort ic valve sclerosis, or valve t hickening wit hout out flow obst ruct ion, is present in
more t han 25% of persons older t han 65 years. Pat ient s are oft en diagnosed when an asympt omat ic murmur is auscult at ed or following an incident al echocardiographic
finding. The progression from aort ic sclerosis t o st enosis is slow, and fewer t han 20% of pat ient s develop valve obst ruct ion over t he next 10 years. When mild st enosis is
present , however, progressive valve st enosis proceeds more rapidly. Classic manifest at ions of aort ic st enosis are angina, syncope, and heart failure. In early st ages, aort ic
st enosis may present subt ly wit h dyspnea or a decrease in exercise t olerance. At rial fibrillat ion can be associat ed wit h rapid and severe clinical det eriorat ion due t o t he more
rapid rat e and loss of at rial cont ribut ion t o left vent ricular filling. Angina occurs in more t han 50% of pat ient s wit h severe st enosis, due in part t o maldist ribut ion of coronary
flow in t he hypert rophied myocardium. Pat ient s wit h aort ic st enosis have increased sensit ivit y t o ischemic injury, and subsequent ly have higher mort alit y. Frank syncope
associat ed wit h aort ic st enosis is rare, wit h prospect ive st udies document ing sudden cardiac deat h rat es less t han 1% annually.
Endocardit is should be suspect ed if an abnormal murmur is heard on examinat ion, part icularly in pat ient s wit h a compelling hist ory or concurrent fever. Incidence is higher in
pat ient s wit h underlying valve abnormalit ies and prost het ic valves. Because of t he absence of fever and t he presence of at rial fibrillat ion as a more likely cause of clinical
det eriorat ion, infect ive endocardit is is unlikely.
Pat ient s wit h a hist ory of rheumat ic fever may have involvement of mult iple heart valves, but t his is not t he case in pat ient s wit h degenerat ive aort ic sclerosis. Furt hermore,
t he physical examinat ion findings of chronic mit ral regurgit at ion include a holosyst olic murmur, heard best at t he apex, wit h radiat ion lat erally or post eriorly. The
auscult at ory findings for mit ral st enosis include an opening snap wit h a low-pit ched middiast olic murmur t hat accent uat es presyst ole. These findings are not present , making
mit ral st enosis or regurgit at ion unlikely.
Key Poi nt
In pat ient s wit h aort ic st enosis, at rial fibrillat ion can be associat ed wit h rapid and severe clinical det eriorat ion due t o t he more rapid rat e and loss of at rial cont ribut ion t o left
vent ricular filling.
Bi bl i ography
Kappet ein AP, van Geldorp M, Takkenberg JJ, Bogers AJ. Opt imum management of elderly pat ient s wit h calcified aort ic st enosis. Expert Rev Cardiovasc Ther.
2008;6(4):491-501. [PMID: 18402539]
Item 43 Answer: A
Educati onal Objecti ve: Diagnose failure of a prosthetic aortic heart valve.
Failure of a prost het ic aort ic valve oft en leads t o aort ic insufficiency. Bioprost het ic valves are less durable t han mechanical valves because of t he progressive degenerat ive
calcificat ion of t he biologic mat erial. In t he first generat ion of bioprost het ic valves, only about 50% of aort ic and 30% of mit ral prost heses were st ill working aft er 15 years.
Alt hough newer valves are more durable and have larger valve areas and improved hemodynamics, t hey are st ill prone t o progressive calcific degenerat ion. Physical
examinat ion in pat ient s wit h chronic aort ic regurgit at ion shows a widened pulse pressure wit h bounding peripheral and carot id pulses. Auscult at ory findings include an early t o
holodiast olic murmur along t he left upper st ernal border, which is high pit ched and may be bet t er heard when t he pat ient is at end-expirat ion, leaning forward.
The charact erist ic physical examinat ion findings in at rial sept al defect are fixed split t ing of t he S
2
and a right vent ricular heave. A pulmonary midsyst olic flow murmur and a
t ricuspid diast olic flow rumble caused by increased flow t hrough t he right -sided valves from a large left -t o-right shunt may be heard.
Aort ic coarct at ion is usually diagnosed in childhood by t he associat ion of a syst olic murmur wit h syst emic hypert ension and reduced femoral pulse amplit ude. More t han 50%
of pat ient s wit h aort ic coarct at ion also have a bicuspid aort ic valve. When coarct at ion is severe, t he murmur may be cont inuous and a murmur from collat eral int ercost al
vessels may also be audible and palpable. An eject ion click and aort ic syst olic murmur suggest t he presence of a bicuspid aort ic valve. An S
4
is common.
The auscult at ory findings for rheumat ic mit ral st enosis include an opening snap wit h a low-pit ched middiast olic murmur t hat accent uat es presyst ole and is best heard over t he
mit ral valve area. The S
1
may be int ensified owing t o higher left at rial pressures.
New-onset vent ricular sept al defect in adult s usually occurs 5 t o 7 days following a myocardial infarct ion. It is charact erized by t he development of cardiogenic shock and a
new syst olic murmur. A t hrill along t he left st ernal border may also be present . This pat ient does not have a hist ory consist ent wit h myocardial infarct ion and does not have
t he t ypical findings.
Key Poi nt
Failure of a prost het ic aort ic valve oft en leads t o aort ic insufficiency.
Bi bl i ography
Choudhry NK, Et chells EE. The rat ional clinical examinat ion. Does t his pat ient have aort ic regurgit at ion? JAMA. 1999;281(23):2231-8. [PMID: 10376577]
Item 44 Answer: D
Educati onal Objecti ve: Manage an asymptomatic benign murmur.
This pat ient has a benign midsyst olic murmur t hat is grade 2/6 in int ensit y and requires no furt her evaluat ion or int ervent ion. Midsyst olic murmurs grade 2/6 or less are
considered innocent murmurs, especially when t hey are short in durat ion, associat ed wit h a physiologically split (normal) S
2
, and are not accompanied by any ot her abnormal
cardiac sounds or murmurs. The most common et iology of t his t ype of murmur in persons older t han 65 years is minor valvular abnormalit ies due t o aort ic sclerosis. Aort ic
sclerosis is charact erized by focal areas of valve t hickening leading t o mild valvular t urbulence, producing t he auscult at ed murmur. A hyperdynamic circulat ion (for example,
from severe anemia, t hyrot oxicosis, or pregnancy) also may produce an innocent midsyst olic pulmonary or aort ic flow murmur. A physiologically split S
2
(apparent during
inspirat ion, absent during exhalat ion) excludes severe aort ic st enosis.
Endocardit is prophylaxis is not indicat ed. The only pat ient s who should receive endocardit is prophylaxis are t hose wit h prost het ic cardiac valves, t hose wit h a known hist ory
of prior infect ive endocardit is, t hose wit h unrepaired cyanot ic congenit al heart disease, t hose wit h complex congenit al heart disease wit h residual abnormalit ies, and cardiac
t ransplant recipient s wit h valve abnormalit ies.
Transt horacic echocardiography is indicat ed when a grade 3/6 or great er syst olic murmur is heard on examinat ion, in t he presence of any diast olic or cont inuous murmur, or
if a new murmur is diagnosed in t he int erval since a normal prior physical examinat ion; none of t hese crit eria are met by t his pat ient .
A screening cardiac st ress t est is not warrant ed because she has no sympt oms indicat ive of angina or risk fact ors for coronary art ery disease. In a pat ient wit h a low pret est
probabilit y of coronary art ery disease, an exercise st ress t est would carry a high false-posit ive rat e.
Key Poi nt
Short , soft , midsyst olic murmurs in t he elderly are usually benign and caused by minor, age-relat ed changes of t he aort ic valve (aort ic sclerosis).
Bi bl i ography
Et chells E, Bell C, Robb K. Does t his pat ient have an abnormal syst olic murmur? JAMA. 1997;277(7):564-571. [PMID: 9032164]
Item 45 Answer: C
Educati onal Objecti ve: Diagnose mitral stenosis.
This pat ient 's clinical hist ory and physical examinat ion findings are consist ent wit h rheumat ic mit ral valve st enosis. Cardiac auscult at ion reveals t he t ypical findings of mit ral
st enosis, including an accent uat ion of P
2
(evidence of elevat ed pulmonary art erial pressure), an opening snap (a high-pit ched apical sound best heard wit h t he diaphragm of
t he st et hoscope), and a low-pit ched, rumbling diast olic murmur.
Mit ral st enosis is usually caused by rheumat ic valve disease. In t he Unit ed St at es, clinical present at ion t ends t o be 20 t o 30 years aft er t he init ial episode of rheumat ic fever,
and most cases occur in women. Pat ient s wit h mit ral st enosis may be asympt omat ic for some t ime, but become sympt omat ic wit h addit ional hemodynamic st ress, such as t he
increased volume load of pregnancy. This hemodynamic st ress may precipit at e an arrhyt hmia, such as at rial fibrillat ion, t hat can furt her exacerbat e heart failure sympt oms.
The diagnosis of acut e aort ic regurgit at ion is suggest ed in pat ient s wit h rapid onset of dyspnea, exercise int olerance, or chest pain (aort ic dissect ion). Physical findings include
t achycardia, hypot ension, a soft S
1
(due t o premat ure closure of t he mit ral valve), an S
3
and/or S
4
gallop, an accent uat ed pulmonic closure sound, and pulmonary crackles. The
t ypical murmur of aort ic regurgit at ion may not be prominent in acut e disease as aort ic and left vent ricular diast olic pressures equilibrat e quickly, result ing in a short and soft
(somet imes inaudible) diast olic murmur at t he base of t he heart .
The charact erist ic physical examinat ion finding in at rial sept al defect is fixed split t ing of t he S
2
. A pulmonic midsyst olic murmur at t he base of t he heart and a t ricuspid
diast olic flow rumble may be heard at t he lower left st ernal border owing t o increased flow t hrough t he valves from t he left -t o-right shunt .
The murmur of t ricuspid regurgit at ion is a syst olic murmur t hat is best heard at t he lower left st ernal border and charact erist ically increases in int ensit y wit h inspirat ion.
Tricuspid regurgit at ion usually occurs as a secondary consequence of pulmonary hypert ension, right vent ricular chamber enlargement wit h annular dilat at ion, or endocardit is.
Key Poi nt
Typical findings of mit ral st enosis include an opening snap and a low-pit ched, rumbling diast olic murmur.
Bi bl i ography
Chizner MA. The diagnosis of heart disease by clinical assessment alone. Dis Mon. 2002;48(1):7-98. [PMID: 11807426]
Item 46 Answer: C
Educati onal Objecti ve: Diagnose hypertrophic cardiomyopathy.
In t his pat ient , t he physical examinat ion is most consist ent wit h hypert rophic cardiomyopat hy. The syst olic murmur of hypert rophic cardiomyopat hy is caused by
obst ruct ion in t he left vent ricular out flow t ract from t he t hickened int ervent ricular sept um. In severe cases, syst olic ant erior mot ion of t he mit ral valve apparat us int o t he
left vent ricular out flow t ract cont ribut es t o t he syst olic murmur. If mit ral valve leaflet coapt at ion is affect ed, t here may be concurrent mit ral regurgit at ion. The st and-t o-
squat maneuver and passive leg lift t ransient ly increase venous ret urn (preload), which increases left vent ricular chamber size and volume. As a consequence, t here is less
relat ive obst ruct ion and t urbulence in t he left vent ricular out flow t ract , decreasing murmur int ensit y. Handgrip exercise also diminishes murmur int ensit y, by increasing
aft erload and decreasing t he relat ive pressure gradient across t he left vent ricular out flow t ract . The Valsalva maneuver and t he squat -t o-st and maneuver t ransient ly decrease
venous ret urn, wit h t he sept um and ant erior mit ral leaflet brought closer t oget her. Turbulent flowand t he murmurare increased. Transt horacic echocardiography can
confirm a diagnosis of hypert rophic cardiomyopat hy.
Aort ic coarct at ion in an adult is charact erized by hypert ension and a cont inuous or lat e syst olic murmur t hat may be heard over t he back. Because pulses dist al t o t he aort ic
obst ruct ion are decreased, aort ic coarct at ion is also associat ed wit h abnormal differences in upper and lower ext remit y blood pressures. The carot id upst roke is normal in
coarct at ion.
A congenit al bicuspid aort ic valve is a common cause of calcific aort ic st enosis. The murmur of aort ic st enosis is an early syst olic murmur t hat oft en radiat es t oward t he
carot id art eries. Hypert rophic cardiomyopat hy is associat ed wit h rapid upst rokes of t he carot id art eries, helping t o dist inguish it from aort ic st enosis, which is associat ed wit h
a carot id art ery pulsat ion t hat has a slow up-rise and is diminished in volume. In addit ion, t he murmur of aort ic st enosis decreases wit h t he Valsalva maneuver. Finally,
alt hough t he presence of a bicuspid aort ic valve accelerat es t he process of aort ic calcificat ion, pat ient s t ypically develop st enosis in t heir t hirt ies or fort ies, not in t he lat e
t eens or early t went ies.
The murmur associat ed wit h a vent ricular sept al defect is a harsh syst olic murmur locat ed parast ernally t hat radiat es t o t he right st ernal edge and may be associat ed wit h a
palpable t hrill but no change in t he carot id art ery pulsat ion. Maneuvers t hat increase aft erload, such as isomet ric handgrip exercise, increase t he left -sided murmurs of mit ral
regurgit at ion and vent ricular sept al defect .
Key Poi nt
The Valsalva maneuver and t he squat -t o-st and maneuver increase t he murmur of hypert rophic cardiomyopat hy.
Bi bl i ography
Et chells E, Bell C, Robb K. Does t his pat ient have an abnormal syst olic murmur? JAMA. 1997;277(7):564-571. [PMID:9032164]
Item 47 Answer: A
Educati onal Objecti ve: Diagnose aortic valve regurgitation.
This pat ient most likely has aort ic regurgit at ion. Physical findings of chronic aort ic regurgit at ion may include cardiomegaly, t achycardia, a widened pulse pressure, a t hrill at
t he base of t he heart , a soft S
1
and a somet imes absent aort ic closure sound, and an S
3
gallop. The charact erist ic high-pit ched diast olic murmur begins immediat ely aft er S
2
and
is heard best at t he second right or t hird left int ercost al space wit h t he pat ient leaning forward, and in end-expirat ion. Manifest at ions of t he widened pulse pressure may
include t he Traube sign (pist ol-shot sounds over t he peripheral art eries), t he de Musset sign (head bobs wit h each heart beat ), t he Duroziez sign (syst olic and diast olic murmur
heard over t he femoral art ery), and t he Quincke sign (syst olic plet hora and diast olic blanching in t he nail bed wit h nail compression).
Mit ral st enosis is associat ed wit h accent uat ion of P
2
(evidence of elevat ed pulmonary art erial pressure), an opening snap (a high-pit ched apical diast olic sound best heard wit h
t he diaphragm of t he st et hoscope) followed by a low-pit ched, rumbling diast olic murmur best heard wit h t he bell of t he st et hoscope at t he apex wit h t he pat ient in t he left
lat eral decubit us posit ion. Presyst olic accent uat ion of t he murmur may be present . As t he severit y of t he st enosis worsens, t he opening snap moves closer t o S
2
as a result of
increased left at rial pressure, and t he murmur increases in durat ion.
A small pat ent duct us art eriosus in an adult produces a cont inuous murmur t hat envelopes t he S
2
and is charact erist ically heard beneat h t he left clavicle. Pat ient s wit h a
moderat e-sized pat ent duct us art eriosus may present wit h sympt oms of heart failure, a cont inuous "machinery-t ype" murmur best heard at t he left infraclavicular area, and
bounding pulses wit h a wide pulse pressure.
Tricuspid valve regurgit at ion usually occurs as a secondary consequence of pulmonary hypert ension, right vent ricular chamber enlargement wit h annular dilat at ion, or
endocardit is. The murmur of t ricuspid regurgit at ion occurs during syst ole and is loudest at t he lower left st ernal border and becomes louder wit h inspirat ion.
Key Poi nt
The charact erist ic high-pit ched diast olic murmur of chronic aort ic regurgit at ion begins immediat ely aft er S
2
and is heard best wit h t he pat ient leaning forward, and in end-
expirat ion at t he second right or t hird left int ercost al space.
Bi bl i ography
Choudhry NK, Et chells EE. The rat ional clinical examinat ion. Does t his pat ient have aort ic regurgit at ion? JAMA. 1999;281(23):2231-2238. [PMID: 10376577]
Item 48 Answer: D
Educati onal Objecti ve: Diagnose mitral valve prolapse.
Mit ral valve prolapse is t he most common cause of mit ral regurgit at ion. The prevalence in t he Unit ed St at es is 2% t o 3% wit h equal sex dist ribut ion. The classic auscult at ory
findings are a midsyst olic click followed by a lat e apical syst olic murmur. A squat -t o-st and maneuver t ransient ly decreases preload on t he heart . This decreases left vent ricular
chamber size and increases syst olic buckling of t he redundant mit ral valve int o t he left at rium, moving t he midsyst olic click earlier in syst ole and increasing mit ral
regurgit at ion.
Most pat ient s wit h mit ral valve prolapse have eit her minimal or no mit ral regurgit at ion, and t he prognosis is benign, wit h annual mort alit y below 1%. Serious complicat ions,
which are rare, include significant mit ral regurgit at ion, infect ive endocardit is, and arrhyt hmia.
The murmur of aort ic st enosis is an early syst olic murmur t hat is heard best at t he right second int ercost al space but can be heard anywhere from t he cardiac base t o t he apex.
The murmur oft en radiat es t oward t he carot id art eries. The murmur of aort ic st enosis decreases wit h t he Valsalva maneuver.
Aort ic coarct at ion in an adult is charact erized by hypert ension and a cont inuous or lat e syst olic murmur t hat may be heard over t he back. Because pulses dist al t o t he aort ic
obst ruct ion are decreased, aort ic coarct at ion is also associat ed wit h abnormal differences in upper and lower ext remit y blood pressures.
The murmur of hypert rophic cardiomyopat hy is a harsh syst olic murmur heard best near t he lower left st ernal border bet ween t he st ernum and apex. The Valsalva maneuver
and t he squat -t o-st and maneuver t ransient ly increase t he int ensit y of t he murmur. Handgrip exercise increases aft erload and decreases t he relat ive pressure gradient across t he
left vent ricular out flow t ract , so murmur int ensit y for hypert rophic cardiomyopat hy is decreased. Carot id upst rokes are brisk. There is no midsyst olic click.
Key Poi nt
The classic auscult at ory findings of mit ral valve prolapse are a midsyst olic click followed by a lat e apical syst olic murmur.
Bi bl i ography
Fost er E. Clinical pract ice. Mit ral regurgit at ion due t o degenerat ive mit ral-valve disease. N Engl J Med. 2010;363(2):156-65. [PMID: 20647211]
Item 49 Answer: D
Educati onal Objecti ve: Follow a patient with an asymptomatic bicuspid aortic valve and preserved left ventricular function.
The most appropriat e management for t his pat ient is clinical follow-up in 1 year. This pat ient has a bicuspid aort ic valve wit h moderat e aort ic regurgit at ion.
Echocardiography demonst rat es normal left vent ricular size and syst olic funct ion. Pulmonary pressures are in t he normal range, and t here is no evidence of adverse
hemodynamic effect s of valve regurgit at ion on t he vent ricle (vent ricular size and funct ion are normal). No specific t reat ment is needed at t his t ime. However, because
worsening of aort ic regurgit at ion can be insidious, rout ine clinical follow-up is indicat ed in at least yearly int ervals, t ypically wit h repeat t ranst horacic echocardiography t o
monit or for disease progression. The presence of a bicuspid aort ic valve is associat ed wit h ascending aort a dilat at ion, and t ranst horacic echocardiography can also monit or for
aort ic enlargement . Most pat ient s wit h bicuspid valves will event ually develop aort ic st enosis, regurgit at ion, or aort ic root dilat at ion or dissect ion t hat will require surgery.
Ant ibiot ic endocardit is prophylaxis is now recommended only in pat ient s wit h prost het ic cardiac valves, t hose wit h a known hist ory of prior infect ive endocardit is, cardiac
t ransplant recipient s wit h valve abnormalit ies, t hose wit h unrepaired cyanot ic congenit al heart disease, and t hose wit h complex congenit al heart disease wit h residual
abnormalit ies. This pat ient , t herefore, should not receive ant ibiot ic endocardit is prophylaxis.
Aort ic valve replacement surgery is recommended in pat ient s wit h severe aort ic regurgit at ion and cardiopulmonary sympt oms. In asympt omat ic pat ient s wit h severe
regurgit at ion, surgery is recommended once t here are signs of left vent ricular enlargement or adverse hemodynamic effect s on t he left vent ricle, or if t he eject ion fract ion
falls below 50% t o 55%. This pat ient is asympt omat ic, and his left vent ricular size and funct ion are normal.
A -blocker (such as met oprolol) is indicat ed for all st ages of syst olic heart failure, even asympt omat ic pat ient s wit h left vent ricular eject ion fract ions less t han 50%. This
pat ient has no evidence of syst olic heart failure eit her by sympt oms or echocardiographic evidence. There is no evidence t hat t reat ment wit h a -blocker delays t he t ime t o
aort ic valve replacement ; t herefore, met oprolol is not indicat ed.
Key Poi nt
Asympt omat ic pat ient s wit h chronic aort ic regurgit at ion and normal left vent ricular size and funct ion have an excellent prognosis and do not require prophylact ic surgery.
Bi bl i ography
Maurer G. Aort ic regurgit at ion. Heart . 2006;92(7):994-1000. [PMID: 16775114]
Secti on 2. Endocri nol ogy and Metabol i sm
Questi ons
Item 1 [Basic]
A 48-year-old man comes t o t he office for a rout ine physical examinat ion. The pat ient is asympt omat ic but overweight . Alt hough he has no pert inent personal medical
hist ory, he has a st rong family hist ory of diabet es mellit us. He current ly t akes no medicat ions.
Result s of physical examinat ion are normal, except for a BMI of 29.
Result s of rout ine laborat ory st udies show a fast ing plasma glucose level of 158 mg/dL (8.8 mmol/L). These result s are confirmed 2 days lat er.
Whi ch of the fol l owi ng terms best descri bes hi s current gl ycemi c status?
(A) Impaired fast ing glucose
(B) Impaired glucose t olerance
(C) Met abolic syndrome
(D) Type 2 diabet es mellit us
Item 2 [Basic]
A 68-year-old woman is re-evaluat ed aft er laborat ory st udies show a fast ing plasma glucose level of 113 mg/dL (6.3 mmol/L). She has a family hist ory of t ype 2 diabet es
mellit us.
On physical examinat ion, blood pressure is 142/88 mm Hg and BMI is 29. Ot her vit al signs and examinat ion findings are normal.
She undergoes an oral glucose t olerance t est , during which her 2-hour plasma glucose level increases t o 135 mg/dL (7.5 mmol/L).
Whi ch of the fol l owi ng i s the most appropri ate treatment recommendati on?
(A) Acarbose
(B) Met formin
(C) Ramipril
(D) Rosiglit azone
(E) Diet and exercise
Item 3 [Advanced]
A 51-year-old man is evaluat ed for a 9-mont h hist ory of chronic abdominal pain. He has a long-st anding hist ory of alcoholism and has been admit t ed t o t he hospit al several
t imes in t he past 8 years for acut e pancreat it is. He report s a 5.5-kg (12.1-lb) weight loss over t he past year. He current ly t akes no medicat ions.
Vit al signs are normal; BMI is 23. Physical examinat ion reveals a scaphoid-appearing abdomen wit h normal bowel sounds and diffuse abdominal t enderness t o palpat ion
wit hout guarding.
A fast ing plasma glucose level is 175 mg/dL (9.7 mmol/L), and a repeat fast ing plasma glucose level is 182 mg/dL (10.1 mmol/L). Urine ket ones are negat ive.
A CT scan of t he abdomen reveals diffuse pancreat ic calcificat ions.
Whi ch of the fol l owi ng i s the best categori zati on of thi s pati ent's di abetes mel l i tus?
(A) Lat e-onset aut oimmune diabet es of adult hood
(B) Secondary diabet es
(C) Type 1 diabet es
(D) Type 2 diabet es
Item 4 [Basic]
An obese 44-year-old woman is evaluat ed for persist ent hyperglycemia. For t he past 3 mont hs, she has followed a st rict regimen of diet and exercise in an at t empt t o cont rol
her hyperglycemia. Home blood glucose monit oring has shown preprandial levels bet ween 120 and 160 mg/dL (6.7 and 8.9 mmol/L) and occasional post prandial levels
exceeding 200 mg/dL (11.1 mmol/L). She t akes no medicat ions.
Vit al signs and physical examinat ion findings are normal, except for a BMI of 30.
Laborat ory st udies show a serum creat inine level of 0.8 mg/dL (70.7 mol/L); t he urine is negat ive for microalbuminuria.
Whi ch of the fol l owi ng i s the most appropri ate treatment?
(A) Begin exenat ide
(B) Begin glimepiride
(C) Begin met formin
(D) Begin pioglit azone
(E) Cont inue t he diet and exercise for an addit ional 3 mont hs
Item 5 [Advanced]
A 78-year-old man is evaluat ed in t he hospit al for poor glycemic cont rol before undergoing femoral-poplit eal bypass surgery. He has been on t he vascular surgery ward for 3
weeks wit h a nonhealing foot ulcer. The pat ient has an ext ensive hist ory of art eriosclerot ic cardiovascular disease, including peripheral vascular disease, and a 20-year-hist ory
of t ype 2 diabet es mellit us. His most recent hemoglobin A
1c
value, obt ained on admission, was 8.9%. His diabet es regimen consist s of glipizide. While in t he hospit al, his
plasma glucose levels have generally been in t he 200 t o 250 mg/dL (11.1 t o 13.9 mmol/L) range. He is eat ing well.
In addi ti on to stoppi ng gl i pi zi de, whi ch of the fol l owi ng i s most appropri ate treatment for thi s pati ent?
(A) Basal insulin and rapid-act ing insulin before meals
(B) Cont inuous insulin infusion
(C) Neut ral prot amine Hagedorn (NPH) insulin t wice daily
(D) Sliding scale regular insulin
Item 6 [Advanced]
A 48-year-old man is evaluat ed for mild blurring of his cent ral vision bilat erally. He has had t ype 1 diabet es mellit us for 24 years. The pat ient is referred for an immediat e
ret inal examinat ion, which reveals macular edema and new neovascularizat ion.
Whi ch of the fol l owi ng i s the most appropri ate next management step?
(A) Addit ion of aspirin
(B) Addit ion of at orvast at in
(C) Decrease in t he insulin dosage
(D) Ret inal phot ocoagulat ion
Item 7 [Basic]
A 67-year-old woman is seen for a follow-up visit . She has had several hypoglycemic episodes t hat have become increasingly frequent over t he past 6 mont hs. Her current
medicat ions are neut ral prot amine Hagedorn (NPH) insulin, 20 unit s, and regular insulin, 5 unit s, bot h inject ed before breakfast and supper. A review of her glucose log shows
blood glucose readings ranging bet ween 70 and 150 mg/dL (3.9 and 8.3 mmol/L) when fast ing and 50 and 250 mg/dL (2.8 and 13.9 mmol/L) during t he day. Her last measured
hemoglobin A
1c
value was 7.8%.
Whi ch of the fol l owi ng changes i s most appropri ate?
(A) Change t o insulin glargine and insulin lispro
(B) Change t o oral met formin and sit aglipt in
(C) Decrease t he dosages of NPH and regular insulin by 10%
(D) Increase her caloric int ake
Item 8 [Basic]
A 20-year-old woman is brought t o t he emergency depart ment by her college roommat e. The pat ient is let hargic wit h rapid respirat ions. Her roommat e report s t hat t he
pat ient has had a cough, fever, and chills for t he 3 days. She has a 12-year hist ory of t ype 1 diabet es mellit us. During t he previous 24 hours, t he pat ient has had poor oral
int ake and has not t aken her insulin. Today she developed abdominal pain, nausea, and vomit ing.
On physical examinat ion, t he pat ient is let hargic but arousable. Temperat ure is 35.5C (96.0F), blood pressure is 90/68 mm Hg, pulse rat e is 120/min, and respirat ion rat e is
28/min and deep. The cardiopulmonary examinat ion is normal. Bowel sounds are diminished but present . Palpat ion elicit s generalized t enderness, but no perit oneal signs are
present . Ot her t han let hargy, t he neurologic examinat ion is normal.
Whi ch the fol l owi ng tests wi l l establ i sh the di agnosi s?
(A) Serum glucose and elect rolyt es and urine ket ones
(B) Serum glucose and pot assium, complet e blood count , and urinalysis
(C) Serum glucose, elect rolyt es, and ket ones and art erial blood gases
(D) Serum glucose, phosphat e, and pot assium and art erial blood gases
(E) Serum ket ones and carbon dioxide, complet e blood count , and urine ket ones
Item 9 [Advanced]
An 83-year-old obt unded woman is evaluat ed in t he emergency depart ment . She has a hist ory of t ype 2 diabet es mellit us t reat ed wit h insulin glargine. The pat ient developed
nausea, vomit ing, and diarrhea 2 days ago. Her oral int ake was limit ed, and she did not receive her insulin. Today, t he pat ient was found minimally responsive.
On physical examinat ion, t he pat ient responds only t o noxious st imuli wit h groaning. Temperat ure is 35.9C (96.7F), blood pressure is 90/50 mm Hg, pulse rat e is 120/min,
and respirat ion rat e is 14/min. She has dry mucous membranes, and her skin demonst rat es prolonged t ent ing. Ot her t han obt undat ion, t he neurologic examinat ion is normal.
Glucose 976 mg/dL (54.2 mmol/L)
Blood urea nit rogen 46 mg/dL (16.4 mmol/L)
Creat inine 2.1 mg/dL (185.6 mmol/L)
Elect rolyt es
Sodium 132 meq/L (132 mmol/L)
Pot assium 4.8 meq/L (4.8 mmol/L)
Chloride 98 meq/L (98 mmol/L)
Carbon dioxide 22 meq/L (22 mmol/L)
Osmolalit y 335 mosm/kg H
2
O
Serum ket ones Negat ive
Art erial pH 7.33
Whi ch of the fol l owi ng i s the best next management step for thi s pati ent?
(A) Administ er broad-spect rum ant ibiot ics
(B) Bicarbonat e replacement
(C) Insulin administ rat ion
(D) Int ravenous fluid administ rat ion
(E) Pot assium replacement
Item 10 [Basic]
A 23-year-old woman wit h t ype 1 diabet es mellit us is admit t ed t o t he hospit al wit h a diagnosis of communit y-acquired pneumonia and let hargy. Before admission, her insulin
pump t herapy was discont inued because of confused ment at ion.
On physical examinat ion, t emperat ure is 37.5C (99.5F), blood pressure is 108/70 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 24 min. There are decreased breat h
sounds in t he post erior right lower lung. Neurologic examinat ion reveals alt ered consciousness.
Creat inine 1.4 mg/dL (123.8 mol/L)
Elect rolyt es
Bicarbonat e 14 meq/L (14 mmol/L)
Urine ket ones Posit ive
Rapid infusion of normal saline is init iat ed.
(A) Add insulin glargine
(B) Add neut ral prot amine Hagedorn (NPH) insulin
(C) Implement a sliding scale for regular insulin
(D) St art an insulin drip
Item 11 [Basic]
A 50-year-old man is evaluat ed during a rout ine physical examinat ion. He is asympt omat ic, has no medical problems, and t akes no medicat ions. He is a nonsmoker and drinks
t wo alcoholic beverages daily. His fat her, uncle, and a brot her had myocardial infarct ions bet ween t he ages of 55 and 60 years.
On physical examinat ion, vit al signs are normal. BMI is 28. On t he skin examinat ion, he has soft , nont ender, yellow plaques measuring bet ween 0.5 and 1 cm on his upper
eyelids. The remainder of t he physical examinat ion result s are normal.
Whi ch of the di agnosti c studi es shoul d be done next?
(A) Aminot ransferase and alkaline phosphat ase
(B) Serum ferrit in
(C) Serum glucose and hemoglobin A
1c
(D) Serum lipids
(E) Thyroid-st imulat ing hormone
Item 12 [Basic]
A 41-year-old man is evaluat ed for follow-up of a lipid profile obt ained a mont h ago. He is a smoker wit h a 15 pack-year hist ory. He works in an office and does not regularly
exercise. He does not have hypert ension and does not have a family hist ory of premat ure coronary heart disease.
On physical examinat ion, vit al signs are normal. BMI is 38. His waist circumference is 94 cm (43 in). The remainder of his physical examinat ion result s are normal.
Serum glucose (fast ing) 98 mg/dL (5.4 mmol/L)
HDL cholest erol 31 mg/dL (0.8 mmol/L)
LDL cholest erol 128 mg/dL (3.3 mmol/L)
(A) Init iat e fibrat e t herapy
(B) Init iat e lifest yle modificat ions
(C) Init iat e st at in t herapy
(D) Ult rasonography t o measure carot id art ery int imal t hickness
Item 13 [Basic]
A 38-year-old man is evaluat ed during a follow-up visit . A fast ing lipid panel was performed 3 weeks ago. The pat ient does not use t obacco and has no hist ory of heart
disease, st roke, t ransient ischemic at t ack, diabet es mellit us, or renal, liver, or t hyroid disease. His fat her has hypert ension. He t akes no medicat ions and has no allergies.
Vit al signs are normal; BMI is 32. Physical examinat ion is unremarkable. Fast ing lipid levels are as follows: t ot al cholest erol, 234 mg/dL (6.1 mmol/L); HDL-cholest erol, 48
mg/dL (1.2 mmol/L); LDL-cholest erol, 158 mg/dL (4.1 mmol/L); t riglycerides: 142 mg/dL (1.6 mmol/L). All ot her laborat ory findings are wit hin normal limit s.
(A) Begin t herapy wit h a fibrat e
(B) Begin t herapy wit h a st at in
(C) Obt ain lipoprot ein(a) level
(D) Repeat lipid screening in 1 t o 2 years
Item 14 [Basic]
A 60-year-old man wit h t ype 2 diabet es mellit us and hypert ension visit s t he office t o est ablish medical care. His daily medicat ions are met formin, lisinopril, amlodipine, and
aspirin.
On physical examinat ion, blood pressure is 128/65 mm Hg and pulse is 76/min; BMI is 26. The remaining physical examinat ion findings are normal.
Cholest erol
Tot al 215 mg/dL (5.6 mmol/L)
HDL 39 mg/dL (1.0 mmol/L)
LDL 145 mg/dL (3.8 mmol/L)
Hemoglobin A
1c
6.5%
Whi ch of the fol l owi ng drugs shoul d be i ni ti ated?
(A) Colest ipol
(B) Ezet imibe
(C) Niacin
(D) Simvast at in
Item 15 [Basic]
A 63-year-old man is evaluat ed during a follow-up appoint ment . One mont h ago, he had a t ransient ischemic at t ack. A carot id ult rasound revealed a 60% left int ernal carot id
art ery st enosis, and a t ranst horacic echocardiogram revealed left vent ricular hypert rophy. He is current ly asympt omat ic. He has hypert ension and quit smoking 10 years ago.
He has no hist ory of coronary art ery disease and no family hist ory of premat ure coronary art ery disease. Current medicat ions are hydrochlorot hiazide and aspirin. An LDL-
cholest erol level 6 mont hs ago was 138 mg/dL (3.6 mmol/L), and he has been compliant wit h recommended lifest yle modificat ions.
On physical examinat ion, blood pressure is 122/78 mm Hg. There are no focal neurologic abnormalit ies. Fast ing lipid levels are as follows: t ot al cholest erol, 206 mg/dL (5.3
mmol/L); HDL-cholest erol, 50 mg/dL (1.3 mmol/L); LDL-cholest erol, 128 mg/dL (3.3 mmol/L); t riglycerides, 144 mg/dL (1.6 mmol/L).
Whi ch of the fol l owi ng i s the most appropri ate management opti on to reduce the ri sk of stroke and coronary artery events i n thi s pati ent?
(A) Add at orvast at in
(B) Add nicot inic acid
(C) Change hydrochlorot hiazide t o amlodipine
(D) Change hydrochlorot hiazide t o carvedilol
Item 16 [Advanced]
A 55-year-old woman is evaluat ed for a 7-mont h hist ory of worsening fat igue. She also report s t hat her hair is t hinning and she has an unexplained weight gain of 4.1 kg (9
lb) despit e t rying t o limit food int ake. She has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, t emperat ure is 36.7C (98.0F), blood pressure is 120/70 mm Hg, pulse rat e is 60/min, and respirat ion rat e is 12/min. BMI is 27. The t hyroid is
t wice it s normal size. Her voice is normal, and deep t endon reflexes are 2+ t hroughout . The remainder of t he physical examinat ion is normal.
Laborat ory evaluat ion reveals a serum t hyroid-st imulat ing hormone (TSH) level of 14.1 U/mL (14.1 mU/L) and a free t hyroxine level of 0.9 ng/dL (12 pmol/L).
Whi ch of the fol l owi ng tests are necessary before i ni ti ati ng therapy?
(A) Measurement of t hyroid peroxidase (TPO) ant ibody
(B) Radionuclide upt ake scanning
(C) Measurement of t hyroglobulin level
(D) No addit ional t est s
Item 17 [Advanced]
A 42-year-old woman is evaluat ed for an asymmet ric enlargement of her t hyroid. She is ot herwise asympt omat ic, and she has no risk fact ors for t hyroid cancer.
On physical examinat ion, a possible t hyroid nodule is palpat ed on t he left side. A complet e blood count , rout ine serum chemist ry t est s, and t hyroid-st imulat ing hormone level
(TSH) are normal. Ult rasound examinat ion reveals a 2.2-cm left -sided solid nodule.
What i s the appropri ate next step i n the eval uati on of thi s pati ent?
(A) Fine-needle aspirat ion of t he t hyroid nodule
(B) Measurement of serum free t hyroxine (T
4
)
(C) Measurement of t hyroglobulin level
(D) Thyroid scan and radioact ive iodine upt ake t est
(E) Thyroidect omy
Item 18 [Advanced]
A 23-year-old woman comes t o t he office for follow-up. She has a 5-year hist ory of hypot hyroidism and has been on a st able dose of levot hyroxine for t he past 3 years. She
is now 4 weeks pregnant wit h her first child.
Physical examinat ion findings are noncont ribut ory.
Result s of laborat ory st udies 2 mont hs ago showed a serum t hyroid-st imulat ing hormone (TSH) level of 2.9 U/mL (2.9 mU/L) and a free t hyroxine level of 1.4 ng/dL (18.1
pmol/L).
(A) Add iodine t herapy
(B) Measure her free t riiodot hyronine (T
3
) level
(C) Recheck her serum TSH level
(D) Cont inue current management
Item 19 [Advanced]
An 18-year-old woman is evaluat ed for t achycardia, nervousness, decreased exercise t olerance, and weight loss of 6 mont hs' durat ion. She has ot herwise been healt hy. Her
sist er has Graves disease. She t akes no medicat ions.
On physical examinat ion, blood pressure is 128/78 mm Hg, pulse rat e is 124/min, respirat ion rat e is 16/min, and BMI is 19. There is no propt osis. An examinat ion of t he
neck reveals a smoot h t hyroid gland t hat is great er t han 1.5 t imes t he normal size. Cardiac examinat ion reveals regular t achycardia. Her lungs are clear t o auscult at ion.
Human chorionic gonadot ropin Negat ive
Thyroid-st imulat ing hormone <0.01 U/mL (0.01 mU/L)
Thyroxine (T
4
), free 5.5 ng/dL (71.0 pmol/L)
Triiodot hyronine (T
3
), free 9.1 ng/L (14.0 pmol/L)
(A) At enolol
(B) At enolol and met himazole
(C) Met himazole
(D) Radioact ive iodine and met himazole
Item 20 [Advanced]
A 26-year-old woman is evaluat ed for a 2-week hist ory of const ipat ion, fat igue, and weight gain. Three mont hs ago, she began experiencing nervousness, heat int olerance,
and weight loss but says t hese sympt oms abat ed aft er 6 weeks. The pat ient delivered a healt hy infant 14 weeks ago. Aft er t hyroid funct ion t est s performed 8 weeks
post part um revealed a t hyroid-st imulat ing hormone (TSH) level of 0.02 U/mL (0.02 mU/L) and a free t hyroxine (T
4
) level of 3.5 ng/dL (45.2 pmol/L), she was placed on
at enolol, 25 mg/d.
On physical examinat ion, blood pressure is 115/70 mm Hg, pulse rat e is 50/min, respirat ion rat e is 14/min, and BMI is 23.3. No propt osis or inflammat ory changes are not ed
on ocular examinat ion. Examinat ion of t he neck reveals no t enderness or bruit s; t he t hyroid gland cannot be palpat ed.
Whi ch of the fol l owi ng i s the best next step i n management?
(A) Met himazole
(B) Repeat measurement of TSH and free T
4
levels
(C) Thyroid scan and 24-hour radioact ive iodine upt ake t est
(D) Thyroid ult rasonography
Item 21 [Advanced]
A 75-year-old man is admit t ed t o t he int ensive care unit wit h sepsis associat ed wit h pneumonia, hypoxemic respirat ory failure requiring vent ilat or support , and hypot ension.
He is t reat ed appropriat ely wit h volume resuscit at ion, vasopressors, and ant ibiot ic t herapy and is ext ubat ed 5 days lat er.
On physical examinat ion, blood pressure is 110/75 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 16/min. Examinat ion of t he neck reveals a t hyroid gland of normal
size and wit hout nodules. There are no t remors in t he ext remit ies.
Because result s of admission laborat ory st udies showed mild hyponat remia, addit ional blood t est s are performed t o evaluat e t he hyponat remia.
Cort isol (8 AM) 30 g/dL (828 nmol/L) (normal range, 5-25 g/dL [138-690 nmol/L])
Thyroid-st imulat ing hormone 0.23 U/mL (0.23 mU/L)
Thyroxine (T
4
Triiodot hyronine (T
3
), free 0.4 ng/L (0.6 pmol/L)
(A) Brain MRI
(B) Levot hyroxine administ rat ion
(C) Repeat t hyroid funct ion t est s in 6 weeks
(D) Ult rasonography of t he t hyroid gland
Item 22 [Advanced]
A 51-year-old woman is evaluat ed in t he office following an emergency depart ment visit for abdominal pain. The pain spont aneously resolved. A CT scan in t he emergency
depart ment revealed an incident ally discovered 1.4-cm left adrenal nodule wit h smoot h borders and low at t enuat ion and vascularit y. She is ot herwise healt hy and t akes no
medicat ions.
On physical examinat ion, t emperat ure is 36.5C (97.7F), blood pressure is 120/80 mm Hg, pulse rat e is 60/min, and respirat ion rat e is 14/min. The remainder of t he physical
examinat ion is normal.
A comprehensive met abolic profile, including elect rolyt es, is normal.
Whi ch of the fol l owi ng di agnosti c tests shoul d be done next?
(A) Aldost erone and renin levels and overnight suppression t est
(B) Aldost erone and renin levels and dehydroepiandrost erone sulfat e (DHEA-S) and t est ost erone levels
(C) Plasma met anephrine levels and overnight dexamet hasone suppression t est
(D) Plasma met anephrine levels, DHEA-S, and t est ost erone levels
(E) No addit ional t est s
Item 23 [Advanced]
A 43-year-old man is evaluat ed for drug-resist ant hypert ension. Hypert ension was diagnosed 1 year ago and has been difficult t o cont rol despit e maximum dosages of
lisinopril, met oprolol, and nifedipine. The pat ient report s feeling well.
On physical examinat ion, t emperat ure is 36.5C (97.7F), blood pressure is 146/92 mm Hg, pulse rat e is 88/min, respirat ion rat e is 17/min, and BMI is 27. Result s of t he
general physical examinat ion and funduscopic examinat ion are unremarkable.
Elect rolyt es
Spot urine pot assium Inappropriat ely high
Urinalysis Normal
Whi ch of the fol l owi ng i s the most appropri ate next di agnosti c test?
(A) CT of t he adrenal glands
(B) Det erminat ion of serum aldost erone t o plasma renin act ivit y rat io
(C) Digit al subt ract ion renal angiography
(D) Measurement of plasma met anephrine and normet anephrine levels
Item 24 [Advanced]
A 34-year-old woman is seen for follow-up aft er result s of laborat ory st udies confirm hypercort isolism.
Adrenocort icot ropic hormone Elevat ed
Urine free cort isol Elevat ed
Cort isol (8 AM)
Aft er 1 mg of dexamet hasone t he night before Elevat ed
Aft er 8 mg of dexamet hasone t he night before Part ial suppression
(A) Adrenal CT
(B) Adrenal MRI
(C) Cosynt ropin st imulat ion t est
(D) Pit uit ary MRI
Item 25 [Basic]
A 55-year-old woman is evaluat ed for a 6-mont h hist ory of recurrent episodes of palpit at ions, sweat ing, and headaches. Medical hist ory is ot herwise unremarkable. She t akes
no medicat ions.
On physical examinat ion, t he pat ient appears anxious. Temperat ure is 36.9C (98.4F), blood pressure is 158/96 mm Hg, pulse rat e is 88/min, respirat ion rat e is 18/min, and
BMI is 30. Findings from a general physical examinat ion, including examinat ion of t he t hyroid gland, are ot herwise unremarkable.
Laborat ory st udies show elevat ed plasma epinephrine and norepinephrine levels.
(A) Abdominal CT scan
(B) Adrenalect omy
(C) Bilat eral adrenal vein sampling
(D) Met aiodobenzylguanidine (MIBG) scan
Item 26 [Advanced]
A 65-year-old woman is evaluat ed for a 3-week hist ory of fat igue, nausea, and poor appet it e. In t he week before sympt om onset , she had acut e bronchit is wit h product ive
cough and fever. The pat ient has a 2-year hist ory of ost eoart hrit is of t he knees t hat requires int ra-art icular cort icost eroid inject ions every 3 t o 4 mont hs; her last inject ion
was 3 mont hs ago. Her only ot her medicat ion is acet aminophen.
On physical examinat ion, t he pat ient looks t ired. Temperat ure is 37.5C (99.5F), blood pressure is 112/58 mm Hg, pulse rat e is 92/min, respirat ion rat e is 17/min, and BMI
is 32. The pat ient has cushingoid feat ures and cent ral obesit y. There are mult iple ecchymoses on t he upper and lower ext remit ies. Decreased axillary and pubic hair is not ed.
There is bony hypert rophy and small effusions of t he knees bilat erally but no evidence of warmt h or eryt hema.
Adrenocort icot ropic hormone (AM) Low normal
Cort isol (8 AM)
Init ial measurement Low
Aft er cosynt ropin st imulat ion Low normal
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's recent symptoms?
(A) Adrenal adenoma
(B) Exogenous cort icost eroids
(C) Pit uit ary microadenoma
(D) Primary adrenal insufficiency
Item 27 [Basic]
A 47-year-old woman is hospit alized for pyelonephrit is. The pat ient has a 6-year hist ory of primary adrenal insufficiency and has been doing well on t herapy wit h oral
hydrocort isone and fludrocort isone. She report s missing t wo doses of t he hydrocort isone t oday because of nausea. She is st art ed on rapid int ravenous infusion of normal saline
and ceft riaxone.
On physical examinat ion, t emperat ure is 38.9C (102.0F), blood pressure is 92/58 mm Hg supine and 76/50 mm Hg sit t ing, pulse rat e is 98/min supine and 112/min sit t ing,
and respirat ion rat e is 19/min.
Result s of laborat ory st udies reveal a serum sodium level of 125 meq/L (125 mmol/L) and a serum pot assium level of 5.5 meq/L (5.5 mmol/L).
Whi ch of the fol l owi ng shoul d be admi ni stered next?
(A) Infusion of 3% saline
(B) St ress dosage of int ravenous hydrocort isone
(C) Usual dosage of fludrocort isone alone
(D) Usual dosage of oral hydrocort isone alone
Item 28 [Basic]
A 66-year-old woman is found t o have a T-score of -2.7 at her hip following a rout ine screening dual energy x-ray absorpt iomet ry (DEXA) scan. The pat ient is ot herwise
healt hy, has no obvious risk fact ors for ost eoporosis, and t akes no medicines.
Calcium 9.8 mg/dL (2.5 mmol/L)
Phosphorus 3.8 mg/dL (1.2 mmol/L)
25-Hydroxy vit amin D 22 ng/mL (54.9 nmol/L)
Alkaline phosphat ase 90 U/L
Parat hyroid hormone 20 pg/mL (20 ng/L)
In addi ti on to starti ng oral bi sphosphonate therapy, whi ch of the fol l owi ng shoul d be done next?
(A) Add est rogen replacement t herapy
(B) Order a parat hyroid scan
(C) Recommend increased sun exposure
(D) St art vit amin D and calcium supplement at ion
Item 29 [Advanced]
A 62-year-old woman is evaluat ed during a follow-up visit for hypert ension. She has no sympt oms and is monogamous wit h her husband of 35 years. Her only medicat ion is
hydrochlorot hiazide. She received an influenza vaccinat ion 3 mont hs ago and a herpes zost er vaccinat ion 1 year ago. Her last Pap smear was 14 mont hs ago and result s were
normal, as were result s of t he previous t hree annual Pap smears.
On physical examinat ion, blood pressure is 136/72 mm Hg and weight is 62 kg (136 lb). Ot her general physical examinat ion findings are normal.
The t ot al cholest erol level is 188 mg/dL (4.9 mmol/L) and t he HDL-cholest erol level is 54 mg/dL (1.4 mmol/L).
Whi ch of the fol l owi ng i s the most appropri ate heal th mai ntenance i nterventi on for thi s pati ent?
(A) Abdominal ult rasonography
(B) Dual-energy x-ray absorpt iomet ry
(C) Pap smear
(D) Pneumococcal vaccine
Item 30 [Basic]
A 69-year-old woman is evaluat ed for a loss of 2 inches in height over t he past 5 years. She is current ly t aking adequat e dosages of supplement al calcium and vit amin D.
Result s of dual-energy x-ray absorpt iomet ry show a T-score of -2.5. An evaluat ion for secondary causes of ost eoporosis is unrevealing.
Whi ch of the fol l owi ng agents shoul d be i ni ti ated i n thi s pati ent?
(A) Alendronat e
(B) Calcit onin
(C) Est rogen
(D) Raloxifene
(E) Teriparat ide
Item 31 [Advanced]
A 70-year-old woman is evaluat ed for worsening gast roesophageal reflux disease wit h heart burn. She first not iced t his sympt om 1 mont h ago when she began t aking
alendronat e, 70 mg orally once weekly, for ost eoporosis. Current medicat ions are alendronat e, calcium, and ergocalciferol.
The alendronat e is discont inued.
Whi ch of the fol l owi ng i s now the most appropri ate treatment for thi s pati ent's osteoporosi s?
(A) Calcit onin
(B) Int ravenous zoledronat e
(C) Raloxifene
(D) Teriparat ide
Item 32 [Basic]
A 72-year-old woman is evaluat ed for mid and low back pain. Her pain has been present for several mont hs, but last week she experienced sharp and int ense pain aft er picking
up a basket of wet laundry. Her medical hist ory is unremarkable, and she t akes no medicat ions. She does not smoke cigaret t es and does not drink alcohol.
On physical examinat ion, BMI is 18. She has t enderness over t he middle and lower t horacic regions. Spine radiographs show compression fract ures at T10, L1, and L2.
Bone mineral densit y Spine T-score: -2.6
Tot al hip T-score: -1.9
(A) Normal bone densit y
(B) Ost eopenia
(C) Ost eoporosis
(D) Secondary ost eoporosis
Item 1 Answer: D
Educati onal Objecti ve: Diagnose type 2 diabetes mellitus.
This pat ient has t ype 2 diabet es mellit us. The diagnosis of diabet es mellit us can be est ablished by a fast ing plasma glucose level of at least 126 mg/dL (7.0 mmol/L), a random
plasma glucose level of at least 200 mg/dL (11.1 mmol/L) and sympt oms of hyperglycemia (for example, polyuria, polydipsia, or blurred vision), or a 2-hour oral glucose
t olerance t est (OGTT) result of at least 200 mg/dL (11.1 mmol/L). In 2010, t he American Diabet es Associat ion endorsed a hemoglobin A
1c
value of 6.5% of great er as
diagnost ic of diabet es.
Impaired fast ing glucose, impaired glucose t olerance, or bot h mark t he t ransit ion from normal glucose t olerance t o t ype 2 diabet es mellit us. Impaired fast ing glucose is
diagnosed when t he fast ing plasma glucose level is in t he range of 100 t o 125 mg/dL (5.6 t o 6.9 mmol/L), and impaired glucose t olerancean analogous prediabet ic st at eis
diagnosed when t he plasma glucose level at t he 2-hour mark of an OGTT is 140 t o 199 mg/dL (7.8 t o 11.0 mmol/L).
For a diagnosis of t he met abolic syndrome t o be made, informat ion about t he pat ient 's blood pressure (130/85 mm Hg), lipid levels (t riglyceride level 150 mg/dL [1.7
mmol/L]; HDL-cholest erol <40 mg/dL in men [1.0 mmol/L]), fast ing plasma glucose level (110 mg/dL [6.1 mmol/L]), and waist circumference (>40 in [>102 cm] in men) is
necessary. Insufficient dat a have been provided for t his diagnosis.
Key Poi nt
Type 2 diabet es mellit us is diagnosed when t he fast ing plasma glucose level is 126 mg/dL (7.0 mmol/L) or great er, t he random plasma glucose level is 200 mg/dL (11.1
mmol/L) or great er, t he plasma glucose level is 200 mg/dL (11.1 mmol/L) or great er aft er a 2-hour oral glucose t olerance t est , or t he venous hemoglobin A
1c
value is 6.5% or
great er.
Bi bl i ography
American Diabet es Associat ion. St andards of medical care in diabet es2010. Diabet es Care. 2010;33 Suppl 1:S11-61. [PMID: 20042772]
Item 2 Answer: E
Educati onal Objecti ve: Treat prediabetes with diet and exercise.
The most appropriat e t reat ment for t his pat ient is diet and exercise. She has impaired fast ing glucose (IFG), defined as a fast ing plasma glucose level in t he range of 100 t o
125 mg/dL (5.6 t o 6.9 mmol/L), and should begin a program of int ensive lifest yle change, including 30 minut es of exercise most days of t he week and a calorie-rest rict ed diet ,
t o achieve weight reduct ion on t he order of 7% of body weight .
Diet and exercise is t he recommended approach for pat ient s wit h eit her IFG or impaired glucose t olerance (IGT), t he prediabet ic st at es. The relat ive risk reduct ion (RRR) in
t he incidence of diabet es in pat ient s wit h IGT associat ed wit h int ensive lifest yle change is 58%.
Pharmacologic t herapy wit h glucose-lowering drugs is not indicat ed for t his pat ient wit h isolat ed IFG. In pharmacologic st udies of diabet es prevent ion, acarbose t herapy
result ed in only a 25% RRR, which is inferior t o t hat obt ained wit h diet and exercise.
Met formin t herapy is associat ed wit h an RRR of 31%, which is also inferior t o t he 58% RRR obt ained wit h diet and exercise. Met formin t herapy may be considered in
pat ient s wit h bot h IFG and IGT, who const it ut e a higher risk group. This pat ient does not have IGT (fast ing plasma glucose level of 140 t o 199 mg/dL [7.7 t o 11.0 mmol/L]
at t he 2-hour mark of an oral glucose t olerance t est ) and so should not receive met formin.
Modulat ors of t he renin-angiot ensin axis, such as ramipril and ot her angiot ensin-convert ing enzyme inhibit ors, do not cont ribut e t o diabet es prevent ion.
Rosiglit azone and pioglit azone have been associat ed wit h 62% and 81% RRRs, respect ively, in t he incidence of diabet es. These agent s, however, are not endorsed for rout ine
pharmacologic use in pat ient s wit h prediabet es because of t heir cost s and adverse effect s, including edema, increased fract ure risk in women, and possible increased
cardiovascular morbidit y.
Key Poi nt
Pat ient s wit h prediabet es should be advised t o adopt a program of lifest yle change t o prevent progression t o t ype 2 diabet es mellit us.
Bi bl i ography
Vijan S. Type 2 diabet es. Ann Int ern Med. 2010;152(5):ITC31-15. [PMID: 20194231]
Item 3 Answer: B
Educati onal Objecti ve: Diagnose secondary diabetes related to chronic pancreatitis.
This pat ient has secondary diabet es relat ed t o chronic pancreat it is. Diabet es mellit us is generally cat egorized as t ype 1, t ype 2, gest at ional, and secondary diabet es. This
pat ient 's diabet es is t he last t ype, which consist s of a group of unrelat ed condit ions t hat are associat ed wit h hyperglycemia t hrough effect s on eit her insulin availabilit y or
insulin sensit ivit y. These include various endocrine disorders, such as Cushing syndrome and acromegaly; several pancreat ic condit ions, such as acut e and chronic pancreat it is
and pancreat ic cancer; drug-induced hyperglycemia; and several genet ic syndromes. This pat ient has a hist ory of alcohol abuse, a hist ory of recurrent pancreat it is, and
pancreat ic calcificat ions on an abdominal CT scan, which collect ively confirm t he diagnosis of chronic pancreat it is.
Some older pat ient s previously diagnosed wit h t ype 2 diabet es mellit us have aut oimmune bet a-cell dest ruct ion, albeit of a more gradually progressive nat ure (t ermed lat ent
aut oimmune diabet es of adult hood). Such pat ient s develop absolut e insulin deficiency over t ime. Lat e-onset aut oimmune diabet es of adult hood is a possibilit y in t his pat ient ,
given his age (51 years), his lean body habit us, and t he insidious onset of diabet es. However, it would be much less common t han secondary diabet es in t his man wit h
confirmed chronic pancreat it is.
This pat ient 's clinical present at ion is at ypical for t ype 1 diabet es, which usually has an acut e or subacut e onset and is charact erized by polyuria, polydipsia, polyphagia,
ket onemia or ket onuria, and weight loss.
Most pat ient s wit h t ype 2 diabet es are obese or at least have abdominal obesit y (high waist -t o-hip rat io). This pat ient is of normal body weight , and his scaphoid-appearing
abdomen makes t ype 2 diabet es even less likely.
Key Poi nt
Secondary causes of diabet es mellit us may result from diseases of t he exocrine pancreas, endocrinopat hies, genet ic syndromes, and drugs or chemicals.
Bi bl i ography
Item 4 Answer: C
Educati onal Objecti ve: Treat type 2 diabetes mellitus with metformin.
The most appropriat e t reat ment for t his pat ient is t o begin met formin. Various oral and inject able agent s are available for t he init ial management of t ype 2 diabet es, most of
which reduce hyperglycemia t o a similar degree. Because of it s low cost , effect iveness, good t olerabilit y, relat ive safet y, favorable effect s on body weight , and absence of
hypoglycemia as a side effect , met formin remains t he best first -line agent available. Met formin is cont raindicat ed in pat ient s wit h renal insufficiency (serum creat inine level
>1.4 mg/dL [123.8 mol/L] for women and >1.5 mg/dL [132.6 mol/L] for men). For t his pat ient , ongoing at t empt s at lifest yle change are unlikely t o reduce her blood
glucose level furt her. Therefore, init iat ion of met formin t herapy is most likely t o improve her glycemic cont rol.
Exenat ide, an inject able agent , is only approved for use in combinat ion regimens wit h oral agent s and is inappropriat e in most circumst ances as monot herapy. Glimepiride
could be used but is associat ed wit h weight gain and t he risk of hypoglycemia. Overall, it remains a less at t ract ive choice t han met formin in most pat ient s, including t his one.
Pioglit azone is also available for monot herapy, but it s side effect s of weight gain, edema, increased peripheral bone fract ure rat es in women, and high cost make it less
at t ract ive t han met formin as a first -line t herapy.
Key Poi nt
Met formin is recommended as t he init ial pharmacologic t herapy for most pat ient s wit h t ype 2 diabet es mellit us.
Bi bl i ography
Nat han DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in t ype 2 diabet es: a consensus algorit hm for t he init iat ion and adjust ment of t herapy: a
consensus st at ement of t he American Diabet es Associat ion and t he European Associat ion for t he St udy of Diabet es. Diabet es Care. 2009;32(1):193-203. [PMID: 18945920]
Item 5 Answer: A
Educati onal Objecti ve: Manage hyperglycemia in a hospitalized patient with basal and preprandial insulins.
The most appropriat e t reat ment for t his pat ient is basal and preprandial insulin administ rat ion. He has uncont rolled diabet es mellit us during hospit alizat ion. Recent guidelines
recommend at t empt ing t o improve glycemic cont rol in all hospit alized pat ient s (140 t o 200 mg/dL [7.8 t o 11.1 mmol/L). Thus, a basal-bolus insulin regimen consist ing of a
long-act ing insulin and a rapid-act ing insulin analogue before meals is recommended for t his hospit alized pat ient . Such an approach allows for a more easily t it rat able regimen
and can convenient ly be held during diagnost ic t est ing or procedures when nut rit ional int ake is int errupt ed.
Cont inuous insulin infusions are difficult t o administ er out side t he int ensive care unit in most hospit als. Therefore, init iat ing one is not t he best t reat ment for t his pat ient and
may not even be necessary t o obt ain good glycemic cont rol.
A regimen of neut ral prot amine Hagedorn (NPH) insulin t wice daily will likely improve glycemic cont rol but is not as easily t it rat able as a basal-bolus correct ion and does not
prevent post prandial glucose spikes.
Sliding scale regular insulin has been associat ed wit h increased hyperglycemic and hypoglycemic excursions and has been found t o result in inferior glycemic cont rol compared
wit h a basal-bolus correct ion regimen in hospit alized pat ient s. Init iat ing t his approach is t herefore inappropriat e.
Key Poi nt
A basal-bolus insulin regimen consist ing of a long-act ing insulin and a rapid-act ing insulin analogue before meals is recommended for hospit alized pat ient s wit h uncont rolled
diabet es.
Bi bl i ography
Umpierrez GE, Smiley D, Zisman A, et al. Randomized st udy of basal-bolus insulin t herapy in t he inpat ient management of pat ient s wit h t ype 2 diabet es (RABBIT 2 t rial).
Diabet es Care. 2007;30(9):2181-2186. [PMID: 17513708]
Item 6 Answer: D
Educati onal Objecti ve: Manage diabetic retinopathy and macular edema with panretinal photocoagulation.
Panret inal phot ocoagulat ion is t he most appropriat e next st ep in management . Diabet ic ret inopat hy is a well-recognized microvascular complicat ion of t ype 1 diabet es
mellit us and is one of t he leading causes of visual loss in adult s in t he Unit ed St at es. Diabet ic ret inopat hy is classified as nonproliferat ive (wit h hard exudat es, microaneurysms,
and minor hemorrhages), which is not associat ed wit h visual decline, and proliferat ive (wit h "cot t on-wool spot s" and neovascularizat ion), which is associat ed wit h loss of
vision. Changes in ret inal blood flow occur aft er several years of diabet es. These changes cause ret inal ischemia, which in t urn promot es growt h fact ors t hat st imulat e
proliferat ion of new blood vessels. This process leads t o scarring and fibrosis. Fibrous t issue can put t ract ion on t he ret ina, which can cause ret inal det achment wit h result ant
vision loss. New vessels can also become more permeable and leak serum, which causes macular edema. Tight glycemic cont rol has been shown t o decrease t he incidence and
progression of ret inopat hy. Blood pressure reduct ion appears t o exert as great a beneficial effect on ret inopat hy as glycemic cont rol. Once proliferat ive ret inopat hy or
macular edema is est ablished, vision can be preserved by appropriat ely t imed laser phot ocoagulat ion.
Randomized clinical t rials have det ect ed no beneficial effect of aspirin on t he incidence or progression of proliferat ive ret inopat hy or visual loss. At t he same t ime, ot her
st udies have not demonst rat ed harm t o t he opt ic syst em of pat ient s who must t ake aspirin for cardiovascular prot ect ion.
Alt hough lipid-lowering drugs, such as at orvast at in, have been associat ed in some st udies wit h reduced rat es of ret inopat hy, t hey cannot alt er t he course of est ablished
ret inopat hy and are not indicat ed in t his pat ient .
Abrupt rapid improvement in glycemic cont rol has been associat ed wit h modest worsening of diabet ic ret inopat hy in early st udies, but t here is no evidence t hat allowing
cont rol t o det eriorat e by reducing t he int ake of insulin will improve ret inopat hy. This pat ient 's glycemic cont rol has been st able, so his insulin regimen should not be changed.
Key Poi nt
Laser phot ocoagulat ion of t he ret ina can help preserve vision in pat ient s wit h proliferat ive diabet ic ret inopat hy and/or macular edema.
Bi bl i ography
Fant e RJ, Durairaj VD, Oliver SC. Diabet ic ret inopat hy: an updat e on t reat ment . Am J Med. 2010;123(3):213-216. [PMID: 20193825]
Item 7 Answer: A
Educati onal Objecti ve: Improve glucose control with the addition of basal and preprandial insulins.
The most appropriat e t herapeut ic change is t o subst it ut e insulin glargine and insulin lispro for her current diabet es medicat ions. Basal and rapid-act ing insulin analogues, when
dosed properly, reduce t he risk of hypoglycemia. Current choices of long- or int ermediat e-act ing basal insulins include insulin glargine, insulin det emir, and neut ral prot amine
Hagedorn (NPH) insulin. The opt imal basal insulin should be peakless and have a 24-hour durat ion of act ion. Bot h insulin glargine and, t o a lesser ext ent , insulin det emir meet
t hese requirement s. NPH insulin, on t he ot her hand, does not and is usually administ ered t wice daily because it s durat ion of act ion t ypically ext ends only 12 t o 18 hours wit h a
peak of act ivit y at 4 t o 8 hours aft er administ rat ion, which can precipit at e hypoglycemic episodes at ot her t imes. In one st udy, t he risk of hypoglycemia was significant ly
higher during t he overnight hours in pat ient s t aking NPH insulin versus insulin glargine at bedt ime. An ideal prandial insulin has a brisk peak and a short overall durat ion of
act ion t o properly cover post prandial glucose excursions. Such pharmacokinet ics are found wit h t he rapid-act ing insulin analogues lispro, aspart , and glulisine. In cont rast ,
regular insulin has a durat ion of act ion of 6 t o 8 hours and so is not an opt imal preprandial product .
She should be encouraged t o swit ch t o a regimen of four inject ions of insulin per day, wit h a once daily inject ion of a basal insulin, such as insulin glargine, and mealt ime
inject ions of a rapid-act ing analogue, such as insulin lispro.
Pat ient s wit h advanced t ype 2 diabet es mellit us who are on insulin should not be t ransferred t o oral agent s because t he need for insulin suggest s an already significant insulin
deficiency t hat oral agent s are unlikely t o overcome. Glycemic cont rol would inevit ably det eriorat e.
Decreasing t he dosage of NPH and regular insulin may diminish her overnight hypoglycemic episodes but would also result in higher blood glucose levels. Therefore, t his
change in t he pat ient 's diabet es regimen is not appropriat e.
Increasing caloric int ake t o combat hypoglycemia is rarely indicat ed. Ideally, t he insulin regimen should be adjust ed on t he basis of t he pat ient 's nut rit ional int ake, not vice-
versa.
Key Poi nt
The combinat ion of basal and rapid-act ing insulin analogues, when dosed properly, reduces t he risk of hypoglycemia.
Bi bl i ography
Item 8 Answer: C
Educati onal Objecti ve: Diagnose diabetic ketoacidosis.
This pat ient has diabet ic ket oacidosis (DKA), and t he t est s t o est ablish t he diagnosis are serum glucose, elect rolyt es, and ket ones and art erial blood gases. The most life-
t hreat ening acut e complicat ion of diabet es is DKA, which most ly affect s pat ient s wit h t ype 1 diabet es and is somet imes it s present ing manifest at ion. At present at ion,
pat ient s wit h DKA usually report a several-day hist ory of polyuria, polydipsia, and blurred vision, culminat ing in nausea, vomit ing, abdominal pain, dyspnea, and alt ered
ment al st at us. Physical examinat ion t ypically reveals deep, labored breat hing (Kussmaul respirat ions), a fruit y odor t o t he breat h (from acet one), poor skin t urgor,
t achycardia, and hypot ension. This complicat ion can occur as a result of precipit at ing acut e st resses such as infect ions (influenza, pneumonia, or gast roent erit is) or acut e
myocardial infarct ion; in pat ient s wit h insulin pumps, when a t echnical int errupt ion of insulin infusion occurs; and in pat ient s who are nonadherent t o t heir medicat ion
regimen. In almost all inst ances, DKA is ent irely prevent able if pat ient s pract ice regular glucose monit oring and underst and t he need for increased insulin doses during acut e
st ress event s. The diagnosis of DKA is based on a blood glucose level less t han 250 mg/dL (13.9 mmol/L), anion gap met abolic acidosis (art erial pH <7.30), a serum carbon
dioxide level less t han 15 meq/L (15 mmol/L), and posit ive serum or urine ket one concent rat ions.
Key Poi nt
The diagnosis of diabet ic ket oacidosis is based on a blood glucose level less t han 250 mg/dL (13.9 mmol/L), anion gap met abolic acidosis (art erial pH <7.30), a serum carbon
dioxide level less t han 15 meq/L (15 mmol/L), and posit ive serum or urine ket one concent rat ions.
Bi bl i ography
Wilson JF. In t he clinic. Diabet ic ket oacidosis. Ann Int ern Med. 2010;152(1):ITC1-1-ITC1-15. [PMID: 20048266]
Item 9 Answer: D
Educati onal Objecti ve: Treat hyperglycemic hyperosmolar syndrome with intravenous fluids.
The next management st ep for t his pat ient is rapid infusion of int ravenous fluids. This pat ient has hyperglycemic hyperosmolar syndrome. Diagnost ic crit eria include plasma
glucose level great er t han 600 mg/dL (33.3 mmol/L), art erial pH great er t han 7.30, serum bicarbonat e great er t han 15 mg/dL (15 mmol/L), serum osmolalit y great er t han
320 mosm/kg H
2
O, and absent urine or serum ket ones. Pat ient s wit h t his disorder usually have a precipit at ing fact or, such as severe infect ion, myocardial infarct ion, or new
kidney insufficiency. Management of hyperglycemic hyperosmolar syndrome mainly involves ident ifying t he underlying precipit at ing illness and rest oring a markedly
cont ract ed plasma volume. Normal saline, which is already comparat ively hypot onic in such pat ient s, is usually chosen first t o replenish t he ext racellular space. If t he pat ient
has hypot ension, fluids should be administ ered as rapidly as t olerat ed t o rest ore plasma (int ravascular) volume. When blood pressure is rest ored and urine out put is est ablished,
administ rat ion rat es should be slowed and hypot onic solut ions should be administ ered. The t ot al body wat er deficit can be calculat ed by using st andard formulas, wit h t he goal
of replacing one-half t he deficit during t he first 24 hours and t he remainder during t he next 2 t o 3 days.
Insulin reduces glucose levels but should be administ ered only aft er expansion of t he int ravascular space has begun. If given earlier, movement of glucose int o cells
t heoret ically can reduce circulat ing volume furt her, which t hreat ens cerebral, kidney, and coronary perfusion.
Elect rolyt es should be monit ored, especially pot assium, because t he pot assium level may fall as urine out put is rest ored and kidney funct ion improves wit h int ravenous fluid
t herapy; in addit ion, pot assium is shift ed int racellularly by t he administ rat ion of insulin t herapy. Pot assium should not be administ ered unt il urine out put is verified, because
t hese pat ient s are prone t o acut e kidney injury. Mild met abolic acidosis does not require bicarbonat e t herapy, because normalizat ion of circulat ing volume will quickly correct
t his defect . Ant ibiot ics are not required unless a bact erial infect ion is ident ified.
Key Poi nt
Management of hyperglycemic hyperosmolar syndrome involves ident ifying t he underlying precipit at ing illness and rest oring plasma volume wit h int ravenous fluids.
Bi bl i ography
Kit abchi AE, Nyenwe EA. Hyperglycemic crises in diabet es mellit us: diabet ic ket oacidosis and hyperglycemic hyperosmolar st at e. Endocrinol Met ab Clin Nort h Am.
2006;35(4):725-51. [PMID: 17127143]
Item 10 Answer: D
Educati onal Objecti ve: Treat diabetic ketoacidosis with an insulin drip.
This pat ient should be st art ed on an insulin drip. Discont inuat ion of insulin pump t herapy result ed in inadequat e insulin coverage; as a result , t he pat ient developed diabet ic
ket oacidosis, as evidenced by t he plasma glucose level of 262 mg/dL (14.5 mmol/L), t he posit ive urine ket ones, and an anion gap. It is imperat ive t o recognize t hat pat ient s
wit h insulin-deficient diabet es mellit us can develop ket oacidosis wit h only moderat e glucose elevat ions. This pat ient should now be st art ed on an insulin drip in a monit ored
set t ing. Int ravenous insulin infusion is usually t he preferred met hod of insulin delivery in an emergency because dehydrat ion may be severe (which decreases subcut aneous
absorpt ion) and rapid t it rat ion of insulin may be required. Her plasma glucose level should be measured every 1 t o 2 hours and adjust ment s made t o t he insulin infusion, as
required, t o gradually normalize her glucose level and reverse t he ket oacidosis. Aft er t he met abolic abnormalit ies have been correct ed and t he pat ient is ready t o be t ransferred
t o subcut aneous administ rat ion of insulin (usually when t he pat ient st art s eat ing), int ravenous and subcut aneous insulin administ rat ion need t o be overlapped t o avoid rebound
ket oacidosis. Short -act ing or rapid-act ing insulins should be given for 1 t o 2 hours or int ermediat e or long-act ing insulins for 2 t o 3 hours before t erminat ing t he insulin
infusion t o ensure adequat e overlap.
Insulin glargine and neut ral prot amine Hagedorn (NPH) insulin are long-act ing preparat ions t hat do not provide t he flexibilit y needed t o aggressively t reat diabet ic
ket oacidosis.
The use of sliding scale insulin will not allow for adequat e insulin coverage, and t he ket oacidosis can be expect ed t o progress.
Key Poi nt
Ket oacidosis can develop in insulin-deficient pat ient s wit h only moderat e plasma glucose elevat ions; an insulin drip is t he most effect ive t reat ment of diabet ic ket oacidosis.
Bi bl i ography
Wilson JF. In t he clinic. Diabet ic ket oacidosis. Ann Int ern Med. 2010;152(1):ITC1-15. [PMID: 20048266]
Item 11 Answer: D
Educati onal Objecti ve: Diagnose xanthelasma.
The pat ient 's skin lesions are xant helasmas, which are t he most common t ype of xant homas. Xant homas are t he charact erist ic skin condit ions associat ed wit h primary (due
t o genet ic defect s) or secondary hyperlipidemias. Xant homas are yellow, orange, reddish, or yellow-brown papules, plaques, or nodules. If t he infilt rat ion is deep, t he
xant homa may be nodular and have normal-appearing overlying skin. The t ype of xant homa closely correlat es wit h t he t ype of lipoprot ein t hat is elevat ed. Xant helasma is a
t ype of xant homa charact erized by soft , nont ender, nonprurit ic plaques localized t o t he eyelids. Xant helasma can occur wit hout hyperlipidemia, but is oft en associat ed wit h
familial dyslipidemias.
Ot her t ypes of xant homas include erupt ive xant homas, which present as clust ers of eryt hemat ous papules t ypically on t he ext ensor surfaces. They are most oft en associat ed
wit h ext remely high (great er t han 3000 mg/dL [33.9 mmol/L]) serum t riglyceride levels. Erupt ive xant homas regress wit h t reat ment of hypert riglyceridemia. Plane
xant homas are yellow-t o-red plaques found in skin folds of t he neck and t runk. They can be associat ed wit h familial dyslipidemias and a variet y of hemat ologic malignancies.
Tendon xant homas are subcut aneous nodules occurring on t he ext ensor t endons. They are associat ed wit h familial hypercholest erolemia.
Hypot hyroidism is associat ed wit h elevat ed lipid levels and can be a cause of secondary hyperlipidemias. However, hypot hyroidism is not direct ly associat ed wit h t he
format ion of xant homas and usually does not result in lipid levels high enough t o cause xant homas. An elevat ed serum ferrit in suggest s t he diagnosis of hemochromat osis, but
hemochromat osis is not associat ed wit h xant homas. Alt hough liver chemist ry t est s may be abnormal in pat ient s wit h ext remely elevat ed lipid levels and are import ant t o
monit or during lipid t herapy wit h st at ins, t hey are not associat ed wit h xant homa format ion. Type 2 diabet es is oft en seen in associat ion wit h dyslipidemias, but abnormal
glucose levels are not direct ly relat ed t o xant homa format ion.
Key Poi nt
Xant helasma is charact erized by soft , nont ender, nonprurit ic plaques localized t o t he eyelids and may be associat ed wit h familial dyslipidemias.
Bi bl i ography
Pit ambe HV, Schulz EJ. Life-t hreat ening dermat oses due t o met abolic and endocrine disorders. Clin Dermat ol. 2005;23(3):258-266. [PMID: 15896541]
Item 12 Answer: B
Educati onal Objecti ve: Manage isolated low HDL cholesterol with therapeutic lifestyle changes.
The most appropriat e next management st ep is t o recommend lifest yle modificat ions. In evaluat ing and managing low HDL cholest erol, it is import ant t o remember t he
primary t arget of t herapy is LDL cholest erol. Aft er LDL cholest erol has been evaluat ed and managed, non-HDL cholest erol is evaluat ed as a secondary t arget in pat ient s wit h
elevat ed t riglycerides. This pat ient has isolat ed low HDL cholest erol. Because of insufficient evidence of risk reduct ion from cont rolled t rials, ATP III has not set a specific
goal for raising HDL cholest erol. In pat ient s in whom t he HDL cholest erol remains low despit e use of st at ins or fibrat es t o t reat high LDL or non-HDL cholest erol, or in
pat ient s wit h isolat ed low HDL cholest erol such as t his pat ient , t he first management st ep is inst it ut ion of lifest yle int ervent ions, including exercise, t obacco cessat ion, and
weight management , because t hese int ervent ions are capable of increasing t he HDL cholest erol level.
The pat ient does not meet crit eria for st at in t herapy because his LDL cholest erol goal is 130 mg/dL (3.4 mmol/L) and his measured LDL cholest erol is 128 mg/dL (3.3
mmol/L). His LDL cholest erol goal is based on t he presence of t wo cardiovascular risk fact ors: smoking and low HDL cholest erol. Fibrat e t herapy is not indicat ed t o t reat his
t riglycerides because his non-HDL cholest erol, measured as t ot al cholest erol-HDL cholest erol, is 157 mg/dL (4.0 mmol/L) and is below his t arget of 160 mg/dL (4.1 mmol/L).
The non-HDL cholest erol goal is calculat ed as 30 mg/dL (0.8 mmol/L) above t he pat ient 's LDL cholest erol goal. Fibrat e t herapy would be indicat ed if t he pat ient had a
coronary heart disease equivalent such as diabet es or peripheral vascular disease, because fibrat e t herapy in t his set t ing result s in reduced mort alit y. Ult rasonography is not
needed t o det ermine carot id int imal t hickness, because such informat ion will not modify t herapeut ic decisions.
Key Poi nt
In pat ient s wit h isolat ed low HDL cholest erol, t he first management st ep is inst it ut ion of lifest yle int ervent ions, including exercise, t obacco cessat ion, and weight
management .
Bi bl i ography
Kopin L, Lowenst ein C. In t he clinic. Dyslipidemia. Ann Int ern Med. 2010;153(3):ITC21. [PMID: 20679557]
Item 13 Answer: D
Educati onal Objecti ve: Manage hyperlipidemia in a low-risk patient.
The best management for t his pat ient is t o repeat a fast ing lipid level in t he fut ure. This pat ient has hyperlipidemia, defined by a t ot al cholest erol level above 200 mg/dL (5.2
mmol/L). The LDL-cholest erol goal varies depending on t he presence or absence of five major cardiovascular risk fact ors: cigaret t e smoking, hypert ension, older age (men
45 years; women 55 years), low HDL-cholest erol level (<40 mg/dL [1.0 mmol/L]), and a family hist ory of coronary art ery disease (first degree male relat ive <55 years;
female relat ive <65 years).
In pat ient s wit h zero or one risk fact or, t he LDL-cholest erol goal is below 160 mg/dL (4.1 mmol/L). This pat ient has no major risk fact ors. Because his current LDL-
cholest erol level is below 160 mg/dL (4.1 mmol/L), no t herapy is indicat ed. The U.S. Prevent ive Services Task Force (USPSTF) concluded t hat t he opt imal int erval for
repeat screening is uncert ain. It would be reasonable t o repeat screening every 5 years, as recommended by t he Nat ional Cholest erol Educat ion Program, or select a short er
int erval if t he lipid levels are close t o t he t hreshold for t reat ment , as in t his pat ient .
Fibrat e t herapy would be indicat ed for hypert riglyceridemia (>200 mg/dL [2.3 mmol/L]) in t he set t ing of elevat ed non-HDL-cholest erol levels, which is not present in t his
pat ient .
St at in t herapy would be appropriat e for t his pat ient wit h no risk fact ors if his LDL-cholest erol level were above 190 mg/dL (5.0 mmol/L) and would be opt ional if t he level
were bet ween 160 mg/dL and 190 mg/dL (4.1 and 5.0 mmol/L).
Lipoprot ein(a) [Lp(a)] level det erminat ion is not recommended for rout ine pract ice. Lp(a) is associat ed wit h increased risk for CAD but does not appear t o be an independent
predict or of risk of CAD.
Key Poi nt
In pat ient s wit h zero or one cardiovascular risk fact or, t he LDL cholest erol goal is below 160 mg/dL (4.1 mmol/L).
Bi bl i ography
Item 14 Answer: D
Educati onal Objecti ve: Treat elevated LDL-cholesterol in a patient with diabetes mellitus.
The most appropriat e t herapy is init iat ion of a st at in, such as simvast at in. This pat ient has mult iple risk fact ors for coronary art ery disease, including diabet es mellit us,
hypert ension, and hypercholest erolemia. Diabet es is a coronary art ery disease equivalent risk fact or, and pat ient s wit h diabet es have t he same LDL-cholest erol goal as
pat ient s who have had a myocardial infarct ion, namely, below 100 mg/dL (2.6 mmol/L). A st at in is t he first -line t reat ment for cholest erol reduct ion. A 40-mg daily dose of
simvast at in would likely reduce t he LDL-cholest erol level by 30% and achieve t he t arget goal.
Colest ipol int errupt s bile acid reabsorpt ion and reduces LDL-cholest erol levels by 10% t o 15%. It is oft en used as a second-line drug wit h st at ins because it act s synergist ically
t o induce LDL recept ors. However, colest ipol can int erfere wit h t he absorpt ion of t his pat ient 's ot her medicat ions and, for t his reason, is not t he best init ial management of
his hyperlipidemia.
Alt hough ezet imibe reduces LDL-cholest erol levels by reducing cholest erol absorpt ion from t he int est ine, t here are present ly no clinical t rial result s showing t hat t his
medicat ion reduces cardiovascular disease event s, in cont rast t o st at ins. Therefore, ezet imibe should be reserved as an adjunct t o ot her cholest erol-lowering medicat ions if goal
level is not achieved or for pat ient s int olerant or allergic t o ot her proven medicat ions.
Niacin is an effect ive medicat ion for modest ly lowering LDL-cholest erol levels and increasing HDL-cholest erol levels but is oft en not t olerat ed because of it s adverse effect s
(nausea and flushing), part icularly at t he dosage needed t o achieve adequat e reduct ion of t he LDL-cholest erol level. Niacin would be a poor choice for t his pat ient because it
can cause glucose int olerance, pot ent ially worsening his glucose cont rol.
Key Poi nt
The indicat ion t o init iat e cholest erol-lowering medicat ion and t he goal level for t reat ment are dependent on t he absolut e level of LDL-cholest erol and t he est imat ed risk for
a coronary art ery disease event .
Bi bl i ography
Item 15 Answer: A
Educati onal Objecti ve: Treat hyperlipidemia in a patient with a history of transient ischemic attack.
The most appropriat e t reat ment is t o begin at orvast at in. This pat ient wit h carot id art ery disease and a t ransient ischemic at t ack (TIA) is considered by t he Adult Treat ment
Panel III t o have coronary art ery-equivalent disease. In such pat ient s, t he LDL-cholest erol goal is lower t han 100 mg/dL (2.6 mmol/L) t o reduce t he risk for fut ure coronary
event s. Addit ionally, t he American Heart Associat ion/American St roke Associat ion and t he Nat ional St roke Associat ion recommend aggressive risk fact or reduct ion for t he
secondary prevent ion of st roke following an ischemic st roke or TIA. There is also accumulat ing evidence t hat reduct ion of blood pressure and t reat ment wit h a st at in may
prevent recurrent st roke even in pat ient s wit h no evidence of hypert ension or hyperlipidemia based upon current t hresholds for t reat ment .
Changing ant ihypert ensive medicat ion t o a -blocker or calcium channel blocker in t his pat ient is not indicat ed. The 2006 American Heart Associat ion/American St roke
Associat ion guidelines support t he use of diuret ics and an angiot ensin-convert ing enzyme inhibit or.
Nicot inic acid is a lipid-lowering agent t hat , in addit ion t o reducing LDL-cholest erol level, reduces t riglyceride level and increases HDL-cholest erol level. However, st at ins are
first -line t herapy for lowering t he LDL-cholest erol level in t he absence of cont raindicat ions, and t his pat ient has normal levels of t riglycerides and HDL-cholest erol.
Key Poi nt
In pat ient s who have had a st roke or t ransient ischemic at t ack, t he LDL-cholest erol goal is less t han 100 mg/dL (2.6 mmol/L).
Bi bl i ography
O'Regan C, Wu P, Arora D, Perri D, Mills EJ. St at in t herapy in st roke prevent ion: a met a-analysis involving 121,000 pat ient s. Am J Med. 2008;121(1):24-33. [PMID:
18187070]
Item 16 Answer: D
Educati onal Objecti ve: Diagnose hypothyroidism.
This pat ient requires no addit ional t est ing before levot hyroxine t herapy is init iat ed for her hypot hyroidism. Hashimot o disease is t he most common cause of
hypot hyroidism, and confirmat ion of t his diagnosis wit h measurement of TPO ant ibody is not necessary. Measurement of TPO ant ibody levels may be helpful in pat ient s
wit h subclinical hypot hyroidism (elevat ed t hyroid-st imulat ing hormone [TSH] level but normal free t hyroxine [T
4
]). In t hese pat ient s, increased t it ers of TPO ant ibody
confer an increased risk of hypot hyroidism (~4% per year), which escalat es as TSH levels rise above t he reference range.
The radioact ive iodine upt ake (RAIU) t est measures t hyroid gland iodine upt ake over a t imed period, usually 24 hours. Pat ient s wit h t hyrot oxicosis t ypically have an above-
normal or high-normal RAIU, which is inappropriat e in t he cont ext of a suppressed TSH level. In pat ient s wit h t hyroidit is or exposure t o exogenous t hyroid hormone, t he
RAIU will be below normal (<5% at 24 hours). Radionuclide upt ake scanning has no role in t he evaluat ion of hypot hyroidism.
Thyroglobulin, a glycoprot ein int egral in follicular st orage of t hyroid hormone, can be det ect ed in serum. Thyroglobulin levels can be elevat ed in hypert hyroidism and
dest ruct ive t hyroidit is. Int ake of exogenous t hyroid hormone generally suppresses t hyroglobulin levels, which makes it s measurement useful in pat ient s wit h t hyrot oxicosis
due t o surrept it ious use of t hyroid hormone. Thyroglobulin is also an effect ive t umor marker in pat ient s wit h papillary or follicular t hyroid cancer aft er t hyroidect omy and
radioact ive iodine ablat ion t herapy, because normal t hyroid release of t hyroglobulin should no longer be present . Measurement of t hyroglobulin levels has no role in t he
evaluat ion of hypot hyroidism.
Key Poi nt
Hashimot o disease is t he most common cause of hypot hyroidism, and confirmat ion of t his diagnosis wit h measurement of TPO ant ibody is not necessary.
Bi bl i ography
McDermot t MT. In t he clinic. Hypot hyroidism. Ann Int ern Med. 2009;151(11):ITC61. [PMID: 19949140]
Item 17 Answer: A
Educati onal Objecti ve: Evaluate a thyroid nodule.
The appropriat e next st ep in t he evaluat ion of t his pat ient is a fine-needle aspirat ion of t he t hyroid nodule. The prevalence of palpable t hyroid nodules is 4% t o 7%. The
cancer risk for a t hyroid nodule is 5% t o 10%. Fact ors associat ed wit h increased cancer risk include ext remes of age (<20 or >60 years), male sex, a hist ory of head or neck
irradiat ion, a family hist ory of t hyroid cancer (especially medullary t hyroid cancer), nodule size larger t han 1 cm, rapid nodule growt h, and hoarseness. Fine-needle aspirat ion
is a simple met hod of det ermining t he presence of malignancy. Sensit ivit y is approximat ely 90% t o 95%, wit h a false-negat ive rat e of 1% t o 11%. Guidelines recommend
biopsy of any nodule great er t han 1 cm in diamet er, and biopsy of smaller nodules should be considered in pat ient s wit h cancer risk fact ors.
Limit ed laborat ory t est ing is t ypically required in t he evaluat ion of a t hyroid nodule. Beyond a rout ine complet e blood count and serum chemist ry panel, t he serum t hyroid-
st imulat ing hormone (TSH) level should be measured, because t he result will help guide t he evaluat ion (aut onomously funct ioning nodules and mult inodular goit ers t hat
suppress TSH levels are rarely malignant ). Concomit ant measurement of t he serum free t hyroxine (T
4
) level is also reasonable if pat ient s have t hyroid-relat ed sympt oms but
unnecessary in an asympt omat ic pat ient wit h a normal TSH level such as t his pat ient .
Thyroglobulin, a glycoprot ein int egral in follicular st orage of t hyroid hormone, can be det ect ed in serum of normal pat ient s. Thyroglobulin levels can be elevat ed in
hypert hyroidism and dest ruct ive t hyroidit is and is an excellent t hyroid cancer marker in pat ient s who have undergone t hyroidect omy or radioact ive iodine ablat ion. In t his
pat ient wit h an int act t hyroid gland, a t hyroglobulin level measurement will not be helpful.
A t hyroid scan and radioact ive iodine upt ake t est are appropriat e in t he cont ext of a suppressed serum TSH level because a t oxic nodule or mult inodular goit er may be
present . Because such hyperfunct ional nodules rarely harbor cancer (<1%), t heir evaluat ion and management are far different . This pat ient does not have a suppressed TSH,
and a t hyroid scan and radioact ive iodine upt ake t est is not indicat ed.
Alt hough surgery is somet imes considered for nodules larger t han 4 cm in diamet er, surgery has no role in t his asympt omat ic pat ient wit h a smaller nodule.
Key Poi nt
Guidelines recommend biopsy of any nodule great er t han 1 cm in diamet er, and biopsy of smaller nodules should be considered in pat ient s wit h cancer risk fact ors.
Bi bl i ography
Miller MC. The pat ient wit h a t hyroid nodule. Med Clin Nort h Am. 2010;94(5):1003-15. [PMID: 20736109]
Item 18 Answer: C
Educati onal Objecti ve: Manage hypothyroidism during pregnancy by monitoring TSH level.
The most appropriat e next st ep is t o recheck t his pat ient 's serum t hyroid-st imulat ing hormone (TSH) level. Because a fet us depends on mat ernal t hyroid hormone for t he
first 10 t o 12 weeks of gest at ion, t he t hyroid levels of pregnant women wit h hypot hyroidism should be carefully monit ored. Recent guidelines recommend t hat TSH and t ot al
t hyroxine (T
4
) levels be monit ored t hroughout pregnancy because st andard free T
4
levels are not as accurat e in pregnant pat ient s. The t ot al T
4
level should be kept st able at
approximat ely 1.5 t imes t he normal range, and t he TSH level should be kept in t he lower range of normal. This may require an increase in t heir levot hyroxine dosage of
approximat ely 35% t o 50% as early as t he first t rimest er. Because of est rogen elevat ion during pregnancy, t hyroid-binding globulin (TBG) levels increase. However, wit hout
an increase in t he dosage of levot hyroxine, free T
4
levels may decrease as more T
4
becomes bound by TBG. Aft er delivery, TBG levels decrease, as do t hyroid hormone
requirement s.
Alt hough mat ernal iodine replacement has been successfully used in count ries wit h prevalent iodine deficiency, it s use in pat ient s who are iodine sufficient can be associat ed
wit h cat ast rophic result s, such as a fet al goit er (pharmacologic amount s of iodine blocks release of t hyroid hormone). Because significant iodine deficiency in t he Unit ed
St at es is rare, iodine t herapy in pregnant U.S. women is not indicat ed.
Measurement of t he free t riiodot hyronine (T
3
) level is not useful in t he evaluat ion of hypot hyroidism because T
3
levels t ypically remain wit hin t he reference range unt il t he
point of severe hypot hyroidism. This pat t ern is unalt ered by pregnancy.
Cont inuing t he current management is inappropriat e because undert reat ment of mat ernal hypot hyroidism can have a pot ent ially negat ive effect on fet al neurocognit ive
development .
Key Poi nt
Levot hyroxine requirement s may increase 30% t o 50% during t he first t rimest er of pregnancy.
Bi bl i ography
Item 19 Answer: B
Educati onal Objecti ve: Treat Graves disease with atenolol and methimazole.
The most appropriat e medical regimen for t his pat ient wit h Graves disease is at enolol and met himazole. Graves disease can present wit h eit her subclinical or overt
t hyrot oxicosis. Physical examinat ion may reveal t achycardia; an elevat ed syst olic blood pressure wit h a widened pulse pressure; a palpable goit er, which is classically smoot h;
a t hyrot oxic st are due t o lid ret ract ion; propt osis; and, infrequent ly, an infilt rat ive dermopat hy. To cont rol her t achycardia, a -blocker, such as at enolol, is indicat ed. Given
t he clinical and laborat ory findings, t his pat ient is also moderat ely hypert hyroid. To t reat her hypert hyroidism, eit her met himazole or propylt hiouracil can be used.
Met himazole, which generally has fewer side effect s and result s in quicker achievement of t he eut hyroid st at e t han propylt hiouracil, is preferred in most pat ient s. Because of
a presumed immunomodulat ory effect , ant it hyroidal drugs result in drug-free remission rat es of bet ween 30% and 50% in pat ient s wit h Graves disease who are t reat ed for 1
year.
At enolol alone would only address t his pat ient 's adrenergic sympt oms and not reduce her t hyroid hormone levels, and met himazole alone would not immediat ely address her
t achycardia.
Radioact ive iodine t herapy preceded or followed by adjunct ive t herapy wit h an ant it hyroidal drug is occasionally used t o t reat Graves disease. The drug is given in an at t empt
t o decrease t he risk of a t ransient worsening of t he t hyrot oxicosis aft er t hyroid ablat ion. Because ant it hyroidal drugs render t he t hyroid radioresist ant , t hey must be st opped
for several days before and aft er giving t he radioact ive iodine. Alt hough an occasional pat ient becomes eut hyroid aft er radioact ive iodine administ rat ion, t he expect ed
out come is hypot hyroidism, which t ypically occurs wit hin 2 t o 3 mont hs of t herapy, at which t ime t hyroid hormone replacement t herapy is begun.
Key Poi nt
Met himazole has fewer side effect s and result s in quicker achievement of t he eut hyroid st at e t han does propylt hiouracil in pat ient s wit h hypert hyroidism.
Bi bl i ography
Nakamura H, Noh JY, It oh K, Fukat a S, Miyauchi A, Hamada N. Comparison of met himazole and propylt hiouracil in pat ient s wit h hypert hyroidism caused by Graves'
disease. J Clin Endocrinol Met ab. 2007;92(6):2157-2162. [PMID: 17389704]
Item 20 Answer: B
Educati onal Objecti ve: Diagnose the hypothyroid stage of postpartum thyroiditis.
The best next management st ep is repeat measurement of t he t hyroid-st imulat ing hormone (TSH) and free t hyroxine (T
4
) levels. Post part um t hyroidit is, which occurs in
approximat ely 5% of women in t he Unit ed St at es wit hin a few mont hs of delivery, is a variant of painless t hyroidit is. At present at ion, pat ient s may have t ransient
t hyrot oxicosis alone, t ransient hypot hyroidism alone, or t hyrot oxicosis t hat is followed by hypot hyroidism and t hen by recovery. This pat ient most likely has post part um
t hyroidit is t hat is now in t he hypot hyroid phase aft er a period of t ransient t hyrot oxicosis. The hypot hyroidism can be confirmed by remeasuring her TSH and free T
4
levels.
In t his pat ient , t he absence of a goit er and eye disease point s away from Graves disease, as does t he recent development of sympt oms associat ed wit h hypot hyroidism.
Met himazole t herapy is inappropriat e for t his pat ient because she most likely has hypot hyroidism, not hypert hyroidism. If t ransient hypot hyroidism is confirmed by a high
TSH level and low free T
4
level, t hyroid hormone replacement , not met himazole, can be considered for bot hersome sympt oms.
Wit h post part um t hyroidit is, result s of t hyroid scans and radioact ive iodine upt ake t est s will be low during t he t hyrot oxic phase and t hen become elevat ed during t he
hypot hyroid phase as t he t hyroid gland recovers and becomes very avid for iodine as st ores are replet ed. Before such t est ing can be advised, however, t he result s of current
t hyroid funct ion t est s are required t o assess t he pat ient 's t hyroid hormone st at us and det ermine if scan result s suggest Graves disease or, what is more likely, recovery
t hyroidit is.
Ult rasound of t he t hyroid gland can be used t o dist inguish t he high vascular flow of Graves disease from t he low-flow pat t ern of aut oimmune t hyroidit is. A more direct t est of
t his pat ient 's t hyroid funct ion, however, is measurement of t he TSH and free T
4
levels, which can quant ify t hyroid funct ion and provide a baseline wit h which t o compare
fut ure t hyroid funct ion t est result s.
Key Poi nt
Post part um t hyroidit is can cause post part um t hyrot oxicosis, hypot hyroidism, or a period of bot h.
Bi bl i ography
Item 21 Answer: C
Educati onal Objecti ve: Diagnose euthyroid sick syndrome.
This pat ient should have repeat t hyroid funct ion t est s in 6 t o 8 weeks. Wit h his hist ory of a recent severe illness, t he result s of his t hyroid funct ion t est s (low t hyroid-
st imulat ing hormone [TSH] and free t riiodot hyronine [T
3
] levels and a low-normal free t hyroxine [T
4
] level) are most consist ent wit h changes from a nont hyroidal illness
(collect ively known as eut hyroid sick syndrome). The classic pat t ern consist s of low TSH and free T
3
levels wit h a free T
4
level in t he normal t o low-normal range (or even
frankly low wit h a prolonged illness). Reverse T
3
levels are elevat ed (if measured), but because result s of t his measurement t ypically t ake several weeks t o obt ain, reverse T
3
level result s are seldom used clinically. The best next st ep is t o allow t he pat ient t o recover for 4 t o 8 weeks and t hen repeat t he t hyroid funct ion t est s. If result s of t hese
t est s are not normal aft er recovery, furt her workup can commence.
Brain MRI is not appropriat e for t his pat ient because no clinical finding suggest s pit uit ary dysfunct ion. Furt hermore, if evaluat ion of t he pit uit ary gland were required, MRI of
t he sella t urcica would be most appropriat e.
There are no dat a showing t hat T
4
replacement t herapy is beneficial for nont hyroidal illness. Therefore, init iat ion of levot hyroxine is not appropriat e.
Thyroid ult rasonography does not help det ermine changes in t hyroid funct ion and t hus is not useful for t his pat ient .
Key Poi nt
Severe illness can cause eut hyroid sick syndrome, which is associat ed wit h abnormal result s on t hyroid funct ion t est s t hat oft en normalize aft er recovery.
Bi bl i ography
Adler SM, Wart ofsky L. The nont hyroidal illness syndrome. Endocrinol Met ab Clin Nort h Am. 2007;36(3):657-672, vi. [PMID: 17673123]
Item 22 Answer: C
Educati onal Objecti ve: Evaluate an incidentally discovered adrenal adenoma.
Plasma-free met anephrine levels and overnight dexamet hasone suppression t est should be done next . The increasing use of imaging st udies has revealed many previously
unrecognized, oft en asympt omat ic adrenal masses (adrenal incident alomas). Init ial assessment should include a careful hist ory and physical examinat ion t o find any suggest ion
of malignant disease or clinical evidence of hormone hypersecret ion. Most pat ient s wit h met ast at ic cancer of t he adrenal glands have clinical evidence of disease elsewhere.
Imaging charact erist ics of t he mass (size, CT at t enuat ion, vascularit y) can provide import ant clues. The risk of primary or met ast at ic cancer is nearly 2% for t umors less
t han 4 cm in diamet er but increases t o 25% for t umors 6 cm or larger. Met ast at ic lesions t o t he adrenal glands t end t o have a high CT at t enuat ion (>20 Hounsfield unit s) and
are oft en bilat eral. Primary adrenocort ical carcinoma t ends t o be large wit h irregular borders and may include areas of necrosis. Pheochromocyt oma, adrenal carcinoma, and
met ast at ic disease t o t he adrenal glands are oft en vascular, whereas benign adrenal adenomas are not highly vascular.
Because overt clinical manifest at ions are t ypically scant , screening t est s are oft en necessary t o ident ify pot ent ially funct ioning adrenal incident alomas secret ing cort isol,
aldost erone, or cat echolamines. Subclinical Cushing syndrome is t he most common abnormalit y associat ed wit h adrenal incident alomas. Because t hese pat ient s have no
sympt oms or physical findings of Cushing syndrome, t he possibilit y of aut onomous hypersecret ion of glucocort icoids should be evaluat ed wit h an overnight dexamet hasone
suppression t est . Addit ionally, measurement s of plasma cat echolamines are reasonable screening t est s t o rule out pheochromocyt oma, which can be asympt omat ic or
associat ed wit h int ermit t ent sympt oms.
Adrenal incident alomas are unlikely t o secret e aldost erone, but pat ient s should be screened for t hat possibilit y if t hey have hypert ension or hypokalemia, bot h of which are
absent in t his pat ient . Similarly, excess adrenal androgen product ion is rare, except when t he mass represent s adrenal cancer, and screening is not rout inely performed in t he
absence of clinical signs or sympt oms of feminizat ion in men or hyperandrogenism in women, which is also absent in t his pat ient .
Key Poi nt
Hypersecret ion of glucocort icoids and cat echolamines should be evaluat ed in all pat ient s, including asympt omat ic pat ient s, wit h incident ally discovered adrenal adenoma.
Bi bl i ography
Nieman LK. Approach t o t he pat ient wit h an adrenal incident aloma. J Clin Endocrinol Met ab. 2010;95(9):4106-13. [PMID: 20823463]
Item 23 Answer: B
Educati onal Objecti ve: Diagnose hyperaldosteronism with measurement of the serum aldosterone to plasma renin activity ratio.
The most appropriat e next diagnost ic t est is det erminat ion of t he serum aldost erone t o plasma renin act ivit y rat io. This pat ient has drug-resist ant hypert ension
(uncont rolled hypert ension on t hree drugs, including a diuret ic), unprovoked hypokalemia, and probable met abolic alkalosis; he also has an inappropriat ely high urine
pot assium level. In t his set t ing, primary hyperaldost eronism is a very likely cause of his hypert ension and hypokalemia, especially given his age. The best screening t est for
primary hyperaldost eronism is a det erminat ion of t he rat io of serum aldost erone (in ng/dL) t o plasma renin act ivit y (in ng/mL/min). A rat io great er t han 20, part icularly
when t he serum aldost erone level is great er t han 15 ng/dL (414 pmol/L), is consist ent wit h t he diagnosis of primary hyperaldost eronism.
Aft er biochemical confirmat ion of hyperaldost eronism, localizat ion procedures are appropriat e t o different iat e aldost erone-producing adenomas, which are amenable t o
surgical resect ion, from bilat eral hyperplasia, which is medically t reat ed. Given t he high incidence of incident al adrenal lesions, however, imaging st udies, such as CT of t he
adrenal glands, should not be performed before biochemical t est ing t hat confirms t he presence of hyperaldost eronism.
This pat ient does not fit t he demographic or clinical profile of a pat ient wit h renovascular hypert ension, and t hus evaluat ing t he renal art eries wit h digit al subt ract ion renal
angiography is not indicat ed. Renovascular hypert ension due t o fibromuscular disease of t he renal art eries usually present s in pat ient s younger t han 35 years, and azot emia is
rarely present . At herosclerot ic renovascular hypert ension is more common in pat ient s older t han 55 years and is frequent ly associat ed wit h vascular disease in ot her vessels;
azot emia is oft en present .
Ot her t han sust ained hypert ension, t his pat ient did not have any of ot her sympt oms or signs suggest ive of a pheochromocyt oma (palpit at ions, headache, t remor,
diaphoresis). Therefore, screening for a pheochromocyt oma wit h measurement of t he plasma met anephrine and normet anephrine levels is less likely t o be helpful t han is
screening for hyperaldost eronism.
Key Poi nt
The best screening t est for primary hyperaldost eronism is a det erminat ion of t he rat io of serum aldost erone t o plasma renin act ivit y.
Bi bl i ography
Funder JW, Carey RM, Fardella C, et al; Endocrine Societ y. Case det ect ion, diagnosis, and t reat ment of pat ient s wit h primary aldost eronism: an Endocrine Societ y clinical
pract ice guideline. J Clin Endocrinol Met ab. 2008;93(9):3266-3281. [PMID: 18552288]
Item 24 Answer: D
Educati onal Objecti ve: Evaluate a patient with suspected Cushing disease with pituitary MRI.
The most appropriat e next diagnost ic t est for t his pat ient is pit uit ary MRI. She has biochemical feat ures of adrenocort icot ropic hormone (ACTH)-dependent Cushing
syndrome (hypercort isolism and elevat ed ACTH). The cause of t he ACTH hypersecret ion is eit her a pit uit ary adenoma or an ect opic source, such as a carcinoid t umor. In
t his pat ient , part ial suppression was achieved wit h high-dose dexamet hasone, which suggest s an ACTH-secret ing pit uit ary microadenoma. High-dose dexamet hasone is usually
not successful in suppressing ACTH product ion from an ect opic source. However, t here are except ions, so caut ion must be exercised in int erpret at ion. In such inst ances,
expert consult at ion is highly recommended.
Adrenal imaging is indicat ed if t he hypercort isolism is ACTH independent (hypercort isolism and normal or low ACTH level). In pat ient s wit h hypercort isolism associat ed
wit h suppressed ACTH secret ion, a CT scan of t he adrenal glands oft en shows a t umor (adenoma or carcinoma). However, t his pat ient 's ACTH level was elevat ed and adrenal
imaging is not indicat ed wit h eit her a CT or MRI scan.
The cosynt ropin st imulat ion t est is used t o det ermine t he adrenal reserve by measuring t he response t o a st andard dose of synt het ic adrenocort icot ropic hormone. The t est
does not det ect Cushing syndrome but , rat her, adrenal insufficiency and is t herefore not indicat ed for t his pat ient .
Key Poi nt
Adrenocort icot ropic hormone (ACTH)-dependent hypercort isolism is most commonly caused by a pit uit ary t umor or an ect opic ACTH source, such as a carcinoid t umor.
Bi bl i ography
Findling JW, Raff H. Cushing's syndrome: import ant issues in diagnosis and management . J Clin Endocrinol Met ab. 2006;91(10):3746-3753. [PMID: 16868050]
Item 25 Answer: A
Educati onal Objecti ve: Diagnose pheochromocytoma with abdominal CT scan.
The most appropriat e next management st ep for t his pat ient is an abdominal CT scan. She has t he classic sympt oms of pheochromocyt omapalpit at ions, sweat ing,
headaches, and hypert ension. Addit ionally, biochemical t est ing revealed increased plasma levels of cat echolamines. Most pheochromocyt omas are locat ed in t he adrenal
medulla, alt hough some are ext ra-adrenal in origin. CT has sensit ivit ies of 93% t o 100% in det ect ing adrenal pheochromocyt oma and approximat ely 90% in det ect ing ext ra-
adrenal cat echolamine-secret ing paragangliomas. MRI is as sensit ive as CT in det ect ing adrenal pheochromocyt omas and superior t o CT in det ect ing ext ra-adrenal
cat echolamine-secret ing paragangliomas.
An adrenalect omy is appropriat e only when a t umor is confirmed. An adrenalect omy would not be indicat ed if t he source of t he cat echolamines were confirmed t o be ext ra-
adrenal.
If an abdominal CT shows no masses, t he next best localizing st udy would be a met aiodobenzylguanidine (MIBG) scan. MIBG scint igraphy is highly specific (99%) but less
sensit ive (80%) t han CT t echniques. MIBG scint igraphy is generally reserved for pat ient s wit h equivocal CT result s, ext ra-adrenal cat echolamine-secret ing t umors, or
suspect ed malignancy.
Adrenal vein sampling is a t echnically difficult and hazardous procedure, especially in a pat ient wit h a pheochromocyt oma. The availabilit y of t he highly specific and
sensit ive MIBG scan should t ake precedence over t his more hazardous procedure.
Key Poi nt
CT has sensit ivit ies of 93% t o 100% in det ect ing adrenal pheochromocyt oma, and approximat ely 90% in det ect ing ext ra-adrenal cat echolamine-secret ing paragangliomas.
Bi bl i ography
Young WF Jr. Adrenal causes of hypert ension: pheochromocyt oma and primary aldost eronism. Rev Endocr Met ab Disord. 2007;8(4):309-320. [PMID: 17914676]
Item 26 Answer: B
Educati onal Objecti ve: Diagnose chronic corticosteroid therapy as the cause of adrenal insufficiency.
This pat ient has cent ral adrenal insufficiency secondary t o exogenous cort icost eroid use. Syst emic cort icost eroids are t he most common cause of cent ral adrenal
insufficiency, wit h supraphysiologic dosages of exogenous cort icost eroids causing disrupt ion of hypot halamic/pit uit ary adrenocort icot ropic hormone (ACTH) product ion.
Consequent ly, t he adrenal cort ex at rophies. When subsequent ly challenged by st ress, t he hypot halamus and pit uit ary gland are unable t o st imulat e adequat e adrenal product ion
of cort isol. This cent ral effect of exogenous cort icost eroids can occur aft er only 3 weeks of suppressive t herapy. The pat ient appears t o have developed Cushing syndrome as
a result of chronic syst emic exposure t o t he int ra-art icular inject ions of cort icost eroids. Despit e her cushingoid feat ures, however, she has clinical and biochemical evidence of
adrenal insufficiency. Her low-normal serum ACTH level and her part ial response t o cosynt ropin st imulat ion indicat e t hat she has cent ral (secondary) adrenal insufficiency.
Pat ient s wit h adrenal insufficiency oft en decompensat e during concurrent illnesses.
An adrenal adenoma could cause a suppressed ACTH level, cushingoid feat ures, and cent ral obesit y, but her sympt oms also suggest glucocort icoid deficiency. Furt hermore, an
adrenal adenoma would cause an elevat ed, not suppressed, cort isol level.
A funct ioning pit uit ary adenoma might produce excessive ACTH, but in t hat case bot h t he ACTH and cort isol levels would be elevat ed, not suppressed as t hey are in t his
pat ient . A nonfunct ioning pit uit ary adenoma might cause suppressed levels of ACTH and cort isol but t here would be no signs of hypercort isolism, as seen in t his pat ient .
Primary adrenal insufficiency (Addison disease) is t ypically associat ed wit h low cort isol product ion and elevat ed ACTH levels.
Key Poi nt
Secondary adrenal insufficiency due t o exogenous cort icost eroids may be associat ed wit h suppression of bot h adrenocort icot ropic hormone and cort isol levels and wit h clinical
findings of excess glucocort icoids.
Bi bl i ography
Chakera AJ, Vaidya B. Addison disease in adult s: diagnosis and management . Am J Med. 2010;123(5):409-413. [PMID: 20399314]
Item 27 Answer: B
Educati onal Objecti ve: Treat adrenal insufficiency during stress with intravenous stress doses of hydrocortisone.
Given her fever and hypot ension, t his pat ient wit h known primary adrenal insufficiency should receive a st ress dosage of int ravenous hydrocort isone. Pat ient s wit h adrenal
insufficiency are educat ed t o increase t heir cort icost eroid dosage during st ressful event s, such as an infect ion or surgery. When t hey do not , sympt oms of adrenal insufficiency
occur. Some pat ient s, such as t his one, develop nausea and vomit ing t hat limit t he use of orally administ ered cort icost eroids. In such pat ient s, cort icost eroids should be
administ ered parent erally. Cort isol replacement wit h cort icost eroids and rest orat ion of int ravascular volume wit h normal saline are vit al t o t reat ment of acut e adrenal
insufficiency. St ress-level dosages of cort icost eroids are considered t o be 10-t imes t he normal daily replacement dosage. For most pat ient s, t his is equivalent t o 100 mg of
hydrocort isone daily, administ ered int ravenously in divided dosages t hree t o four t imes per day. Once t he dosage of hydrocort isone is over 60 mg per day, fludrocort isone is
unnecessary because t hat dose of hydrocort isone has adequat e mineralocort icoid act ivit y.
Hyponat remia is a common feat ure of adrenal insufficiency and is easily correct ed wit h hydrocort isone and normal saline t o rest ore plasma volume. Administ ering 3% saline
t o correct t he low sodium level is t herefore inappropriat e.
Fludrocort isone is a mineralocort icoid t hat is required in pat ient s wit h primary adrenal insufficiency. Treat ment wit h fludrocort isone is usually not necessary in a hospit alized
pat ient receiving normal saline and high dosages of hydrocort isone, which has mineralocort icoid act ivit y. This t herapy will maint ain vascular volume and suppress
vasopressin, which is responsible for t he hyponat remia. Fludrocort isone t herapy alone is insufficient for a pat ient wit h primary adrenal insufficiency who is experiencing
physiologic st ress.
Alt hough t his pat ient requires close observat ion, making no changes t o her t herapeut ic regimen (maint aining baseline dosages) would be inappropriat e, given t he need for a
higher dosage of t he cort icost eroid during t his st ressful event .
Key Poi nt
St ress-level dosages of cort icost eroids are administ ered t o pat ient s wit h adrenal insufficiency during t imes of increased physiological st ress.
Bi bl i ography
Chakera AJ, Vaidya B. Addison disease in adult s: diagnosis and management . Am J Med. 2010;123(5):409-413. [PMID: 20399314]
Item 28 Answer: D
Educati onal Objecti ve: Treat osteoporosis with bisphosphonate therapy and vitamin D and calcium.
Vit amin D supplement at ion is an import ant part of t reat ment for ost eoporosis. Vit amin D levels are best measured by looking at st ores of 25-Hydroxy vit amin D. A wide
range of "opt imal" levels are report ed (15-80 ng/mL [37-200 nmol/L]). Generally, levels lower t han 30 ng/mL (74.8 nmol/L) are defined as insufficient , and levels lower t han
20 ng/mL (49.9 nmol/L) are defined as deficient . Vit amin D is obt ained t hrough ult raviolet (sunlight ) radiat ion and nat ural foods, fort ified foods, and vit amin supplement s.
Many variables such as lat it ude, season, sunscreen use, and clot hing prevent sunlight from being an effect ive met hod t o maint ain adequat e vit amin D st ores. Because t he
vit amin D cont ent of most foods is relat ively low, most pat ient s will need vit amin D supplement at ion. A common supplement at ion st rat egy includes a loading dose followed
by maint enance dosing. A loading dose of 50,000 IU of vit amin D is given orally once a week for 10 weeks and is t hen followed by a daily dose of 2000 IU. Vit amin D
deficiency cont ribut es t o bone loss from decreased vit amin D-dependent int est inal calcium absorpt ion and secondary hyperparat hyroidism. Vit amin D supplement s can also
improve muscle st rengt h, which can lead t o fewer falls in t he ost eoporot ic pat ient .
The Unit ed St at es Prevent ive Services Task Force advises against using est rogen or est rogen plus progest in for t he prevent ion of chronic diseases, including ost eoporosis,
aft er menopause, cit ing dat a from t he Women's Healt h Init iat ive t hat showed at least a t rend t oward an increased risk of breast cancer, coronary heart disease, st roke, venous
t hromboembolism, dement ia and cognit ive decline, and urinary incont inence wit h such use.
In pat ient s wit h hyperparat hyroidism, localizat ion of abnormal parat hyroid glands preoperat ively by means of ult rasonography, t echnet ium Tc 99m sest amibi scint igraphy,
or MRI offers t he possibilit y of a less invasive surgical approach. However, t he accuracy of t hese radiologic modalit ies is variable. This pat ient 's serum calcium and
parat hyroid hormone levels are normal, excluding hyperparat hyroidism as t he cause of t his pat ient 's ost eoporosis.
Key Poi nt
The prevent ion and t reat ment of ost eoporosis includes vit amin D and calcium supplement at ion.
Bi bl i ography
Kennel KA, Drake MT, Hurley DL. Vit amin D deficiency in adult s: when t o t est and how t o t reat . Mayo Clin Proc. 2010;85(8):752-7. [PMID: 20675513]
Item 29 Answer: B
Educati onal Objecti ve: Screen for osteoporosis with dual-energy x-ray absorptiometry.
Dual-energy x-ray absorpt iomet ry is an appropriat e screening t est for t his pat ient . Guidelines recommend t hat screening for ost eoporosis begin at age 65 years for women.
Women aged 60 t o 64 years should be screened if t hey are at higher t han average risk for ost eoporosis. The most predict ive risk fact or for ost eoporosis is weight below 70 kg
(154 lb), as wit h t his pat ient .
The U.S. Prevent ive Services Task Force (USPSTF) recommends against screening for abdominal aort ic aneurysm in women because of t he low prevalence of abdominal
aort ic aneurysm in t his group. Abdominal ult rasonography, t herefore, is not indicat ed.
Aft er t hree consecut ive negat ive annual cyt ology smears, t he risk of cervical cancer is reduced t o approximat ely 1/100,000 person-years. In t his monogamous pat ient wit h
t hree consecut ive normal Pap smears whose last Pap smear was 14 mont hs ago, it would be reasonable t o increase t he screening int erval t o every 2 t o 3 years, wit h
considerat ion of st opping screening at age 65 years if her Pap smears cont inue t o be normal.
Pneumococcal vaccine is indicat ed for persons age 65 years and older or for t hose younger t han 65 years who live in long-t erm care facilit ies, or who have chronic illnesses,
or who are Alaskan nat ives or American Indians. This pat ient has no indicat ion for pneumococcal vaccinat ion at t his t ime.
Key Poi nt
Screening for ost eoporosis is recommended for women age 65 years and older and in women 60 t o 64 years old who are at increased risk for ost eoporosis.
Bi bl i ography
Davison KS, Kendler DL, Ammann P, et al. Assessing fract ure risk and effect s of ost eoporosis drugs: bone mineral densit y and beyond. Am J Med. 2009;122(11):992-997.
[PMID: 19854322]
Item 30 Answer: A
Educati onal Objecti ve: Treat osteoporosis with a bisphosphonate.
This pat ient should be st art ed on a bisphosphonat e, such as alendronat e. These drugs are pyrophosphat e derivat ives t hat bind t o t he bone surface and inhibit ost eoclast ic bone
resorpt ion. They are poorly absorbed and must be t aken in t he fast ing st at e t o opt imize absorpt ion. Alendronat e is effect ive in lowering fract ure risk in pat ient s wit h
ost eoporosis. Zoledronat e is one of several newer bisphosphonat es t hat can be administ ered int ravenously and is associat ed wit h a long durat ion of act ion. A single inject ed
dose of zoledronat e suppresses bone t urnover markers for a full year and induces significant gains in bone mineral densit y over t he same period. Zoledronat e also reduces
fract ure risk.
Calcit onin nasal spray increases bone mass in t he spine and decreases vert ebral fract ures but does not affect t he incidence of hip fract ures. This drug is indicat ed for women
who are more t han 5 years post menopausal. It is a second-line drug t o t he bisphosphonat es.
Hormone replacement t herapy is no longer regarded as t he mainst ay of t herapy for ost eoporosis. In t he Women's Healt h Init iat ive, t he use of conjugat ed est rogens and
medroxyprogest erone in post menopausal women increased bone mass but also increased t he risk of cardiovascular disease, breast cancer, st roke, deep venous t hrombosis, and
pulmonary embolism.
Raloxifene is a select ive est rogen recept or modulat or t hat has est rogen-like effect s on bone but inhibit s t he effect s of est rogen in t he breast and ut erus. Raloxifene increases
bone mass and decreases t he risk of vert ebral fract ures in post menopausal women but does not affect t he incidence of hip fract ures. Raloxifene is not associat ed wit h adverse
cardiovascular event s and decreases t he risk of breast cancer in high-risk women. Side effect s include hot flushes and an increase in t he risk of t hromboembolism. It is a
second-line drug t o t he bisphosphonat es.
Teriparat ide (recombinant human PTH [1-34]) is t he only anabolic agent list ed, whereas all t he ot her medicat ions are ant iresorpt ive. When given int ermit t ent ly, t eriparat ide
st imulat es ost eoblast ic bone format ion. Given as a subcut aneous inject ion, t eriparat ide should not be used for more t han 2 years. The drug significant ly increases bone mass
and can decrease t he incidence of bot h vert ebral and nonvert ebral fract ures. Animal st udies have shown an increased risk of ost eosarcoma; t herefore, t his agent should be
avoided in pat ient s wit h Paget disease of bone, unexplained elevat ion of alkaline phosphat ase level, previous radiat ion involving t he skelet on, and a hist ory of skelet al
cancer. Teriparat ide should be considered in pat ient s who are int olerant of ot her medicat ions and in t hose wit h t he great est fract ure risk (T-score <-3.5 or <-3.0 wit h a
fragilit y fract ure).
Key Poi nt
Bisphosphonat es are a class of drugs t hat can lower t he fract ure rat e in pat ient s wit h ost eoporosis.
Bi bl i ography
Bilezikian JP. Efficacy of bisphosphonat es in reducing fract ure risk in post menopausal ost eoporosis. Am J Med. 2009;122(2 Suppl):S14-21. [PMID: 19187808]
Item 31 Answer: B
Educati onal Objecti ve: Treat postmenopausal osteoporosis with intravenous zoledronate.
This pat ient should st op t aking alendronat e and inst ead receive int ravenous zoledronat e. Bisphosphonat es are first -line drugs for t reat ing post menopausal women wit h
ost eoporosis. Alendronat e and risedronat e reduce t he risk of bot h vert ebral and nonvert ebral fract ures. Some pat ient s wit h ost eoporosis, however, may be int olerant of oral
bisphosphonat es because of aggravat ion of underlying gast roesophageal reflux disease. For t hese pat ient s, once yearly int ravenous infusion of zoledronat e is a pot ent and
effect ive alt ernat ive. An inject able bisphosphonat e, such as zoledronat e, should also be considered when oral bisphosphonat es are unsuccessful, cont raindicat ed (as in
esophageal st rict ure or achalasia), or likely t o be poorly absorbed (as in uncont rolled celiac disease and inflammat ory bowel disease) and when a pat ient is unable t o remain
upright for 30 t o 60 minut es aft er dosing. An alt ernat ive t o annual int ravenous alendronat e is int ravenous ibandronat e every 3 mont hs.
Calcit onin is not a first -line drug for post menopausal ost eoporosis t reat ment . It s efficacy against fract ures is not st rong, and it s effect s on bone mineral densit y are less t han
t hose of ot her agent s.
Alt hough raloxifene, a select ive est rogen recept or modulat or, can prevent bone loss and reduces t he risk of vert ebral fract ures, it s effect iveness in reducing ot her fract ures is
uncert ain. Ext raskelet al risks (including risk of t hromboembolism and fat al st roke) and benefit s must be considered before st art ing post menopausal women on raloxifene
t herapy. For t his pat ient , t he safer alt ernat ive of int ravenous zoledronat e or ibandronat e is available and is recommended as first -line t herapy.
Teriparat ide (recombinant human parat hyroid hormone [1-34]) is reserved for t reat ing pat ient s at high risk of fract ure, including t hose wit h very low bone mineral densit y
(T-score below -3.0) wit h a previous vert ebral fract ure and cont raindicat ions t o bisphosphonat e use. This t herapy improves bone mineral densit y, st imulat es new bone
format ion, and reduces t he risk of new vert ebral and nonvert ebral fract ures. Dosage requirement s, such as daily subcut aneous inject ions, may limit it s use. Teriparat ide is an
anabolic agent , whereas t he ot her ost eoporosis drugs are ant iresorpt ive agent s. Since t his pat ient does not have a previous fract ure and is probably able t o t olerat e once yearly
int ravenous zoledronat e, t eriparat ide is not indicat ed.
Key Poi nt
Once yearly int ravenous infusion of zoledronat e is a pot ent t herapy for t reat ing post menopausal ost eoporosis of t he spine and hip.
Bi bl i ography
[PMID: 19854322]
Item 32 Answer: C
Educati onal Objecti ve: Diagnose osteoporosis.
This pat ient has ost eoporosis. She had recent vert ebral compression fract ures in response t o minimal t rauma (fragilit y fract ure). Ost eoporosis is diagnosed by t he presence of
fragilit y fract ures (fract ure secondary t o minor t rauma, such as falling from a st anding posit ion), or by a bone mineral densit y (BMD) T-score less t han -2.5 in pat ient s who
have not experienced a fragilit y fract ure. Bone densit y scan result s are report ed in t erms of T-scores (t he st andard deviat ion from t he mean BMD of a young healt hy
populat ion) and Z-scores (t he st andard deviat ion from t he BMD of an age- and sex-mat ched group). At t he spine, a T-score of -1 represent s approximat ely 10% bone loss.
The T-score is used t o diagnose ost eoporosis.
Ost eopenia is defined as a BMD T-score t hat is bet ween -1 and -2.5. In all pat ient s, t he presence of a fragilit y fract ure t akes priorit y over BMD result s in diagnosing
ost eoporosis. This pat ient has also had an evaluat ion for causes of secondary bone loss. The normal serum calcium, phosphorus, and alkaline phosphat ase levels and normal
urine calcium level are consist ent wit h ost eoporosis and exclude secondary ost eoporosis.
Key Poi nt
Ost eoporosis is diagnosed by t he presence of fragilit y fract ures or by a bone mineral densit y T-score less t han -2.5 in pat ient s who have not experienced a fragilit y fract ure.
Bi bl i ography
[PMID: 19854322]
Secti on 3. Gastroenterol ogy and Hepatol ogy
Questi ons
Item 1 [Basic]
A 42-year-old man is evaluat ed in t he clinic for 1 day of acut e onset , left -sided colicky flank pain. The pain radiat es from his left upper quadrant t o t he left lower quadrant
and upper t high. Wit h t he onset of t he pain, he has developed nausea but no vomit ing. He has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, t emperat ure is 37.4C (99.3F), blood pressure is 154/78 mm Hg, heart rat e 85/min, and respirat ion rat e is 18/min. He report s no t enderness t o
abdominal or cost overt ebral angle palpat ion. The remainder of t he physical examinat ion is normal.
Urinalysis shows many eryt hrocyt es, but no leukocyt es or bact eria.
Whi ch of the fol l owi ng tests shoul d be done next?
(A) Abdominal x-ray
(B) Int ravenous pyelography
(C) Kidney ult rasound
(D) Noncont rast helical abdominal CT scan
Item 2 [Basic]
A 67-year-old woman is evaluat ed in t he hospit al for acut e abdominal pain. She was admit t ed for communit y-acquired pneumonia, and her condit ion was improving on
t herapy wit h ant ibiot ics and fluids. However, on day 3 she developed acut e abdominal pain associat ed wit h nausea. Her medical hist ory includes a 7-year hist ory of peripheral
art erial disease, t ype 2 diabet es mellit us, hyperlipidemia, and an episode of divert iculit is 2 years ago. Her medicat ions are pravast at in, aspirin, dipyridamole, and met formin.
On physical examinat ion, she is in dist ress; t emperat ure is 38.3C (101.0F), blood pressure is 170/100 mm Hg, pulse rat e is 120/min, and respirat ion rat e is 25/min. She rat es
her pain as 10 out of 10. She has diffuse abdominal t enderness, more pronounced in t he left lower quadrant wit h rebound t enderness.
(A) Colonoscopy
(B) CT scan of t he abdomen
(C) Left pelvic ult rasonography
(D) Supine and upright abdominal radiographs
Item 3 [Advanced]
A 70-year-old man is evaluat ed in t he emergency depart ment for severe lower abdominal and back pain t hat began suddenly 12 hours ago and was associat ed wit h a syncopal
episode. Since t hat t ime, he has had vague lower abdominal and back discomfort . There has been no change in bowel or urinary habit s and no fever or chills. The pat ient has a
40 pack-year hist ory of smoking cigaret t es. He also has hypert ension and hyperlipidemia. His medicat ions are at orvast at in, aspirin, lisinopril, and hydrochlorot hiazide.
On physical examinat ion, t emperat ure is 37.7C (99.8F), blood pressure is 90/60 mm Hg, pulse rat e is 110/min and regular, and respirat ion rat e is 18/min. Result s of t he
cardiac and neurologic examinat ions are normal. There is moderat e t enderness t o palpat ion in t he infra-umbilical and suprapubic regions but no guarding or rebound
t enderness. The remainder of t he abdominal examinat ion is normal.
Laborat ory result s include a hemat ocrit of 29% and a leukocyt e count of 12,000/L (12.0 10
9
/L). Result s of liver chemist ry st udies and urinalysis are normal. A st ool
sample t est s negat ive for occult blood. Elect rocardiogram shows normal sinus rhyt hm and left vent ricular hypert rophy. A plain abdominal radiograph shows no free air or air-
fluid levels.
(B) Divert iculit is
(C) Nephrolit hiasis (renal colic)
(D) Rupt ured abdominal aort ic aneurysm
Item 4 [Advanced]
A 25-year-old woman is evaluat ed for a 2-year hist ory of almost daily bloat ing and lower abdominal cramping; t he sympt oms are associat ed wit h const ipat ion, relieved wit h
bowel movement s, and seem worse when she is under st ress. She has one or t wo small bowel movement s a week and oft en has a feeling of incomplet e evacuat ion. She never
has diarrhea and has not had blood in t he st ool, noct urnal awakening wit h pain or for bowel movement s, or weight loss. She has t aken a fiber supplement wit hout relief. The
pat ient is ot herwise healt hy, and her only medicat ion is an oral cont racept ive pill t hat she has been t aking for 1 year.
On physical examinat ion, vit al signs are normal; t here is mild lower abdominal t enderness wit h no rebound, guarding, or palpable abdominal masses. Hemoglobin level and
serum biochemist ry t est s, including t hyroid-st imulat ing hormone, are all normal.
Whi ch of the fol l owi ng i s the most appropri ate next step i n the management of thi s pati ent?
(A) Colonoscopy
(B) CT scan of t he abdomen and pelvis
(C) Discont inue t he oral cont racept ive
(D) Reassurance and polyet hylene glycol
Item 5 [Advanced]
A 75-year-old woman is evaluat ed in t he emergency depart ment for t he acut e onset of passage of bright red blood per rect um. This morning she had crampy abdominal pain
and had t wo episodes of diarrhea aft er which she passed bright red blood. The pat ient has a hist ory of hypert ension and coronary art ery disease. Medicat ions are aspirin,
ramipril, met oprolol, and simvast at in. She had a colonoscopy 6 mont hs ago, which was normal.
On physical examinat ion, t he pat ient is not in acut e dist ress; t emperat ure is 36.8C (98.2F), blood pressure is 130/80 mm Hg, pulse rat e is 70/min, and respirat ion rat e is
14/min. The heart and lungs are normal. The abdomen is soft wit h t enderness in t he left lower quadrant wit hout rebound or guarding. Rect al examinat ion shows t he presence
of bright red blood. Laborat ory st udies reveal a hemoglobin level of 11.9 g/dL (119 g/L), a leukocyt e count of 8400/L (8.4 10
9
/L), and plat elet count 246,000/L (246
10
9
/L). Serum elect rolyt es, glucose, creat inine, and urea nit rogen are normal. CT scan of t he abdomen and pelvis shows segment al t hickening in t he sigmoid colon.
(A) Crohn disease
(B) Irrit able bowel syndrome
(C) Ischemic colit is
Item 6 [Basic]
A 63-year-old man is evaluat ed for a 2-day hist ory of left lower quadrant abdominal pain. The pain is const ant and is not relieved by a bowel movement or by posit ional
changes. The pat ient is slight ly nauseat ed and has no appet it e but is not vomit ing. He has never had a similar episode. The pat ient is ot herwise healt hy.
On physical examinat ion, t emperat ure is 38.0C (100.4F), blood pressure is 125/85 mm Hg, pulse rat e is 95/min, and respirat ion rat e is 14/min. There is fullness and
t enderness of t he left lower quadrant wit h no rebound or guarding; bowel sounds are decreased. Rect al examinat ion is normal; examinat ion of st ool for occult blood is negat ive.
Leukocyt e count is 14,000/L (14 10
9
/L); all ot her laborat ory result s are normal. A plain abdominal radiograph is unremarkable, and a chest radiograph shows no free air
beneat h t he diaphragms.
Whi ch of the fol l owi ng i s the most appropri ate next step i n the eval uati on of thi s pati ent?
(A) Barium enema
(B) Colonoscopy
(C) Cont rast -enhanced CT scan of t he abdomen and pelvis
(D) Small-bowel radiographic series
Item 7 [Advanced]
A 42-year-old man is evaluat ed in t he hospit al for a 1-year hist ory of post prandial abdominal pain t hat radiat es t o t he back, is worse aft er eat ing, and is associat ed wit h
bloat ing and nausea. He has not lost weight . The pat ient has had at least five alcohol-cont aining drinks a day for 20 years.
On physical examinat ion, vit al signs are normal; BMI is 21. There is mild epigast ric t enderness wit h no guarding or rebound and normal bowel sounds.
Laborat ory st udies reveal a normal complet e blood count and normal glucose and liver chemist ry t est s; amylase is 221 U/L and lipase is 472 U/L. A plain film of t he abdomen
is shown.
(A) Acut e cholangit is
(B) Chronic pancreat it is
(C) Divert iculit is
Item 8 [Advanced]
A 14-year-old boy is evaluat ed for a 1-week hist ory of fever, abdominal pain, and bloody diarrhea. He report s no recent t ravel or medicat ion use but did go t o a barbeque 1
week ago and at e hamburgers. His medical hist ory is ot herwise unremarkable.
On physical examinat ion, t emperat ure is 38.4C (101.2F), blood pressure is 150/96 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 14/min. He has pet echiae on his
legs. The abdomen is diffusely t ender. The remainder of t he examinat ion is normal.
Hemoglobin 7.6 g/dL (76 g/L)
Leukocyt e count 15,000/L (15 10
9
/L)
Plat elet count 46,000/L (24 10
9
/L)
Urinalysis is posit ive for many eryt hrocyt es per high-power field.
Whi ch of the fol l owi ng i s the most appropri ate next management step for thi s pati ent?
(A) Empiric ant ibiot ics
(B) Peripheral blood smear
(C) Plat elet t ransfusion
(D) Rout ine st ool cult ure (shigella, salmonella, campylobact er)
(E) St ool for fecal leukocyt es
Item 9 [Advanced]
A 64-year-old woman is evaluat ed for 2 weeks of nonbloody diarrhea. She was recent ly diagnosed wit h st age IV rect al cancer and underwent t reat ment wit h chemot herapy and
radiat ion t herapy 4 weeks ago. She has 10 small, loose bowel movement s daily associat ed wit h t enesmus. She has no nausea, vomit ing, abdominal pain, fever, or weight loss.
On physical examinat ion, vit al signs are normal. The abdomen is soft , and no evidence of rect al fissures or fist ulas is seen.
Whi ch i s the fol l owi ng i s the most appropri ate di agnosti c test?
(A) Abdominal/pelvic CT scan
(B) Flexible sigmoidoscopy
(C) St ool cult ure
(D) St ool osmolalit y
Item 10 [Advanced]
A 41-year-old man is evaluat ed for an 8-mont h hist ory of mid-epigast ric pain t hat is worse aft er eat ing and six t o eight oily bowel movement s a day usually occurring aft er a
meal. He has lost 6.8 kg (15 lb) over t he past 6 mont hs. The pat ient drinks six t o eight cans of beer a day, and he has been admit t ed t o t he hospit al t wice wit h acut e
pancreat it is. He t akes no medicat ions.
On physical examinat ion, BMI is 21. He has normal bowel sounds and mid-epigast ric t enderness but no evidence of hepat osplenomegaly or masses. Rect al examinat ion
reveals brown st ool t hat is negat ive for occult blood. The remainder of t he examinat ion is normal. Plain radiograph of t he abdomen shows a normal bowel gas pat t ern and is
ot herwise normal.
Fast ing plasma glucose 124 mg/dL (6.9 mmol/L)
Aspart at e aminot ransferase 191 U/L
Alanine aminot ransferase 82 U/L
Amylase 132U/L
Lipase 289 U/L
Whi ch of the fol l owi ng tests i s most l i kel y to establ i sh the di agnosi s i n thi s pati ent?
(A) Colonoscopy
(B) CT scan of t he abdomen
(C) Measurement of serum ant iendomysial ant ibodies
(D) St ool for leukocyt es, cult ure, ova, and parasit es
Item 11 [Basic]
A 30-year-old woman is evaluat ed for a 9-mont h hist ory of cramping midepigast ric discomfort t hat is relieved by defecat ion; t he discomfort is somet imes accompanied by
bloat ing. The st ool is oft en wat ery. She has not had fever, chills, or weight loss. The pat ient is ot herwise healt hy and t akes no medicat ions; t here is no family hist ory of
gast roint est inal disease.
On physical examinat ion, t he pat ient is afebrile; blood pressure is 105/70 mm Hg, pulse rat e is 72/min, and respirat ion rat e is 14/min; BMI is 23. The abdomen is soft and not
t ender or dist ended; t he st ool is brown and negat ive for occult blood. Complet e blood count and serum biochemist ry st udies, including liver st udies, vit amin B
12
, vit amin D,
and t hyroid-st imulat ing hormone, are normal. A flexible sigmoidoscopy is normal.
(A) Colonoscopy
(B) CT ent eroscopy
(C) Glut en-free diet
(D) Sympt omat ic management
Item 12 [Basic]
A 74-year-old woman is evaluat ed in t he emergency depart ment wit h a 2-day hist ory of diarrhea charact erized by t en bowel movement s daily, wit h worsening abdominal pain
and fever. Five weeks ago, t he pat ient was hospit alized wit h necrot izing fasciit is of t he right t high for which she underwent debridement , received nafcillin and clindamycin
t herapy, and was discharged aft er 2 weeks. On discharge, she was prescribed a 2-week course of nafcillin, which she complet ed 1 week ago.
On physical examinat ion, t emperat ure is 38.6C (101.5F), blood pressure is 90/55 mm Hg, pulse rat e is 122/min, and respirat ion rat e is 24/min. The abdomen is dist ended
and t ender t o palpat ion, and bowel sounds are absent .
Laborat ory st udies indicat e a leukocyt e count of 32,500/L (32.5 10
9
/L). St ool, blood, and urine samples are obt ained for cult ure.
(A) Clostridium difficile infect ion
(B) Crohn disease
(C) Divert iculit is
(D) Divert iculosis
(E) Ischemic colit is
Item 13 [Advanced]
A 30-year-old man is evaluat ed for a 3-day hist ory of fever and diarrhea. He has not recent ly t raveled and he is ot herwise healt hy.
On physical examinat ion, he appears fat igued but not severely ill. Temperat ure is 38.7C (101.7F); ot her vit al signs are normal. There is mild diffuse abdominal t enderness
t o deep palpat ion. A st ool specimen is submit t ed for diagnost ic t est ing and is found t o be posit ive for Salmonella species.
Whi ch of the fol l owi ng i s the most appropri ate next step i n management?
(A) Administ er loperamide
(B) Begin oral ciprofloxacin
(C) Begin oral met ronidazole
(D) Reassure and set up follow-up phone call
Item 14 [Basic]
A 24-year-old man is evaluat ed for a 6-day hist ory of malaise, fat igue, and jaundice following a camping t rip in rural Mexico 3 weeks ago. His alcohol consumpt ion is
approximat ely 6 beers per week, never exceeding more t han 2 beers per occasion. Two weeks ago he part icipat ed in a marat hon race and finished t he race wit hout incident .
His sist er was recent ly diagnosed wit h primary biliary cirrhosis. The remainder of his hist ory is unremarkable.
On examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 132/72 mm Hg, pulse rat e is 104/min, and t he respirat ion rat e is 16/min. BMI is 21. Examinat ion shows
sclera ict erus and hepat omegaly. The remainder of t he examinat ion findings are normal.
Bilirubin (t ot al) 4.6 mg/dL (78.7 mol/L)
Bilirubin (direct ) 3.5 mg/dL (59.9 mol/L)
Whi ch of the fol l owi ng patterns of hepati c i njury i s present?
(A) Cholest at ic injury
(B) Hepat ocellular injury
(C) Mixed hepat ocellular and cholest at ic injury
(D) Nonhepat ic injury pat t ern (muscle injury)
Item 15 [Advanced]
A 30-year-old woman is evaluat ed because of an abnormal serum t ot al bilirubin level det ect ed when she had a life insurance examinat ion. Medical hist ory is unremarkable. Her
only medicat ion is an oral cont racept ive agent . Physical examinat ion is normal.
Mean corpuscular volume 88 fL
Red cell dist ribut ion widt h 10.8%
Serum t ot al bilirubin 2.4 mg/dL (41.0 mol/L)
Serum direct bilirubin 0.2 mg/dL (3.4 mol/L)
Serum aspart at e aminot ransferase 23 U/L
Serum alanine aminot ransferase 22 U/L
Serum alkaline phosphat ase 82 U/L
Whi ch of the fol l owi ng i s the most appropri ate management at thi s ti me?
(A) Discont inue t he oral cont racept ive agent
(B) No furt her int ervent ion required
(C) Obt ain a ret iculocyt e count and hapt oglobin level
(D) Repeat t he liver chemist ry t est s in 3 mont hs
(E) Schedule abdominal ult rasonography
Item 16 [Basic]
A 62-year-old man is evaluat ed in t he hospit al following an episode of acut e cholecyst it is 3 days ago. He had sympt oms of right upper quadrant abdomin several t imes over
t he past few mont hs, but t hey resolved spont aneously. At t he t ime of hospit al admission, ult rasonography showed an enlarged gallbladder wit h a t hickened wall and evidence
of st ones in t he gallbladder. He was t reat ed wit h ant ibiot ics and analgesics and his sympt oms resolved. He current ly feels well. He has no significant medical hist ory.
On physical examinat ion, t emperat ure is normal, blood pressure is 112/64 mm Hg, pulse rat e is 68/min, and respirat ion rat e is 12/min. BMI is 28. He is not jaundiced. On
abdominal examinat ion, normal bowel sounds are present wit hout t enderness. Murphy sign is absent .
(A) Cholecyst ect omy
(B) Endoscopic ret rograde cholangiopancreat ography (ERCP) wit h sphinct erot omy
(C) Low-fat diet and weight loss
(D) Ursodeoxycholic acid
Item 17 [Advanced]
A 42-year-old man is evaluat ed for a 1-mont h hist ory of progressive jaundice, prurit us, and dark urine. The pat ient has a 15-year hist ory of ulcerat ive colit is. He is t reat ed
wit h mesalamine and occasionally requires cort icost eroid t herapy. He t akes no ot her medicat ions.
On physical examinat ion, vit al signs are normal. There is jaundice and hepat omegaly but no splenomegaly, ascit es, or abdominal t enderness. There is no ast erixis.
Hemoglobin 14 g/dL (140 g/L)
(A) Gilbert syndrome
(B) Hepat it is A
(C) Hepat it is C
(D) Primary sclerosing cholangit is
Item 18 [Basic]
A 64-year-old woman is evaluat ed in t he emergency depart ment for a 3-week hist ory of post prandial right upper quadrant abdominal pain t hat has become increasingly
int ense. The pain is now const ant , radiat es t o her right shoulder, and is accompanied by fever, nausea, and vomit ing.
On physical examinat ion, t emperat ure is 38.3C (101.0F), blood pressure is 110/65 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 20/min. There is pain on palpat ion
in t he right upper quadrant of t he abdomen wit h a Murphy sign. There is no rebound, t enderness, or jaundice.
Amylase 58 U/L
Lipase 36 U/L
Ult rasonography shows pericholecyst ic fluid wit h st ones in t he gallbladder. The wall of t he gallbladder is t hickened (6 mm), and t here is no dilat at ion of t he bile duct s.
(B) Acut e cholecyst it is
(C) Acut e pancreat it is
(D) Gallbladder dyskinesia
Item 19 [Advanced]
A 63-year-old man comes t o t he emergency depart ment because of significant epigast ric pain, nausea, and fever of 24 hours' durat ion. On physical examinat ion, t he pat ient
is jaundiced. Temperat ure is 38.5C (101.3F), blood pressure is 100/68 mm Hg, and pulse rat e is 100/min. Abdominal examinat ion discloses significant right upper quadrant
t enderness.
Leukocyt e count 12,100/L (12.1 10
9
/L)
Serum lipase 240 U/L
Serum t ot al bilirubin 2.9 mg/dL (49.6 mol/L)
Abdominal ult rasonography shows a dilat ed 11-mm common bile duct and a gallbladder cont aining mult iple st ones.
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s accounti ng for al l the pati ent's fi ndi ngs?
(B) Acut e cholecyst it is
(C) Acut e pancreat it is
(D) Cholelit hiasis
Item 20 [Advanced]
A 59-year-old woman is evaluat ed in t he emergency depart ment for a 9-hour hist ory of epigast ric pain, nausea, and vomit ing. She had been previously healt hy.
On physical examinat ion, t he pat ient appears ill. Temperat ure is 36.5C (97.8F), blood pressure is 148/84 mm Hg, pulse rat e is 112/min, and respirat ion rat e is 14/min. BMI
is 30. Abdominal examinat ion reveals diffuse t enderness.
9
/L)
Tot al bilirubin 3.4 mg/dL (58.1 mol/L)
Amylase 410 IU/L
Lipase 360 IU/L
Ult rasonography shows cholelit hiasis and a dilat ed common bile duct .
(A) Emergency laparoscopic cholecyst ect omy
(B) Endoscopic ret rograde cholangiopancreat ography (ERCP)
(C) Jejunal ent eral feedings
(D) Magnet ic resonance cholangiopancreat ography (MRCP)
Item 21 [Basic]
A 55-year-old woman is evaluat ed in t he hospit al for a 2-day hist ory of severe epigast ric abdominal pain, nausea and vomit ing, and anorexia. The pat ient has no significant
medical hist ory, t akes no medicat ions, and does not drink alcohol.
On physical examinat ion, t emperat ure is 38.0C (100.4F), blood pressure is 124/76 mm Hg, pulse rat e is 99/min, and respirat ion rat e is 16/min. There is scleral ict erus and
jaundice. There is mid-epigast ric and right upper quadrant t enderness.
Amylase 1284 U/L
Lipase 6742 U/L
Abdominal ult rasonography shows a biliary t ree wit h a dilat ed common bile duct of 12 mm and cholelit hiasis but no choledocholit hiasis.
(A) Alcoholic pancreat it is
(B) Aut oimmune pancreat it is
(C) Gallst one pancreat it is
(D) Hypert riglyceridemic pancreat it is
Item 22 [Advanced]
A 34-year-old woman is evaluat ed for cont inued severe mid-epigast ric pain t hat radiat es t o t he back, nausea, and vomit ing 5 days aft er being hospit alized for alcohol-relat ed
pancreat it is. She has not been able eat or drink since being admit t ed.
On physical examinat ion, t emperat ure is 38.2C (100.8F), blood pressure is 132/84 mm Hg, pulse rat e is 101/min, and respirat ion rat e is 20/min. There is no scleral ict erus
or jaundice. The abdomen is dist ended and diffusely t ender wit h hypoact ive bowel sounds but no perit oneal signs.
Amylase 388 U/L
Lipase 924 U/L
CT scan of t he abdomen shows a diffusely edemat ous pancreas wit h mult iple peripancreat ic fluid collect ions and no evidence of pancreat ic necrosis.
(A) Begin prednisone
(B) Ent eral nut rit ion wit h nasojejunal feeding t ube
(C) Int ravenous imipenem
(D) Pancreat ic debridement
Item 23 [Basic]
A 68-year-old man is evaluat ed for a 15-year hist ory of acid reflux sympt oms and a 6-mont h hist ory of worsening midst ernal burning chest discomfort . The pain is
nonexert ional and exacerbat ed by lying down or bending over. He also not es occasional difficult y swallowing solids described as a sensat ion of food "st icking" at about t he
level of t he lower st ernum. The pain is part ially alleviat ed by over-t he-count er ant acids, but t hey have no effect on t he dysphagia. He does not smoke or drink, he has no
ot her medical problems, and he t akes no prescript ion medicat ions.
On physical examinat ion, vit al signs are normal. BMI is 27. Cardiopulmonary and abdominal examinat ions are unremarkable.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al di agnosti c test for thi s pati ent?
(B) Empiric t reat ment wit h omeprazole
(C) Helicobacter pylori t est ing
(D) Upper endoscopy
Item 24 [Advanced]
A 30-year-old woman is evaluat ed in t he emergency depart ment for abdominal pain and hemat emesis. She undergoes upper endoscopy, which demonst rat es a 1-cm duodenal
ulcer wit h a clean base. Helicobacter pylori is seen on biopsy, and t he pat ient is discharged home wit h appropriat e t herapy for H. pylori. She is adherent t o her t herapy and
her sympt oms rapidly resolve.
The pat ient ret urns t o t he office 3 mont hs lat er wit h 3 weeks of midepigast ric abdominal discomfort ; regurgit at ion; and burning chest discomfort t hat worsens wit h bending
over, lying down, or aft er eat ing large meals. Repeat endoscopy demonst rat es complet e healing of her duodenal ulcer; erosive esophagit is is present .
(A) Met oclopramide
(B) Omeprazole
(C) Ranit idine
(D) Sucralfat e
Item 25 [Advanced]
A 61-year-old man is evaluat ed for a 3-week hist ory of abdominal discomfort and early sat iet y. During t his t ime, he has experienced a 1.4-kg (3-lb) weight loss. For t he past
10 days he has t reat ed t hese sympt oms wit h an over-t he-count er prot on pump inhibit or wit h part ial relief of sympt oms. He t akes no ot her medicat ions.
On physical examinat ion, t emperat ure is 37C (98.6F), blood pressure is 132/76 mm Hg, pulse rat e is 68/min, and respirat ion rat e is 12/min. His abdominal examinat ion
reveals a rounded, soft abdomen wit h act ive bowel sounds. No masses are palpable. Deep epigast ric palpat ion result s in mild t enderness.
Upper endoscopy reveals a 9-mm ulcer in t he gast ric ant rum proximal t o t he pylorus.
Whi ch of the fol l owi ng i s the most appropri ate management for thi s pati ent's ul cer?
(A) Biopsy
(B) Omeprazole, amoxicillin, and clarit hromycin
(C) Rapid urease t est
(D) Urea breat h t est
Item 26 [Basic]
A 65-year-old woman is evaluat ed 1 week aft er undergoing an esophagogast roduodenoscopy for persist ent abdominal pain. The procedure showed a 1-cm, clean-based ulcer in
t he duodenal bulb and scat t ered ant ral erosions. Biopsy specimens from t he st omach showed nonspecific gast rit is but no evidence of Helicobacter pylori infect ion. Serum
ant ibody t est ing for H. pylori was also negat ive. Prot on pump inhibit or t herapy was st art ed, and t he pat ient 's sympt oms were alleviat ed. The pat ient has a hist ory of mild
ost eoart hrit is and ost eoporosis. Medicat ions are over-t he-count er ibuprofen for art hrit is and a calcium supplement , vit amin D, and alendronat e.
On physical examinat ion, vit al signs are normal. The abdominal examinat ion reveals no t enderness, hepat omegaly, or palpable masses. Complet e blood count is normal.
(A) Measure serum gast rin
(B) Perform fecal ant igen t est for Helicobacter pylori
(C) Repeat endoscopy and ulcer biopsy
(D) St op t he alendronat e
(E) St op t he ibuprofen
Item 27 [Basic]
A 46-year-old man is evaluat ed for a 5-mont h hist ory of int ermit t ent midabdominal discomfort t hat occurs aft er eat ing. Each episode last s bet ween 30 minut es and1 hour.
The discomfort is described as fullness; he report s no sympt oms charact erist ic of esophageal reflux or biliary colic. He has no vomit ing, dysphagia, or changes in bowel habit s.
He has gained approximat ely 4.5 kg (10 lb) during t he past 5 mont hs. Medical hist ory includes low back pain for which he t akes ibuprofen. He has no family hist ory of
malignancy.
On physical examinat ion, vit al signs are normal. BMI is 28. The remainder of t he physical examinat ion is normal.
A met abolic panel and complet e blood count are normal.
What i s the most appropri ate next management step for thi s pati ent?
(A) St art met oclopramide
(B) St op ibuprofen
(C) Obt ain an upper endoscopy
(D) Test for Helicobacter pylori infect ion
Item 28 [Basic]
A 58-year-old woman is evaluat ed for a 3-mont h hist ory of burning midepigast ric pain aft er eat ing and early sat iet y. The pain feels t he same as a gast ric ulcer she had 10
years ago. She report s no associat ed sour t ast e, belching, bloat ing, or worsening sympt oms wit h recumbency or at night . She has no nausea, vomit ing, painful swallowing,
changes in bowel habit s, or weight loss. She is ot herwise in good healt h and has no sympt oms of anxiet y or depression.
On physical examinat ion, vit al signs are normal. Mild midepigast ric t enderness is present , but her physical examinat ion is ot herwise normal.
A t hyroid-st imulat ing hormone level, complet e blood count , and met abolic panel are normal. An upper endoscopy is performed and it is normal. Test ing for H. pylori is
negat ive.
(B) Psychiat ric evaluat ion
(C) Surgical evaluat ion
(D) Trial of a prot on pump inhibit or (PPI)
Item 29 [Advanced]
A 57-year-old woman is evaluat ed for recurrent gast roint est inal bleeding. She has a hist ory of heart burn wit hout dysphagia but no ot her medical problems. She has no obvious
source of bleeding. She report s no menst rual blood loss, hemat ochezia, hemat emesis, easy bruising, or bleeding. She t akes no medicat ions ot her t han t herapeut ic doses of
ferrous sulfat e wit h which she is adherent . Three mont hs ago, an upper endoscopy was normal except for a hiat al hernia. A colonoscopy was normal.
Her st ool cont inues t o t est posit ive for fecal occult blood. Hemoglobin is 10.2 g/dL (102 g/L). Serum iron st udies are compat ible wit h iron deficiency.
(A) Barium swallow
(B) Double balloon ent eroscopy
(C) Repeat colonoscopy
(D) Repeat upper endoscopy
Item 30 [Advanced]
A 78-year-old man hospit alized 3 days ago for heart failure is evaluat ed for 1 day of cramping left lower abdominal pain and t he explosive passage of t wo bloody st ools. His
medical hist ory is remarkable for hypert ension and t ype 2 diabet es. Medicat ions are lisinopril, met oprolol, furosemide, digoxin, insulin glargine, and premeal insulin lispro.
On physical examinat ion, t he pat ient is slight ly uncomfort able. Temperat ure is 37.2C (99.0F), blood pressure is 130/68 mm Hg, pulse rat e is 60/min, and respirat ion rat e is
12/min. Bowel sounds are present . An S
3
is present and lung auscult at ion reveals clear lungs fields. The abdomen is t ender in t he left lower quadrant wit hout rebound or
guarding. No masses or t enderness is found on rect al examinat ion.
Hemoglobin is 11.1 g/dL (111 g/L). Clostridium difficile t oxin assay is negat ive.
Colonoscopy shows pet echial hemorrhages int erspersed wit h areas of pale, edemat ous mucosa in t he sigmoid region.
(A) Acut e mesent eric ischemia
(B) Divert iculit is
(C) Divert iculosis
(D) Ischemic colit is
Item 31 [Basic]
A 68-year-old man is evaluat ed in t he emergency depart ment for a 6-hour hist ory of nausea and vomit ing wit h some bright -red emesis. For t he past 2 hours he has felt
light headed and weak.
On physical examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 88/51 mm Hg, pulse rat e is 114/min, and respirat ion rat e is 18/min. Nasogast ric aspirat ion shows a
mixt ure of coffee grounds and dark blood. The abdomen is not t ender, and bowel sounds are normal. Laborat ory st udies reveal a hemoglobin level of 9.4g/dL (94 g/L); all
ot her t est s are normal. Int ravenous omeprazole t herapy is begun, and t he pat ient is st abilized wit h infusion of normal saline and t ransfusion of t wo unit s of packed
eryt hrocyt es.
Whi ch of the fol l owi ng i s the best management opti on for thi s pati ent?
(A) Esophagogast roduodenoscopy
(B) Immediat e surgical int ervent ion
(C) Observat ion
(D) Oct reot ide infusion
(E) Ranit idine infusion
Item 32 [Basic]
A 60-year-old man hospit alized for advanced cirrhosis complicat ed by ascit es and encephalopat hy is evaluat ed for massive hemat emesis and hypot ension. The pat ient 's
medicat ions are spironolact one, propranolol, furosemide, and lact ulose.
On physical examinat ion, t emperat ure is 35.6C (96.1F), blood pressure is 80/50 mm Hg, pulse rat e is 146/min, and respirat ion rat e is 20/min. The pat ient has just vomit ed
red blood. Laborat ory st udies show a hemoglobin level of 9g/dL (90 g/L), a plat elet count of 60,000/L (60 10
9
/L), and an INR of 3.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al management of thi s pati ent?
(A) Art eriography
(B) Esophagogast roduodenoscopy
(C) Int ravenous nadolol
(D) Rapid volume replacement
Item 33 [Basic]
A 76-year-old man is evaluat ed in t he emergency depart ment aft er having suddenly passed a large amount of red and maroon blood per rect um. He has not had abdominal
pain, nausea, vomit ing, fever, or weight loss. He had a colonoscopy 1 year ago t hat showed a benign polyp and divert iculosis. He is ot herwise healt hy and t akes no
medicat ions.
On physical examinat ion, t he pat ient is pale; blood pressure is 105/65 mm Hg and pulse rat e is 100/min. Abdominal examinat ion is normal; t here is dried blood in t he perianal
area, and rect al examinat ion reveals fresh blood on t he examinat ion glove.
Laborat ory st udies reveal a hemoglobin level of 10.1 g/dL (101 g/L) and normal biochemical st udies, including blood urea nit rogen. Leukocyt e count is 5600/L (5.6 10
9
/L)
and plat elet count is 348,000/L (348 10
9
/L); prot hrombin t ime and act ivat ed part ial t hromboplast in t ime are normal.
Int ravenous access is obt ained and volume resuscit at ion wit h normal saline is begun. A nasogast ric t ube aspirat e is posit ive for bile but negat ive for blood.
Whi ch of the fol l owi ng i s the most l i kel y cause of the gastroi ntesti nal bl eedi ng?
(A) Colon cancer
(B) Colonic ischemia
(C) Divert iculosis or vascular ect asia
(D) Inflammat ory bowel disease
Item 34 [Basic]
A 51-year-old woman has a 3-mont h hist ory of int ermit t ent rect al bleeding and pain on defecat ion. Bloody st reaks cover t he st ool, and t he t oilet paper is also bloody. She is
ot herwise well and t akes no medicat ions.
One mont h before t he bleeding developed, she underwent an elect ive ort hopedic surgical procedure and required narcot ic drugs for several weeks post operat ively. The
narcot ics caused significant const ipat ion. The pat ient had her first screening colonoscopy less t han 1 year ago, and result s were normal. At t hat t ime, a ret roflexed view of
t he rect um revealed small int ernal hemorrhoids.
Visual inspect ion of t he anal opening reveals small ext ernal hemorrhoids and several anal skin t ags. Hemoglobin is 13.9 g/dL (139 g/L).
Whi ch of the fol l owi ng i s most l i kel y causi ng thi s pati ent's rectal bl eedi ng and pai n?
(A) Anal fissure
(B) Colon cancer
(C) Colonic divert icula
(D) Rect al cancer
Item 35 [Advanced]
A 45-year-old woman is evaluat ed during a rout ine office visit . She was diagnosed wit h chronic act ive hepat it is B infect ion 10 years ago. She has no sympt oms and no ot her
medical problems. A liver biopsy performed 3 years ago revealed changes consist ent wit h chronic act ive inflammat ion wit h no cirrhosis. She is t aking int erferon alfa.
On physical examinat ion, vit al signs are normal. No evidence of t elangiect asias or ot her st igmat a of chronic liver disease is present . The abdomen is unremarkable wit hout
evidence of hepat omegaly, liver t enderness, or ascit es. The remainder of t he examinat ion findings are normal.
Serum aspart at e aminot ransferase is 200 U/L and alanine aminot ransferase is 100 U/L. (unchanged from 6 mont hs ago). Prot hrombin t ime and act ivat ed part ial
t hromboplast in t ime are normal. Hepat it is C ant ibody is negat ive.
Whi ch of the fol l owi ng i s the most appropri ate screeni ng strategy for hepatocel l ul ar carci noma i n thi s pati ent?
(A) -Fet oprot ein
(B) Abdominal ult rasonography
(C) CT of t he liver wit h cont rast
(D) Screening is not indicat ed
Item 36 [Basic]
A 22-year-old college st udent has recent ly ret urned from a 3-mont h ant hropology course in Thailand where she lived wit h a local village family. She has a 2-week hist ory of
fat igue and nausea wit h occasional vomit ing and a 2-day hist ory of jaundice. She was previously well, t akes no medicat ions, and has no hist ory of liver disease, inject ion drug
use, blood t ransfusions, sexual exposures, or known exposure t o anyone wit h hepat it is. She t ook malarial prophylaxis and her hepat it is B vaccinat ion st at us is current . She
does not recall vaccinat ion for hepat it is A.
Physical examinat ion is significant only for jaundice and a slight ly enlarged, nont ender liver. There are no spider angiomat a or signs of encephalopat hy.
(A) Hepat it is A
(B) Hepat it is B
(C) Hepat it is C
(D) Hepat it is D
Item 37 [Basic]
A 55-year-old man is hospit alized for a 2-week hist ory of jaundice and alt ered ment al st at us. The pat ient has a 10-year hist ory of alcohol dependence. His family report s t hat
he had been drinking heavily every day unt il about 3 weeks ago.
On physical examinat ion, t he pat ient is confused and let hargic; t emperat ure is 38.0C (100.4F), blood pressure is 90/60 mm Hg, pulse rat e is 120/min, and respirat ion rat e is
30/min. Examinat ion reveals scleral ict erus. There is no guarding on palpat ion of t he abdomen. The liver edge is t ender and palpable. There is no ascit es, edema, or evidence
of bleeding.
INR 4.0
Hepat it is B surface ant igen Negat ive
Hepat it is B surface ant igen ant ibody Posit ive
Hepat it is C ant ibody Negat ive
Hepat it is A ant ibody (IgM) Negat ive
Hepat it is A ant ibody (IgG) Posit ive
Ant inuclear ant ibody t it er Negat ive
Ult rasonography shows an enlarged, fat t y liver wit h no nodules, ascit es, pericholecyst ic fluid, or bile duct dilat at ion.
(A) Alcoholic hepat it is
(B) Aut oimmune hepat it is
(C) Hepat it is A
(D) Hepat it is B
(E) Hepat it is C
Item 38 [Basic]
A 38-year-old woman is evaluat ed for abnormal liver chemist ry t est s det ect ed in an evaluat ion for new-onset fat igue, joint pains, and jaundice. She has a hist ory of
aut oimmune hypot hyroidism, and her only medicat ions are levot hyroxine and a mult ivit amin. She has never used illicit drugs and does not drink alcohol. Her mot her has
syst emic lupus eryt hemat osus.
On physical examinat ion, t he pat ient is afebrile. Blood pressure is 130/75 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 14/min. There is scleral ict erus; t he rest of t he
Bilirubin (direct ) 3.6 mg/dL (61.6 mol/L)
Ant inuclear ant ibody Tit er 1:40
Ant i-smoot h muscle ant ibody Tit er 1:640
Ant imit ochondrial ant ibody Negat ive
Viral serologic t est s are negat ive.
(A) Acut e cholecyst it is
(B) Aut oimmune hepat it is
(C) Drug-induced liver injury
(D) Primary biliary cirrhosis
Item 39 [Basic]
A 32-year-old man is evaluat ed for a 2-week hist ory of nausea, malaise, low-grade fever, vomit ing, and jaundice. Ot her t han having mult iple sex part ners, he has no ot her
significant medical hist ory and t akes only ibuprofen for headache and fever.
On physical examinat ion, t emperat ure is 37.6C (99.7F), blood pressure is 110/75 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 22/min. Examinat ion reveals scleral
ict erus, jaundice, hepat omegaly, ast erixis, and somnolence. There are no st igmat a of chronic liver disease.
INR 2.3
Hepat it is B surface ant igen Posit ive
Hepat it is B core ant igen (IgM) Posit ive
Hepat it is C virus RNA Negat ive
Hepat it is A IgM ant ibody Negat ive
Hepat it is A IgG ant ibody Posit ive
Ult rasonography shows hepat omegaly and increased echogenicit y, a normal spleen, and perihepat ic ascit es. There is no duct al dilat at ion.
(A) Acut e hepat it is A
(B) Acut e hepat it is B
(C) Chronic hepat it is B
(D) Hepat it is C
Item 40 [Basic]
A 55-year-old woman recent ly had elevat ed liver chemist ry t est s det ect ed on examinat ion for life insurance. She has no sympt oms of liver disease and no hist ory of jaundice,
ascit es, lower ext remit y edema, or encephalopat hy. While in college she received 3 unit s of blood following a major mot or vehicle accident t hat result ed in a rupt ured spleen.
She has no ot her significant medical hist ory and t akes no medicat ions. She has had only one sex part ner in her lifet ime.
On physical examinat ion, vit al signs are normal. There are spider angiomat a on t he upper body, and a nodular liver edge is not ed.
Hepat it is C ant ibody Posit ive
Hepat it is A ant ibody (IgM) Negat ive
Hepat it is A ant ibody (IgG) Posit ive
Abdominal CT scan shows changes in t he liver consist ent wit h cirrhosis.
(A) Hepat it is A
(B) Hepat it is B
(C) Hepat it is C
(D) Hepat it is D
Item 41 [Advanced]
A 60-year-old woman is evaluat ed for a 2-week hist ory of jaundice, weight gain, and increased abdominal girt h. She has no fever or abdominal pain. Her medical hist ory is
significant for t ype 2 diabet es, hyperlipidemia, and obesit y. She drinks 2 t welve-ounce bot t les of beer per week and has never exceeded t his amount . She was an int ravenous
drug abuser for 10 years beginning at t he age of 20 years but has not used any illicit drugs since t hen. Her medicat ions are met formin, glyburide, pravast at in, and aspirin.
On physical examinat ion, vit al signs are normal. BMI is 32. She is jaundiced. Spider angiomat a are present over t he upper chest . Her abdomen is prot uberant and nont ender
wit h shift ing dullness. The liver and spleen are not palpable. The ankles show pit t ing edema.
Ant i-hepat it is C ant ibody Negat ive
Ant ibody t o hepat it is B surface ant igen Posit ive
Whi ch of the fol l owi ng i s the most l i kel y cause of the pati ent's l i ver di sease?
(A) Alcohol
(B) Chronic hepat it is B infect ion
(C) Chronic hepat it is C infect ion
(D) Nonalcoholic st eat ohepat it is
(E) Primary biliary cirrhosis
Item 42 [Advanced]
A 40-year-man is evaluat ed for fat igue, yellow eyes, and increasingly severe prurit us over t he past 8 weeks. He report s no fever, abdominal pain, recent t ravel, or risk fact ors
for hepat it is. He was diagnosed wit h ulcerat ive colit is at age 32 years, and t he disease has been well cont rolled wit h sulfasalazine. He does not drink alcohol, and he t akes no
ot her medicat ions.
On examinat ion, vit al signs are normal. Scleral ict erus is present . Spider angiomat a are present over t he upper chest , and gynecomast ia is present . The abdomen is nont ender,
and t he liver and spleen are not palpable. No ascit es are present .
Hepat it is A IgG ant ibody Posit ive
Hepat it is A IgM ant ibody Negat ive
Ant imit ochondrial ant ibody Negat ive
Whi ch of the fol l owi ng i s the most l i kel y cause of the pati ent's l i ver di sease?
(A) Aut oimmune hepat it is
(B) Hepat it is A
(C) Primary biliary cirrhosis
(D) Primary sclerosing cholangit is
Item 43 [Basic]
A 43-year-old woman has a 3-mont h hist ory of gradually increasing abdominal dist ent ion and jaundice. She has no ot her sympt oms, and her medical hist ory is
noncont ribut ory.
On physical examinat ion, t he pat ient has jaundice, palmar eryt hema, and spider angiomat a. Abdominal examinat ion discloses hepat osplenomegaly and moderat e ascit es.
Albumin 2.9 g/dL (29 g/L)
Abdominal ult rasonography shows hepat omegaly, a coarse echot ext ure of t he liver, pat ent port al and hepat ic veins, mild splenomegaly, moderat e ascit es, and no bile duct
dilat at ion. Paracent esis is performed. The ascit ic fluid leukocyt e count is 80/L, and albumin is 0.7 g/dL (7 g/L). Gram st ain and cult ure are pending.
Whi ch of the fol l owi ng i s the most l i kel y cause of the asci tes?
(A) Cirrhosis
(B) Nephrot ic syndrome
(C) Ovarian cancer
(D) Tuberculosis
Item 44 [Advanced]
A 45-year-old man is evaluat ed in t he emergency depart ment for let hargy and disorient at ion. The pat ient has a hist ory of alcoholic cirrhosis complicat ed by esophageal
variceal bleeding, ascit es, and edema. His medicat ions are furosemide, spironolact one, propranolol, and lact ulose. He has been sober for 1 year.
On physical examinat ion, t he pat ient is somnolent but arousable. He is afebrile; blood pressure is 100/78 mm Hg, pulse rat e is 65/min, and respirat ion rat e is 12/min. There
are no focal neurologic deficit s; t he pupils are equal and react ive t o light . There is shift ing abdominal dullness and 2+ lower ext remit y edema. The st ool is negat ive for occult
blood.
Leukocyt e count 5600/L (5.6 10
9
/L)
Glucose (random) 112 mg/dL (6.2 mmol/L)
Ammonia 230 g/dL (135 mol/L)
Urinalysis is posit ive for leukocyt es. Urine dipst ick is posit ive for 3+ leukocyt e est erase and nit rit es. CT scan of t he head is normal. A diagnost ic perit oneal fluid t ap excludes
spont aneous bact erial perit onit is. Diuret ics are discont inued and empiric ant ibiot ic t herapy is st art ed.
(A) Cort icost eroids
(B) Hemodialysis
(C) Increase lact ulose t herapy
(D) Transjugular int rahepat ic port osyst emic shunt
Item 45 [Advanced]
A 45-year-old man wit h alcoholic cirrhosis is admit t ed t o t he hospit al for worsening ascit es and abdominal pain. His medicat ions are propranolol, lact ulose, spironolact one,
and furosemide.
On physical examinat ion, t emperat ure is 37.2C (99.0F), blood pressure is 110/60 mm Hg, pulse rat e is 56/min, and respirat ion rat e is 16/min. Tense ascit es is present , and
t he abdomen is t ender t o palpat ion. The remainder of t he examinat ion is noncont ribut ory.
Admission serum creat inine is 0.8 mg/dL (70.7 mol/L). A diagnost ic paracent esis reveals 350 leukocyt es/L. Cefot axime and albumin infusions are begun.
On hospit al day 3 t he pat ient is oliguric. Laborat ory st udies reveal a blood urea nit rogen level of 15 mg/dL (5.4 mmol/L) and a serum creat inine level of 2.0 mg/dL (176.8
mol/L). Urinalysis reveals a spot urine sodium of 10 meq/L (10 mmol/L). Furosemide and spironolact one are discont inued and infusions of normal saline and albumin are
init iat ed, but he remains oliguric.
Kidney ult rasound shows normal kidney size, and t here is no hydronephrosis.
Whi ch of the fol l owi ng i s the most l i kel y cause of hi s acute ki dney i njury?
(A) Hepat orenal syndrome
(B) Obst ruct ive nephropat hy
(C) Prerenal azot emia
(D) Renal art ery st enosis
Item 46 [Basic]
A 24-year-old woman wit h a 1-year hist ory of Crohn disease is evaluat ed for t ender bumps on her shins. She has been experiencing more abdominal pain and increased bowel
movement s for t he past 3 mont hs. St art ing 2 weeks ago, she developed low-grade fever, increased fat igue, and art hralgia. Her only medicat ion is sulfasalazine.
On physical examinat ion, vit al signs are normal. On abdominal examinat ion, bowel sounds are present and palpat ion produces slight t enderness in t he right lower quadrant . A
t ypical skin lesion found on t he lower ext remit y is shown (Plat e 1).
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s for the ski n fi ndi ng?
(A) Dermat it is herpet iformis
(B) Eryt hema nodosum
(C) Pyoderma gangrenosum
(D) Rheumat oid nodule
Item 47 [Basic]
A 55-year-old man is evaluat ed for a 4-mont h hist ory of frequent and urgent defecat ion wit h loose and bloody st ool, mild abdominal cramping, and fat igue. He has up t o eight
bowel movement s a day and oft en wakes at night wit h sympt oms. He does not have fever, nausea, or vomit ing, but he has lost 3 kg (7 lb). He has mild joint pain in his knees
and ankles t hat also began 4 mont hs ago, is worse in t he morning, and resolves somewhat during t he day. The pat ient is a former cigaret t e smoker but quit smoking 2 years
ago. He has no ot her medical problems.
On physical examinat ion, vit al signs are normal. There is mild lower abdominal t enderness wit hout rebound or guarding; t here are no palpable abdominal masses. Examinat ion
of t he rect um shows gross blood.
Laborat ory st udies reveal a hemoglobin level of 12.3 g/dL (123 g/L) wit h a mean corpuscular volume of 76 fL. Fecal leukocyt es are present , but st ool cult ure is negat ive.
Colonoscopy shows cont inuous eryt hema, friabilit y, and loss of vascular pat t ern from t he rect um t o t he splenic flexure; t he rest of t he colon and t erminal ileum is normal.
Hist ology shows crypt it is, crypt abscesses, and crypt archit ect ure dist ort ion.
(A) Crohn colit is
(B) Infect ious colit is
(C) Ischemic colit is
(D) Microscopic colit is
(E) Ulcerat ive colit is
Item 48 [Advanced]
A 52-year-old man is evaluat ed for a 5-mont h hist ory of t hree t o four loose, bloody st ools a day wit h mild urgency, abdominal cramping, and fat igue. He has not lost weight
during t his episode. He is ot herwise healt hy.
On physical examinat ion, vit al signs are normal. There is mild lower abdominal t enderness wit hout rebound or guarding; t here are no palpable abdominal masses. Examinat ion
of t he rect um shows gross blood. Colonoscopy shows cont inuous mild eryt hema and loss of vascular pat t ern from t he rect um t o t he t ransverse sigmoid colon; t he rest of t he
colon and t erminal ileum are normal. Biopsy specimens from t he abnormal mucosa show crypt it is, crypt abscesses, and dist ort ion of crypt archit ect ure.
Whi ch of the fol l owi ng i s the most appropri ate therapy for thi s pati ent?
(A) Azat hioprine
(B) Ciprofloxacin
(C) Infliximab
(D) Mesalamine
(E) Met ronidazole
Item 49 [Advanced]
A 65-year-old woman is evaluat ed for a 6-mont h hist ory of wat ery, nonbloody diarrhea; she has from 3 t o 20 bowel movement s a day. She also has abdominal cramps and
bloat ing and has lost 2.2 kg (5 lb) since t he beginning of t he episode. She had been previously healt hy. She has not t raveled recent ly, been hospit alized, or used ant ibiot ics.
On physical examinat ion, t he vit al signs are normal. The heart rat e is regular and t he chest is clear. The abdomen is soft wit h slight dist ent ion.
Colonoscopy is grossly normal. Mult iple biopsy specimens are obt ained.
(A) Clostridium difficile colit is
(B) Crohn disease
(C) Microscopic colit is
(D) Tropical sprue
(E) Ulcerat ive colit is
Item 1 Answer: D
Educati onal Objecti ve: Diagnose nephrolithiasis with helical CT scan.
A noncont rast helical abdominal CT scan should be t he next diagnost ic t est . Acut e renal colic is charact erized by t he sudden onset of unilat eral flank pain. Acut e renal colic
also may cause nausea and vomit ing, and pat ient s wit h st ones locat ed in t he uret ers or uret hra may have irrit at ive sympt oms such as urinary urgency and frequency. Nearly
90% of pat ient s wit h nephrolit hiasis have eit her gross or microscopic hemat uria. Noncont rast helical abdominal CT has replaced int ravenous pyelography as t he gold
st andard for diagnosing kidney st ones. This t est reveals urinary t ract obst ruct ion wit h hydronephrosis, det ect s st ones as small as 1 mm in diamet er, and helps evaluat e ot her
pot ent ial causes of abdominal pain and hemat uria. However, noncont rast helical abdominal CT is expensive and has a higher radiat ion exposure t han ot her imaging st udies.
Most kidney st ones are radiopaque and are easily visualized on plain radiographs of t he abdomen, which are inexpensive, noninvasive, and widely available. However, false-
negat ive result s may occur in pat ient s wit h small st ones or radiolucent st ones composed of uric acid or relat ed t o use of indinavir, and wit h int erference of t he overlying
bowel. Similarly, vascular calcificat ion and phlebolit hs may cause false-posit ive result s for kidney st ones. As such, plain abdominal radiography has a low sensit ivit y and
specificit y for t he diagnosis of t his condit ion.
Int ravenous pyelography has a high sensit ivit y and specificit y in t he diagnosis of kidney st ones. However, t his st udy requires bowel preparat ion and t he use of int ravenous
iodinat ed cont rast agent s, which are cont raindicat ed in pat ient s wit h acut e kidney injury and chronic kidney disease.
Kidney ult rasonography has a low sensit ivit y for kidney st ones but a higher specificit y t han plain abdominal radiography. This st udy is relat ively inexpensive, widely
available, and provides a funct ional assessment of t he severit y of t he st one disease. Kidney ult rasonography also can det ect urinary t ract obst ruct ion wit h associat ed
hydronephrosis but may not reveal small st ones or st ones in t he uret ers and uret hra.
Key Poi nt
Noncont rast helical abdominal CT scan is t he imaging modalit y of choice for t he diagnosis of nephrolit hiasis.
Bi bl i ography
Goldfarb DS. In t he clinic. Nephrolit hiasis. Ann Int ern Med. 2009;151(3):ITC2. [PMID: 19652185]
Item 2 Answer: D
Educati onal Objecti ve: Evaluate acute abdominal pain with supine and upright abdominal radiographs.
The most appropriat e next diagnost ic t est s are supine and upright abdominal radiographs. The t erm acute abdomen refers t o sudden and severe abdominal pain less t han 24
hours in durat ion. Rebound t enderness and severe diffuse abdominal pain are suggest ive of an acut e abdomen wit h perit onit is. Pain t hat is acut e in onset generally point s t o
acut e inflammat ory, infect ious, or ischemic causes. Upper abdominal pain is usually of gast ric, hepat obiliary, or pancreat ic origin, whereas pain in t he lower abdomen
originat es from t he hindgut and genit ourinary organs. All pat ient s wit h abdominal pain should have measurement s of serum amylase and lipase t o evaluat e for acut e
pancreat it is.
Chest radiograph and supine and upright abdominal radiographs should be obt ained in every pat ient wit h significant acut e abdominal pain t o exclude bowel obst ruct ion or
perforat ion or int rat horacic processes (for example, pneumonia, pneumot horax, or aort ic dissect ion) t hat can present as abdominal pain. This pat ient 's hist ory of
divert iculit is suggest s possible divert icular rupt ure.
Colonoscopy is not indicat ed in a pat ient wit h acut e perit oneal signs and has t he pot ent ial t o worsen t he sit uat ion by causing a perforat ion of inflamed bowel wall.
Alt hough an abdominal CT scan is usually necessary for a definit ive diagnosis of acut e abdominal pain, init ial screening wit h supine and upright abdominal radiographs should
be done first t o look for air-fluid levels, suggest ive of a bowel obst ruct ion, and free perit oneal air, suggest ive of a perforat ed viscus.
Based on it s relat ively low cost , convenience, and noninvasive nat ure, ult rasonography has been ut ilized as a diagnost ic t ool for acut e divert iculit is. However, t he examinat ion
remains operat or-dependent and, in t he absence of well-designed prospect ive comparat ive st udies, it remains a second-line diagnost ic t ool.
Key Poi nt
In pat ient s wit h acut e abdominal pain, init ial screening should include supine and upright abdominal radiographs t o look for air-fluid levels, suggest ive of a bowel obst ruct ion,
and free perit oneal air, suggest ive of a perforat ed viscus.
Bi bl i ography
Cart wright SL, Knudson MP. Evaluat ion of acut e abdominal pain in adult s. Am Fam Physician. 2008;77(7):971-978. [PMID: 18441863]
Item 3 Answer: D
Educati onal Objecti ve: Diagnose ruptured abdominal aortic aneurysm.
The pat ient 's clinical present at ionsevere abdominal or back pain wit h syncope followed by abdominal discomfort is t ypical for a rupt ured abdominal aort ic aneurysm
(AAA) t hat has been locally cont ained, prevent ing his immediat e deat h. The sent inel event of severe sudden abdominal and back pain associat ed wit h loss of consciousness
marks t he occurrence of rupt ure. Leukocyt osis and anemia are common. A CT scan should be performed for diagnosis, and t he aneurysm should be repaired emergent ly.
Cont ained rupt ure of AAA, when misdiagnosed, is most oft en mist aken for renal colic, acut e myocardial infarct ion, or divert iculit is. Renal colic may produce severe pain in
t he lower back, flank, or groin. Typically, t he pain waxes and wanes. It is unlikely t hat renal colic would present wit h syncope, and t he normal urinalysis also makes t his
diagnosis unlikely.
Acut e myocardial infarct ion can be associat ed wit h syncope, and t he elect rocardiogram is not always diagnost ic, part icularly if t here are findings such as left vent ricular
hypert rophy, which may obscure subt le abnormalit ies. However, t he presence of abdominal and lower back pain rat her t han chest pain makes t his diagnosis less likely.
Divert iculit is would present wit h fever and crampy abdominal pain, most commonly in t he left lower quadrant and oft en associat ed wit h a change in bowel habit s.
Leukocyt osis may be present . Syncope associat ed wit h t he onset of pain would be a very unusual present at ion for t his ent it y.
Key Poi nt
Abdominal pain, back pain, and syncope oft en herald an abdominal aort ic aneurysm rupt ure.
Bi bl i ography
Lederle FA. In t he clinic. Abdominal aort ic aneurysm. Ann Int ern Med. 2009;150(9):ITC5-1-15; quiz ITC5-16. [PMID: 19414835]
Item 4 Answer: D
Educati onal Objecti ve: Diagnose and treat constipation-predominant irritable bowel syndrome.
The most appropriat e next st ep in t he management of t his pat ient is reassurance and polyet hylene glycol. This pat ient has irrit able bowel syndrome. As a young woman, she
fit s t he demographic profile, and she meet s t he Rome III crit eria, wit h abdominal pain relieved by defecat ion and a change in bowel habit s. The most recent diagnost ic crit eria
require t he presence of at least t wo of t hree sympt oms occurring for 3 mont hs (not necessarily consecut ive) during a 12-mont h period. These sympt oms include pain relieved
wit h defecat ion, onset associat ed wit h change in st ool frequency, or onset associat ed wit h change in t he consist ency of t he st ool. In clinical pract ice, t hese crit eria have a
posit ive predict ive value of 98%. Import ant ly, she has no alarm indicat ors, including older age, male sex, noct urnal awakening, rect al bleeding, weight loss, or family hist ory
of colon cancer. In t he absence of alarm sympt oms, addit ional t est s have a diagnost ic yield of 2% or less. Furt hermore, laborat ory st udies indicat e no anemia or t hyroid
deficiency. Irrit able bowel syndrome is a clinical diagnosis, and t here are no laborat ory, radiographic, or endoscopic findings t hat aid in diagnosis. Addit ional evaluat ion is not
only unnecessary and expensive but also pot ent ially harmful, especially when invasive procedures are ordered. The pat ient should be reassured t hat alt hough t his problem is
annoying and inconvenient , it is not life-t hreat ening. Because fiber supplement at ion has not been helpful, a nonabsorbed osmot ic laxat ive such as polyet hylene glycol will
likely provide her significant relief.
There is no indicat ion for t he pat ient t o undergo a CT scan or colonoscopy. Oral cont racept ives are not t ypically associat ed wit h t he syndrome, and she began t aking t he
medicat ion aft er t he onset of her sympt oms.
Key Poi nt
Irrit able bowel syndrome is a clinical diagnosis t hat can be made confident ly when pat ient s meet t he Rome III crit eria and do not have alarm indicat ors.
Bi bl i ography
Wilson JF. In t he clinic. Irrit able bowel syndrome. Ann Int ern Med. 2007;147(1):ITC7-1-ITC7-16. [PMID: 17606954]
Item 5 Answer: C
Educati onal Objecti ve: Diagnose ischemic colitis.
This pat ient likely has ischemic colit is, t he most frequent form of ischemia of t he gast roint est inal t ract . This t ype of ischemia usually affect s t he elderly wit h at herosclerot ic
disease, and in most cases is t ransient and resolves wit h conservat ive management . Pat ient s wit h acut e colonic ischemia usually present wit h rapid onset of abdominal pain
and t enderness over t he affect ed bowel. Rect al bleeding or bloody diarrhea usually develops wit hin 24 hours of t he onset of abdominal pain. The t ypical finding on CT scan is
t hickening of t he bowel wall in a segment al pat t ern, which is not specific for ischemia and can be seen in infect ious colit is and Crohn disease. The finding of pat chy segment al
ulcerat ions on colonoscopy in a pat ient wit h a compat ible hist ory est ablishes t he diagnosis. Colonic st rict ures are a rare complicat ion.
The pat ient 's acut e onset of sympt oms wit h bloody diarrhea is not consist ent wit h Crohn disease. Pat ient s wit h Crohn disease commonly present wit h a chronic hist ory of
abdominal pain, diarrhea, and weight loss. Pept ic ulcer disease could present wit h bright red rect al bleeding but only in t he set t ing of a large and rapid bleed and could not
explain t he findings on t he CT scan. Irrit able bowel syndrome is a diagnosis of exclusion and does not present wit h rect al bleeding and t he changes not ed on t he CT scan.
Key Poi nt
Ischemic colit is present s most commonly in elderly pat ient s wit h at herosclerot ic vascular disease wit h crampy abdominal pain and bloody st ool; in most cases it is self-
limit ed.
Bi bl i ography
Sreenarasimhaiah J. Diagnosis and management of ischemic colit is. Curr Gast roent erol Rep. 2005;7(5):421-426. [PMID: 16168242]
Item 6 Answer: C
Educati onal Objecti ve: Evaluate diverticulitis with CT scan.
The most appropriat e next st ep in t he evaluat ion of t his pat ient is a cont rast -enhanced CT scan of t he abdomen and pelvis. This pat ient 's left lower quadrant pain, fever, and
elevat ed leukocyt e count are classic sympt oms and signs of divert iculit is. The most sensit ive imaging modalit y t o confirm t his diagnosis as well as evaluat e for any
complicat ions such as perforat ion, abscess, obst ruct ion, and fist ula is a cont rast -enhanced CT scan of t he abdomen and pelvis. A number of prospect ive invest igat ions have
report ed a sensit ivit y of 69% t o 95% and specificit y of 75% t o 100% for CT scan in acut e divert iculit is. The presence of severe disease found on CT scan was prognost ically
very useful by accurat ely predict ing failure of medical t reat ment and risk of secondary complicat ions.
Colonoscopy is generally avoided during an episode of acut e divert iculit is for concern of increased risk of perforat ion wit h air insufflat ion; furt hermore, colonoscopy would
miss t he ext raluminal complicat ions such as abscess format ion. A small-bowel series evaluat es t he small int est ine, which is not affect ed in divert iculit is. Before t he availabilit y
of CT scanning, barium enema was used t o diagnose divert iculit is but , like colonoscopy, present s a risk for perforat ion and is not sensit ive t o t he presence of ext raluminal
complicat ions.
Key Poi nt
The best imaging modalit y t o confirm suspect ed divert iculit is and evaluat e for ext raluminal complicat ions is a cont rast -enhanced CT scan.
Bi bl i ography
Shet h AA, Longo W, Floch MH. Divert icular disease and divert iculit is. Am J Gast roent erol. 2008;103(6):1550-1556. [PMID: 18479497]
Item 7 Answer: B
Educati onal Objecti ve: Diagnose chronic pancreatitis confirmed by pancreatic calcification.
The diagnosis of chronic pancreat it is should be st rongly considered in t he appropriat e clinical set t ing, such as a pat ient wit h a hist ory of alcoholism who present s wit h
chronic upper abdominal pain radiat ing t o t he back, diabet es, and st eat orrhea. Such pat ient s may not need addit ional t est ing. However, most pat ient s have only nonspecific
abdominal pain and elevat ed pancreat ic enzyme levels and require diagnost ic radiographic imaging st udies. The presence of pancreat ic calcificat ions on plain films or CT scan
confirms t he diagnosis. Plain films of t he abdomen will show pancreat ic calcificat ions in some pat ient s, as it did in t his pat ient . Most pat ient s, however, require abdominal CT
scans t o det ect t he calcificat ions and t o exclude ot her causes of pain.
Acut e cholangit is is associat ed wit h biliary obst ruct ion and is charact erized by t he t riad of pain, fever, and jaundice, which are absent in t his pat ient . If biliary obst ruct ion
involves t he pancreat ic duct as well, pancreat ic enzymes may be elevat ed. Acut e cholangit is is not compat ible wit h an illness last ing 1 year.
Divert iculit is is anot her acut e illness charact erized by left lower quadrant pain, fever, and localized abdominal t enderness. Neit her acut e cholangit is nor divert iculit is is
associat ed wit h pancreat ic calcificat ions. Acut e divert iculit is is not associat ed wit h pancreat ic enzyme elevat ions.
Pain associat ed wit h pept ic ulcer disease is likely t o be epigast ric, is usually described as burning or gnawing, and t ends t o occur during fast ing or at night . It is not associat ed
wit h elevat ed pancreat ic enzyme levels or pancreat ic calcificat ions.
Key Poi nt
The diagnosis of chronic pancreat it is should be st rongly considered in pat ient s wit h a hist ory of alcoholism present ing wit h chronic upper abdominal pain radiat ing t o t he
back, diabet es, st eat orrhea, and pancreat ic calcificat ions on abdominal radiographs.
Bi bl i ography
Conwell DL, Banks PA. Chronic pancreat it is. Curr Opin Gast roent erol. 2008;24(5):586-590. [PMID: 19122499]
Item 8 Answer: B
Educati onal Objecti ve: Diagnose hemolytic uremic syndrome.
The most appropriat e next management st ep is a peripheral blood smear. This pat ient likely has hemolyt ic uremic syndrome (HUS), which is charact erized by
t hrombocyt openia and t hrombot ic microangiopat hy. Thrombot ic microangiopat hy is a clinical syndrome t hat affect s mult iple organ syst ems but is always charact erized by
t hrombocyt openia and microangiopat hic hemolyt ic anemia (schist ocyt es on t he peripheral blood smear, elevat ed ret iculocyt e count , and elevat ed lact at e dehydrogenase
level). Thrombot ic microangiopat hy may manifest as t hrombot ic t hrombocyt openic purpura or HUS. HUS is usually caused by infect ion wit h Shiga t oxin-producing
Escherichia coli (O157:H7), oft en relat ed t o ingest ion of cont aminat ed, under-cooked beef, or by complement dysregulat ion caused by genet ic mut at ions. Addit ional
manifest at ions of HUS may include acut e kidney injury and neurologic findings (for example, headache, confusion) but t he only diagnost ic crit eria are t hrombocyt openia and
microangiopat hic hemolyt ic anemia in t he absence of any ot her pot ent ial cause.
Ant ibiot ics are not recommended in t he t reat ment of HUS. St udies in children have shown eit her no benefit or increased complicat ions when ant ibiot ics are used. The
mainst ay of t reat ment is support ive, wit h adequat e fluids and close monit oring of elect rolyt es and blood count s; dialysis may be required for acut e renal failure. Transfusion of
packed red blood cells may be indicat ed if anemia worsens, but plat elet t ransfusion is cont roversial, because it may worsen t he t hrombot ic process and is t ypically used only
when bleeding is significant .
Rout ine st ool cult ures only t est for salmonella, shigella, and campylobact er. Therefore, in pat ient s wit h bloody diarrhea, st ool should also be sent specifically for E. coli
O157:H7 t est ing. Fecal leukocyt e t est ing has poor sensit ivit y and specificit y in t he diagnosis of infect ious diarrhea, will not specifically diagnose HUS, and will not add useful
diagnost ic informat ion.
Key Poi nt
Hemolyt ic uremic syndrome diagnosis is based on t he presence of microangiopat hic hemolyt ic anemia and t hrombocyt openia.
Bi bl i ography
Razzaq S. Hemolyt ic uremic syndrome: an emerging healt h risk. Am Fam Physician. 2006;74(6):991-6. [PMID: 17002034]
Item 9 Answer: B
Educati onal Objecti ve: Diagnose radiation proctitis.
Flexible sigmoidoscopy is t he most appropriat e next diagnost ic t est . The most likely cause of diarrhea in t his pat ient is radiat ion proct it is, which occurs commonly in
pat ient s receiving pelvic radiat ion. Acut e radiat ion proct it is usually manifest s wit hin 6 weeks of t herapy wit h sympt oms of diarrhea and t enesmus. The proct it is is due t o
direct radiat ion injury t o t he rect al mucosal and usually resolves soon aft er radiat ion is discont inued. Chronic proct it is can occur mont hs t o years aft er t reat ment and is
associat ed wit h a worse prognosis. Diagnosis is est ablished by endoscopic findings of mucosal t elangiect asia, wit h biopsy showing submucosal fibrosis and art eriole endart erit is.
The t emporal relat ionship bet ween t he pat ient 's radiat ion t herapy and onset of her diarrheal sympt oms wit hin 6 weeks most st rongly suggest s radiat ion proct it is. Evaluat ion
for an infect ious cause of diarrhea is unlikely t o est ablish a diagnosis, because t he pret est probabilit y of an infect ious cause of diarrhea is low. Abdominal/pelvic CT scan will
not be helpful, because no specific radiologic feat ures define radiat ion proct it is; t he diagnosis is est ablished by direct visualizat ion of t he affect ed mucosa.
Measuring st ool osmolalit y may occasionally be helpful in dist inguishing osmot ic diarrhea from secret ory diarrhea and in t hose few pat ient s suspect ed of having fact it ious
diarrhea (low st ool osmolalit y). This t est will not be helpful in a pat ient wit h a hist ory compat ible wit h radiat ion proct it is.
Key Poi nt
Acut e radiat ion proct it is can cause diarrhea and t enesmus wit hin 6 weeks of t herapy.
Bi bl i ography
Leiper K, Morris AI. Treat ment of radiat ion proct it is. Clin Oncol (R Coll Radiol). 2007;19(9):724-9. [PMID: 17728120]
Item 10 Answer: B
Educati onal Objecti ve: Diagnose chronic pancreatitis with abdominal CT scan.
The t est most likely t o est ablish t he diagnosis is CT scan of t he abdomen. This pat ient has chronic pancreat it is secondary t o alcohol abuse, which has result ed in
malabsorpt ion. The t hree classic findings in chronic pancreat it is are abdominal pain t hat is usually mid-epigast ric, post prandial diarrhea, and diabet es mellit us secondary t o
pancreat ic endocrine insufficiency. Malabsorpt ion occurs in pat ient s wit h chronic pancreat it is when approximat ely 80% of t he pancreas is dest royed. Malabsorpt ion present s
wit h diarrhea and st eat orrhea, weight loss, and deficiencies of fat -soluble vit amins because t he damaged pancreat ic gland is no longer producing t he pancreat ic exocrine
enzymes t o absorb food. Addit ional clues t o t he diagnosis include elevat ed pancreat ic enzyme levels and liver chemist ry t est s. Pat ient s wit h a t ypical present at ion may not
need addit ional t est ing. However, most pat ient s wit h chronic pancreat it is have only nonspecific abdominal pain (and normal pancreat ic enzyme concent rat ions) and require
diagnost ic radiographic imaging st udies. The presence of pancreat ic calcificat ions on radiographs confirms t he diagnosis. Plain films of t he abdomen will show pancreat ic
calcificat ions in approximat ely 30% of pat ient s. Most pat ient s, however, require abdominal CT scans, which are able t o det ect pancreat ic calcificat ion in up t o 90% of
pat ient s. CT scanning can also exclude ot her causes of pain.
Ant iendomysial ant ibodies are a marker for celiac disease, which is unlikely in t his pat ient wit h an evident hist ory of pancreat ic malabsorpt ion. Alt hough colonoscopy is
indicat ed as a screening t ool for average risk asympt omat ic pat ient s beginning at t he age of 50 years and for pat ient s wit h a change in bowel habit s and weight loss, t his
pat ient 's hist ory suggest s pancreat ic malabsorpt ion, and colonoscopy is less likely t han abdominal CT scan t o confirm t he diagnosis. St ool st udies are appropriat e for
det ermining t he cause of an acut e infect ious diarrhea, but t his pat ient has had diarrhea for 8 mont hs, and infect ious diarrhea is not usually associat ed wit h such a degree of
weight loss or elevat ion of pancreat ic enzymes.
Key Poi nt
Pat ient s wit h chronic pancreat it is present wit h abdominal pain and, in more severe cases, malabsorpt ion and endocrine insufficiency.
Bi bl i ography
Wit t H, Apt e MV, Keim V, Wilson JS. Chronic pancreat it is: challenges and advances in pat hogenesis, genet ics, diagnosis, and t herapy. Gast roent erology. 2007;132(4):1557-
1573. [PMID: 17466744]
Item 11 Answer: D
Educati onal Objecti ve: Diagnose and treat diarrhea-predominant irritable bowel syndrome.
The most appropriat e management for t his pat ient is sympt om cont rol. Irrit able bowel syndrome (IBS) is t he most common gast roint est inal condit ion diagnosed in t he
Unit ed St at es. This pat ient present s wit h sympt oms t hat meet t he Rome III crit eria for IBS. The Rome crit eria were developed t o est ablish consensus guidelines for diagnosis
of funct ional bowel disorders. Crit eria for IBS are sympt oms of recurrent abdominal pain or discomfort and a marked change in bowel habit for at least 6 mont hs, wit h
sympt oms experienced on at least 3 days a mont h for at least 3 mont hs. Two or more of t he following must also apply: (1) pain is relieved by a bowel movement ; (2) onset
of pain is relat ed t o a change in frequency of st ool; and/or (3) onset of pain is relat ed t o a change in t he appearance of st ool. In t his ot herwise healt hy young woman,
reassurance t hat she has a chronic but not a life-t hreat ening disease wit h recommendat ion of a high-fiber diet should be t he init ial t herapy.
CT ent eroscopy or colonoscopy would be premat ure at t his point given t he absence of alarm sympt oms: fever, weight loss, blood in st ool, abnormal physical examinat ion,
family hist ory of inflammat ory bowel disease or colon cancer, or pain or diarrhea t hat awakens/int erferes wit h sleep.
This pat ient does not have evidence of malabsorpt ion, anemia, or weight loss t o suggest a diagnosis of celiac disease; t herefore, an empiric glut en-free diet would be
inappropriat e. An empiric glut en-free diet is never appropriat e wit hout first est ablishing t he hist ological diagnosis of celiac disease wit h a small-bowel biopsy.
Key Poi nt
Irrit able bowel syndrome is a clinical diagnosis of exclusion and, in t he absence of alarm sympt oms, invasive workup is not necessary.
Bi bl i ography
Wilson JF. In t he clinic. Irrit able bowel syndrome. Ann Int ern Med. 2007;147(1):ITC7-1-ITC7-16. [PMID: 17606954]
Item 12 Answer: A
Educati onal Objecti ve: Diagnose a patient with severe Cl ostri di um di ffi ci l e infection.
This pat ient most likely has severe Clostridium difficile infect ion (CDI). CDI t ypically present s wit h wat ery diarrhea, alt hough t he range of sympt oms span an asympt omat ic
carrier st at e t o severe fulminant colit is wit h t oxic megacolon. Pat ient s wit h CDI and associat ed colit is t ypically have diarrhea up t o 10 or 15 t imes daily, lower abdominal
pain, cramping, fever, and leukocyt osis t hat oft en exceeds 15,000/L (15 10
9
/L). CDI wit h colit is is most commonly associat ed wit h prior ant ibiot ic administ rat ion. The
colit is is produced by t wo t oxins, A and B. These have different mechanisms of act ion, but bot h are highly pot ent and cause cyt ot oxicit y at ext remely low concent rat ions.
The t oxins can be det ect ed in t he clinical laborat ory and t he presence of eit her t oxin confirms t he diagnosis. Treat ment of severe CDI wit h colit is consist s of oral
vancomycin and int ravenous met ronidazole.
The t ypical present at ion of Crohn disease is abdominal pain, diarrhea, and weight loss t hat occurs over a period of mont hs, if not years. This pat ient 's severe and rapidly
progressive course is not consist ent wit h Crohn disease.
Pat ient s wit h uncomplicat ed divert iculit is present wit h abdominal pain and fever. Physical examinat ion discloses left lower quadrant abdominal t enderness. Leukocyt osis is
present , and urinalysis may show st erile pyuria due t o inflammat ion close t o t he bladder. The pat ient 's 2 day hist ory of severe diarrhea is not consist ent wit h divert iculit is.
Divert iculosis consist s of t he presence of divert icula in t he colon. Divert iculosis is common in aging West ern populat ions and is not associat ed wit h pain or diarrhea.
Ischemic colit is sympt oms include left lower quadrant abdominal pain and bloody diarrhea, which are oft en self-limit ed. Treat ment is support ive and includes int ravenous
fluids and bowel rest . Most sympt oms resolve wit hin 48 hours. This pat ient 's progressive sympt oms are not consist ent wit h a diagnosis of ischemic colit is.
Key Poi nt
Pat ient s wit h previous exposure t o ant ibiot ics may develop Clostridium difficile, infect ion and associat ed colit is, which is charact erized by diarrhea up t o 10 or 15 t imes daily,
lower abdominal pain, cramping, fever, and leukocyt osis.
Bi bl i ography
Bart let t JG, Gerding DN. Clinical recognit ion and diagnosis of Clost ridium difficile infect ion. Clin Infect Dis. 2008;46:S12-S18. [PMID: 18177217]
Item 13 Answer: D
Educati onal Objecti ve: Manage Sal monel l a gastroenteritis.
This pat ient has Salmonella gast roent erit is, but he does not require t reat ment at t his t ime. Because Salmonella gast roent erit is is usually self-limit ed, ant ibiot ic t reat ment is
generally not required for most healt hy persons. If t he diarrhea worsens t o t he point t hat he cannot replace lost fluids or if he shows evidence of t oxicit y (persist ent high
fever, declining ment at ion, end-organ dysfunct ion) or likely bact eremia, he will need more aggressive int ervent ion.
Treat ment is recommended only for (1) immunocompet ent pat ient s younger t han 2 years or older t han 50 years t o avoid t he increased incidence of complicat ions in t hese
age groups; (2) immunocompet ent pat ient s wit h severe illness requiring hospit alizat ion; (3) immunocompet ent pat ient s wit h known or suspect ed at herosclerot ic plaques or
endovascular or bone prost heses because of seeding of salmonellae t o t hese areas during a bloodst ream infect ion; and (4) immunocompromised pat ient s, such as pat ient s wit h
uncont rolled HIV infect ion or t hose requiring cort icost eroids and ot her immunosuppressive agent s.
There is a great t empt at ion t o t reat pat ient s wit h document ed or suspect ed bact erial diarrhea. Alt hough t here is evidence t hat ant ibact erial t reat ment of Shigella or t ravelers'
diarrhea (caused by cert ain t oxin-producing st rains of Escherichia coli) might hast en recovery, t he benefit s of early t reat ment are modest and diminish wit h t ime. The
t reat ment of presumed or document ed Salmonella diarrhea is even more problemat ic. For most pat ient s wit h salmonellosis, recovery occurs equally fast wit h or wit hout
ant ibiot ics. In addit ion, t here may be a delay in clearing t he salmonellae from t he st ool of ant ibiot ic-t reat ed pat ient s, and t he effect s of t he ant ibiot ics can independent ly
cont ribut e t o t oxicit y, including Clostridium difficile t oxin-mediat ed diarrhea.
Of t he ant ibiot ics t hat might be useful in t reat ing salmonellosis, ciprofloxacin would be reasonably likely t o be effect ive in vit ro, alt hough resist ance t o t he fluoroquinolones
is increasing in many part s of t he world.
Met ronidazole would not have any benefit for Salmonella or any ot her bact erial diarrhea. The use of ant idiarrheal agent s such as loperamide is probably safe for individuals
wit h t ravelers' diarrhea but is not recommended for pot ent ially invasive pat hogens such as Salmonella. In addit ion, pat ient s wit h fever, bloody st ools, or signs of syst emic
t oxicit y should not be given bowel paralyt ics because t hese agent s can worsen t he acut e disease course.
Key Poi nt
Because Salmonella gast roent erit is is usually self-limit ed, ant ibiot ic t reat ment is generally not required for most healt hy persons.
Bi bl i ography
Pawlowski SW, Warren CA, Guerrant R. Diagnosis and t reat ment of acut e or persist ent diarrhea. Gast roent erology. 2009;136(6):1874-1886. [PMID: 19457416]
Item 14 Answer: B
Educati onal Objecti ve: Diagnose hepatocellular injury pattern on laboratory testing.
This pat ient has acut e hepat ocellular damage associat ed wit h mild hyperbilirubinemia t hat could be caused by acut e hepat it is. Hepat ocellular injury most oft en result s in an
elevat ion of serum alanine aminot ransferase (ALT) and aspart at e aminot ransferase (AST) concent rat ions, which reflect release of int racellular enzymes from injured
hepat ocyt es. AST is also released from ot her t issues, such as t he heart and skelet al muscle. Therefore, elevat ions of ALT, which is minimally produced in nonhepat ic t issues,
are more specific for diagnosing liver disease. Hepat ocyt e dysfunct ion is oft en associat ed wit h conjugat ed hyperbilirubinemia, in which t he direct bilirubin fract ion is great er
t han 50%.
Cholest at ic injury (cholest asis), which consist s of a lack of or an abnormalit y in t he flow of bile, is indicat ed primarily by an elevat ion of serum alkaline phosphat ase and
relat ively minimal elevat ions of AST and ALT. Cholest asis may occur wit hout jaundice because of t he capacit y of t he liver t o cont inue t o secret e bile sufficient ly unt il t he
injury t o t he bile duct s is significant . Profound disrupt ion of t he bile secret ory mechanisms is likely t o result in conjugat ed hyperbilirubinemia wit h elevat ion of t he direct
fract ion of serum bilirubin. The first evaluat ive st ep in a pat ient wit h a cholest at ic pat t ern of injury is t o obt ain an ult rasound st udy t o det ermine if int rahepat ic or
ext rahepat ic biliary obst ruct ion is present .
Liver disorders can also present wit h a mixed pat t ern of liver injury t hat is charact erized by moderat e t o severe elevat ions of aminot ransferase, alkaline phosphat ase, and
bilirubin levels. Hepat it is B and C are examples of condit ions t hat can occasionally present wit h a mixed liver injury pat t ern.
This pat ient 's predominant ly elevat ed aminot ransferase levels wit h mildly elevat ed alkaline phosphat ase concent rat ion and direct bilirubin fract ion clearly point s t o a
hepat ocellular injury pat t ern. A nonhepat ic injury pat t ern, such as muscle injury, would be associat ed wit h st riking elevat ions of AST, lesser elevat ions of ALT, and would not
be associat ed wit h elevat ions of conjugat ed bilirubin.
Key Poi nt
Hepat ocellular injury most oft en result s in an elevat ion of serum alanine aminot ransferase (ALT) and aspart at e aminot ransferase (AST) concent rat ions and oft en is
associat ed wit h direct hyperbilirubinemia.
Bi bl i ography
Burke MD. Liver funct ion: t est select ion and int erpret at ion of result s. Clin Lab Med. 2002;22(2):377-90. [PMID: 12134466]
Item 15 Answer: B
Educati onal Objecti ve: Diagnose Gilbert syndrome.
This pat ient has indirect (unconjugat ed) hyperbilirubinemia, which in an asympt omat ic pat ient wit h a normal hemoglobin level and ot herwise normal liver t est s is suggest ive
of Gilbert syndrome. Bilirubin is measured as conjugat ed (direct ) and unconjugat ed (indirect ) fract ions. In pat ient s wit h cholest at ic diseases leading t o jaundice, approximat ely
half of t he bilirubin is measured as t he conjugat ed fract ion. Predominance of t he unconjugat ed fract ion indicat es eit her t he overproduct ion of bilirubin (as occurs in hemolysis)
or impairment of bilirubin conjugat ion. The lat t er is relat ively common, given t he 5% prevalence of Gilbert syndrome in t he general populat ion. This benign syndrome, also
known as const it ut ional hepat ic dysfunct ion and familial nonhemolyt ic jaundice, is charact erized by t ot al bilirubin concent rat ions up t o 3.0 mg/dL (51.3 mmol/L) result ing
from a reduced expression of t he enzyme t hat conjugat es bilirubin. Gilbert syndrome is t he most common inherit ed disorder of bilirubin met abolism. In adult s, it is a benign
disorder, and no addit ional diagnost ic st udies or t herapy is required at t his t ime.
Cholest asis due t o an oral cont racept ive agent will cause conjugat ed (direct ) hyperbilirubinemia and an elevat ed serum alkaline phosphat ase level, neit her of which t his pat ient
has. Pat ient s wit h hemolysis significant enough t o cause unconjugat ed hyperbilirubinemia generally have a low hemoglobin level and abnormal values for mean corpuscular
volume (low) and red cell dist ribut ion widt h (high). Abdominal ult rasonography may be a helpful st udy for pat ient s wit h direct hyperbilirubinemia, which is usually associat ed
wit h liver disease, but is not indicat ed in t his pat ient who has indirect hyperbilirubinemia and no evidence of liver disease.
Key Poi nt
The incident al finding of indirect (unconjugat ed) hyperbilirubinemia in an asympt omat ic pat ient wit h a normal hemoglobin level and ot herwise normal liver t est s is indicat ive
of Gilbert syndrome.
Bi bl i ography
Krier M, Ahmed A. The asympt omat ic out pat ient wit h abnormal liver funct ion t est s. Clin Liver Dis. 2009;13(2):167-177. [PMID: 19442912]
Item 16 Answer: A
Educati onal Objecti ve: Manage symptomatic gallstone disease.
The best management for t his pat ient is elect ive cholecyst ect omy before hospit al discharge. Most pat ient s wit h asympt omat ic st ones are managed conservat ively. About
70% of pat ient s wit h gallst ones and single or infrequent episodes of pain have a rat e of biliary complicat ions of 1% t o 2% per year. Pat ient s wit h an episode of complicat ed
biliary disease (acut e cholecyst it is or gallst one pancreat it is) have a 30% chance of having a recurrence of complicat ed disease wit hin 3 mont hs. This pat ient has had recurrent
episodes of biliary colic and cholecyst it is and is at risk for complicat ed gallbladder disease. In uncomplicat ed gallbladder disease, laparoscopic cholecyst ect omy is preferred t o
open laparot omy, because it result s in short er hospit al st ays, less pain, and a more rapid recovery.
ERCP wit h sphinct erot omy is indicat ed for pat ient s wit h biliary obst ruct ion due t o choledocholit hiasis. It has no role in removing nonobst ruct ing st ones from t he gallbladder.
Alt hough ursodeoxycholic acid may decrease t he risk for fut ure st one format ion in some pat ient s, it is less effect ive t han cholecyst ect omy in pat ient s wit h exist ing st ones,
and it s use is limit ed t o pat ient s who are unable t o undergo surgery. Diet ary changes and weight loss may be useful for prevent ing development of gallst ones, but do not t reat
st ones t hat are already present .
Key Poi nt
Cholecyst ect omy provides definit ive t herapy for pat ient s wit h sympt omat ic gallst one disease.
Bi bl i ography
Sanders G, Kingsnort h AN. Gallst ones. BMJ. 2007;335(7614):295-9. [PMID: 17690370]
Item 17 Answer: D
Educati onal Objecti ve: Diagnose primary sclerosing cholangitis.
This pat ient likely has primary sclerosing cholangit is, a chronic cholest at ic liver disease associat ed wit h inflammat ory bowel disease and charact erized by fibrosis,
inflammat ion, and st rict uring of t he biliary t ree. Up t o 85% of affect ed pat ient s have underlying inflammat ory bowel disease, but less t han 5% of pat ient s wit h inflammat ory
bowel disease have primary sclerosing cholangit is. Cholest at ic liver diseases primarily cause elevat ion of serum alkaline phosphat ase values and minor elevat ions of t he
aminot ransferase levels. The disorder is more common in pat ient s wit h ulcerat ive colit is t han wit h Crohn disease. Most pat ient s are diagnosed while asympt omat ic wit h
abnormal result s on liver biochemist ry t est s, but jaundice and prurit us can occur in pat ient s wit h advanced disease. The diagnosis is usually made by endoscopic ret rograde
cholangiopancreat ography, which is especially useful in advanced disease where hist ologic samples can be t aken t o rule out cholangiocarcinoma and st ent s can be placed if
t here is a dominant st rict ure. Magnet ic resonance cholangiopancreat ography can also be used.
Gilbert syndrome is a common disorder associat ed wit h indirect hyperbilirubinemia. Pat ient s wit h t his syndrome generally have a serum t ot al bilirubin level of less t han 3.0
mg/dL (51.3 mol/L), whereas t he serum direct bilirubin level is less t han or equal t o 0.3 mg/dL (5.1 mol/L). A presumpt ive diagnosis of Gilbert syndrome can be made in an
ot herwise healt hy pat ient who has indirect hyperbilirubinemia, normal liver enzyme values, and a normal hemoglobin concent rat ion (which excludes hemolysis). This pat ient
does not fulfill t he crit eria for Gilbert syndrome.
Pat ient s wit h acut e hepat it is C are usually asympt omat ic and t herefore rarely present clinically, but 60% t o 85% of persons who acquire acut e hepat it is C develop chronic
infect ion. The cholest at ic pict ure in t he absence of ot her signs of advanced liver disease is inconsist ent wit h chronic hepat it is C. Pat ient s wit h acut e hepat it is A oft en have
fat igue, nausea, mild upper abdominal pain, and jaundice. Serum aspart at e aminot ransferase and alanine aminot ransferase values are usually great er t han 500 U/L. Hepat it is A
does not present wit h a cholest at ic biochemical profile as seen in t his pat ient .
Key Poi nt
Pat ient s wit h acut e hepat it is have a marked elevat ion of aminot ransferases, whereas pat ient s wit h primary sclerosing cholangit is have a cholest at ic pat t ern (primary
elevat ion of bilirubin and alkaline phosphat ase levels).
Bi bl i ography
Broome U, Bergquist A. Primary sclerosing cholangit is, inflammat ory bowel disease, and colon cancer. Semin Liver Dis. 2006;26(1):31-41. [PMID: 16496231]
Item 18 Answer: B
Educati onal Objecti ve: Diagnose acute cholecystitis.
The pat ient likely has acut e cholecyst it is; she has a hist ory of biliary colic, including pain t hat radiat es t o t he right shoulder, a Murphy sign elicit ed on examinat ion, fever,
leukocyt osis, mild bilirubin and aminot ransferase elevat ion, gallst ones and pericholecyst ic fluid, and t hickening of t he gallbladder wall on ult rasonography. When
ult rasonography reveals gallst ones and a posit ive ult rasonographic Murphy sign, t he posit ive predict ive value for acut e cholecyst it is is 92%. Murphy sign is int errupt ion of
deep inspirat ion when pressure is applied beneat h t he right cost al arch. When t he pat ient has t he addit ional findings of gallst ones and gallbladder wall t hickening (>3 mm), t he
posit ive predict ive value is 95% for acut e cholecyst it is. Surgical cholecyst ect omy is advisable once gallst ones lead t o such complicat ions as acut e cholecyst it is.
Acut e cholangit is is associat ed wit h biliary obst ruct ion and t he subsequent development of a suppurat ive infect ion wit hin t he biliary t ree. Obst ruct ion is most oft en due t o
gallst ones. Charcot t riad (pain, fever, and jaundice) occurs in most pat ient s wit h cholangit is. The absence of biliary t ract obst ruct ion on ult rasonography rules out acut e
cholangit is.
Alt hough t he present at ion of pancreat it is varies, t he most common signs and sympt oms are t he sudden onset of const ant , severe upper abdominal pain associat ed wit h nausea
and vomit ing. The hallmark of diagnosis is t he presence of markedly increased levels of circulat ing pancreat ic enzymes, which are not found in t his pat ient .
Gallbladder dyskinesia, charact erized by a reduced rat e of gallbladder empt ying, is cont roversial as a cause of right upper quadrant pain. Some pat ient s have feat ures t hat
overlap wit h t hose of funct ional bowel disease. It is not associat ed wit h fever, a posit ive Murphy sign, hyperbilirubinemia, or gallst ones.
Key Poi nt
The classic findings of acut e cholecyst it is are biliary colic, a Murphy sign, fever, leukocyt osis, mild bilirubin and aminot ransferase elevat ion, gallst ones, pericholecyst ic fluid,
and t hickening of t he gallbladder wall on ult rasonography.
Bi bl i ography
Trowbridge RL, Rut kowski NK, Shojania KG. Does t his pat ient have acut e cholecyst it is? [errat um in JAMA. 2009;302(7):739]. JAMA. 2003;289(1):80-86. [PMID:
12503981]
Item 19 Answer: A
Educati onal Objecti ve: Diagnose acute cholangitis.
This pat ient has classic acut e cholangit is. The clinical diagnosis is based upon t he presence of Charcot t riad (fever, jaundice, and right upper quadrant abdominal pain). In t his
set t ing, bile duct dilat ion, wit h st ones in t he gallbladder, suggest s acut e cholangit is due t o choledocholit hiasis. Broad-spect rum ant ibiot ics t o cover aerobic and anaerobic gram-
negat ive bacilli and ent erococci should be st art ed immediat ely. Endoscopic ret rograde cholangiopancreat ography wit h sphinct erot omy should t hen be performed t o remove
impact ed st ones.
Pat ient s wit h acut e cholecyst it is may have right upper quadrant pain and gallst ones, but t he bilirubin level is usually not great er t han 2 mg/dL (34.2 mol/L), and
aminot ransferase levels are normal. Uncomplicat ed cholecyst it is is not associat ed wit h common bile duct obst ruct ion. Pat ient s wit h simple cholelit hiasis are generally
asympt omat ic. This pat ient may have pancreat it is t hat is relat ed t o obst ruct ion of t he common bile duct and is support ed by t he finding of elevat ed lipase level. However,
pancreat it is alone cannot explain all of t his pat ient 's sympt oms and in part icular cannot account for t he right upper quadrant pain or dilat ed common bile duct .
Key Poi nt
The clinical diagnosis of acut e cholangit is is based upon t he presence of fever, jaundice, and right upper quadrant abdominal pain and t he finding of common bile duct
obst ruct ion.
Bi bl i ography
At t asaranya S, Fogel EL, Lehman GA. Choledocholit hiasis, ascending cholangit is, and gallst one pancreat it is. Med Clin Nort h Am. 2008;92:925-960, x. [PMID: 18570948]
Item 20 Answer: B
Educati onal Objecti ve: Manage gallstone pancreatitis with ERCP.
The most appropriat e next st ep in management is ERCP. Pat ient s wit h acut e pancreat it is usually have t he sudden onset of epigast ric pain, oft en radiat ing t o t he back. These
sympt oms are oft en accompanied by nausea, vomit ing, fever, and t achycardia. The physical examinat ion shows epigast ric t enderness, abdominal dist ension, hypoact ive bowel
sounds, and occasional guarding. The diagnosis is confirmed by laborat ory result s showing serum concent rat ions of amylase and lipase at least t hree t imes t he upper limit of
normal. Abdominal ult rasonography should be used t o det ect cholelit hiasis in pat ient s wit h suspect ed gallst one pancreat it is. ERCP is recommended in pat ient s wit h evidence
of gallst one pancreat it is and suspect ed biliary obst ruct ion. Biliary obst ruct ion is suspect ed if cholelit hiasis or choledocholit hiasis is present , bile duct s are dilat ed, and liver
enzymes are elevat ed. Aminot ransferase concent rat ions rise init ially in gallst one pancreat it is, wit h subsequent rise of alkaline phosphat ase and bilirubin if obst ruct ion persist s.
ERCP wit h sphinct erot omy has been shown t o lower morbidit y and mort alit y in t hese pat ient s, significant ly reducing rat es of cholangit is and biliary sepsis.
Alt hough elect ive cholecyst ect omy will be required in t he fut ure, ERCP is t he preferred immediat e int ervent ion for removing obst ruct ing st ones in acut e pancreat it is. MRCP
may be used t o evaluat e biliary obst ruct ion if ult rasonography is nondiagnost ic. In a pat ient wit h choledocholit hiasis ident ified by ult rasonography, MRCP is unlikely t o
provide addit ional diagnost ic informat ion and cannot be used t herapeut ically t o remove t he obst ruct ing st one. Finally, definit ive t reat ment should not be delayed t o obt ain
furt her imaging st udies. Jejunal ent eral feedings are indicat ed in pat ient s wit h severe pancreat it is when it is ant icipat ed t he pat ient will not be able t o eat for a prolonged
period of t ime. In t his case, it is likely t he pat ient will be able t o resume oral int ake aft er t he obst ruct ing st one is removed.
Key Poi nt
ERCP wit h sphinct erot omy and st one ext ract ion is t he init ial t reat ment of choice for gallst one pancreat it is.
Bi bl i ography
Gupt a K, Wu B. In t he clinic. Acut e pancreat it is. Ann Int ern Med. 2010;153(9):ITC51-5. [PMID: 21041574]
Item 21 Answer: C
Educati onal Objecti ve: Diagnose gallstone pancreatitis.
The most likely diagnosis is gallst one pancreat it is. This pat ient has a classic present at ion of acut e pancreat it is wit h t he acut e onset of epigast ric abdominal pain, nausea, and
vomit ing associat ed wit h markedly elevat ed pancreat ic enzymes. About 80% of all cases of acut e pancreat it is are due t o gallst ones and alcohol abuse. About 10% of cases are
classified as idiopat hic; obst ruct ion, drugs, and met abolic, genet ic, infect ious, and vascular disorders cause t he remaining 10% of cases. The presence of st ones in t he
gallbladder, a dilat ed bile duct , and elevat ed aminot ransferase levels highly suggest gallst ones as t he cause of pancreat it is. The scleral ict erus, jaundice, and elevat ed bilirubin
level suggest cont inuing bile duct obst ruct ion. Abdominal ult rasonography has a sensit ivit y of only 50% t o 75% for choledocholit hiasis, and a common duct st one should be
suspect ed in t he correct clinical sit uat ion even when ult rasonography does not show a st one. Endoscopic ret rograde cholangiopancreat ography (ERCP) wit h sphinct erot omy
and st one removal is t he most appropriat e procedure in pat ient s wit h acut e gallst one pancreat it is.
The absence of alcohol consumpt ion excludes alcoholic pancreat it is. Pat ient s whose serum t riglyceride level exceeds 1000 mg/dL (11.3 mmol/L) may develop
hypert riglyceridemic pancreat it is, but t his pat ient 's t riglyceride level is only high normal. Aut oimmune pancreat it is is a t ype of chronic pancreat it is. Findings include
hypergammaglobulinemia, diffuse pancreat ic enlargement , a mass lesion in t he pancreas, an irregular main pancreat ic duct , and t he presence of aut oant ibodies such as
ant inuclear ant ibody. Pat ient s are usually asympt omat ic or have only mild sympt oms. This pat ient 's acut e onset of pain and evidence of gallst one disease is not compat ible
wit h t he diagnosis of aut oimmune pancreat it is.
Key Poi nt
The presence of st ones in t he gallbladder, a dilat ed bile duct , and elevat ed aminot ransferase levels highly suggest gallst ones as t he cause of acut e pancreat it is.
Bi bl i ography
Wang GJ, Gao CF, Wei D, Wang C, Ding SQ. Acut e pancreat it is: et iology and common pat hogenesis. World J Gast roent erol. 2009;15(12):1427-1430. [PMID: 19322914]
Item 22 Answer: B
Educati onal Objecti ve: Manage severe acute pancreatitis with enteral nutrition.
The most appropriat e management st ep is ent eral nut rit ion wit h nasojejunal t ube feeding. This pat ient has moderat e t o severe acut e pancreat it is and aft er 5 days remains
febrile, cont inues t o be in pain, and cannot t ake in any oral nut rit ion. The pat ient will likely have an ext ended period before being able t o t ake in oral nut rit ion. Two rout es
are available for providing nut rit ion in pat ient s wit h severe acut e pancreat it is: ent eral nut rit ion and parent eral nut rit ion. Ent eral nut rit ion is provided t hrough a feeding t ube,
ideally placed past t he ligament of Treit z so as not t o st imulat e t he pancreas. Parent eral nut rit ion is provided t hrough a large peripheral or cent ral int ravenous line. Ent eral
nut rit ion is preferred over parent eral nut rit ion because of it s lower complicat ion rat e. Ent eral nut rit ion is associat ed wit h a significant ly lower incidence of infect ions, reduced
surgical int ervent ions t o cont rol complicat ions of pancreat it is, and a reduced lengt h of hospit al st ay.
Imipenem t herapy is only helpful in acut e pancreat it is when t here is evidence of pancreat ic necrosis. Pancreat ic necrosis is diagnosed by a cont rast -enhanced CT scan t hat
shows nonenhancing pancreat ic t issue. In pat ient s wit h noninfect ed pancreat ic necrosis, ant ibiot ics may decrease t he incidence of sepsis, syst emic complicat ions (for
example, respirat ory failure), and local complicat ions (for example, infect ed pancreat ic necrosis or pancreat ic abscess). There is no benefit from ant ibiot ic use in acut e
pancreat it is wit hout pancreat ic necrosis, and such t reat ment may lead t o development of nosocomial infect ions wit h resist ant pat hogens. Similarly, pancreat ic debridement is
recommended only in pat ient s wit h pancreat it is and infect ed pancreat ic necrosis. There is no role for cort icost eroid t herapy in pat ient s wit h acut e pancreat it is of any
et iology. Cort icost eroid use may increase t he risk for nosocomial relat ed infect ions and met abolic complicat ions such as hyperglycemia.
Key Poi nt
Ent eral feeding is t he preferred rout e for providing nut rit ion in pat ient s wit h severe acut e pancreat it is.
Bi bl i ography
Pet rov MS, van Sant voort HC, Besselink MG, van der Heijden GJ, Windsor JA, Gooszen HG. Ent eral nut rit ion and t he risk of mort alit y and infect ious complicat ions in
pat ient s wit h severe acut e pancreat it is: a met a-analysis of randomized t rials. Arch Surg. 2008;143(11):1111-1117. [PMID: 19015471]
Item 23 Answer: D
Educati onal Objecti ve: Evaluate gastroesophageal reflux disease (GERD) alarm symptoms with upper endoscopy.
The init ial diagnost ic t est for t his pat ient is upper endoscopy. His present at ion is t ypical for GERD: burning pain relieved by ant acids and worsened by lying down and bending
forward. Response t o empiric t reat ment wit h a prot on pump inhibit or such as omeprazole would be sufficient ly sensit ive and specific t o diagnose GERD; however, t his pat ient
also has t he alarm sympt om of dysphagia. Upper endoscopy should be performed next t o evaluat e for acid-induced esophageal st rict ure and esophageal carcinoma.
Test ing for H. pylori is not indicat ed for pat ient s wit h GERD, because t he presence or absence of H. pylori does not correlat e wit h t he presence or absence of GERD or guide
t herapy. Ambulat ory esophageal pH monit oring is t he gold st andard for diagnosing GERD and is t ypically used in pat ient s in whom t he diagnosis is uncert ain or who are
unresponsive t o empiric t herapy. In t his pat ient who present s wit h sympt oms t ypical for GERD wit h alarm sympt oms, t he primary goal of t est ing is t o est ablish t he presence
of a GERD complicat ion such as acid st rict ure or esophageal carcinoma.
Key Poi nt
In pat ient s wit h gast roesophageal reflux disease, endoscopy is indicat ed for pat ient s wit h alarm sympt oms.
Bi bl i ography
Wilson JF. In t he clinic. Gast roesophageal reflux disease. Ann Int ern Med. 2008;149(3):ITC2-1-15; quiz ITC2-16. [PMID: 18678841]
Item 24 Answer: B
Educati onal Objecti ve: Treat erosive esophagitis with a proton pump inhibitor.
The st andard of care for t he medical management of gast roesophageal reflux disease (GERD), including pat ient s wit h erosive esophagit is, is prot on pump inhibit or (PPI)
t herapy. Alt hough hist amine
2
recept or ant agonist t herapy relieves sympt oms and heals esophagit is in 50% t o 60% of pat ient s, PPI t herapy provides result s in t he 80%
range. Five PPIs are available in t he Unit ed St at es: omeprazole, esomeprazole, lansoprazole, pant oprazole, and rabeprazole; t hey all have similar efficacy.
A promot ilit y agent such as met oclopramide can t heoret ically be beneficial in t he t reat ment of pat ient s wit h GERD by increasing lower esophageal sphinct er pressure,
enhancing gast ric empt ying, or improving perist alsis. However, promot ilit y agent s have significant side effect s and t he FDA has imposed a black box warning on
met oclopramide, and specialt y guidelines recommend against t he use of met oclopramide because of quest ionable efficacy and numerous side effect s.
Sucralfat e (aluminum sucrose sulfat e) is a t opical t herapy for pept ic ulcer disease and GERD. Sucralfat e adheres t o t he mucosal surface and promot es healing by an unknown
mechanism. Sucralfat e is approximat ely as effect ive as a hist amine
2
recept or ant agonist for t he t reat ment of GERD and nonerosive esophagit is but subst ant ially less effect ive
t han a PPI and has no role in t he t reat ment of erosive esophat it is.
Key Poi nt
Prot on pump inhibit or t herapy is t he t reat ment of choice for erosive or severe esophagit is.
Bi bl i ography
Wang WH, Huang JQ, Zheng GF, Xia HH, Wong WM, Lam SK, Wong BC. Head-t o-head comparison of H2-recept or ant agonist s and prot on pump inhibit ors in t he
t reat ment of erosive esophagit is: a met a-analysis. World J Gast roent erol. 2005;11(26):4067-77. [PMID: 15996033]
Item 25 Answer: A
Educati onal Objecti ve: Biopsy a gastric ulcer.
The most appropriat e management for t his pat ient 's gast ric ulcer is biopsy. Biopsies of all gast ric ulcers should be performed, because even small, benign-appearing gast ric
ulcers may harbor malignancy. In benign ulcers, biopsies can also provide evidence for t he presence of Helicobacter pylori infect ion and guide appropriat e t herapy.
Test ing for H. pylori is indicat ed in pat ient s wit h act ive pept ic ulcer disease (duodenal or gast ric) and in pat ient s wit h a hist ory of pept ic ulcer disease who have not been
previously t reat ed for H. pylori infect ion. The most commonly used endoscopic t est s include biopsy and hist ologic assessment and t he rapid urease t est . The sensit ivit y of t he
rapid urease t est can be reduced by as much as 25% in pat ient s who have t aken a prot on pump inhibit or (PPI), such as omeprazole, wit hin 2 weeks or bismut h or ant ibiot ic
t herapy wit hin 4 weeks of t he endoscopy; t herefore, biopsy followed by hist ologic evaluat ion for evidence of H. pylori infect ion is t he endoscopic t est of choice for t his
pat ient . The sensit ivit y of urea breat h t est ing, like t hat of t he rapid urease t est , is reduced by medicat ions t hat affect urease product ion such as a PPI.
Treat ment for pept ic ulcer disease is guided by t he biopsy and presence of H. pylori infect ion. In t he presence of document ed infect ion, t riple t herapy consist ing of a PPI,
amoxicillin, and clarit hromycin is t he most commonly used init ial t reat ment . Triple t herapy is not indicat ed in t he absence of document ed infect ion. In t his pat ient , t riple
t herapy should be wit hheld pending document at ion of infect ion.
Key Poi nt
Biopsies of all gast ric ulcers should be performed, because even small, benign-appearing gast ric ulcers may harbor malignancy.
Bi bl i ography
McColl KE. Clinical pract ice. Helicobact er pylori infect ion. N Engl J Med. 2010:29;362(17):1597-604. [PMID: 20427808]
Item 26 Answer: E
Educati onal Objecti ve: Treat peptic ulcer disease by stopping an NSAID.
The most appropriat e next st ep in t he management of t his pat ient is t o st op t he ibuprofen. The t wo most common causes of pept ic ulcer disease are NSAIDs and
Helicobacter pylori infect ion, which account for more t han 90% of cases. This pat ient has a hist ory of art hrit is for which she t akes over-t he-count er ibuprofen; many
pat ient s who t ake such nonprescript ion medicat ions are unaware t hat t hey are t aking an NSAID t hat can cause ulcer disease.
H. pylori infect ion has been ruled out in t his pat ient by t he negat ive hist ology for t he organism as well as negat ive serum ant ibody t est ing; t herefore, no furt her t est ing for H.
pylori is needed.
Measuring serum gast rin should be considered in a pat ient in whom t here is a suspicion of an acid hypersecret ion st at e, such as a gast rinoma (Zollinger-Ellison syndrome),
clinical feat ures of which include mult iple pept ic ulcers, ulcers in unusual locat ions, severe esophagit is, or fat malabsorpt ion, none of which t his pat ient has.
Malignancy always needs t o be considered in a pat ient wit h a gast ric ulcer; t herefore, biopsies of t he ulcer and follow-up endoscopy t o ensure ulcer healing would be
recommended. However, t his pat ient has a duodenal ulcer, which is much less likely t o represent a malignancy, and biopsy of t he ulcer or follow-up endoscopy t o assess for
healing is not needed.
Alendronat e t herapy for ost eoporosis has been associat ed wit h esophagit is and rare cases of gast ric or duodenal ulcers; however, st opping alendronat e wit hout considering t he
more common causes of pept ic ulcer disease would not be appropriat e at t his t ime.
Key Poi nt
The t wo most common causes of pept ic ulcer disease are NSAIDs and Helicobacter pylori infect ion, which account for more t han 90% of cases.
Bi bl i ography
Jones R, Rubin G, Berenbaum F, Scheiman J. Gast roint est inal and cardiovascular risks of nonst eroidal ant i-inflammat ory drugs. Am J Med. 2008;121(6):464-474. [PMID:
18501223]
Item 27 Answer: B
Educati onal Objecti ve: Diagnose NSAID use as a cause of dyspepsia.
For a pat ient wit h dyspepsia who is t aking nonst eroidal ant i-inflammat ory drugs (NSAIDs) and has no concerning alarm feat ures, st opping t he NSAID is t he most appropriat e
next st ep. NSAIDs are t he drugs most frequent ly associat ed wit h dyspepsia. If st opping or changing t he NSAID is not a viable opt ion, init iat ion of a prot on pump inhibit or is
warrant ed.
Met oclopramide is a t reat ment t hat may have efficacy in pat ient s wit h dysmot ilit y-like dyspepsia. However, t his diagnosis is based on pat ient sympt oms (early sat iet y,
nausea), a normal upper endoscopy, and absence of ot her more common causes of dyspepsia such as NSAID use.
NSAID use is a much more common cause of dyspepsia t han Helicobacter pylori infect ion. Test ing for H. pylori before st opping t he ibuprofen may lead t o unnecessary
t reat ment or misdiagnosis in t his pat ient . Simply st opping or changing t he NSAID may obviat e t he need for furt her t est ing for H. pylori and unnecessary t reat ment if t he
pat ient 's dyspepsia improves. If sympt oms cont inue aft er st opping t he NSAID, t est ing for H. pylori is warrant ed.
Alarm feat ures such as unexplained iron deficiency anemia, unint ent ional weight loss, dysphagia, odynophagia, palpable abdominal masses, or jaundice would necessit at e an
urgent upper endoscopy. Because t he incidence of malignancy is significant ly great er in pat ient s older t han 55 years, upper endoscopy is indicat ed in any pat ient older t han
55 years wit h new-onset dyspepsia even wit hout alarm feat ures. This pat ient has no indicat ion for upper endoscopy.
Key Poi nt
NSAIDs are pot ent ial causes of dyspepsia and should be st opped or changed in pat ient s wit h dyspept ic sympt oms.
Bi bl i ography
Talley NJ, Vakil NB, Moayyedi P. American Gast roent erological Associat ion t echnical review on t he evaluat ion of dyspepsia. Gast roent erology. 2005;129(5):1756-80.
[PMID: 16285971]
Item 28 Answer: D
Educati onal Objecti ve: Empirically treat functional dyspepsia with a proton pump inhibitor.
The most appropriat e management for t his pat ient is an empiric t rial wit h a prot on pump inhibit or (PPI). Funct ional dyspepsia is defined as chronic or recurrent discomfort
in t he epigast rium wit h no organic cause det ermined. Upper endoscopy is necessary t o rule out organic causes, and only aft er t his is performed can t he diagnosis of funct ional
dyspepsia be dist inguished from organic dyspepsia (e.g., dyspepsia caused by pept ic ulcer disease, reflux esophagit is, malignancy). Because t his pat ient 's funct ional dyspepsia
sympt oms are ulcer-like, an empiric t rial of a PPI is t he recommended t reat ment .
Ambulat ory esophageal pH monit oring, which consist s of insert ing a pH monit or in t he dist al esophagus and recording t he result s over a period of 24 hours, is t he most
accurat e means t o confirm t he diagnosis of gast roesophageal reflux disease (GERD). The t echnique also allows det erminat ion of an associat ion bet ween sympt oms and t he
amount and pat t ern of esophageal acid exposure. This procedure may be helpful when t he diagnosis of GERD is in doubt or appropriat e GERD t herapy is nonsuccessful. This
pat ient 's sympt oms are not compat ible wit h GERD and ambulat ory pH monit oring is not indicat ed.
Funct ional dyspepsia does not have an apparent organic cause t hat requires surgery. Therefore, surgical consult at ion is not indicat ed. Wit h no ot her signs or sympt oms t o
suggest a psychiat ric illness, psychiat ric consult at ion is not warrant ed.
Key Poi nt
An empiric t rial of a prot on pump inhibit or is indicat ed for ulcer-like funct ional dyspepsia.
Bi bl i ography
Tack J, Lee KJ. Pat hophysiology and t reat ment of funct ional dyspepsia. J Clin Gast roent rol. 2005:39(5 suppl 3):S211-S216. [PMID: 15798487]
Item 29 Answer: D
Educati onal Objecti ve: Diagnose gastrointestinal bleeding of obscure cause.
The next st ep in t he management of t his pat ient is t o repeat t he upper endoscopy. Init ial endoscopy may miss lesions t hat are difficult t o see or bleed int ermit t ent ly.
Bet ween one t hird and t wo t hirds of sources of gast roint est inal bleeding of obscure et iology are found wit hin t he reach of upper endoscopy, which is t ypically t he next
procedure performed following nondiagnost ic upper and lower endoscopy. Repeat upper endoscopy is part icularly appealing in t his pat ient wit h a hiat al hernia because of t he
possibilit y of Cameron lesions. Cameron lesions are linear gast ric ulcers or erosions in t he hiat al hernia sac. Cameron lesions are usually an incident al finding and are seen in
5% of pat ient s wit h hiat al hernias who undergo endoscopic examinat ion, but t hey can cause chronic or, less oft en, acut e blood loss.
If repeat upper endoscopy is negat ive, considerat ion can be given t o repeat colonoscopy or capsule endoscopy. In wireless capsule endoscopy, a pat ient swallows a video
capsule t hat , by int est inal mot ilit y, passes t hrough t he st omach and int o t he small int est ine. The video capsule t ransmit s images t o a recording device worn by t he pat ient .
This procedure has been shown t o det ect sources of bleeding in 70% of pat ient s and is considered t he t est of choice following upper and lower endoscopy st udies.
Barium swallow has a low sensit ivit y and specificit y in t he diagnosis of gast roint est inal bleeding compared wit h upper endoscopy and can int erfere wit h subsequent endoscopic
st udies. The double balloon endoscope is a syst em t hat uses t wo lat ex balloons, one mount ed on t he endoscope and a second balloon on t he overt ube, which are successively
inflat ed and deflat ed t o pleat t he bowel over t he endoscope and achieve deep int ubat ion of t he small int est ine. Double balloon endoscopy may be performed t hrough an oral
or a t ransanal rout e and has replaced int raoperat ive ent eroscopy in many cases. The role for double balloon endoscopy is t o evaluat e or t reat findings seen on capsule
endoscopy, for evaluat ion of ongoing bleeding when bleeding is brisk enough t hat t he need for endoscopic hemost asis is expect ed, and as a complement ary t est when a small-
bowel source of bleeding remains a concern despit e a nondiagnost ic capsule endoscopy.
Key Poi nt
In gast roint est inal bleeding of obscure origin, repeat upper endoscopy will ident ify a bleeding source in a significant proport ion of pat ient s.
Bi bl i ography
Concha R, Amaro R, Barkin JS. Obscure gast roint est inal bleeding: diagnost ic and t herapeut ic approach. J Clin Gast roent erol. 2007;41(3):242-51. [PMID: 17426461]
Item 30 Answer: D
Educati onal Objecti ve: Diagnose ischemic colitis.
The most likely diagnosis is ischemic colit is. Alt hough an underlying cause is oft en not ident ified, colonic ischemia can occur in associat ion wit h colonic hypoperfusion in t he
set t ing of aort ic or cardiac bypass surgery, prolonged physical exert ion (for example, long-dist ance running), and any cardiovascular event accompanied by hypot ension.
Medicat ions such as oral cont racept ives, drugs such as cocaine, vasculit ides, and hypercoagulable st at es have also been ident ified as risk fact ors. Most pat ient s wit h colonic
ischemia are older t han 60 years and usually present wit h left lower quadrant pain, urgent defecat ion, and red or maroon rect al bleeding t hat does not require t ransfusion.
Pat ient s may have mild t enderness over t he involved segment of colon; hypovolemia and perit onit is are rare. Colonoscopic findings are generally segment al and include
hemorrhagic nodules, linear and circumferent ial ulcerat ion, and gangrene. Therapy includes int ravenous fluids and ant ibiot ics t o cover anaerobes and gram-negat ive bact eria,
alt hough dat a t o support t his lat t er pract ice are weak.
Most pat ient s wit h acut e mesent eric ischemia are older t han 50 years. Severe abdominal pain is almost invariably present , but early physical examinat ion findings are
minimal, illust rat ing t he classic t eaching of "pain out of proport ion t o examinat ion." Alt hough occult blood-posit ive st ool is common, overt bleeding is rare. Lat e signs and
sympt oms include nausea, vomit ing, fever, hemat emesis, obst ruct ion, back pain, and shock.
Divert icular disease encompasses bot h divert icular hemorrhage and divert iculit is. Divert iculosis is an import ant cause of massive painless lower gast roint est inal bleeding in
older pat ient s. Divert iculit is result s from obst ruct ion at t he divert iculum neck by fecal mat t er, leading t o mucus and bact erial overgrowt h. Because 85% of divert iculit is occurs
in t he sigmoid or left colon, left lower quadrant pain is t he most common clinical manifest at ion, oft en accompanied by fever and leukocyt osis; overt rect al bleeding is
t ypically not seen. In pat ient s wit h suspect ed divert iculit is, colonoscopy is not performed because of t he risk of colonic perforat ion.
Key Poi nt
Most pat ient s wit h colonic ischemia are older t han 60 years and usually present wit h left lower quadrant pain, urgent defecat ion, and red or maroon rect al bleeding t hat does
not require t ransfusion.
Bi bl i ography
Feuerst adt P, Brandt LJ. Colon ischemia: recent insight s and advances. Curr Gast roent erol Rep. 2010;12(5):383-90. [PMID: 20690005]
Item 31 Answer: A
Educati onal Objecti ve: Recognize risks of rebleeding in a patient with upper gastrointestinal bleeding.
Upper endoscopy should be performed at t he t ime of an upper gast roint est inal bleed aft er appropriat e volume resuscit at ion t o provide a diagnosis as t o t he cause of bleeding,
provide a prognosis, and perform endoscopic guided t herapy if required. For example, an ulcer wit h a visible vessel has an approximat ely 50% risk of rebleeding if not t reat ed
endoscopically. These ulcers can be effect ively t reat ed wit h inject ion t herapy, t hermal coagulat ion via endoscopic probes, or mechanical modalit ies such as endoclips. Clean-
based ulcers rebleed in less t han 5% of cases and do not require endoscopic t herapy.
There is a 5% t o 10% rebleeding rat e for endoscopic hemost asis. In t hese pat ient s, endoscopic t herapy may be repeat ed if t he pat ient remains hemodynamically st able. If
repeat endoscopy is unsuccessful or t he bleeding vessel is inaccessible or t oo large, surgical consult at ion should be obt ained. However, endoscopic int ervent ion is t he first
management choice for upper gast roint est inal bleeding.
Int ravenous omeprazole has been shown t o reduce t he risk of recurrent upper gast roint est inal bleeding in pept ic ulcers aft er endoscopic hemost asis. Oral omeprazole also may
decrease rebleeding. A met a-analysis showed t hat adjuvant high-dose prot on pump inhibit or t herapy following endoscopic hemost asis for ulcers at high risk of rebleeding
reduces rebleeding, surgery, and mort alit y. Oct reot ide may have a marginal benefit by decreasing t he rat e of nonvariceal bleeding but is inferior t o int ravenous prot on pump
inhibit ors. Ranit idine, a hist amine H
2
blocker, is inferior t o prot on pump inhibit ors as an adjunct t o endoscopic t herapy, and t here is no benefit of adding a hist amine H
2
blocker t o prot on pump inhibit or t herapy.
Key Poi nt
Upper endoscopy should be performed at t he t ime of an upper gast roint est inal bleed aft er appropriat e volume resuscit at ion t o provide a diagnosis as t o t he cause of bleeding,
provide a prognosis, and perform endoscopic guided t herapy if required.
Bi bl i ography
Cappell MS, Friedel D. Init ial management of acut e upper gast roint est inal bleeding: from init ial evaluat ion up t o gast roint est inal endoscopy. Med Clin Nort h Am.
2008;92(3):491-509, xi. [PMID: 18387374]
Item 32 Answer: D
Educati onal Objecti ve: Manage upper gastrointestinal bleeding with restoration of the intravascular volume.
The first st ep in t he management of acut e variceal hemorrhage is t he rest orat ion of t he int ravascular volume using a large bore peripheral int ravenous line or a cent ral line.
Packed eryt hrocyt es are used as needed t o replace blood loss and clot t ing fact ors are replaced as needed. Plat elet t ransfusions may be indicat ed if values fall below 50,000/L
(50 10
9
/L).
Following rest orat ion of t he int ravascular volume, t his pat ient should undergo urgent esophagogast roduodenoscopy and band ligat ion of esophageal varices. Band ligat ion has
been shown t o be as effect ive as sclerot herapy for prevent ing early rebleeding. Therapy should also be st art ed wit h int ravenous oct reot ide, which reduces port al venous blood
inflow t hrough inhibit ion of t he release of vasodilat ory hormones and is more effect ive for cont rolling bleeding t han placebo; however, it s ult imat e effect on survival is
unknown.
Art eriography is not first -line t herapy in pat ient s wit h a variceal bleed from venous port al hypert ension, and no int ervent ion should t ake precedence over rest orat ion of t he
int ravascular volume. Art eriography is reserved for pat ient s wit h a presumed art erial source of bleeding as can be seen in pept ic ulcer disease or t umors anywhere along t he
gast roint est inal t ract . In such cases, art eriography can be used t o ident ify and embolize t he specific vessel involved. This met hod is usually reserved for cases in which t he
pat ient is act ively bleeding and eit her endoscopic t herapy has failed t o st op t he bleeding or t he presence of act ive bleeding int erferes wit h ident ificat ion of t he bleeding sit e
and t he pat ient is unst able.
Int ravenous nadolol is not appropriat e because t his pat ient is hypot ensive and needs volume replacement and endoscopic int ervent ion rat her t han medical t herapy. A
nonselect ive -blocker is useful in t he primary and secondary prevent ion of variceal bleeding but not as acut e t herapy.
Key Poi nt
Volume rest orat ion is a priorit y management int ervent ion for gast roint est inal bleeding in hemodynamically unst able pat ient s.
Bi bl i ography
Cappell MS, Friedel D. Init ial management of acut e upper gast roint est inal bleeding: from init ial evaluat ion up t o gast roint est inal endoscopy. Med Clin Nort h Am.
2008;92(3):491-509, xi. [PMID: 18387374]
Item 33 Answer: C
Educati onal Objecti ve: Diagnose diverticulosis or vascular ectasia as the most likely cause of painless lower gastrointestinal bleeding.
The most likely sources of painless lower gast roint est inal bleeding are divert iculosis and vascular ect asia. Aft er hemodynamic st abilizat ion, t he next st ep is t o dist inguish
upper from lower gast roint est inal bleeding. The presence of blood or coffee-ground-like mat erial on gast ric lavage indicat es ongoing or recent upper gast roint est inal bleeding
and t he need for upper endoscopy. Negat ive nasogast ric t ube lavage is reliable in ruling out upper gast roint est inal bleeding only if t he aspirat e cont ains bile (a yellow or green
fluid t hat t est s posit ive for bile wit h a urine dipst ick), indicat ing passage of t he t ube beyond t he pylorus int o t he duodenum.
The most common causes of acut e, severe lower gast roint est inal bleeding are colonic divert icula, angiect asia (also known as angiodysplasia), colit is (for example,
inflammat ory bowel disease, infect ion, ischemia, or radiat ion), and colonic neoplasia. Bleeding from a colonic divert iculum and vascular ect asia is t ypically acut e and painless.
Ischemic colit is t ypically occurs in older individuals wit h significant cardiac and peripheral vascular disease who present wit h abdominal pain and only a small amount of
bleeding. Pat ient s wit h inflammat ory bowel disease and bleeding usually have an est ablished hist ory of inflammat ory bowel disease and abdominal pain. The pat ient 's recent
colonoscopy and large-volume bleeding make a neoplasm unlikely.
Key Poi nt
The most likely sources of painless lower gast roint est inal bleeding are divert iculosis and vascular ect asia.
Bi bl i ography
Zuccaro G. Epidemiology of lower gast roint est inal bleeding. Best Pract Res Clin Gast roent erol. 2008;22(2):225-232. [PMID: 18346680]
Item 34 Answer: A
Educati onal Objecti ve: Diagnose anal fissure as a cause of painful hematochezia.
This pat ient most likely has an anal fissure t hat is causing rect al out let bleeding and pain wit h defecat ion and t hat is probably due t o her recent const ipat ion. An anal fissure is
a t ear in t he lining of t he anal canal. Careful rect al examinat ion by gent ly spreading t he but t ocks apart may reveal t he fissure, but t his finding may not always be present . The
pat ient may have t oo much pain t o allow digit al rect al examinat ion or anoscopy. Chronic fissures are oft en accompanied by ext ernal skin t ags, as seen in t his pat ient .
Recurrent or nonhealing fissures should raise concern for underlying diseases, part icularly Crohn disease.
Rect al cancer and colon cancer must always be considered in someone wit h new-onset rect al out let bleeding. However, t his pat ient underwent colonoscopy less t han 1 year
ago, and result s were normal. Even if t his pat ient had colonic divert icula, t he fact t hat her bleeding occurs wit h painful defecat ion and has been present over a 3-mont h period
is not t ypical of divert icular bleeding, which t ends t o cause significant acut e painless hemat ochezia t hat oft en st ops spont aneously.
Key Poi nt
Anal fissures generally cause rect al out let bleeding and pain wit h defecat ion.
Bi bl i ography
Chong PS, Bart olo DC. Hemorrhoids and fissure in ano. Gast roent erol Clin Nort h Am. 2008;37(3):627-644, ix. [PMID: 18794000]
Item 35 Answer: B
Educati onal Objecti ve: Screen for hepatocellular carcinoma in a patient with hepatitis B.
The most appropriat e screening st rat egy for hepat ocellular carcinoma in t his pat ient is liver ult rasonography. Hepat ocellular carcinoma is t he most common primary
int rahepat ic t umor and t he fast est growing cause of cancer-relat ed deat h in men in t he Unit ed St at es. The cancer usually develops in pat ient s wit h cirrhosis. The most
common causes of cirrhosis leading t o hepat ocellular carcinoma are chronic hepat it is B and hepat it is C viral infect ions and alcoholic liver disease; however, pat ient s wit h
chronic hepat it is B infect ion in t he absence of cirrhosis may develop hepat ocellular carcinoma. Pat ient s wit h a compat ible ult rasound imaging st udy and a subsequent serum -
fet oprot ein level great er t han 500 ng/mL (500 g/L) can be diagnosed wit h hepat ocellular carcinoma wit hout a biopsy. The opt imal t ime t o init iat e a screening program and
it s ideal frequency are unknown.
Combined use of -fet oprot ein measurement and ult rasonography increases t he sensit ivit y of det ect ion but at t he expense of increased false-posit ive result s. -Fet oprot ein is
not specific for hepat ocellular carcinoma and should not be used alone as a screening t est unless ult rasound is not available. Liver CT scanning exposes t he pat ient t o
unnecessary radiat ion, part icularly if screening is performed frequent ly.
Key Poi nt
Pat ient s wit h chronic hepat it is B infect ion in t he absence of cirrhosis may develop hepat ocellular carcinoma and should undergo periodic screening.
Bi bl i ography
Lim SG, Mohammed R, Yuen MF, Kao JH. Prevent ion of hepat ocellular carcinoma in hepat it is B virus infect ion. J Gast roent erol Hepat ol. 2009;24(8):1352-7. [PMID:
19702903]
Item 36 Answer: A
Educati onal Objecti ve: Diagnose hepatitis A.
This pat ient most likely has acut e hepat it is A. The pat ient has clinical sympt oms and laborat ory findings consist ent wit h acut e hepat it is (fat igue, jaundice, aminot ransferase
concent rat ions >1000 U/L). The major rout es of t ransmission are ingest ion of cont aminat ed food or wat er and cont act wit h an infect ed person. Groups at part icularly high
risk include people living in or t raveling t o underdeveloped count ries, children in day care cent ers, men who have sex wit h men, and perhaps people who ingest raw shellfish.
Alt hough any of t he hepat it is viruses can cause sympt omat ic acut e hepat it is, hepat it is A is t he most likely infect ion in a t raveler t o an undeveloped count ry wit hout ot her
risk fact ors. Hepat it is A is almost always a self-limit ed infect ion, alt hough acut e hepat it is A may rarely present as fulminant hepat it is t hat may require liver t ransplant at ion.
The clinical course may include a prolonged cholest at ic phase charact erized by persist ence of jaundice for up t o 6 mont hs. Treat ment of acut e hepat it is A is support ive.
Serum immune globulin should be administ ered t o all household and int imat e cont act s wit hin 2 weeks of exposure. Hepat it is A virus vaccine should be offered t o t ravelers who
go t o underdeveloped count ries, men who have sex wit h men, inject ion drug users, and pat ient s wit h chronic liver disease.
Hepat it is B, C, and D are less likely wit hout a hist ory of parent eral exposure. Hepat it is D virus (HDV or delt a agent ) depends upon t he presence of HBsAg for it s replicat ion
and, t herefore, cannot survive on it s own. In a pat ient infect ed wit h hepat it is B, HDV infect ion may present as an acut e hepat it is (in which case it is a coinfect ion) or an
exacerbat ion of preexist ing chronic hepat it is (in which case it is a superinfect ion). Pat ient s wit h a hist ory of inject ion drug use are at great est risk for acquiring HDV
infect ion. Finally, acut e hepat it is C rarely causes sympt oms.
Key Poi nt
Pat ient s wit h acut e hepat it is generally have fat igue, nausea, vomit ing, jaundice, and aminot ransferase values great er t han 1000 U/L.
Bi bl i ography
Brundage SC, Fit zpat rick AN. Hepat it is A. Am Fam Physician. 2006;73:2162-2168. [PMID: 16848078]
Item 37 Answer: A
Educati onal Objecti ve: Diagnose alcoholic hepatitis.
This pat ient has severe alcoholic hepat it is. Excessive alcohol int ake may cause liver disease direct ly or may increase t he risk of an unfavorable out come in pat ient s wit h
preexist ing liver disease. This pat ient wit h chronic alcohol abuse has many of t he charact erist ic findings of alcoholic hepat it is: a hist ory of recent heavy alcohol use, elevat ed
serum aspart at e aminot ransferase (AST) and alanine aminot ransferase (ALT) values (usually less t han 500 U/L and frequent ly less t han 300 U/L), AST t o ALT rat io great er
t han 2 t o 1, elevat ed alkaline phosphat ase concent rat ion, jaundice, coagulopat hy, and encephalopat hy. Moreover, ot her major causes of acut e and chronic liver disease have
been excluded.
The pat ient 's serology t est s confirm past infect ion wit h hepat it is B virus and current immunit y (posit ive hepat it is B surface ant igen ant ibody). Similarly, t he serologic t est s
for hepat it is A are compat ible wit h past infect ion and current immunit y (posit ive IgG hepat it is A ant ibody). The negat ive hepat it is C ant ibody serology rules out chronic
hepat it is C virus infect ion.
Aut oimmune hepat it is is an inflammat ory condit ion of t he liver of unknown cause. It primarily develops in persons 20 t o 40 years of age, but all age groups and most et hnic
groups are affect ed. Women develop aut oimmune hepat it is more oft en t han men. Most pat ient s present wit h feat ures of chronic liver disease. Ant inuclear ant ibody, ant i-
smoot h-muscle ant ibody, or ant ibody t o liver/kidney microsome t ype 1 (ant i-LKM1) is present in 87% of pat ient s and helps t o support a diagnosis of aut oimmune hepat it is.
Finally, aut oimmune hepat it is does not cause a fat t y liver.
Key Poi nt
Pat ient s wit h alcoholic hepat it is have a hist ory of recent heavy alcohol use, elevat ed serum aspart at e aminot ransferase (AST) and alanine aminot ransferase (ALT)
concent rat ions, an AST:ALT rat io great er t han 2 t o 1, and elevat ed alkaline phosphat ase concent rat ion.
Bi bl i ography
Lucey MR, Mat hurin P, Morgan TR. Alcoholic hepat it is. N Engl J Med. 2009;360(26):2758-2769. [PMID: 19553649]
Item 38 Answer: B
Educati onal Objecti ve: Diagnose autoimmune hepatitis.
This pat ient has aut oimmune hepat it is, a disorder t hat occurs most commonly in girls and young women. Like t his pat ient wit h hypot hyroidism, many affect ed pat ient s have
ot her aut oimmune disorders and a family hist ory of aut oimmunit y. These pat ient s usually present wit h vague sympt oms. Fat igue, which occurs in 85% of pat ient s, is t he most
common present ing sympt om, followed by jaundice (46%), anorexia (30%), myalgias (30%), and diarrhea. On physical examinat ion, most pat ient s have an enlarged liver.
Pat ient s can have aminot ransferase concent rat ions int o t he t housands (but t ypically less t han 500 IU at present at ion), elevat ed bilirubin, oft en near-normal alkaline
phosphat ase, and hypergammaglobulinemia. Aut oimmune serologic t est s, specifically ant inuclear ant ibodies, ant i-smoot h muscle ant ibodies, and ant ibody t o liver/kidney
microsome t ype 1 (ant i-LKM1), may be posit ive but are not det ect ed in up t o 25% of pat ient s.
Primary biliary cirrhosis is a chronic progressive cholest at ic liver disease of unknown cause. It is an aut oimmune disorder t hat occurs predominant ly in women (80% t o 90%
of cases) bet ween 40 and 60 years of age. The diagnost ic t riad associat ed wit h primary biliary cirrhosis includes a cholest at ic liver profile, posit ive ant imit ochondrial ant ibody
t it ers, and compat ible hist ologic findings on liver biopsy. Serum alkaline phosphat ase level is usually elevat ed 10 t imes or more above normal. The pat ient 's near-normal
alkaline phosphat ase concent rat ion and negat ive ant imit ochondrial ant ibody essent ially rule out primary biliary cirrhosis.
Alt hough drug-induced liver injury can cause similar liver t est abnormalit ies, t he pat ient has not t aken any new medicat ions recent ly, making t his diagnosis unlikely, and
levot hyroxine would be a very unusual cause of drug-induced hepat it is. Addit ionally, drug-induced hepat it is is not associat ed wit h posit ive ant i-smoot h muscle ant ibody
findings. She has no pain t o suggest acut e cholecyst it is.
Key Poi nt
Laborat ory findings in pat ient s wit h aut oimmune hepat it is include elevat ed serum aminot ransferase values, hypergammaglobulinemia, mild hyperbilirubinemia, mildly elevat ed
serum alkaline phosphat ase values, and t he presence of aut oant ibodies.
Bi bl i ography
Krawit t EL. Clinical feat ures and management of aut oimmune hepat it is. World J Gast roent erol. 2008;14(21):3301-3305. [PMID: 18528927]
Item 39 Answer: B
Educati onal Objecti ve: Diagnose acute hepatitis B.
The markedly elevat ed aminot ransferase levels, posit ive hepat it is B surface ant igen, and IgM ant ibody t o hepat it is B core ant igen est ablish t he diagnosis of acut e hepat it is B
infect ion. Pat ient s at great est risk for exposure t o hepat it is B virus infect ion are t hose wit h a hist ory of mult iple sexual part ners and inject ion drug users. Most adult pat ient s
will clear t heir infect ion aft er a few mont hs. However, about 5% pat ient s develop acut e progressive hepat it is B wit h hepat ic decompensat ion and need urgent liver
t ransplant at ion, as does t his pat ient .
These pat ient s t end t o have an elevat ed INR and a rising bilirubin level and may develop encephalopat hy, a marker of fulminant hepat ic failure.
Pat ient s wit h chronic hepat it is B have posit ive hepat it is B surface ant igen and posit ive IgG ant ibody t o hepat it is B core ant igen; IgM ant ibody t o hepat it is B core ant igen is
negat ive. In addit ion, t his pat ient 's fulminant course is not compat ible wit h chronic hepat it is B infect ion.
Acut e hepat it is A is diagnosed by t he presence of IgM ant ibody t o hepat it is A virus (IgM ant i-HAV), which appears at t he onset of t he acut e phase of t he illness and becomes
undet ect able in 3 t o 6 mont hs. IgG ant i-HAV also becomes posit ive during t he acut e phase but persist s for decades and is a marker of immunit y t o furt her infect ion. A person
wit h a posit ive IgG ant i-HAV t it er but a negat ive t it er for IgM ant i-HAV has had hepat it is A in t he remot e past or has received hepat it is A vaccine.
Pat ient s wit h acut e hepat it is C are usually asympt omat ic and t herefore rarely present clinically, but 60% t o 85% of persons who acquire acut e hepat it is C develop chronic
infect ion. Alt hough det erminat ion of ant ibody t o hepat it is C virus (HCV) is a reliable and inexpensive t est for diagnosing hepat it is C, t he diagnost ic "gold st andard" is t he
presence of HCV RNA in serum.
Key Poi nt
Posit ive hepat it is B surface ant igen and IgM ant ibody t o hepat it is B core ant igen est ablish t he diagnosis of acut e hepat it is B infect ion.
Bi bl i ography
Liang TJ. Hepat it is B: t he virus and disease. Hepat ology. 2009;49(suppl 5):S13-S21. [PMID: 19399811]
Item 40 Answer: C
Educati onal Objecti ve: Diagnose chronic hepatitis C virus infection.
This pat ient most likely has chronic hepat it is C infect ion. Hepat it is C virus (HCV) is t he most common bloodborne infect ion in t he Unit ed St at es. Alt hough screening of
blood product s and reduced t ransmission among inject ion drug users have result ed in a decreasing number of new HCV infect ions, t he number of deat hs is increasing because of
t he "backlog" of chronic infect ions and t he long durat ion of chronic infect ion before cirrhosis develops. Pat ient s wit h acut e hepat it is C are usually asympt omat ic and
t herefore rarely present clinically, but 60% t o 85% of persons who acquire acut e hepat it is C develop chronic infect ion. The ant i-HCV ant ibody t est is t he screening t est for
at -risk persons; a posit ive t est in a person wit h one of t he risk fact ors confirms exposure t o t he virus. The HCV RNA t est is required t o det ermine act ive infect ion rat her
t han just exposure t o t he virus.
Hepat it is A does not cause chronic liver disease. The pat ient 's serology is compat ible wit h eit her a past infect ion wit h hepat it is A virus or immunizat ion wit h hepat it is A
vaccine.
Hepat it is B virus (HBV) causes 20% t o 30% of cases of acut e viral hepat it is and 15% of cases of chronic viral hepat it is in t he Unit ed St at es. Mult iple sex part ners and
inject ion drug use are t he major risk fact ors for disease acquisit ion in t his count ry. This pat ient is negat ive for hepat it is B surface ant igen and t herefore does not have chronic
hepat it is B infect ion.
Hepat it is D virus (HDV or t he delt a agent ) is a defect ive virus t hat requires t he presence of HBsAg t o replicat e. In t he Unit ed St at es, inject ion drug users wit h hepat it is B are
t he group at highest risk for acquiring hepat it is D.
Key Poi nt
The ant i-hepat it is C virus ant ibody t est is t he screening t est for at -risk persons; a posit ive t est in a person wit h one of t he risk fact ors confirms exposure t o t he virus.
Bi bl i ography
Jou JH, Muir AJ. In t he clinic. Hepat it is C. Ann Int ern Med. 2008;148(11):ITC6-1-ITC6-16. [PMID: 18519925]
Item 41 Answer: D
Educati onal Objecti ve: Diagnose nonalcoholic steatohepatitis as the cause of cirrhosis.
The most likely cause of t his pat ient 's liver disease is nonalcoholic st eat ohepat it is (NASH). Ascit es and elevat ed aminot ransferase and bilirubin levels suggest port al
hypert ension caused by cirrhosis. Nonalcoholic fat t y liver disease (NAFLD) consist s of variable degrees of fat accumulat ion, inflammat ion, and fibrosis in t he absence of
significant alcohol int ake. Fat t y liver disease in t he absence of inflammat ion is more common in women t han in men and occurs in 60% of obese pat ient s. NASH is a
subcat egory of NAFLD defined as t he presence of inflammat ion occurring in about 20% of obese pat ient s of which 2% t o 3% will develop cirrhosis. NASH is most commonly
seen in pat ient s wit h underlying consequences of obesit y, including insulin resist ance, hypert ension, and hyperlipidemia (met abolic syndrome). NAFLD is usually diagnosed
when pat ient s wit h charact erist ic clinical risk fact ors are found t o have mildly t o moderat ely elevat ed serum aminot ransferase concent rat ions. Imaging wit h ult rasonography,
CT, or MRI can confirm t he presence of st eat osis. Liver biopsy is somet imes necessary t o est ablish t he diagnosis of NASH.
Alcohol and chronic hepat it is C infect ion are t he most common causes of cirrhosis in t he Unit ed St at es; however, t his pat ient does not have evidence of hepat it is C infect ion
(negat ive ant i-hepat it is C ant ibody) nor does she consume alcohol in sufficient quant it y t o cause cirrhosis (6 alcoholic drinks per day for men and 3 alcoholic drinks per day
for women for 10 years). Alt hough chronic hepat it is B infect ion can lead t o cirrhosis, t his pat ient 's serologies indicat e immunit y t o hepat it is B (negat ive hepat it is B surface
ant igen, posit ive ant i-hepat it is B surface ant ibody), not chronic hepat it is B infect ion. Alt hough primary biliary cirrhosis is more common in women t han men, it is
charact erized by marked elevat ions of t he alkaline phosphat ase (cholest at ic liver disease) not seen in t his pat ient .
Key Poi nt
Nonalcoholic st eat ohepat it is (NASH) is associat ed wit h obesit y, t ype 2 diabet es, and hyperlipidemia and is a pot ent ial cause of cirrhosis.
Bi bl i ography
Hashimot o E, Tokushige K. Prevalence, gender, et hnic variat ions, and prognosis of NASH. J Gast roent erol. 2011;46(suppl 1):63-9. [PMID: 20844903]
Item 42 Answer: D
Educati onal Objecti ve: Diagnose primary sclerosing cholangitis.
This pat ient has cholest at ic liver disease charact erized by st riking elevat ions of t he alkaline phosphat ase level and only modest elevat ions of t he aminot ransferase levels. The
most likely diagnosis is primary sclerosing cholangit is. The most common sympt oms of primary sclerosing cholangit is are prurit us and fat igue; as t he disease progresses, most
pat ient s develop jaundice. Primary sclerosing cholangit is is a chronic condit ion t hat usually present s in t he fourt h or fift h decade of life; it is more common in men t han in
women and is charact erized by progressive bile duct inflammat ion and dest ruct ion and, ult imat ely, fibrosis of t he int rahepat ic and ext rahepat ic bile duct s, leading t o cirrhosis.
The cause of t he disorder is unknown, but a st rong associat ion exist s wit h ulcerat ive colit is, which is present in more t han 80% of pat ient s wit h primary sclerosing cholangit is.
However, t he severit y of ulcerat ive colit is does not correlat e wit h t he severit y of primary sclerosing cholangit is, and t reat ment of ulcerat ive colit is does not significant ly
affect t he prognosis of cholangit is.
Primary biliary cirrhosis, anot her cholest at ic liver disease, is a slowly progressive aut oimmune disease t hat mainly affect s women older t han 25 years. Prurit us usually predat es
t he development of jaundice, and pat ient s oft en have ot her immune disorders such as hypot hyroidism, Sjogrenor sicca syndrome, and syst emic sclerosis (scleroderma);
ant imit ochondrial ant ibodies are found in 95% of cases.
Aut oimmune hepat it is is more common in women and usually present s in adult hood. Approximat ely 50% of pat ient s are asympt omat ic and are diagnosed as a result of
screening t est s. In most cases, serum aminot ransferase levels are elevat ed, ranging from mild increases in serum concent rat ions t o values great er t han 1000 U/L.
Hyperbilirubinemia may occur wit h a normal or near-normal serum alkaline phosphat ase level. Cert ain aut oant ibodies may be elevat ed, including ant i-smoot h-muscle
ant ibody, ant inuclear ant ibody, and rarely ant i-liver-kidney-microsomal ant ibody t ype 1.
Many adult s have IgG ant ibodies t o hepat it is A, indicat ing previous exposure and immunit y t o t he virus. Unlike hepat it is B and hepat it is C, hepat it is A does not cause chronic
liver disease.
Key Poi nt
Primary sclerosing cholangit is is st rongly associat ed wit h ulcerat ive colit is and is associat ed wit h marked elevat ions of alkaline phosphat ase.
Bi bl i ography
Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ; American Associat ion for t he St udy of Liver Diseases. Diagnosis and management of
primary sclerosing cholangit is. Hepat ology. 2010;51(2):660-78. [PMID: 20101749]
Item 43 Answer: A
Educati onal Objecti ve: Diagnose cirrhosis as the cause of ascites.
This pat ient has cirrhosis wit h ascit es. Ascit es is t he most common complicat ion of port al hypert ension secondary t o cirrhosis. Any pat ient who develops new-onset ascit es
should undergo diagnost ic paracent esis. Init ial evaluat ion of ascit ic fluid should include measurement of albumin and cell count wit h different ial, Gram st ain, and cult ure. The
serum-t o-ascit es albumin gradient (SAAG) is calculat ed by subt ract ing t he ascit ic fluid albumin level from t he serum albumin level. A gradient great er t han 1.1 g/dL (11 g/L)
indicat es t hat t he pat ient has port al hypert ension wit h a high degree of accuracy. In addit ion t o cirrhosis, ot her causes of port al hypert ension, such as const rict ive
pericardit is, right -sided heart failure, and t he Budd-Chiari syndrome, should be considered. A gradient of less t han 1.1 g/dL (11 g/L) is not associat ed wit h port al hypert ension
but wit h condit ions t hat can cause ascit es by ot her mechanisms, including infect ion, inflammat ion, or low serum oncot ic pressure, such as t he nephrot ic syndrome,
malignancy, or t uberculosis. Analysis of t his pat ient 's ascit ic fluid shows a SAAG of 2.2 g/dL (22 g/L), which is consist ent wit h ascit es due t o sinusoidal hypert ension from a
chronic liver disease such as cirrhosis.
Key Poi nt
Ascit ic fluid analysis showing a serum-t o-ascit es albumin gradient great er t han 1.1 g/dL is consist ent wit h ascit es caused by chronic liver disease, such as cirrhosis, right -sided
heart failure, and t he Budd-Chiari syndrome.
Bi bl i ography
Wong CL, Holroyd-Leduc J, Thorpe KE, St raus SE. Does t his pat ient have bact erial perit onit is or port al hypert ension? How do I perform a paracent esis and analyze t he
result s? JAMA. 2008;299(10):1166-1178. [PMID: 18334692]
Item 44 Answer: C
Educati onal Objecti ve: Manage hepatic encephalopathy.
The most appropriat e management for t his pat ient is t o increase t he lact ulose t herapy. This pat ient has severe encephalopat hy manifest ed by worsening somnolence.
Encephalopat hy progresses from subt le findings, such as reversal of t he sleep-wake cycle or mild ment al st at us changes, t o irrit abilit y, confusion, slurred speech, and
ult imat ely coma if not recognized and t reat ed. There can be mult iple incit ing causes of encephalopat hy in pat ient s wit h cirrhosis, including dehydrat ion, infect ion (especially
spont aneous bact erial perit onit is), diet indiscret ions, gast roint est inal bleeding, and medicat ions. This pat ient likely became worse wit h t he development of t he urinary t ract
infect ion.
The best course of management is t o t reat t he infect ion and t o discont inue t he diuret ics and increase t he lact ulose t o respond t o t he encephalopat hy. The dose of lact ulose
should be t it rat ed t o achieve t wo t o t hree soft st ools per day wit h a pH below 6.0. Approximat ely 70% t o 80% of pat ient s wit h hepat ic encephalopat hy improve on lact ulose
t herapy, and t reat ment is usually well t olerat ed.
Cort icost eroids have no role in t he reversal of hepat ic encephalopat hy. Transjugular int rahepat ic port osyst emic shunt (TIPS) is not appropriat e because placement of TIPS
is likely t o precipit at e worsening hepat ic encephalopat hy as more blood is bypassed t hrough t he shunt rat her t han processed by t he liver. There is no role for hemodialysis in
t he t reat ment of hepat ic encephalopat hy and t here appear t o be no ot her indicat ions for dialysis (severe acidosis, hyperkalemia, renal failure wit h hypervolemia).
Key Poi nt
First -line t herapy for hepat ic encephalopat hy is lact ulose.
Bi bl i ography
Kalait zakis E, Bjornsson E. Lact ulose t reat ment for hepat ic encephalopat hy, gast roint est inal sympt oms, and healt h-relat ed qualit y of life. Hepat ology. 2007;46(3):949-950.
[PMID: 17879365]
Item 45 Answer: A
Educati onal Objecti ve: Diagnose hepatorenal syndrome.
This pat ient most likely has hepat orenal syndrome, which is defined as development of kidney failure in pat ient s wit h port al hypert ension and normal renal t ubular funct ion.
Int ense renal vasoconst rict ion leads t o a syndrome of acut e kidney dysfunct ion charact erized by increased renal sodium avidit y, a relat ively normal urine sediment , and
oliguria in some pat ient s. This condit ion is diagnosed aft er ot her causes of acut e kidney injury such as prerenal azot emia, renal parenchymal disease, or obst ruct ion have been
excluded. Spont aneous bact erial perit onit is, vigorous diuret ic t herapy, paracent esis wit hout volume expansion, and gast roint est inal bleeding also may precipit at e hepat orenal
syndrome. The most effect ive t reat ment for hepat orenal syndrome is liver t ransplant at ion.
Alt hough pat ient s wit h complet e obst ruct ion have significant ly decreased urine out put , t hose wit h part ial obst ruct ion may have polyuria caused by loss of t ubular funct ion or
excret ion of excess ret ained solut e. Kidney ult rasonography in most pat ient s wit h obst ruct ion reveals hydronephrosis and was absent in t his pat ient .
This pat ient had no signs of hypovolemia such as hypot ension or t achycardia, and his kidney dysfunct ion did not improve aft er discont inuat ion of diuret ics and
administ rat ion of volume replacement wit h normal saline albumin. This makes prerenal azot emia an unlikely diagnosis.
The diagnosis of renal art ery st enosis as t he cause of t his acut e kidney injury is unlikely considering his end-st age cirrhosis, no evidence of hypert ension, and no signs of
diffuse vascular disease.
Key Poi nt
The hepat orenal syndrome is defined as development of kidney dysfunct ion in pat ient s wit h port al hypert ension aft er exclusion of prerenal azot emia, renal parenchymal
disease, or obst ruct ion.
Bi bl i ography
Arroyo V, Fernandez J, Gines P. Pat hogenesis and t reat ment of hepat orenal syndrome. Semin Liver Dis 2008;28:81-95. [PMID: 18293279]
Item 46 Answer: B
Educati onal Objecti ve: Diagnose erythema nodosum associated with inflammatory bowel disease.
The most likely diagnosis is eryt hema nodosum. Ext raint est inal manifest at ions occur in approximat ely 10% t o 20% of pat ient s wit h inflammat ory bowel disease at some
t ime in t he course of t heir disease. Eryt hema nodosum, which manifest s as small, exquisit ely t ender nodules on t he ant erior t ibial surface, is t he most common cut aneous
manifest at ion of inflammat ory bowel disease and occurs more commonly in Crohn disease, whereas pyoderma gangrenosum is more common in ulcerat ive colit is. The t ypical
clinical present at ion of eryt hema nodosum is t he sudden onset of one or more t ender, eryt hemat ous nodules on t he ant erior legs t hat are more easily palpat ed t han visualized.
The erupt ion is oft en preceded by a prodrome of fever, malaise, and art hralgia. A residual ecchymot ic appearance is common as t he lesions age. In pat ient s wit h
inflammat ory bowel disease, t reat ing t he underlying bowel disease usually result s in remission of eryt hema nodosum.
Dermat it is herpet iformis is charact erized by grouped, prurit ic, eryt hemat ous papulovesicles on t he ext ensor surfaces of t he arms, legs, cent ral back, but t ocks, and scalp. A
genet ic predisposit ion is linked t o t he same genes associat ed wit h celiac disease. Virt ually all pat ient s wit h dermat it is herpet iformis have celiac disease, but gast roint est inal
sympt oms occur in only about 25% of pat ient s.
Pyoderma gangrenosum occurs in approximat ely 10% of pat ient s wit h ulcerat ive colit is. Pyoderma gangrenosum is an uncommon, neut rophilic, ulcerat ive skin disease.
Lesions t end t o be mult iple and t o appear on t he lower ext remit ies. They begin as t ender papules, pust ules, or vesicles t hat spont aneously ulcerat e and progress t o painful
ulcers wit h a purulent base and undermined, ragged, violaceous borders.
Rheumat oid nodules are t he most common cut aneous manifest at ion of rheumat oid art hrit is. They may be asympt omat ic or painful and int erfere wit h funct ion. Rheumat oid
nodules are frequent ly found in t he subcut aneous t issue just dist al t o t he elbow on t he ext ensor surface of t he forearm. Nodules also may be found on t he ext ensor surface of
t he hand and over t he Achilles t endons. Rheumat oid nodules and inflammat ory bowel disease are not linked.
Key Poi nt
Eryt hema nodosum, which manifest s as small, exquisit ely t ender nodules on t he ant erior t ibial surface, is t he most common cut aneous manifest at ion of inflammat ory bowel
disease.
Bi bl i ography
Requena L, Yus ES. Eryt hema nodosum. Dermat ol Clin. 2008;26(4):425-38, v. [PMID: 18793974]
Item 47 Answer: E
Educati onal Objecti ve: Diagnose ulcerative colitis.
This pat ient has mild t o moderat e left -sided ulcerat ive colit is based on his clinical present at ion and endoscopic and hist ologic findings. His ex-smoking st at us, microcyt ic
anemia, and t he presence of art hrit is, which is t he most common ext raint est inal manifest at ion of inflammat ory bowel disease, furt her support t he diagnosis. Ulcerat ive colit is
t ypically involves t he rect um and ext ends proximally wit h cont iguous inflammat ion t hat is generally limit ed t o t he mucosa of t he colon and rect um. Pat ient s usually present
wit h bloody diarrhea associat ed wit h rect al discomfort , fecal urgency, and cramps. Alt hough most pat ient s have bloody diarrhea, t hose wit h proct it is can present wit h
const ipat ion.
Alt hough many colit ides can have overlapping clinical, endoscopic, and even hist ologic feat ures, t here are import ant differences t o consider. Microscopic colit is present s
wit h nonbloody diarrhea, and colonoscopy shows normal mucosa macroscopically and hist ology shows eit her increased int raepit helial lymphocyt es (lymphocyt ic colit is) or
an increased submucosal collagen layer (collagenous colit is). Bleeding is less oft en a feat ure of Crohn colit is, and endoscopic inflammat ory changes are pat chy and generally
spare t he rect um but can ext end t hroughout t he ent ire gast roint est inal t ract ; hist ologic feat ures, however, may be indist inguishable from t hose of ulcerat ive colit is. Infect ious
colit is usually present s wit h more acut e sympt oms, and chronic changes such as crypt archit ect ure dist ort ion are absent . Ischemic colit is also generally has a more acut e
course and spares t he rect um because of t he dual blood supply t o t his region and is oft en associat ed wit h ot her evidence of at herosclerot ic vascular disease.
Key Poi nt
Ulcerat ive colit is t ypically involves t he rect um and ext ends proximally wit h cont iguous inflammat ion t hat is generally limit ed t o t he mucosa of t he colon and rect um.
Bi bl i ography
Baumgart DC, Sandborn WJ. Inflammat ory bowel disease: clinical aspect s and est ablished and evolving t herapies. Lancet . 2007; 369(9573):1641-1657. [PMID: 17499606]
Item 48 Answer: D
Educati onal Objecti ve: Treat ulcerative colitis.
The most appropriat e t reat ment is mesalamine. This pat ient has mild left -sided ulcerat ive colit is based on his clinical present at ion, endoscopic, and hist ologic findings.
Topical t herapy is appropriat e for dist al disease. Opt ions include cort isone foam and mesalamine or cort icost eroid supposit ories for proct it is and hydrocort isone or
mesalamine enemas for left -sided colit is. Oral 5-aminosalicylat es, including sulfasalazine, mesalamine, balsalazide, and olsalazine, are appropriat e for dist al disease t hat does
not respond t o t opical t herapy or for mild t o moderat e pancolit is.
Oral prednisone is used when sympt oms do not respond t o 5-aminosalicylat es. Because prednisone and ot her cort icost eroids have many acut e and chronic t oxic effect s t hat
are dose- and durat ion-dependent , t he lowest effect ive dose should be given for t he short est t ime. Azat hioprine (AZA) or 6-mercapt opurine (6-MP) may be used for pat ient s
who have incomplet e disease remission while on cort icost eroids. However, because bot h agent s have delayed onset of act ion, concomit ant administ rat ion of eit her AZA or 6-
MP t oget her wit h a 3- t o 4-mont h course of prednisone is oft en necessary.
Ant ibiot ics, including bot h met ronidazole and ciprofloxacin, have not been shown t o be effect ive in ulcerat ive colit is.
Infliximab is a chimeric ant ibody against t umor necrosis fact or ; in pat ient s wit h severe disease or who do not respond t o cort icost eroid t herapy for remission, infliximab
may be effect ive, but it would not be an appropriat e first -line medicat ion for mild ulcerat ive colit is.
Key Poi nt
First -line t herapy for induct ion and maint enance of remission in mild t o moderat e ulcerat ive colit is is mesalamine or anot her 5-aminosalicylat e agent .
Bi bl i ography
Ng SC, Kamm MA. Therapeut ic st rat egies for t he management of ulcerat ive colit is. Inflamm Bowel Dis. 2009;15(6):935-950. [PMID: 18985710]
Item 49 Answer: C
Educati onal Objecti ve: Diagnose microscopic colitis.
This pat ient most likely has microscopic colit is, which is charact erized by chronic wat ery diarrhea wit hout bleeding. There are t wo t ypes of microscopic colit is: collagenous
colit is and lymphocyt ic colit is. The average age of onset for collagenous colit is is in t he sixt h decade of life and it t ends t o affect more women t han men. The average age of
onset for lymphocyt ic colit is is in t he sevent h decade of life, and women seem t o be affect ed slight ly more oft en t han men. The cause of microscopic colit is is unknown. One
t heory is t hat t he use of NSAIDs may cont ribut e t o t he development of t he disorder. Anot her t heory is t hat it is caused by an aut oimmune response. Colonoscopy in affect ed
pat ient s is grossly normal; t o make a diagnosis, several biopsies must be t aken from t he colon. In collagenous colit is, biopsy specimens show more t han normal amount s of
collagen beneat h t he lining of t he colon. In lymphocyt ic colit is, t he specimen may also show an increased number of lymphocyt es. Loperamide, diphenoxylat e, and bismut h
subsalicylat e, eit her alone or in combinat ion, are effect ive and well t olerat ed when used as init ial t herapy.
Ulcerat ive colit is is charact erized by bloody diarrhea associat ed wit h rect al discomfort , which t his pat ient does not have. Fever, weight loss, t achycardia, dehydrat ion, and
significant abdominal t enderness or rebound indicat es more severe disease. Endoscopic findings can be subt le in pat ient s wit h mild ulcerat ive colit is, and examinat ion may
show only mucosal edema and eryt hema. Increased inflammat ion causes friabilit y, ulcerat ion, and bleeding. Pat ient s wit h Crohn disease commonly present wit h abdominal
pain, diarrhea, and weight loss. Disease involving t he small int est ine oft en causes nonbloody diarrhea, whereas hemat ochezia is more likely when t he colon is involved.
Endoscopic examinat ion may show apht hous ulcers or large ulcers t hat can coalesce and cause a "cobblest one" appearance. The pat ient has not t aken any ant ibiot ics and does
not have ot her est ablished risk fact ors for Clostridium difficile colit is, including recent hospit alizat ion, advanced age, and severe illness. Colonoscopy will show
pseudomembranes appearing as raised yellow or off-whit e plaques scat t ered over t he colorect al mucosa. She has not t raveled out of t he count ry recent ly, and t herefore, is not
at risk for t ropical sprue.
Key Poi nt
Microscopic colit is is charact erized by chronic wat ery diarrhea wit hout bleeding; t he diagnosis must be made by hist ologic examinat ion of colonoscopic biopsy specimens.
Bi bl i ography
Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S. Diagnosis and management of microscopic colit is. World J Gast roent erol. 2008;14(48):7280-7288. [PMID: 19109861]
Secti on 4. General Internal Medi ci ne
Questi ons
Item 1 [Basic]
A new t est t o screen for prost at e cancer has been developed and t he result s are compared wit h t he result s of needle biopsy of t he prost at e gland. A t rial assessing t he result s of
t he new t est against biopsy result s is summarized below:
Biopsy + Biopsy + Biopsy - Biopsy -
Test - Test + Test + Test -
Pat ient s 5 20 15 60
What are the sensi ti vi ty and speci fi ci ty for thi s new test?
(A) Sensit ivit y, 0.25; specificit y, 0.75
(B) Sensit ivit y, 0.33; specificit y, 0.67
(C) Sensit ivit y, 0.8; specificit y, 0.8
(D) Sensit ivit y, 0.96; specificit y, 0.96
Item 2 [Basic]
A new diagnost ic t est is developed and t est ed in an experiment al set t ing. The t est 's sensit ivit y and specificit y are 0.80. In t he populat ion of pat ient s in which t he t est was
used, t he posit ive and negat ive predict ive values were 0.57 and 0.92, respect ively. The prevalence of disease in t he t est populat ion was 0.25. The usual prevalence of t his
disease in t he communit y is 0.025.
When used i n the communi ty, whi ch of the fol l owi ng measures i s most l i kel y to decrease?
(A) Sensit ivit y
(B) Specificit y
(C) Posit ive predict ive value
(D) Negat ive predict ive value
(E) Posit ive likelihood rat io
Item 3 [Advanced]
A 54-year-old woman is evaluat ed during an insurance examinat ion t hat requires human immunodeficiency virus (HIV) t est ing. She has no sympt oms of HIV disease. She has
had a monogamous sexual relat ionship wit h her husband of 24 years, uses no recreat ional drugs, and has had one blood t ransfusion because of t rauma from a mot or vehicle
accident in 1970. Result s of t he physical examinat ion are normal.
Result s from an enzyme-linked immunosorbent assay (ELISA) are posit ive, wit h a t est sensit ivit y and specificit y of 98%. The prevalence of HIV posit ivit y in similar pat ient s
is approximat ely 1 in 10,000.
What i s the probabi l i ty that thi s pati ent has HIV i nfecti on?
(A) 98%
(B) 90%
(C) 10%
(D) 0.5%
Item 4 [Advanced]
A 19-year-old woman is evaluat ed in t he emergency depart ment for right lower-quadrant abdominal pain and fever of 3 hours' durat ion. The pat ient is not sexually act ive.
On physical examinat ion, t he abdomen is t ender t o palpat ion in t he right lower quadrant but wit hout evidence of guarding or rebound t enderness. Pelvic examinat ion is
normal wit hout cervical mot ion t enderness or right adenexal pain. Following clinical examinat ion, t he probabilit y of acut e appendicit is is est imat ed t o be 50%. An abdominal
"appendiceal" CT scan is ordered. An appendiceal CT scan showing inflammat ion and a t hickened appendiceal wall is associat ed wit h a likelihood rat io of 13.3 for t he
diagnosis of acut e appendicit is.
If the CT scan i s i nterpreted as posi ti ve for appendi ci ti s, what i s the posttest probabi l i ty that the pati ent has appendi ci ti s?
(A) 50%
(B) 65%
(C) 80%
(D) 95%
Item 5 [Advanced]
A series of 4 new t est s (A, B, C, and D) are developed t o diagnose hemachromat osis. The operat ing charact erist ics for a variet y of different cut point s for each of t he four
t est s are plot t ed on a receiver operat ing charact erist ic (ROC) curve.
Whi ch of the fol l owi ng tests has the best overal l accuracy?
(A) A
(B) B
(C) C
(D) D
Item 6 [Advanced]
A 67-year-old man is evaluat ed during a rout ine physical examinat ion. His medical hist ory is remarkable for hypert ension and hyperlipidemia. He has a 20 pack-year hist ory
of cigaret t e smoking but st opped smoking 18 mont hs ago. He has no sympt oms and no ot her medical problems. Medicat ions are hydrochlorot hiazide and simvast at in. He
received his influenza vaccine t his year and t he pneumococcal vaccine last year. Screening colonoscopy was performed 5 years ago and was normal.
On physical examinat ion, t emperat ure is normal, blood pressure is 120/70 mm Hg, pulse rat e is 79/min, and respirat ion rat e is 16/min. BMI is 27. The remainder of t he
physical examinat ion is normal.
Lipid panel reveals LDL and non-LDL cholest erol levels at t arget values.
Whi ch of the fol l owi ng shoul d be done next for thi s pati ent?
(B) Dual-energy x-ray absorpt iomet ry
(C) Pneumococcal vaccinat ion
(D) Rest ing elect rocardiogram
Item 7 [Advanced]
A 51-year-old man is evaluat ed during a rout ine follow-up examinat ion in November. He was diagnosed wit h GOLD st age I chronic obst ruct ive pulmonary disease 2 years ago
and also has hypert ension. He has a 20-pack-year hist ory of cigaret t e smoking but st opped smoking 18 mont hs ago. Current medicat ions are inhaled albut erol as needed and
hydrochlorot hiazide. He had influenza and pneumococcal vaccinat ions 1 year ago.
Whi ch of the fol l owi ng i s the most appropri ate i mmuni zati on strategy for thi s pati ent?
(A) Pneumococcal vaccinat ion only
(B) Trivalent int ranasal live influenza and pneumococcal vaccinat ions
(C) Trivalent int ranasal live influenza vaccinat ion only
(D) Trivalent killed influenza and pneumococcal vaccinat ions
(E) Trivalent killed influenza vaccinat ion only
Item 8 [Advanced]
A randomized clinical t rial is conduct ed t o det ermine if screening for lung cancer wit h high-resolut ion CT will improve pat ient out comes.
Whi ch of the fol l owi ng cancer screeni ng end poi nts i s l east affected by bi as?
(A) Case-fat alit y rat io
(B) Incidence of early-st age cancer
(C) Incidence of lat e-st age cancer
(D) Lung cancer-specific mort alit y
(E) Survival of pat ient s diagnosed wit h cancer
Item 9 [Advanced]
A 68-year-old woman is evaluat ed during a rout ine examinat ion. She st at es t hat last year she had a painful rash on t he right side of her back t hat was self-limit ed. She t akes no
medicat ions and has no allergies.
Vit al signs are normal, and t he physical examinat ion is unremarkable. Complet e blood count , liver enzymes, and serum chemist ry st udies are all normal. She is scheduled t o
receive her annual influenza vaccinat ion t oday.
Whi ch of the fol l owi ng i s the most appropri ate vacci nati on strategy for thi s pati ent?
(A) Zost er vaccinat ion if negat ive for varicella ant ibodies
(B) Zost er vaccinat ion if posit ive for varicella ant ibodies
(C) Zost er vaccinat ion now
(D) Zost er vaccinat ion not indicat ed
Item 10 [Advanced]
A 30-year-old man is evaluat ed in t he emergency depart ment for a left foot injury t hat occurred 2 days ago during a camping t rip. A small wood splint er became impaled in
t he plant ar surface of his left foot . The pat ient removed t he splint er and hiked home yest erday. He t hen not ed mild pain and eryt hema surrounding t he punct ure sit e. He
report s no fever or significant pain over t he injury area. The pat ient 's elect ronic medical record indicat es t hat he complet ed t he t et anus vaccinat ion series and received a
t et anus boost er 8 years ago. He has never received t he t et anus-dipht heria t oxoid and acellular pert ussis (Tdap) vaccine. He has no drug allergies.
On physical examinat ion, vit al signs are normal. There is t enderness and eryt hema around t he wound sit e, and t here is a small amount of purulent drainage. There is no
foreign body in t he wound.
The wound is cleaned, and appropriat e ant ibiot ic t herapy is prescribed.
Whi ch of the fol l owi ng i s the most appropri ate tetanus preventi on strategy for the pati ent?
(A) Tdap vaccine
(B) Tdap vaccine and t et anus immune globulin
(C) Tet anus immune globulin
(D) No t et anus boost er is required
Item 11 [Basic]
A 19-year-old asympt omat ic woman is evaluat ed at a rout ine annual physical examinat ion. The pat ient st at es she is not sexually act ive and has not engaged in prior sexual
act ivit y. She has a boyfriend whom she has dat ed for t he past year. She has no pert inent family hist ory or known drug allergies and t akes no medicat ions. She has not received
a human papillomavirus vaccine.
Result s of t he physical examinat ion, including a breast and pelvic examinat ion, are normal.
Whi ch of the fol l owi ng i s the most appropri ate opti on for preventi on of human papi l l omavi rus i nfecti on for thi s pati ent?
(A) Human papillomavirus (HPV) vaccine at age 21 years
(B) HPV vaccine at onset of sexual act ivit y
(C) HPV vaccine at t ime of HPV seroconversion
(D) HPV vaccine now
Item 12 [Basic]
A 52-year-old man is evaluat ed during a rout ine examinat ion t hat includes a discussion of healt h maint enance issues. Aft er discussing screening for colorect al cancer, he
refuses colonoscopy. He is willing t o consider ot her opt ions for screening and st at es t hat if an abnormalit y is found, he would be willing t o undergo colonoscopy. There is no
family hist ory of colorect al cancer and no previous colonoscopy. On physical examinat ion, vit al signs and t he heart , lungs, and abdomen are normal.
Whi ch of the fol l owi ng i s the most appropri ate col orectal cancer screeni ng strategy for thi s pati ent?
(A) Annual home fecal occult blood t est ing
(B) Annual office rect al examinat ion and fecal occult blood t est ing
(C) Double-cont rast barium enema every 10 years
(D) Flexible sigmoidoscopy every 10 years
Item 13 [Basic]
A 57-year-old woman is evaluat ed as a new pat ient . She is asympt omat ic and has no significant medical hist ory. Her fat her died of a myocardial infarct ion at age 71 years,
and her 81-year-old mot her is alive and healt hy. There is no family hist ory of cancer.
On physical examinat ion, vit al signs and general physical examinat ion are normal. Laborat ory result s are all wit hin normal limit s.
Whi ch of the fol l owi ng i s an appropri ate screeni ng strategy for col on cancer i n thi s pati ent?
(A) Annual digit al rect al examinat ion
(B) Colonoscopy every 10 years
(C) Double-cont rast barium enema every 3 years
(D) Flexible sigmoidoscopy every 10 years
Item 14 [Basic]
A 69-year-old man is evaluat ed for syncope t hat occurred t his morning while walking wit h his wife. Before t he event , he had no palpit at ions, light headedness, or diaphoresis.
His wife report s t hat he suddenly fell t o t he ground, st riking his face, and was very pale. He regained consciousness aft er about 10 seconds. On regaining consciousness, he was
not confused and did not experience bowel or bladder incont inence, t ongue bit ing, chest pain, or short ness of breat h. His medical hist ory is significant for hypert ension and
coronary art ery disease requiring percut aneous coronary int ervent ion 1 year ago. His medicat ions are carvedilol, simvast at in, aspirin, and lisinopril.
On physical examinat ion, t emperat ure is 36.6C (97.8F), blood pressure is 134/72 mm Hg sit t ing and 132/70 mm Hg aft er 3 minut es of st anding, pulse rat e is 75/min and
regular, and respirat ion rat e is 12/min. The cardiopulmonary and neurologic examinat ions are normal.
Elect rocardiogram shows an old ant erior wall myocardial infarct ion wit h evidence of new ischemic changes.
(A) Ort host at ic hypot ension
(B) Seizure
(C) Sit uat ional syncope
Item 15 [Basic]
A 53-year-old woman is evaluat ed for syncope. She became dizzy aft er get t ing out of bed t his morning and t hen briefly lost consciousness wit hout injury. She had no
diaphoresis, palpit at ions, or chest pain before t he event . She had no incont inence, t ongue bit ing, or post syncopal confusion. She has recent ly experienced dizziness on rising
t oo quickly from a chair. She has a 15-year hist ory of diabet es for which she t akes insulin glargine. She has a 3-year hist ory of peripheral neuropat hy and microalbuminuria.
In addit ion t o insulin, she t akes lisinopril.
On physical examinat ion, t emperat ure is 37.1C (98.9F), blood pressure is 137/78 mm Hg, pulse rat e is 82/min, and respirat ion rat e is 14/min. Cardiopulmonary and vascular
examinat ions are normal. She has significant ly decreased sensat ion in her lower ext remit ies bilat erally t o her midshins. The remainder of t he neurologic examinat ion is
normal.
Fingerst ick blood glucose measurement is 140 mg/dL (7.8 mmol/L).
(A) 24-Hour ambulat ory elect rocardiography
(B) Head CT
(C) Ort host at ic blood pressure measurement s
(D) Ult rasound of t he carot id art eries
Item 16 [Basic]
A 36-year-old woman is evaluat ed in t he emergency depart ment aft er collapsing suddenly while wait ing in line at a count y fair on a hot summer day. The pat ient st at es she
felt nauseat ed and became diaphoret ic and light headed. She sat on t he ground and t hen lost consciousness. According t o her son, she was unconscious for less t han a minut e,
exhibit ed some t wit ching movement s when she first lost consciousness, but had no incont inence, confusion, or furt her sympt oms on regaining consciousness.
On physical examinat ion, t emperat ure is normal, blood pressure is 142/80 mm Hg supine and 138/78 mm Hg st anding, pulse rat e is 84/min supine and 92/min st anding, and
respirat ion rat e is 14/min. Cardiac and neurologic examinat ion findings are normal. An elect rocardiogram is normal.
(A) Echocardiogram
(B) Elect roencephalogram
(C) Exercise st ress t est
(D) Tilt -t able t est ing
(E) No furt her t est ing
Item 17 [Advanced]
A 57-year-old man is evaluat ed in t he emergency depart ment aft er experiencing an episode of syncope while st anding. The pat ient has had t wo ot her episodes of syncope in
t he past 6 mont hs, bot h under 10 seconds in durat ion and occurring when sit t ing. There is no prodrome t o t he syncopal episodes. He has no palpit at ions and no seizure
act ivit y and denies confusion following t he event . He has no cardiac hist ory and t akes no medicat ions.
On physical examinat ion, blood pressure is 128/75 mm Hg wit h no ort host at ic changes, and pulse is 56/min. He has a forehead bruise. Result s of t he cardiac and neurologic
examinat ions are normal.
An elect rocardiogram shows left axis deviat ion, first -degree at riovent ricular block, and right bundle branch block (t rifascicular block). An echocardiogram shows normal
valves, normal left vent ricle size and funct ion, and normal aort ic root size.
(B) Int ermit t ent complet e heart block
(C) Neurocardiogenic syncope
Item 18 [Advanced]
A 76-year-old man is evaluat ed for a syncope event t hat occurred a few weeks ago. He was st anding in line at t he grocery st ore and lost consciousness wit hout any preceding
sympt oms. He est imat es t hat t he durat ion of t he episode was less t han a minut e, and he drove himself home. He has had t wo ot her syncopal event s in t he last 3 years, one
while sit t ing, and one during a walk. He is ot herwise asympt omat ic wit h no chest pain, dyspnea, ort hopnea, edema, or palpit at ions. He is healt hy and act ive and he t akes no
medicat ions.
On physical examinat ion, his blood pressure is 140/85 mm Hg wit hout ort host at ic changes and his pulse rat e is 82/min. Cardiopulmonary examinat ion is normal.
The elect rocardiogram and echocardiogram are bot h normal.
Whi ch of the fol l owi ng di agnosti c tests i s most l i kel y to yi el d useful resul ts for thi s pati ent?
(A) Elect rophysiology st udy
(B) Event monit oring
(C) Implant able loop recorder
(D) 24-Hour ambulat ory monit oring
Item 19 [Advanced]
A 70-year-old woman is evaluat ed because of depressed mood, anhedonia, decreased appet it e, impaired sleep, and decreased energy. Alt hough t he pat ient feels somewhat
hopeless about t he fut ure, she adamant ly st at es t hat she would never t ake her own life. Her judgment appears int act . Medical hist ory is unremarkable, and she has not had
previous episodes of depression. She is t aking no medicat ions. Findings on physical examinat ion and laborat ory evaluat ion, including t hyroid funct ion t est ing and vit amin B
12
measurement , are unremarkable.
Sert raline, 50 mg/d, is begun. The pat ient ret urns for a follow-up visit 5 weeks lat er and report s t hat she is t olerat ing t he medicat ion well but has no significant change in
sympt oms, which is validat ed wit h a st andardized sympt om assessment t ool. The sert raline is t herefore increased t o 100 mg/d. Six weeks lat er, she again report s no side
effect s and no improvement .
Whi ch of the fol l owi ng i s most appropri ate at thi s ti me?
(A) Add met hylphenidat e
(B) Discont inue sert raline and begin cit alopram
(C) Reassess in 4 weeks
(D) Refer for elect roconvulsive t herapy
Item 20 [Basic]
A 25-year-old woman is evaluat ed for a 2-mont h hist ory of feeling guilt y, "down", and hopeless aft er her fiance ended t heir engagement . She is spending less t ime wit h
friends, rest rict ing previously enjoyable social act ivit ies, and having difficult y concent rat ing. During t he past week, she has been t hinking about ending her life by cut t ing her
wrist s. She lives at home wit h her mot her and t wo sist ers, who have expressed feelings of support and willingness t o help. She has no hist ory of previous suicide at t empt s.
Medical hist ory is unremarkable, and she t akes no medicat ions.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al care for thi s pati ent?
(A) Corroborat e her account by cont act ing her former fiance
(B) Reassurance and careful follow-up and observat ion
(C) St art an ant idepressant and follow up in 2 weeks
(D) Urgent ment al healt h referral
Item 21 [Advanced]
A 72-year-old woman is evaluat ed for a 4-mont h hist ory of insomnia wit h difficult y falling asleep. The pat ient was t he major caret aker for her husband, who had advanced
heart failure and died suddenly 4 mont hs ago. She has lost 3.6 kg (8 lb) and does not have much of an appet it e. The pat ient used t o volunt eer at t he hospit al, but she does not
enjoy going t here any longer. She also does not have much energy. The pat ient is t earful and says t hat nearly everyt hing reminds her of her husband. Medical hist ory is
ot herwise unremarkable. Physical examinat ion findings are unremarkable.
(A) Begin dext roamphet amine
(B) Begin mirt azapine at bedt ime
(C) Begin zolpidem at bedt ime
(D) Reassure t he pat ient
Item 22 [Basic]
A 22-year-old woman is evaluat ed because of decreased energy, increased sleep, weight gain, and feeling depressed. The pat ient always did very well academically, but since her
graduat ion from college several mont hs ago, she has been unable t o find a job so she had t o move back in wit h her parent s. She st at es t hat her life is not working out well but
denies t hinking about suicide. She previously had periods of unlimit ed energy when she could st ay up all night t o do schoolwork or socialize wit hout ever feeling t ired. During
some of t hese periods, she had several sexual part ners, somet imes wit h men she met for t he first t ime in a bar, and occasionally did not use condoms.
Medical hist ory is unremarkable. She has never been t reat ed for depression and t akes no medicat ions, including oral cont racept ive agent s. Findings on physical examinat ion
are unremarkable.
(A) At t ent ion-deficit /hyperact ivit y disorder
(B) Bipolar disorder
(C) Borderline personalit y disorder
(D) Generalized anxiet y disorder
Item 23 [Basic]
A 48-year-old man is brought by his wife for evaluat ion. He t ypically drinks 1 lit er of vodka daily and has done so for more t han 2 years, but is now t rying t o quit . His last
drink was almost 24 hours ago. He feels anxious and nervous and admit s t o having audit ory hallucinat ions. He had a seizure previously when he st opped drinking abrupt ly. He
has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, t emperat ure is 37.2C (99.0F), blood pressure is 170/100 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 18/min. He is t remulous and has
difficult y focusing. The remainder of t he examinat ion is normal. On t he Clinical Inst it ut e Wit hdrawal Assessment Scale for Alcohol, Revised, t he pat ient scores 16 point s.
Arrangement s are made t o admit t he pat ient t o t he hospit al.
Whi ch of the fol l owi ng medi cati ons shoul d be admi ni stered now?
(A) At enolol
(B) Clonidine
(C) Haloperidol
(D) Lorazepam
(E) Phenyt oin
Item 24 [Advanced]
A 28-year-old man who is known t o use cocaine is found in a parking lot , t hrowing himself against cars. En rout e t o t he hospit al, he has a generalized t onic-clonic seizure
t hat last s approximat ely 3 minut es.
His t emperat ure is 38.8C (101.8F), pulse rat e is 120/min, respirat ion rat e is 18/min, and blood pressure is 170/98 mm Hg. He is agit at ed, diaphoret ic, and voicing paranoid
t hought s. Rest raint s are applied, and int ravenous access is obt ained.
Whi ch one of the fol l owi ng agents shoul d be admi ni stered to thi s pati ent at thi s ti me?
(A) Haloperidol
(B) Lorazepam
(C) Phenyt oin
(D) Propranolol
Item 25 [Advanced]
A 48-year-old man wit h a long hist ory of alcohol abuse is seen for ongoing care aft er an inpat ient st ay for alcohol wit hdrawal. This is his t hird episode of acut e
det oxificat ion, wit h t he longest period of abst inence being 4 mont hs. He does not have any current sympt oms of depression and st at es t hat he is not using any illicit drugs or
prescript ion medicat ions. His last alcohol int ake was 2 weeks before his visit t o t he office, and he is now enrolled in an alcohol t reat ment program.
Whi ch of the fol l owi ng pharmacol ogi c agents i s the best adjunct to thi s pati ent's treatment?
(A) Buspirone
(B) Diazepam
(C) Disulfiram
(D) Nalt rexone
(E) Paroxet ine
Item 26 [Advanced]
A 46-year-old man is evaluat ed aft er being found unresponsive in a cit y park. Needles and syringes are found in his possession.
The pat ient is difficult t o arouse. Temperat ure is 35.5C (96.0F), blood pressure is 130/80 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 8/min. Oxygen sat urat ion
wit h t he pat ient breat hing ambient air is less t han 80%. Fresh needle marks are found on his arms. He has decreased bibasilar breat h sounds; heart sounds are normal. His pupils
are dilat ed. Neurologic examinat ion reveals no focal abnormalit ies. The pat ient 's airway is prot ect ed.
Art erial blood gases (ambient air)
pH 7.08
PCO
2
80 mm Hg (10.6 kPa)
PO
2
40 mm Hg (5.3 kPa)
Calculat ed alveolar-art erial difference Normal
Treat ment is st art ed wit h 100% oxygen by face mask.
Whi ch of the fol l owi ng i s the most appropri ate i ntravenous anti dote for thi s pati ent?
(A) Diazepam
(B) Fomepizole
(C) Naloxone
(D) Sodium t hiosulfat e
Item 27 [Basic]
A 58-year-old man is evaluat ed as a new pat ient . He report s t hat he is healt hy, he drinks one mart ini before dinner, and has wine wit h dinner. There is no family hist ory of
alcohol problems. He has recent ly ret ired.
Whi ch of the fol l owi ng i s the best al cohol screeni ng test for thi s pati ent?
(A) Alanine and aspart at e aminot ransferase concent rat ions
(B) CAGE quest ionnaire
(C) Complet e blood count and mean corpuscular volume
(D) Et hanol level
Item 28 [Advanced]
A 65-year old woman is evaluat ed for an 8-mont h hist ory of low back pain due t o lumbar spinal st enosis confirmed by MRI. The pat ient report s daily sympt oms of pain and
bilat eral t ingling in her t highs wit h difficult y walking. She has no bowel or bladder incont inence. She has t aken acet aminophen and ibuprofen wit h minimal relief of
sympt oms, and despit e physical t herapy, her sympt oms have worsened. Previously she was a very act ive woman and her sympt oms are now impairing her lifest yle. She is
ot herwise healt hy and t akes no medicat ions.
On physical examinat ion, vit al signs are normal. Physical examinat ion is significant for absent ankle reflexes and foot drop bilat erally. The remainder of t he physical
(A) Elect romyography and nerve conduct ion st udy
(B) Epidural st eroid inject ion
(C) Spinal t ract ion
(D) Surgery
Item 29 [Advanced]
A 58-year old man is evaluat ed in t he emergency depart ment for severe low back pain of 3 week's durat ion. The pat ient report s no recent t rauma but has felt feverish. He has
no radicular sympt oms and report s no bowel or bladder incont inence. He is a current smoker and act ive user of illicit int ravenous drugs.
On physical examinat ion, t emperat ure is 38.9C (102.0F), blood pressure is 140/90 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 14/min. Mult iple needle marks are
not ed on t he arms and legs. He has t enderness over t he first and second lumbar vert ebrae. Upper and lower ext remit y mot or st rengt h and sensat ion are normal as are t he
t endon reflexes. Anal sphinct er t one is normal. Lower ext remit y and perianal sensat ion is int act .
Leukocyt e count is 8000/L (8 10
9
/L). Eryt hrocyt e sediment at ion rat e is 110 mm/h.
(A) Empiric ant ibiot ic t herapy
(B) Spine CT
(C) Spine MRI
(D) Spine x-ray
Item 30 [Basic]
A 42-year-old man is evaluat ed for low back pain t hat began aft er he lift ed a box 5 days ago. The pain is moderat ely severe, and almost any movement makes it worse. Lying
down result s in some, but not complet e, relief. He report s t hat he has had no t rouble urinat ing. He has no ot her sympt oms and is ot herwise healt hy.
Physical examinat ion reveals t enderness over t he L4 paravert ebral musculat ure bilat erally. His gait is slow because of t he pain. Result s of a st raight leg raising t est are normal.
There is no mot or weakness or sensory loss, including perineal sensat ion. Deep t endon reflexes are normal bilat erally.
Whi ch of the fol l owi ng i s the best i ni ti al management opti on?
(A) Acet aminophen
(B) MRI of t he lumbar spine
(C) Plain radiographs of t he lumbar spine
(D) St rict bed rest
Item 31 [Basic]
A 70-year-old man is evaluat ed because of increasing new-onset midback pain t hat is worse at night , int erferes wit h his sleep, and does not improve wit h NSAIDs. The pat ient
underwent radical prost at ect omy for prost at e cancer 2 years ago. He has had urinary incont inence since surgery, which has significant ly increased over t he past few weeks.
Physical examinat ion findings include t enderness over t he midt horacic vert ebrae, mild flexor weakness, and hyperreflexia of t he lower ext remit ies.
Whi ch of the fol l owi ng di agnosti c studi es shoul d be done next?
(A) Bone scan
(B) MRI of t he brain
(C) MRI of t he t horacolumbar spine
(D) Plain radiographs of t he t horacic spine
Item 32 [Advanced]
A 27-year-old man is evaluat ed for a 6-mont h hist ory of cough, which is worse at night and aft er exposure t o cold air. His cough oft en is brought on by his t aking a deep
breat h or laughing. He does not have post nasal drip, wheezing, or heart burn. He has a st rong family hist ory of allergies. He received no benefit from a previous 3-mont h t rial
of gast ric acid suppression t herapy, int ranasal cort icost eroids, and an ant ihist amine-decongest ant combinat ion.
Physical examinat ion findings, a chest radiograph, and spiromet ry result s are normal.
Whi ch of the fol l owi ng i s most l i kel y to provi de a di agnosi s of thi s pati ent's chroni c cough?
(A) Bronchoscopy
(B) CT of t he chest
(C) CT of t he sinuses
(D) Esophageal pH monit oring over 24 hours
(E) Trial of inhaled albut erol
Item 33 [Basic]
A 52-year-old man is evaluat ed for a daily cough for t he past 6 mont hs. It occurs t hroughout t he day and occasionally at night , but he does not not ice any specific t riggers.
There is occasional product ion of small amount s of whit e sput um but no hemopt ysis. He does not have any known allergies, has no new pet s or exposures, and does not
smoke. He does have nasal discharge. He has not not iced any wheezing and has no hist ory of ast hma. He has no sympt oms of heart burn. He has had no fever, weight loss, or
foreign t ravel, and t akes no medicat ions.
Vit al signs are normal. There is a cobblest one appearance of t he oropharyngeal mucosa but no mucus dripping down t he oropharynx. Lungs are clear t o auscult at ion. A chest
radiograph is normal.
(A) Ant ihist amine/decongest ant combinat ion
(B) CT scan of chest
(C) Inhaled flut icasone
(D) Prot on-pump inhibit or
(E) Pulmonary funct ion t est ing
Item 34 [Basic]
A 48-year-old woman is evaluat ed for a cough t hat has last ed for 3 mont hs. She describes t he cough as occurring daily, nonproduct ive, and wit hout hemopt ysis. She has
experienced no associat ed dyspnea, wheezing, fever, weight loss, night sweat s, or recent illness. She has not t raveled recent ly or been exposed t o anyone else who has been ill.
She has never smoked. She was diagnosed wit h essent ial hypert ension 6 mont hs ago and has t aken lisinopril daily since her diagnosis.
Physical examinat ion is unremarkable. A chest radiograph is normal.
Whi ch of the fol l owi ng i s the most appropri ate management opti on for thi s pati ent at thi s ti me?
(A) Discont inue t he lisinopril
(B) Order a chest CT
(C) Order spiromet ry
(D) St art an ant ihist amine/decongest ant combinat ion
(E) St art a prot on-pump inhibit or
Item 35 [Basic]
A 59-year-old man is evaluat ed because of a chronic morning cough product ive of clear or yellow sput um t hat has been blood-t inged for t he past 2 weeks. He has had no fever
or weight loss. He has smoked 1.5 packs of cigaret t es daily for t he past 35 years.
On physical examinat ion, blood pressure is 148/74 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 20/min. Chest examinat ion reveals decreased breat h sounds t hroughout
t he t horax but no ot her sympt oms. Ot her t han evidence of hyperinflat ion, a chest radiograph is normal. The rest of t he physical examinat ion is unremarkable.
(A) Chest CT
(B) Cyt ologic evaluat ion and immunost aining of sput um
(C) Pulmonary funct ion t est ing
(D) Follow-up in 6 mont hs
Item 36 [Basic]
A healt hy 42-year-old man has a 15-day hist ory of a cough t hat was init ially associat ed wit h rhinorrhea, nasal congest ion, and a sore t hroat . All sympt oms have resolved
except t he cough, which is product ive of purulent sput um. He has not had fever, malaise, dyspnea, pleurit ic chest pain, myalgia, paroxysms of coughing, or post t ussive
vomit ing. The pat ient 's medical hist ory is unremarkable, he has never smoked cigaret t es, and he t akes no medicat ions.
On physical examinat ion, vit al signs, including t emperat ure, are normal. There is no pharyngeal eryt hema or exudat e and no lymphadenopat hy. The lungs are clear t o
auscult at ion.
Whi ch of the fol l owi ng i s the best i ni ti al management?
(A) Albut erol inhaler
(B) Azit hromycin
(C) Chest radiograph
(D) Nasopharyngeal swab for influenza virus cult ure
(E) Sympt omat ic t reat ment
Item 37 [Basic]
A 66-year-old woman wit h chronic obst ruct ive pulmonary disease is evaluat ed because of chronic cough and dyspnea. She current ly uses a long-act ing bronchodilat or t wice
daily, an inhaled cort icost eroid t wice daily, iprat ropium four t imes per day, and albut erol four t o six t imes per day. She smokes 1 pack of cigaret t es daily.
On physical examinat ion, her vit al signs are normal. Her oxygen sat urat ion at rest and wit h exert ion is 94%. She has diminished breat h sounds, a prolonged expirat ory phase,
and no wheezes. Her cardiac examinat ion is normal. Chest radiograph reveals hyperinflat ion, increased ret rost ernal airspace, and flat t ened hemidiaphragms bilat erally.
Whi ch of the fol l owi ng shoul d be done to manage thi s pati ent's cough and dyspnea?
(A) Help her quit smoking
(B) Increase t he dosage of t he inhaled cort icost eroid
(C) Increase t he dosage of t he long-act ing bronchodilat or
(D) St art supplement al oxygen
Item 38 [Advanced]
A 54-year-old woman is evaluat ed because of a chronic cough and dyspnea on exert ion of 6 years' durat ion. She has smoked 1.5 packs of cigaret t es daily for 38 years. On
physical examinat ion, she has prolonged expirat ory t ime and wheezes. Spiromet ry shows a FEV
1
of 2.2 L (66% of predict ed) and an FEV
1
/FVC rat io of 0.65.
If she i s successful i n stoppi ng her ci garette smoki ng, whi ch of the fol l owi ng changes i n l ung functi on can be expected?
(A) Improvement in lung funct ion and a decrease in t he rat e of decline
(B) Improvement in lung funct ion, but no decrease in t he rat e of decline
(C) No improvement in lung funct ion, but a decrease in t he rat e of decline
(D) No improvement in lung funct ion or decrease in t he rat e of decline
Item 39 [Basic]
A 49-year-old woman is evaluat ed for a rout ine physical examinat ion. She has a sedent ary lifest yle and does not exercise. She has not experienced chest pain or dyspnea. She
is a current smoker wit h a 32-pack-year hist ory. She t akes no medicat ions. Her fat her had a myocardial infarct ion at age 58 years.
On physical examinat ion, her blood pressure is 132/85 mm Hg and her pulse rat e is 86/min. Her BMI is 31. The remainder of t he physical examinat ion is normal.
Whi ch of the fol l owi ng l i festyl e modi fi cati ons wi l l have the greatest i mpact on reduci ng thi s pati ent's ri sk of cardi ovascul ar di sease?
(A) Aerobic exercise 30 minut es 3 or 4 days weekly
(B) Cessat ion of cigaret t e smoking
(C) Sodium-rest rict ed diet
(D) Weight loss
Item 40 [Advanced]
A 52-year-old woman is evaluat ed at a rout ine appoint ment and seeks advice on smoking cessat ion. She smokes one and one half packs of cigaret t es daily and want s help t o
st op. She has t ried t o st op smoking on t hree previous occasions, each t ime using nicot ine replacement t herapy, and she would like t o t ry somet hing different . She has a
seizure disorder t hat is well cont rolled on valproat e.
The pat ient is provided wit h a brief smoking cessat ion counseling int ervent ion.
Whi ch of the fol l owi ng i s the most appropri ate pharmacol ogi c therapy?
(A) Bupropion
(B) Nort ript yline
(C) Sert raline
(D) Varenicline
Item 41 [Advanced]
A 43-year-old woman is evaluat ed for obesit y. She has been unsuccessful at mult iple at t empt s at weight loss, including several diet s, meet ing wit h a diet ician, an exercise
program, and a t rial of orlist at . Medical hist ory is remarkable for poorly cont rolled t ype 2 diabet es mellit us, hypert ension, and hyperlipidemia. Medicat ions are lisinopril,
simvast at in, aspirin, met formin, and insulin glargine.
On physical examinat ion, t emperat ure is normal, blood pressure is 130/70 mm Hg, pulse rat e is 79/min, and respirat ion rat e is 16/min. BMI is 42. Ot her t han changes
associat ed wit h obesit y, her physical examinat ion is normal.
Hemoglobin A
1c
is 9% and LDL cholest erol is 100 mg/dL (2.6 mmol/L).
Whi ch of the fol l owi ng i s the most appropri ate management for her obesi ty?
(A) A regular walking program
(B) Bariat ric surgery
(C) Low carbohydrat e diet (Medit erranean st yle diet )
(D) Low fat diet
Item 42 [Advanced]
A 41-year-old asympt omat ic man is evaluat ed during a rout ine physical examinat ion. His only medical problem is obesit y for which he has never sought t reat ment . Medical
hist ory is ot herwise unremarkable, and he t akes no medicat ions.
On physical examinat ion, t emperat ure is normal, blood pressure is 127/79 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 14/min. BMI is 39. Waist circumference is
112.2 cm (44 in). The remainder of t he physical examinat ion is normal.
The pat ient is counseled regarding his obesit y.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al eval uati on for thi s pati ent?
(A) Complet e blood count and serum elect rolyt es
(B) Elect rocardiogram and chest x-ray
(C) Fast ing glucose, lipid profile, and serum creat inine
(D) Sleep st udy and pulse oximet ry
Item 43 [Advanced]
A 44-year-old woman is evaluat ed for obesit y. She has been t rying t o lose weight over t he past 3 years. The pat ient has t ried several diet s and has also at t empt ed t o increase
her physical act ivit y. Medical hist ory is remarkable for t ype 2 diabet es mellit us, hypert ension, and hyperlipidemia. Current medicat ions are lisinopril, simvast at in, aspirin,
met formin, and glipizide.
On physical examinat ion, t emperat ure is normal, blood pressure is 138/90 mm Hg, pulse rat e is 72/min, and respirat ion rat e is 14/min. BMI is 30. Her hemoglobin A
1c
is
6.9%.
Whi ch of the fol l owi ng i s the most appropri ate management opti on?
(A) Add orlist at
(B) Add sibut ramine
(C) Discont inue glipizide, init iat e insulin glargine
(D) Refer for bariat ric surgery
Item 44 [Advanced]
A 41-year-old woman is evaluat ed for persist ent nausea and vomit ing aft er laparoscopic gast ric bypass surgery 6 weeks ago for morbid obesit y. The pat ient somet imes not ices
dull epigast ric discomfort aft er t he vomit ing. She also has early sat iet y. She has lost 4.5 kg (10 lb) since her surgery. She t akes naproxen for ost eoart hrit is.
On physical examinat ion, vit al signs are normal. BMI is 43. There is no abdominal discomfort t o deep palpat ion.
Complet e blood count , hepat ic enzyme levels, and serum chemist ry st udies are normal.
Whi ch of the fol l owi ng management opti ons i s the best choi ce for thi s pati ent?
(A) Omeprazole
(B) Right upper quadrant ult rasound
(C) Surgical laparot omy
(D) Upper endoscopy
Item 45 [Advanced]
A 60-year-old woman is evaluat ed for an unexplained weight loss during 1 year. The pat ient feels well and report s no fevers, night sweat s, dysphagia, change in bowel habit s,
blood in her st ool, joint pain, rash, or short ness of breat h. She report s no depressed mood. She works as an account ant . She does not smoke or drink alcohol. Result s of age-
and sex-appropriat e cancer screening t est s performed 6 mont hs ago were normal.
On physical examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 128/76 mm Hg, pulse rat e is 84/min, and respirat ion rat e is 16/min. BMI is 23. Her weight is 4.1
kg (9 lb) less t han it was 12 mont hs ago. The remainder of t he physical examinat ion is normal.
C-react ive prot ein 0.1 mg/dL (1 mg/L)
Lact at e dehydrogenase 130 U/L
Thyroid-st imulat ing hormone 3 U/mL (3 mU/L)
Chest x-ray and abdominal ult rasound examinat ions are normal.
Whi ch of the fol l owi ng i s the most appropri ate management step?
(A) Begin diet ary supplement s
(B) Measure ant inuclear ant ibodies
(C) Order chest CT
(D) Order upper endoscopy
(E) Re-evaluat e in 6 mont hs
Item 46 [Basic]
A 50-year-old man is evaluat ed for unint ent ional weight loss during a 1 year period. His appet it e and energy level are reduced. He has lost int erest in his usual act ivit es, which
he previously enjoyed. He also report s waking up several t imes per night . He report s no fevers, night sweat s, fat igue, dysphagia, change in bowel habit s, blood in his st ool,
joint pain, polydipsia, or short ness of breat h. He works as a general cont ract or but has been out of work for several mont hs. He does not smoke or drink alcohol. Result s of
age- and sex-appropriat e cancer screening t est s performed 6 mont hs ago were normal.
On physical examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 120/74 mm Hg, pulse rat e is 74/min and regular, and respirat ion rat e is 16/min. BMI is 25.7. His
weight t oday is 7.3 kg (16 lb) less t han it was 1 year ago. The remainder of t he physical examinat ion is normal.
Fast ing glucose 98 mg/dL (5.4 mmol/L)
C-react ive prot ein 0.1 mg/dL (1 mg/L)
Whi ch of the fol l owi ng i s the most l i kel y cause of the pati ent's wei ght l oss?
(A) Colon cancer
(B) Depression
(C) Prost at e cancer
(D) Type 2 diabet es
Item 47 [Advanced]
A 65-year-old woman is seen for evaluat ion of unint ent ional weight loss. Her medical hist ory is significant for depression t hat began 7 mont hs ago and was t reat ed wit h
bupropion, which result ed in a rapid remission of sympt oms. This was her first episode of depression. The pat ient now report s loss of appet it e for several mont hs but cannot
precisely pinpoint when t he sympt om began. She has never smoked cigaret t es, has no pulmonary or gast roint est inal sympt oms, and has no ot her medical problems.
Bupropion is her only medicat ion, and she t akes no supplement s.
On examinat ion, her weight has decreased by 4 kg (9 lb) from her baseline weight of 50 kg (110 lb) measured 6 mont hs ago. No lymphadenopat hy is present , and abdominal
examinat ion findings are normal.
Result s of laborat ory st udies are normal, including a complet e blood count , eryt hrocyt e sediment at ion rat e det erminat ion, liver chemist ry t est s, and measurement s of t hyroid-
st imulat ing hormone level, elect rolyt e levels, and serum creat inine level. A Pap t est , colonoscopy, and mammography performed 1 year ago were negat ive for cancer.
What i s the most appropri ate next management step?
(A) CT of t he chest , abdomen, and pelvis
(B) Discont inuat ion of t he bupropion
(C) Init iat ion of an appet it e st imulant , such as megest rol acet at e
(D) Upper endoscopy
Item 48 [Advanced]
A 70-year-old woman is evaluat ed for a 6-mont h hist ory of fat igue, an unint ent ional weight loss of 4.4 kg (10 lb), an increase in chronic cough wit h sput um product ion, and a
decrease in exercise capacit y. The pat ient has a 40-pack-year hist ory of cigaret t e smoking but st opped smoking 10 years ago when chronic obst ruct ive pulmonary disease was
diagnosed. She has no ot her sympt oms. Her medicat ions are albut erol as needed, an inhaled cort icost eroid, and salmet erol. She has been on st able dosages of t hese drugs for 18
mont hs. Result s of age- and sex-appropriat e cancer screening t est s performed 6 mont hs ago were normal.
On physical examinat ion, t emperat ure is 37.5C (99.5F), blood pressure is 128/76 mm Hg, pulse rat e is 94/min and regular, respirat ion rat e is 16/min, and BMI is 20. A pulse
oximet ry reading is 60% on ambient air. Heart sounds are dist ant , and breat h sounds are diminished bilat erally. There are no abdominal masses or organomegaly and no
peripheral edema.
Spiromet ry shows an FEV
1
of 40% of predict ed and an FEV
1
t o FVC rat io of 45%. A chest radiograph shows only hyperinflat ion.
Whi ch of the fol l owi ng i s the most l i kel y reason for thi s pati ent's wei ght l oss?
(A) Breast cancer
(B) Cervical cancer
(C) Chronic obst ruct ive pulmonary disease
(D) Colon cancer
Item 49 [Advanced]
A 42-year-old woman is evaluat ed for a 6-mont h hist ory of heavy menst rual bleeding. She has been menst ruat ing for t he last 8 days and is st ill going t hrough 10 pads or more
a day wit h frequent clot s. She has fat igue but no dizziness. Previous evaluat ion for t his problem has included normal t hyroid funct ion and prolact in t est ing. She has no ot her
medical problems and t akes no medicat ions. Pelvic ult rasonography has demonst rat ed a large post erior submucosal fibroid. A surgical t reat ment is planned in 2 weeks.
On examinat ion, vit al signs are normal. Her abdominal examinat ion is benign, and t he pelvic examinat ion reveals a moderat e amount of blood in t he vaginal vault .
Hemoglobin level is 10.5 g/dL (105 g/L). Pregnancy t est is negat ive.
(A) Emergency surgery
(B) Int ravenous est rogen
(C) Once daily oral cont racept ives
(D) Oral medroxyprogest erone acet at e
(E) Reevaluat ion in 1 week
Item 50 [Basic]
A 21-year-old woman is evaluat ed for a 7-year hist ory of oligomenorrhea and slowly progressive hirsut ism. Menses began at age 14 years and were always irregular. She has
gained weight at a rat e of approximat ely 4.5 kg (10 lb) per year. Her facial hair has become progressively t hicker since age 18 years, and she now menst ruat es only t hree t o
four t imes per year. She is sexually act ive but does not want t o become pregnant at t his t ime. Family hist ory is noncont ribut ory, and she t akes no medicat ions.
On physical examinat ion, vit al signs are normal, and BMI is 28. Prominent t erminal hairs are not ed on t he upper lip and chin, wit h some on t he upper cheeks and chest ;
t here is t hick hair from t he pubis t o t he umbilicus. Result s of a pelvic examinat ion and Pap smear are normal.
Dehydroepiandrost erone sulfat e 4.3 g/mL (11.6 mol/L)
Human chorionic gonadot ropin Negat ive
17-Hydroxyprogest erone 105 ng/dL (3.1 nmol/L) (normal, <400 ng/dL [12.0 nmol/L])
Prolact in 11 ng/mL (11 g/L)
Test ost erone, t ot al 84 ng/dL (2.9 nmol/L)
A progest in wit hdrawal challenge wit h medroxyprogest erone acet at e result s in a t emporary resumpt ion of menses.
(A) Adrenal t umor
(B) Ovarian t umor
(C) Polycyst ic ovary syndrome
(D) Prolact inoma
Item 51 [Basic]
A 56-year-old woman is evaluat ed for hot flushes t hat have been int erfering wit h her sleep and causing discomfort while at work. She want s some relief from her sympt oms,
which have been persist ent since she experienced menopause 3 years ago. She is a nonsmoker and has no hist ory of t hromboembolic disease and no personal or family hist ory
of cancer.
(A) Black cohosh
(B) Est rogen replacement t herapy
(C) Raloxifene
(D) Red clover
(E) Soy prot ein
Item 52 [Advanced]
A 26-year-old woman is evaluat ed for a 4-mont h hist ory of amenorrhea. Menses began at age 13 years. At age 18 years, t he pat ient was placed on an oral cont racept ive pill
t o cont rol heavy bleeding. She discont inued t he oral cont racept ive pill 4 mont hs ago because she and her husband want t o become pregnant , and she has had no menses since
t hen. There is no family hist ory of infert ilit y or premat ure menopause.
On physical examinat ion, vit al signs are normal, and BMI is 24. There is no acne, hirsut ism, or galact orrhea. Examinat ion of t he t hyroid gland and visual field t est ing yield
normal findings. Pelvic examinat ion findings are also normal. An office pregnancy t est is negat ive.
Follicle-st imulat ing hormone 2 mU/mL (2 U/L)
Prolact in 17 ng/mL (17 g/L)
Thyroxine (T
4
(A) Measurement of t he plasma dehydroepiandrost erone sulfat e level
(B) Measurement of serum est radiol level
(C) MRI of t he pit uit ary gland
(D) Progest in wit hdrawal challenge
Item 53 [Advanced]
A 23-year-old woman is evaluat ed aft er having no menses for 6 mont hs. She began menst ruat ing at age 12 years, and menses have always been regular. The pat ient report s no
recent weight gain, voice change, or facial hair growt h; she says she may even have lost some weight recent ly and t ends t o feel warm. She is not sexually act ive. There is no
family hist ory of infert ilit y or premat ure menopause.
On physical examinat ion, vit al signs are normal; and BMI is 22. She has no acne, hirsut ism, or galact orrhea. Her t hyroid gland is slight ly enlarged. Visual field t est ing yields
normal result s.
Result s of st andard laborat ory st udies are normal, including t hyroid-st imulat ing hormone and free t hyroxine (T
4
) levels; a human chorionic gonadot ropin level is negat ive for
pregnancy.
Whi ch of the fol l owi ng i s the most appropri ate fi rst step i n eval uati on?
(A) Brain MRI
(B) Measurement of serum follicle-st imulat ing hormone and prolact in levels
(C) Measurement of t ot al serum t est ost erone level
(D) Pelvic ult rasonography
Item 54 [Advanced]
A 48-year-old woman present s wit h a hist ory of heavy painless menst rual bleeding for t he past 4 days. Her last period was 20 days ago, but before t hat , her periods had
become more irregular over t he previous 2 years, wit h light er t han usual bleeding.
On physical examinat ion, t he vit al signs are normal. There is no evidence of hypovolemia or conjunct ival pallor. The skin examinat ion is negat ive for ecchymoses and
pet echiae. The bimanual pelvic examinat ion reveals a nont ender, normal-sized, and regular ut erus. Speculum examinat ion reveals a normal-appearing cervix wit h dark blood
in t he cervical os but no ot her abnormalit ies. A Pap smear is performed. A urine pregnancy t est is negat ive.
(A) Begin an oral cont racept ive
(B) Begin est rogen replacement t herapy
(C) Measure serum lut einizing hormone and follicle-st imulat ing hormone
(D) Obt ain an endomet rial biopsy
Item 55 [Basic]
A 56-year-old man is evaluat ed for a fever and a 2-day hist ory of an expanding, well-demarcat ed area of warmt h, swelling, t enderness, and eryt hema on his right foot , leg, and
upper t high. He report s feeling feverish and slight ly nauseat ed, but has not had chills, rigors, or it ching. His medical hist ory is significant for varicose veins and chronic ankle
edema. He t akes no medicat ions.
On physical examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 140/88 mm Hg, and pulse rat e is 100/min. His skin findings are shown (Plat e 2). The remainder
of t he physical examinat ion is normal.
(A) Allergic cont act dermat it is
(B) At opic dermat it is
(C) Cellulit is
(D) Venous st asis dermat it is
Item 56 [Advanced]
A 65-year-old man is evaluat ed for a recurrent , it chy, eryt hemat ous rash t hat involves his eyebrows and cheeks. He has t ried t opical ant ibiot ic oint ment wit hout effect . He
report s no fever, phot osensit ivit y, art hralgia, muscle weakness, flushing, or any ot her sympt oms. He has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, his vit al signs are normal. The rash is shown (Plat e 3). The remainder of t he physical examinat ion is normal.
(A) Dermat omyosit is
(B) Rosacea
(C) Seborrheic dermat it is
(D) Syst emic lupus eryt hemat osus
Item 57 [Basic]
A 58-year-old man is evaluat ed because of a chronic skin rash involving t he groin. The condit ion has been present for so long t hat he cannot remember when it st art ed, but it
probably has been present for a year or more. It is minimally sympt omat ic but does it ch. He has no ot her medical problems and t akes no medicat ions.
The skin rash in t he groin is shown (Plat e 4). He also has a scaling erupt ion on t he sides of his feet .
(A) Cut aneous candidiasis
(B) Psoriasis
(D) Tinea cruris
Item 58 [Basic]
A 28-year-old man is evaluat ed in t he emergency depart ment for an 8-hour hist ory of fever, malaise, and a rash on his shoulders, lower back, arms, and palms. Ten days ago
he was st art ed on oral t rimet hoprim-sulfamet hoxazole t herapy for met hicillin-resist ant Staphylococcus aureus cellulit is. His last dose of t rimet hoprim-sulfamet hoxazole was
t aken t his morning. He t akes no ot her medicat ions and has no allergies.
On physical examinat ion, t emperat ure is 38.6C (101.4F), blood pressure is 110/70 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 20/min. There are eryt hemat ous,
urt icarial, t arget oid plaques on t he shoulders t hat are st udded wit h small, t ense blist ers. Eryt hemat ous t arget oid lesions are also not ed on t he lower back and palms. There are
small vesicles and crust s on t he upper and lower lips, as well as small areas of erosion on t he soft palat e. His eye examinat ion is normal. All t ot aled, t he rash involves less
t han 10% of t he pat ient 's body surface area.
(A) Allergic cont act dermat it is
(B) Cellulit is
(C) "Red man syndrome"
(D) St evens-Johnson syndrome
Item 59 [Advanced]
A 33-year-old woman is evaluat ed for a 3-day hist ory of a rash on her palms. The rash first appeared on her palms as small red macules t hat increased in size over 24 t o 48
hours, followed by t he appearance of similar lesions on her arms and sores in her mout h. Three mont hs ago she had a similar episode t hat resolved spont aneously. She t akes
no medicat ions or supplement s. She has not been exposed t o anyone wit h similar skin lesions, but she did recent ly t ravel t o Nort h Carolina. She has a remot e hist ory of
genit al herpes but has had no out breaks in several years.
On physical examinat ion, she appears well. Temperat ure is 37.2C (98.9F), blood pressure is 118/70 mm Hg, and pulse rat e is 68/min. Typical lesions are shown (Plat e 5).
Whi ch of the fol l owi ng i s most l i kel y di agnosi s?
(A) Eryt hema mult iforme
(B) Lyme disease
(C) Rocky Mount ain spot t ed fever
(D) St rept ococcal infect ion
Item 60 [Basic]
A 70-year-old man has a 1-day hist ory of a painful rash on t he left side of his chest . Three days before t he rash became apparent ; he developed severe pain and parest hesias
in t he same area.
Skin examinat ion findings of t he left side of t he chest are shown (Plat e 6).
The remainder of t he examinat ion findings are unremarkable.
In addi ti on to anal gesi c agents, whi ch of the fol l owi ng i s the most appropri ate treatment?
(A) Cort icost eroids
(B) Int ravenous acyclovir
(C) Oral famciclovir
(D) Topical penciclovir
Item 61 [Advanced]
A 45-year-old woman is evaluat ed in t he office for a facial rash of 6 mont hs' durat ion t hat involves t he cheeks and nose. She is unsure if sun exposure worsens t he rash. She
does not have a rash elsewhere and does not have fat igue, ulcers, serosit is, or joint pain.
Physical examinat ion reveals a rash t hat is limit ed t o t he face as shown (Plat e 7).
The remainder of t he examinat ion is unremarkable.
(B) Psoriasis
(C) Rosacea
(D) Seborrheic dermat it is
(E) Syst emic lupus eryt hemat osus
Item 62 [Basic]
A 76-year-old man is seen in t he office for a rout ine physical examinat ion. He is healt hy and has no complaint s about his healt h, t akes no medicat ions, and does not smoke
or drink alcohol. Unt il he ret ired 5 years ago, he was a farmer. On physical examinat ion, several darkly pigment ed lesions are not ed on his t runk, as shown (Plat e 8).
(A) Basal cell carcinoma
(B) Malignant melanoma
(C) Seborrheic kerat oses
(D) Squamous cell carcinoma
Item 63 [Advanced]
A 17-year-old male high school st udent is evaluat ed for acne. The acne has been present for 4 years but seems t o be get t ing worse rat her t han bet t er as he get s older. He has
t ried t o cont rol t he acne by showering and scrubbing wit h soap and wat er at least t wice per day. He has never been on any medicat ions for his acne. He has no ot her medical
problems, t akes no medicat ions, and has no allergies.
On physical examinat ion, t he acne is ext ensively dist ribut ed on t he face, shoulders, back, and chest . The back is shown (Plat e 9).
Whi ch of the fol l owi ng i s the best i ni ti al treatment for thi s pati ent?
(A) Oral ant ibiot ics
(B) Oral isot ret inoin
(C) Salicylic acid
(D) Topical ret inoid
Item 64 [Basic]
A 34-year-old woman has a 1-week hist ory of generalized, very prurit ic, red plaques and papules t hat appear suddenly, last for less t han 24 hours, t hen disappear only t o
reappear at a different body locat ion. She has had t hese it chy bumps before, and t hey spont aneously resolved aft er 1 t o 2 weeks. She has no idea what makes t he rash appear
or disappear. She t ypically t reat s t he it ching wit h over-t he-count er ant ihist amines.
On physical examinat ion, vit al signs are normal. A represent at ive skin lesion is shown (Plat e 10).
What i s the most l i kel y di agnosi s?
(A) Acut e urt icaria
(B) Angioedema
(C) Chronic urt icaria
(D) Eryt hema mult iforme
Item 65 [Basic]
A 25-year-old woman is evaluat ed for swollen glands locat ed in her neck, under her arms, and in her groin. They are not t ender. Two weeks ago, she had a head cold and a
sore t hroat and felt hot and sweat y for a few days. All sympt oms resolved in about a week. She has no ot her sympt oms, and her weight has been st able. She t akes no
medicat ions. She has t raveled t o Peru several t imes during t he past 3 years but has never got t en ill and follows all t he t ravel recommendat ions for vaccines and disease
prevent ion. She does not smoke or use alcohol or ot her drugs. She has never had a sexually t ransmit t ed disease.
On physical examinat ion, her vit al signs are normal and she appears healt hy. She has ant erior and post erior cervical, axillary, and inguinal lymphadenopat hy. The nodes are
all nont ender, rubbery, and mobile. Most are less t han a cent imet er, alt hough t he largest is 1.5 cm in t he left groin.
(A) Biopsy of t he largest lymph node
(B) Complet e blood count and chest radiograph
(C) Epst ein-Barr early ant igen ant ibody (ant i-EA) t est
(D) Reassurance and wat chful wait ing
Item 66 [Advanced]
A 42-year-old woman is evaluat ed for a lump under her right arm present for 1 mont h. It is nont ender and enlarging. She has never had a mammogram. She ot herwise feels
well. She has no chronic medical condit ions, t akes no medicat ions, and has no family hist ory of malignancy. She does not smoke, drink alcohol, or use ot her drugs. She had a
posit ive t uberculin skin t est (PPD) 15 years ago t hat was t reat ed wit h isoniazid for 9 mont hs. HIV t est ing and chest radiograph were negat ive at t he t ime.
On physical examinat ion, her vit al signs are normal. A 2.5-cm, firm, mobile, nont ender lymph node is present in t he right axilla. No dominant mass is palpat ed in eit her
breast . The remainder of a complet e physical examinat ion is normal.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al step i n the management of thi s pati ent?
(A) Chest radiograph
(B) Lymph node aspirat e
(C) Lymph node biopsy
(D) Repeat examinat ion in 2 mont hs
Item 67 [Basic]
A 66-year-old woman, who resides in a nursing home, is evaluat ed for urinary incont inence. Neit her t he nursing home st aff nor family members report previous problems
wit h incont inence. Medical hist ory is significant for a cerebrovascular accident wit h severe aphasia and left hemiparesis, hypert ension, and t ype 2 diabet es mellit us. Current
medicat ions are aspirin, dipyridamole, lisinopril, pravast at in, and glipizide.
On physical examinat ion, t emperat ure is 36.8C (98.2F), blood pressure is 164/96 mm Hg, pulse rat e is 92/min, and respirat ion rat e is 18/min. Art erial oxygen sat urat ion is
98% on ambient air. Result s of cardiopulmonary, abdominal, and rect al examinat ions are normal. On neurologic examinat ion, t he pat ient is confused. There is expressive
aphasia and moderat e weakness of t he left arm and leg.
Complet e blood count Normal
Calcium Normal
Elect rolyt es Normal
Urinalysis 2+ glucose, moderat e prot ein, 40-50 leukocyt es and 3-5 eryt hrocyt es/hpf
Whi ch of the fol l owi ng i s the best management for thi s pati ent's i nconti nence?
(A) Begin ciprofloxacin
(B) Discont inue glipizide
(C) Insert an indwelling urinary cat het er
(D) Schedule a CT scan of t he head
Item 68 [Advanced]
A 78-year-old man comes for a rout ine annual physical examinat ion. The pat ient feels well. He is accompanied by his wife, who is concerned about his hearing. The review of
syst ems is normal, and t he pat ient st at es t hat he does not have any difficult y hearing.
Whi ch of the fol l owi ng i s the best way to screen thi s pati ent for heari ng i mpai rment?
(A) Administ er t he Screening Hearing Handicap Invent ory
(B) Perform t he Weber and Rinne t est s
(C) Perform t he whispered-voice t est
(D) Refer for audiomet ric t est ing
(E) No furt her evaluat ion is needed
Item 69 [Advanced]
An 82-year-old woman is evaluat ed in t he office aft er having fallen in her home 2 days ago. She st at es t hat she "t ripped." She did not have prodromal sympt oms, including
loss of consciousness, dizziness, light headedness, or imbalance. There is no hist ory of falls. Medical hist ory is significant for hypert ension. Current medicat ions are
hydrochlorot hiazide and lisinopril.
On physical examinat ion, t he pat ient is alert and orient ed. Temperat ure is 36.9C (98.5F), blood pressure is 140/85 mm Hg wit hout post ural changes, pulse rat e is 74/min,
and respirat ion rat e is 17/min. BMI is 36. Visual acuit y is 20/40 in bot h eyes wit h glasses. The cardiopulmonary and neurologic examinat ions are normal.
Whi ch of the fol l owi ng di agnosti c studi es shoul d be done next?
(A) CT scan of t he head
(B) "Get up and go" t est
(C) 24-Hour elect rocardiographic monit oring
(D) Transt horacic echocardiography
Item 70 [Advanced]
A 68-year-old man has a 6-mont h hist ory of urinary incont inence t hat occurs t wo t o t hree t imes each week and result s in loss of about one cup of urine each t ime. Before
most episodes, he feels t he need t o urinat e but oft en is unable t o get t o t he bat hroom in t ime. He st art ed wearing adult diapers 1 mont h ago. The pat ient has not had dysuria,
urinary frequency or hesit ancy, noct uria, or post void dribbling. He has recent ly not ed some memory loss. Alt hough his wife has t aken over managing t heir finances, t he
pat ient cont inues t o drive and perform all act ivit ies of daily living but has st opped playing golf because of embarrassment about his incont inence. Medical hist ory is
significant for ost eoart hrit is of t he right knee and hyperlipidemia. Current medicat ions are acet aminophen and pravast at in.
Vit al signs are normal. Abdominal examinat ion shows no suprapubic mass or t enderness. On rect al examinat ion, t he prost at e gland is normal. His score on t he Mini-Ment al
St at e Examinat ion is 23/30 (normal is 24/30). The remainder of t he neurologic examinat ion is normal. Pert inent laborat ory result s, including serum creat inine, elect rolyt es,
and prost at e-specific ant igen levels, are normal. A urinalysis is normal, and a urine cult ure is negat ive.
Whi ch of the fol l owi ng medi cati ons shoul d be prescri bed?
(A) Doxazosin
(B) Imipramine
(C) Oxybut ynin
(D) Phenylpropanolamine
Item 71 [Basic]
A 78-year-old asympt omat ic man comes for an init ial rout ine office visit . Medical hist ory is significant for hypert ension and hyperlipidemia, and current medicat ions are
hydrochlorot hiazide, at enolol, and simvast at in. The pat ient has never smoked. His wife recent ly had a st roke, and t he couple just moved from t heir home of many years t o
live in an assist ed living facilit y. The result s of a rout ine screening examinat ion and laborat ory t est s are normal.
Whi ch of the fol l owi ng screeni ng tests shoul d be done next?
(B) Ankle-brachial index
(C) Depression screening
(D) Mini-Ment al St at e Examinat ion
Item 72 [Advanced]
An 89-year-old woman is evaluat ed for dizziness t hat she has had for t he past year, mainly while st anding and ambulat ing. The dizziness is described as a sense of unst eadiness.
The sympt oms can last for minut es t o hours, and she has at least 4 t o 5 episodes per day. She does not describe ot her mot or or sensory sympt oms. Medical hist ory is
remarkable for a 15-year hist ory of t ype 2 diabet es mellit us, hypert ension, and hyperlipidemia. Current medicat ions are hydrochlorot hiazide, ramipril, simvast at in,
met formin, insulin glargine, and low-dose aspirin.
Vit al signs are normal; t here is no evidence of ort host asis. A cardiopulmonary examinat ion is normal. The pat ient has a posit ive Romberg sign and is unst eady on t andem
gait . Rapid alt ernat ing movement s are slowed. The pat ient has a correct ed visual acuit y of 20/50 in t he right eye and 20/70 in t he left eye. Vibrat ory sense and light t ouch are
diminished in a st ocking pat t ern in t he lower ext remit ies. She has no mot or abnormalit ies and no cranial nerve abnormalit ies. A Dix-Hallpike maneuver does not elicit
vert igo or nyst agmus.
A complet e blood count , met abolic profile, and t hyroid funct ion st udies are normal.
Whi ch of the fol l owi ng management opti ons i s the best choi ce for thi s pati ent?
(A) Brain MRI
(B) Meclizine
(C) Physical t herapy
(D) Replace aspirin wit h aspirin/ext ended-release dipyridamole
Item 73 [Basic]
A 22-year-old man comes for a rout ine evaluat ion. He feels well but has gained 6.8 kg (15 lb) during t he past 4 years. He has a sedent ary job as a soft ware engineer, has a 3-
pack-year hist ory of cigaret t e smoking, and consumes t wo beers on most night s. His parent s bot h have hypert ension, and his mot her has t ype 2 diabet es mellit us.
On physical examinat ion, blood pressure is 140/95 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 12/min; BMI is 29. There is no evidence of edema.
Laborat ory st udies, including a plasma fast ing glucose level, fast ing lipid panel, serum elect rolyt e level, serum creat inine level, and urinalysis result s, are normal.
(A) At enolol
(B) Dilt iazem
(C) Hydrochlorot hiazide
(D) Lifest yle modificat ions
(E) Lisinopril
Item 74 [Advanced]
An 85-year-old woman comes for a follow-up evaluat ion of hypert ension. She does not smoke and adheres t o a Diet ary Approaches t o St op Hypert ension (DASH) diet . At
an office visit 1 mont h ago, her blood pressure was 170/70 mm Hg. She was diagnosed wit h hypert ension and chronic st able angina 7 years ago and current ly t akes
met oprolol, sublingual nit roglycerin as needed, and aspirin.
On physical examinat ion, blood pressure is 186/70 mm Hg, pulse rat e is 60/min, and respirat ion rat e is 12/min; BMI is 22. Cardiopulmonary examinat ion reveals no jugular
venous dist ent ion, carot id bruit s, murmur, ext ra cardiac sounds, or pulmonary crackles. The abdomen is soft wit hout masses or bruit s. Neurologic examinat ion findings are
normal.
Urinalysis Normal
Whi ch of the fol l owi ng i s the most appropri ate addi ti onal therapy?
(A) Chlort halidone
(B) Lisinopril
(C) Losart an
(D) Terazosin
Item 75 [Basic]
A 55-year-old man comes for a follow-up office visit aft er laborat ory st udies reveal a diagnosis of t ype 2 diabet es mellit us. He has no hist ory of heart or kidney disease.
On physical examinat ion, he is afebrile; blood pressure is 138/84 mm Hg, pulse rat e is 78/min, and respirat ion rat e is 16/min. BMI is 28. The remainder of t he examinat ion is
normal.
Laborat ory st udies show normal serum elect rolyt e, blood urea nit rogen, and serum creat inine levels and a urine albumin-creat inine rat io of 20 mg/g.
Whi ch of the fol l owi ng i s the maxi mal al l owabl e target bl ood pressure for thi s pati ent?
(A) Less t han 115/75 mm Hg
(B) Less t han 125/75 mm Hg
(C) Less t han 130/80 mm Hg
(D) Less t han 140/90 mm Hg
Item 76 [Advanced]
An asympt omat ic 25-year-old man is evaluat ed for hypert ension diagnosed during a recent pre-employment physical examinat ion. He does not remember being t old about
hypert ension in t he past , and he has no family hist ory of hypert ension. He is not t aking any medicat ions.
On physical examinat ion, his blood pressure is 170/60 mm Hg in bot h arms. The heart rat e is 65/min and regular. Carot id examinat ion is normal; est imat ed cent ral venous
pressure is normal. The apical impulse is displaced and sust ained. An eject ion click is not ed at t he apex and left st ernal border. There is a grade 2/6 early syst olic murmur
not ed at t he second right int ercost al space. No diast olic murmur is not ed over t he ant erior precordium. Syst olic and diast olic murmurs are not ed over t he pat ient 's back.
There is no abdominal bruit . The lower ext remit y pulses are reduced and delayed.
A chest radiograph is shown.
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s i n thi s pati ent?
(A) Coarct at ion of t he aort a
(B) Essent ial hypert ension
(C) Pheochromocyt oma
(D) Renal art ery st enosis
Item 77 [Advanced]
A 35-year-old man comes for a new pat ient evaluat ion. He t akes no medicat ions. His parent s bot h have diabet es mellit us.
On physical examinat ion, blood pressure is 165/104 mm Hg and BMI is 31. The remainder of t he examinat ion is unremarkable.
Laborat ory st udies, including serum elect rolyt e, blood urea nit rogen, and creat inine levels and urinalysis result s, are normal.
Lifest yle modificat ions are recommended, but blood pressure findings are unchanged on a subsequent visit 2 weeks lat er.
Admi ni strati on of whi ch of the fol l owi ng i s the most appropri ate treatment?
(A) Hydrochlorot hiazide
(B) Lisinopril and hydrochlorot hiazide
(C) Met oprolol
(D) Terazosin
Item 78 [Basic]
A 50-year-old woman is evaluat ed during a rout ine office visit . She is asympt omat ic and t akes no medicat ions. Her fat her and sist er have essent ial hypert ension.
On physical examinat ion, vit al signs are normal except for a blood pressure of 136/86 mm Hg. BMI is 24. The remainder of t he physical examinat ion, including
cardiopulmonary and funduscopic examinat ions, is normal.
The blood pressure is confirmed on t hree ot her occasions, t wice out side t he office.
(A) Ambulat ory blood pressure monit oring
(B) Hydrochlorot hiazide
(C) Lifest yle modificat ion
(D) Lisinopril
Item 1 Answer: C
Educati onal Objecti ve: Calculate sensitivity and specificity.
The sensit ivit y and specificit y of t he new screening t est for prost at e cancer is 0.8. All t est s should be compared wit h a gold st andard, which represent s t he current pract ice
st andard; for prost at e cancer, it is t he prost at e biopsy. (Figure) Sensit ivit y quant ifies t he percent age of pat ient s wit h disease (in t his case, pat ient s wit h a posit ive prost at e
cancer biopsy) who have a posit ive screening t est . Sensit ivit y is equal t o a/(a + c). Specificit y quant ifies t he percent age of normal pat ient s (a negat ive biopsy for prost at e
cancer) wit h a negat ive screening t est . Specificit y is equal t o d/(b + d).
A highly sensit ive t est reduces t he probabilit y of missing t he diagnosis. Because a highly sensit ive screening ident ifies most pat ient s wit h t he condit ion, a negat ive screening
t est helps t o "rule out " t he diagnosis. Highly sensit ive t est s oft en have a high false-posit ive rat e (posit ive t est result s in pat ient s wit hout t he disease). Therefore, a posit ive
screening t est is usually followed by a highly specific (and somet imes more invasive) t est , which oft en is t he gold st andard for t he diagnosis. Because a highly specific t est is
negat ive in pat ient s wit hout t he disease, a posit ive t est helps "rule in" t he diagnosis. The concept s of sensit ivit y and specificit y can be remembered by t he mnemonics "SpIN"
and "SnOUT," indicat ing t hat a very specific t est , when posit ive, rules in a disease and a highly sensit ive t est , when negat ive, rules out disease.
Key Poi nt
A highly specific t est , when posit ive, rules in a disease, and a highly sensit ive t est , when negat ive, rules out a disease.
Bi bl i ography
Akobeng AK. Underst anding diagnost ic t est s 1: sensit ivit y, specificit y and predict ive values. Act a Paediat r. 2007;96(3):338-41. [PMID: 17407452]
Item 2 Answer: C
Educati onal Objecti ve: Understand the effect of disease prevalence on sensitivity, specificity, likelihood ratios, and predictive values.
The measure t hat is most likely t o change is t he posit ive predict ive value. Sensit ivit y and specificit y are t est charact erist ics t hat do not change as populat ions vary.
Likelihood rat ios are based on sensit ivit y and specificit y and do not change as populat ions vary. Predict ive values address t he chance of disease given a posit ive or negat ive
t est result and are based on t he prevalence of disease in t he populat ion being t est ed; t herefore, predict ive values do change as t he populat ions vary. As t he prevalence of
disease decreases (for example, t he prevalence in t he communit y compared wit h t hat in an experiment ), t he posit ive predict ive value decreases and t he negat ive predict ive
value increases. The opposit e is t rue if t he disease prevalence increases. The example below demonst rat es t hese concept s.
Key Poi nt
Predict ive values change wit h disease prevalence whereas sensit ivit y, specificit y and likelihood rat ios do not .
Bi bl i ography
Item 3 Answer: D
Educati onal Objecti ve: Calculate the positive predictive value of a diagnostic test.
The probabilit y t hat t his pat ient has HIV disease is approximat ely 0.5%. The reliabilit y of screening t est s is a funct ion of t he t est 's sensit ivit y and specificit y as well as t he
prevalence of t he disease in t he populat ion under considerat ion. In t his clinical scenario, disease prevalence of 1 in 10,000 t ranslat es t o 10 pat ient s wit h HIV infect ion in a
populat ion of 100,000 subject s. A t est t hat is 98% sensit ive will correct ly ident ify 9.8 of t hese pat ient s as having HIV infect ion. This is t he t rue posit ive (TP) rat e. This
number is derived by mult iplying t he number of subject s wit h disease by t he t est 's sensit ivit y (10 0.98). In t his same populat ion of 100,000 subject s, 99,990 subject s do not
have disease (100,000 - 10). A t est t hat is 98% specific will correct ly ident ify 97,900 pat ient s wit h a negat ive t est result . This is t he t rue negat ive (TN) rat e. This number is
derived by mult iplying t he number of subject s wit hout disease by t he t est 's specificit y (99,990 0.98). However, t his also means t hat 2090 normal subject s will have a false
posit ive (FP) t est result (t he difference bet ween 99,990 subject s wit hout HIV and 97,900 wit h a TN t est result ).
The posit ive predict ive value (PPV) answers t he quest ion, "What is t he probabilit y t hat a posit ive t est result is a t rue posit ive result ?" PPV is calculat ed as t he t rue posit ive
rat e divided by all posit ive t est result s. In t his example, t he PPV = TP/(TP + FP) = 9.8/(2090 + 9.8) = 0.0046. This phenomenon underscores t he need for specific
confirmat ory t est s, such as West ern blot analysis in t his case, and t he hazards of screening for disease in populat ions at low risk.
Key Poi nt
The posit ive predict ive value (PPV) is calculat ed as t he t rue posit ive rat e divided by all posit ive t est result s.
Bi bl i ography
Item 4 Answer: D
Educati onal Objecti ve: Use a likelihood ratio to calculate posttest probability.
The likelihood rat io (LR) of a t est is t he proport ion of pat ient s wit h t he disease who t est posit ive divided by t he proport ion of pat ient s wit hout t he disease who also t est
posit ive. The numerat or of t his rat io is t he t est 's sensit ivit y; t he denominat or is t he false-posit ive rat e for t he t est . LRs can be used t o approximat e t he probabilit y of disease
aft er a t est is performed, but t o perform t his funct ion, t hree associat ions must be remembered: posit ive LRs of 2, 5, and 10 increase t he probabilit y of disease by 15%, 30%,
and 45%, respect ively. An appendiceal CT scan has a posit ive LR for appendicit is of 13.3; t herefore, if t he pret est probabilit y of appendicit is was 50%, a posit ive scan result
increases t he probabilit y for disease by roughly 45%, result ing in a post t est probabilit y of 95% (45% added t o t he 50% pret est probabilit y of disease).
Key Poi nt
Posit ive likelihood rat ios of 2, 5, and 10 increase t he probabilit y of disease by 15%, 30%, and 45%, respect ively.
Bi bl i ography
McGee S. Simplifying likelihood rat ios. J Gen Int ern Med. 2002;17:646-9. [PMID: 12213147]
Item 5 Answer: A
Educati onal Objecti ve: Compare different tests using a receiver operating characteristic (ROC) curve.
Test A has t he best overall performance. Many t est out comes are cont inuous variables, which are arbit rarily divided at some point int o normal and abnormal values by using a
cut point . One way t o visually compare t he operat ing charact erist ics of different t est s is t o plot t he cut point s of each t est on a receiver operat ing charact erist ic (ROC)
curve. The ROC curve is a visual represent at ion of t he t rue posit ive rat e (sensit ivit y) plot t ed as a funct ion of t he false posit ive rat e (1.0-specificit y) for different cut point s.
A t est wit h t he best sensit ivit y and specificit y for each of it s cut point s will have a curve t hat "crowds" t he upper left margins of t he ROC curve. This concept is part icularly
valuable when comparing t wo or more t est s. The t est wit h t he great est overall accuracy will have t he largest area under t he ROC curve and will be locat ed closest t o t he upper
left corner.
Key Poi nt
In a comparison of t wo or more t est s on a receiver operat ing charact erist ic (ROC) curve, t he t est wit h t he best overall accuracy for each of it s cut point s will have t he largest
area under t he ROC curve.
Bi bl i ography
Akobeng AK. Underst anding diagnost ic t est s 3: receiver operat ing charact erist ic curves. Act a Paediat r. 2007;96(5):644-647. Epub 2007 Mar 21. [PMID: 17376185]
Item 6 Answer: A
Educati onal Objecti ve: Screen for abdominal aortic aneurysm with abdominal ultrasonography.
One-t ime screening for abdominal aort ic aneurysm (AAA) wit h ult rasonography is recommended for all men aged 65 t o 75 years who have ever smoked. Dat a from
randomized clinical t rials indicat e t hat ult rasound ident ificat ion and repair of AAA larger t han 5 cm in diamet er reduces AAA-relat ed mort alit y in older men. Deat h from
abdominal aort ic aneurysm rupt ure is rare aft er a single normal screening t est and repeat screening in t hese persons is not recommended.
The U.S. Prevent ive Services Task Force recommends t hat women aged 65 years and older be screened rout inely for ost eoporosis and t hat rout ine screening begin at age 60
years for women at increased risk for ost eoporot ic fract ures. The evidence is not as st rong for men, but screening may be indicat ed for men wit h cert ain risk fact ors (such as
long-t erm cort icost eroid use, androgen deprivat ion). This man has no high-risk fact ors t o warrant screening.
The pneumococcal vaccine is associat ed wit h subst ant ial reduct ions in morbidit y and mort alit y among t he elderly and high-risk adult s and is, t herefore, recommended for all
adult s aged 65 years and older or wit h ot her risk fact ors (diabet es, cirrhosis, asplenia). Pat ient s who receive t heir init ial vaccine at older t han 65 years of age should receive a
second dose aft er 5 years. One-t ime revaccinat ion is also recommended in 5 years for pat ient s wit h chronic kidney disease, asplenia, or cancer or t hose who are
immunosuppressed. This pat ient has no indicat ion for revaccinat ion.
Rout ine screening for coronary art ery disease in asympt omat ic persons wit hout cardiovascular risk fact ors is not recommended. Screening elect rocardiograms are not
recommended because abnormalit ies of t he rest ing elect rocardiogram are rare, not specific for coronary art ery disease, and do not predict subsequent mort alit y from coronary
disease. Exercise t est ing may ident ify persons wit h coronary art ery disease, but t wo fact ors limit rout ine t est ing in asympt omat ic adult s. First , t he prevalence of significant
coronary art ery disease is low in t his populat ion, rendering t he predict ive value of a posit ive exercise t est low (false-posit ive result s are common). Second, abnormalit ies of
exercise t est ing do not accurat ely predict major coronary event s in asympt omat ic persons.
Key Poi nt
One-t ime screening for abdominal aort ic aneurysm wit h ult rasonography is recommended for all men aged 65 t o 75 years who have ever smoked.
Bi bl i ography
Lederle FA. In t he clinic. Abdominal aort ic aneurysm. Ann Int ern Med. 2009;150(9):ITC5-1-ITC5-15. [PMID: 19414835]
Item 7 Answer: E
Educati onal Objecti ve: Immunize a patient with chronic obstructive pulmonary disease against influenza with trivalent killed vaccine.
The most appropriat e immunizat ion st rat egy for t his pat ient is t rivalent killed influenza vaccinat ion. Annual influenza vaccinat ion is recommended in pat ient s wit h chronic
obst ruct ive pulmonary disease (COPD), regardless of t heir age. For t he 2010-2011 influenza season, t he Cent ers for Disease Cont rol and Prevent ion has recommended
universal annual influenza vaccinat ion for all persons age 6 mont hs and older.
If t his pat ient received influenza and pneumococcal vaccinat ion 1 year ago, he needs only influenza vaccinat ion. Pneumococcal vaccinat ion is recommended for all adult s
older t han 65 years and for younger pat ient s who are act ive smokers or who have COPD, ast hma, and ot her disorders t hat increase t heir risk for invasive pneumococcal
disease. Influenza vaccinat ion is also recommended for pregnant women whose last t wo t rimest ers coincide wit h t he influenza season (lat e December t hrough mid-March).
The main vaccine used in t he Unit ed St at es is a t rivalent inact ivat ed virus, but an int ranasally administ ered vaccine from a t rivalent live at t enuat ed virus is also available for
pat ient s age 5 t o 49 years who are not pregnant , immunosuppressed, or living wit h an immunosuppressed person. Because of t he pat ient 's age, t he most appropriat e
vaccinat ion is t he t rivalent killed influenza vaccinat ion.
A single revaccinat ion wit h pneumococcal vaccine is recommended in adult s older t han 65 years if t hey were vaccinat ed more t han 5 years previously at a t ime when t hey
were less t hen 65 years of age and in immunosuppressed pat ient s 5 years or more aft er t he first dose. Pat ient s wit h COPD who received t heir first pneumococcal vaccinat ion
aft er age 65 years do not need revaccinat ion.
Key Poi nt
Influenza vaccinat ion is recommended annually for all pat ient s wit h chronic obst ruct ive pulmonary disease, regardless of age.
Bi bl i ography
Hessen MT. In t he clinic. Influenza. Ann Int ern Med. 2009;151(9):ICT5-1-ICT5-15. [PMID: 19894285]
Item 8 Answer: D
Educati onal Objecti ve: Recognize the relative importance of the most commonly reported end points in cancer screening studies.
Lung cancer-specific mort alit y is t he best end point for measuring t he effect of cancer screening on pat ient out comes. The case-fat alit y rat io (t he number of deat hs from a
specific cancer divided by t he number of pat ient s wit h t hat cancer) is subject t o serious art ifact s from length bias, which is t he preferent ial det ect ion of asympt omat ic, more
indolent cancers by any screening t est . These cancers are more likely t o be det ect ed during screening because t hey are det ect able for a great er lengt h of t ime t han fast er
growing, more aggressive cancers. Likewise, pat ient survival aft er cancer diagnosis is art ificially prolonged by screening because of lengt h bias as well as lead-time bias, which
is an advance in t he dat e of cancer diagnosis wit hout necessarily changing t he pat ient 's out come. Alt hough a screening t est t hat result ed in a higher incidence of early-st age
cancer would suggest an improvement in life expect ancy, t he relat ive shift in t he proport ion of pat ient s diagnosed at early st ages is not a good assessment of screening-t est
efficacy due t o select ion of less aggressive t umors (lengt h bias). An absolut e decrease in t he incidence of lat e-st age (met ast at ic) cancer is an early indicat or t hat a t est may be
effect ive because met ast at ic cancer frequent ly leads t o deat h; however, lead-t ime bias and t he result ing st age shift may st ill confound t he absolut e incidence of lat e-st age
disease. Cause-specific mort alit y is least subject t o t he above pot ent ially confounding effect s.
Key Poi nt
Cancer-specific mort alit y is t he best end point for measuring t he effect of cancer screening on pat ient out comes.
Bi bl i ography
Gat es TJ. Screening for cancer: evaluat ing t he evidence. Am Fam Physician. 2001;63:513-22. [PMID: 11272300]
Item 9 Answer: C
Educati onal Objecti ve: Immunize a patient with a previous history of herpes zoster with the zoster vaccine.
The most appropriat e st rat egy is zost er vaccinat ion now. The zost er vaccine is indicat ed in immunocompet ent pat ient s older t han 60 years for prevent ion of herpes zost er
(shingles). Live at t enuat ed zost er vaccine in adult s 60 years or older reduces t he incidence of herpes zost er by 51% and post herpet ic neuralgia by 67%. The vaccine is more
efficacious in prevent ing herpes zost er among adult s 60 t o 69 years of age t han among t hose 70 years or older. On t he ot her hand, t he vaccine prevent s post herpet ic
neuralgia t o a great er ext ent among adult s aged 70 years or more. A report ed hist ory of possible herpes zost er is not a cont raindicat ion t o vaccinat ion. While recurrence of
herpes zost er is rare, t here are no recognized safet y concerns in giving t he vaccine t o a pat ient wit h a hist ory of shingles. Excluding pat ient s wit h a possible hist ory would be a
barrier t o vaccinat ion and impose a burden on physicians t o assess t he reliabilit y of t he prior diagnosis.
The zost er vaccine is a live vaccine and is cont raindicat ed in people wit h act ive, unt reat ed t uberculosis; in pregnant women; in immunocompromised pat ient s; and in pat ient s
receiving chemot herapy, radiot herapy, or large doses of cort icost eroids. Immunizat ion should be avoided if an immunocompromised person is living in t he household.
Zost er vaccine can be given concomit ant ly wit h all ot her live and inact ivat ed vaccines, including influenza and pneumococcal vaccine. Zost er vaccine is given as a single
subcut aneous dose. A boost er dose is not recommended.
More t han 99% of pat ient s 40 years or older have serologic evidence of prior varicella infect ion. Therefore, rout ine serologic t est ing for varicella ant ibodies t o det ermine
who should be vaccinat ed is not cost -effect ive or necessary.
Key Poi nt
Zost er vaccine is indicat ed in all pat ient s age 60 years and older wit hout cont raindicat ions, regardless of hist ory of prior varicella infect ion.
Bi bl i ography
Advisory Commit t ee on Immunizat ion Pract ices. Recommended adult immunizat ion schedule: Unit ed St at es, 2010. Ann Int ern Med. 2010;152(1):36-39. [PMID: 20048270]
Item 10 Answer: A
Educati onal Objecti ve: Provide the appropriate tetanus prevention strategy in a patient with an infected wound.
This pat ient should receive t et anus-dipht heria t oxoid and acellular pert ussis (Tdap) vaccine. All pat ient s evaluat ed for wounds should have t heir t et anus vaccinat ion st at us
reviewed. Most pat ient s who develop t et anus are not complet ely vaccinat ed. If t here is any doubt about a pat ient 's vaccinat ion hist ory, t he complet e series should be
administ ered. The first dose and second dose should be separat ed by 4 weeks, and t he t hird dose should be given 6 t o 12 mont hs lat er. Because suscept ibilit y t o t et anus and
dipht heria oft en co-exist , bot h t et anus and dipht heria t oxoid (Td) should be administ ered, not just t et anus t oxoid alone. It is also recommended t hat t he Tdap vaccine be used
in place of one of t he Td vaccinat ions in adult s age 19 t o 64 years who have not received t heir single recommended boost er dose of t his vaccine.
Tet anus immune globulin is indicat ed for pat ient s who have not complet ed t he primary series of t et anus immunizat ions or in pat ient s who have an unclear immunizat ion
hist ory. As t his pat ient 's immunizat ion hist ory is clear, t et anus immune globulin is not indicat ed.
Tet anus boost er vaccinat ion can be omit t ed in pat ient s who received a t et anus boost er wit hin t he past 5 years and in pat ient s wit h clean minor wounds who have received
vaccinat ion wit hin t he past 10 years. However, t his pat ient 's wound is infect ed, and his last boost er was 8 years ago. Therefore, Tdap vaccine should be administ ered.
Key Poi nt
Tet anus boost er vaccinat ion can be omit t ed in pat ient s who received a t et anus boost er wit hin t he past 5 years and in pat ient s wit h clean minor wounds who have received
vaccinat ion wit hin t he past 10 years.
Bi bl i ography
Item 11 Answer: D
Educati onal Objecti ve: Immunize against human papillomavirus.
The most appropriat e opt ion for t his pat ient is human papillomavirus (HPV) vaccinat ion now. The Advisory Commit t ee on Immunizat ion Pract ices of t he Cent ers for
Disease Cont rol and Prevent ion recommends HPV vaccine for cervical cancer prevent ion. The vaccine is recommended for all females bet ween ages 9 and 26 years regardless
of sexual act ivit y. The vaccine has a high success rat e in prevent ing infect ions wit h HPV st rains which cause most cases of genit al wart s and cervical cancer.
HPV infect ion is predominant ly spread by sexual cont act . This pat ient st at es she is not sexually act ive. However, t he vaccine should be recommended now as it is of low risk,
and vaccine efficacy last s for at least several years. The vaccine does not prot ect against all t ypes of HPV, and roughly 30% of cervical cancers will not be prevent ed by t he
vaccine, so women should cont inue t o get regular Pap smears even aft er complet ing t he vaccinat ion series.
The HPV vaccine is not effect ive in prevent ing HPV-relat ed diseases in women who have an est ablished infect ion at t he t ime of vaccinat ion; t herefore, wait ing for HPV
seroconversion prior t o vaccinat ion is inappropriat e.
Key Poi nt
A human papillomavirus quadrivalent vaccinat ion series should be offered t o all girls and women ages 9 t hrough 26 years, and women should cont inue t o get regular Pap
smears even aft er complet ing t he vaccinat ion series.
Bi bl i ography
Item 12 Answer: A
Educati onal Objecti ve: Screen for colorectal cancer with annual home fecal occult blood testing.
The most appropriat e management opt ion for t his pat ient is annual home fecal occult blood t est ing. St art ing at t he age of 50 years, average-risk pat ient s should be offered
several met hods of screening, because personal preference and insurance coverage variat ions may render some met hods more appropriat e t han ot hers for individual pat ient s.
Even t hough sensit ivit y and specificit y vary among t he different screening met hods, it is more import ant t o choose and follow a screening program t han it is t o be concerned
about which met hod is used. Screening met hods include st ruct ural t est s (such as colonoscopy and sigmoidoscopy) t hat can accomplish bot h det ect ion and prevent ion (by
ident ificat ion and removal of precursor lesions) and st ool-based t est s (such as fecal occult blood t est ing [FOBT]), which det ect exist ing cancers and, t o a lesser degree, polyps.
Annual home high-sensit ivit y FOBT, sampling t wo t o t hree consecut ive specimens, is a met hod recommended by t he U.S. Prevent ive Services Task Force (USPSTF) for
screening if t he pat ient is willing t o undergo colonoscopy if result s are posit ive. Ot her screening programs recommended by t he USPSTF are colonoscopy every 10 years or
flexible sigmoidoscopy every 5 years combined wit h annual high-sensit ivit y FOBT every 3 years.
Annual rect al examinat ion wit h office FOBT is not considered adequat e screening for colorect al cancer because of poor sensit ivit y (4.9% for advanced neoplasia and only 9%
for cancer).
The American Cancer Societ y, U.S. Mult i-Societ y Task Force on Colorect al Cancer, and American College of Radiology joint t ask force considers double-cont rast barium
enema an accept able screening met hod; however, it should be performed every 5 years. Double cont rast barium enema is not endorsed by t he USPSTF. The American Cancer
Societ y, U.S. Mult i-Societ y Task Force on Colorect al Cancer, and American College of Radiology joint t ask force also differs from t he USPSTF by recommending flexible
sigmoidoscopy every 5 years t oget her wit h an annual high-sensit ivit y FOBT.
Key Poi nt
USPSTF endorsed colorect al cancer screening met hods for average-risk pat ient s include annual home st ool t est ing, colonoscopy every 10 years, and flexible sigmoidoscopy
every 5 years t oget her wit h high-sensit ivit y fecal occult blood t est ing every 3 years.
Bi bl i ography
Weinberg DS. In t he clinic. Colorect al cancer screening. Ann Int ern Med. 2008;148(3):ITC2-1-ITC2-16. [PMID: 18252680]
Item 13 Answer: B
Educati onal Objecti ve: Screen a patient at average risk for colon cancer with colonoscopy every 10 years.
Of t he list ed screening st rat egies, colonoscopy every 10 years is t he most appropriat e for t his pat ient . She is at average risk for colorect al cancer; t his populat ion includes
persons wit h no personal or family hist ory of colon adenoma or cancer and who do not have a condit ion t hat predisposes t hem t o cancer, such as inflammat ory bowel
disease. Screening for colorect al cancer is cost effect ive and well t olerat ed; it also saves lives. Screening is feasible because t he 10 t o 15 years needed for a polyp t o develop
int o cancer are sufficient t ime t o det ect and remove an adenoma. Screening in t he average-risk populat ion should be st art ed at age 50 years; t here are various effect ive
screening st rat egies in average-risk pat ient s, wit h surveillance int ervals depending upon chosen st rat egy.
Annual fecal occult blood t est ing is a screening opt ion but requires t hat t wo samples be collect ed from each of t hree spont aneously passed st ools. Digit al examinat ion t o
ret rieve a sample is not an accept able subst it ut e because it is approximat ely five t imes less sensit ive compared t o t he t echnique of obt aining t wo samples from each of t hree
st ools. Flexible sigmoidoscopy in combinat ion wit h fecal occult blood t est ing in 5-year int ervals is an accept able opt ion as well. Double-cont rast barium enema is no longer
considered t o be a primary met hod of colorect al cancer screening by t he U.S. Prevent ive Services Task Force. If double-cont rast barium enema must be used for t echnical or
anat omical reasons, t he correct screening int erval is 5 t o 10 years.
Key Poi nt
Screening for colorect al cancer in t he average-risk populat ion should be st art ed at age 50 years.
Bi bl i ography
Weinberg DS. In t he clinic. Colorect al cancer screening. Ann Int ern Med. 2008;148(3):ITC2-1-ITC2-16. [PMID: 18252680]
Item 14 Answer: D
Educati onal Objecti ve: Diagnose ventricular tachycardia as the cause of syncope.
The most likely cause of t his pat ient 's syncope is vent ricular t achycardia (VT). The pat ient 's cardiac hist ory, lack of presyncopal prodrome, and head lacerat ion all suggest
cardiac arrhyt hmia as t he cause of t he syncope. VT is perhaps t he most feared cause of syncope because of it s t endency t o recur and cause sudden cardiac deat h. VT is most
commonly seen in pat ient s wit h advanced syst olic heart failure and underlying ischemic heart disease. Myocardial scarring from a previous myocardial infarct ion can serve as
t he reent rant focus for vent ricular arrhyt hmias.
Ort host at ic hypot ension is a frequent cause of syncope and presyncope. It is defined as a syst olic blood pressure decrease of at least 20 mm Hg or a diast olic blood pressure
decrease of at least 10 mm Hg wit hin 3 minut es of st anding. Ort host at ic hypot ension may be classified int o medicat ion-induced, neurogenic, and nonneurogenic cat egories.
Common medicat ions associat ed wit h ort host at ic hypot ension include -adrenergic blockers, nit rat es, diuret ics, phosphodiest erase inhibit ors, and ant idepressant s. Examples
of diseases causing neurogenic ort host at ic hypot ension are diabet ic or alcoholic polyneuropat hy, mult iple sclerosis, and mult iple syst ems at rophy. Nonneurogenic ort host at ic
hypot ension may be caused by disorders such as adrenal insufficiency, venous pooling, or volume deplet ion from an acut e medical illness. This pat ient has no risk fact ors or
findings suggest ive of ort host at ic hypot ension.
The pat ient 's syncope was wit nessed by his wife who did not report any seizure act ivit y, post ict al confusion, t ongue bit ing, or incont inence, making seizure an unlikely
diagnosis.
Sit uat ional syncope is a neurocardiogenic reflex mediat ed in response t o a part icular st imulus, t ypically coughing, mict urit ion, or defecat ion. No st imulus occurred before t he
syncope and no prodrome of diaphoresis, nausea, or light headedness was report ed, making sit uat ional syncope unlikely.
Key Poi nt
Vent ricular t achycardia is most commonly seen in pat ient s wit h advanced syst olic heart failure and underlying ischemic heart disease.
Bi bl i ography
Ouyang H, Quinn J. Diagnosis and evaluat ion of syncope in t he emergency depart ment . Emerg Med Clin Nort h Am. 2010;28(3):471-85. [PMID: 20709239]
Item 15 Answer: C
Educati onal Objecti ve: Diagnose orthostatic hypotension as a cause of syncope.
Det erminat ion of ort host at ic blood pressure measurement s is most likely t o est ablish t he cause of t his pat ient 's syncope. She most likely has diabet ic aut onomic neuropat hy.
Pat ient s wit h aut onomic neuropat hy experience sympt oms of dizziness due t o st anding-induced hypot ension. Ort host at ic hypot ension is a frequent cause of syncope and
presyncope. It is defined as a syst olic blood pressure decrease of at least 20 mm Hg or a diast olic blood pressure decrease of at least 10 mm Hg wit hin 3 minut es of st anding.
Ort host at ic hypot ension may be classified int o medicat ion-induced, neurogenic, and nonneurogenic cat egories. Examples of diseases causing neurogenic ort host at ic
hypot ension are diabet ic or alcoholic polyneuropat hy, mult iple sclerosis, and mult iple syst ems at rophy. Pat ient s wit h ort host at ic hypot ension should be educat ed t o avoid
rising t o st anding posit ions quickly, t o wear elast ic support hose, and t o avoid volume deplet ion and large meals.
If t he cause of syncope is unexplained from t he init ial evaluat ion, cont inuous t elemet ry may be useful t o screen for paroxysmal arrhyt hmias. If sympt oms are frequent , 24-
hour ambulat ory monit oring may be useful t o exclude arrhyt hmia as a cause of sympt oms. If sympt oms are infrequent , an event monit or or loop recorder should be used. This
pat ient 's hist ory is compat ible wit h ort host at ic hypot ension, and det erminat ion of ort host at ic blood pressure measurement s will probably confirm t he diagnosis, making
furt her invest igat ion unnecessary.
Neuroimaging, such as CT scanning, is of limit ed use in evaluat ing syncope. It has t he highest yield in pat ient s who are older t han 65 years and have neurologic sympt oms
such as headache, neurologic examinat ion abnormalit ies, head t rauma, or are t aking ant icoagulant s.
Bilat eral carot id st enosis is a rare cause of syncope, and rout ine carot id duplex ult rasonography is not recommended. Typical sympt oms of carot id art ery st enosis include
t ransient ischemic at t ack, amaurosis fugax, and st roke.
Key Poi nt
Ort host at ic hypot ension is a frequent cause of syncope and presyncope and is defined as a syst olic blood pressure decrease of at least 20 mm Hg or a diast olic blood pressure
decrease of at least 10 mm Hg wit hin 3 minut es of st anding.
Bi bl i ography
Ouyang H, Quinn J. Diagnosis and evaluat ion of syncope in t he emergency depart ment . Emerg Med Clin Nort h Am. 2010;28(3):471-85. [PMID: 20709239]
Item 16 Answer: E
Educati onal Objecti ve: Diagnose vasovagal syncope by history.
The best management opt ion for t his pat ient is no furt her t est ing. The pat ient 's hist ory is consist ent wit h vasovagal (neurocardiogenic) syncope on t he basis of t he hist ory
of prolonged st anding and prodromal sympt oms of nausea, light headedness, and diaphoresis. These presyncopal warning sympt oms are highly sensit ive for t he diagnosis of
vasovagal syncope if last ing for more t han 10 seconds. Brief myoclonic jerking aft er losing consciousness is not unusual wit h syncope, especially vasovagal syncope. In
addit ion, t he normal physical examinat ion findings, t he normal elect rocardiogram, and t he lack of ort host asis on vit al sign assessment all point t oward vasovagal syncope.
Advanced cardiovascular diagnost ic t est ing, such as an echocardiogram or exercise st ress t est , is not needed aft er a first episode of syncope when sympt oms are charact erist ic
for vasovagal syncope.
An elect roencephalogram might be indicat ed t o evaluat e a first , unprovoked seizure, but despit e t his pat ient 's few myoclonic jerks, t here is no evidence of seizure act ivit y,
such as t ongue bit ing, incont inence, or post ict al confusion.
In suspect ed vasovagal syncope, a t ilt -t able t est can be useful, providing a diagnosis in up t o 60% of pat ient s when performed wit h pharmacologic st imulat ion. This t est is
indicat ed in pat ient s wit h recurrent syncope and in t hose wit h one episode who are at high risk on t he basis of t heir occupat ion. However, t his t est has poor sensit ivit y,
specificit y, and reproducibilit y and is not indicat ed in most pat ient s wit h suspect ed vasovagal syncope.
Key Poi nt
Vasovagal syncope is t ypically associat ed wit h a prodrome of nausea, light headedness, and diaphoresis.
Bi bl i ography
Huff JS, Decker WW, Quinn JV, et al; American College of Emergency Physicians. Clinical policy: crit ical issues in t he evaluat ion and management of adult pat ient s
present ing t o t he emergency depart ment wit h syncope. Ann Emerg Med. 2007;49(4):431-444. [PMID:17371707]
Item 17 Answer: B
Educati onal Objecti ve: Diagnose intermittent complete heart block as the cause of recurrent syncope.
This 57-year-old man has had t hree episodes of syncope in t he past 6 mont hs. His forehead bruise is a classic sign of syncope due t o heart block, wit h t he sudden loss of
consciousness and lack of preceding sympt oms result ing in t he pat ient falling and injuring himself. Most pat ient s wit h t rifascicular block are asympt omat ic and do not have
progressive conduct ion syst em disease. Some st udies suggest t hat only about 1% progress t o complet e heart block, but ot her st udies report much higher rat es.
In pat ient s wit h t rifascicular block, permanent pacer implant at ion is recommended for int ermit t ent t hird-degree at riovent ricular block, t ype II second-degree at riovent ricular
block, and alt ernat ing bundle branch block. A pacer is not indicat ed for asympt omat ic t rifascicular block. The first principle of diagnosis of a suspect ed cardiac arrhyt hmia is
t o record t he abnormal rhyt hm. The best approach in t his pat ient is an implant able loop recorder t hat cont inuously records t he elect rocardiogram and allows t he pat ient t o
save t he previous 30 seconds t o 2 minut es (adjust able) aft er regaining consciousness.
Three major groups of disorders cause syncope of cardiac origincardiac out flow obst ruct ion, arrhyt hmias, and cardiac ischemia. Causes of obst ruct ed cardiac out put leading
t o syncope include severe aort ic st enosis, hypert rophic obst ruct ive cardiomyopat hy, and pulmonary embolism. The pat ient 's normal examinat ion and echocardiogram
eliminat es aort ic st enosis and hypert rophic cardiomyopat hy, and t he absence of dyspnea, chest pain, and risk fact ors makes pulmonary embolism unlikely. Syncope
associat ed wit h aort ic st enosis is usually associat ed wit h exert ion. The pat ient has no ot her sympt oms t o suggest cardiac ischemia.
Neurocardiogenic (vasovagal) syncope is one of t he most common t ypes of syncope. In neurocardiogenic syncope, t riggers lead t o increased parasympat het ic t one, causing a
drop in heart rat e and blood pressure (cardioinhibit ory response); decreased sympat het ic t one, causing vasodilat ion and hypot ension (vasodepressor response); or a
combinat ion of t he t wo. The increased vagal t one seen in neurocardiogenic syncope t ypically causes a prodrome of nausea, diaphoresis, and pallor, which was not present in
t his pat ient .
Key Poi nt
Sudden loss of consciousness irrespect ive of body posit ion and lack of preceding sympt oms suggest t he possibilit y of cardiac arrhyt hmia.
Bi bl i ography
Sud S, Klein GJ, Skanes AC, Gula LJ, Yee R, Krahn AD. Predict ing t he cause of syncope from clinical hist ory in pat ient s undergoing prolonged monit oring. Heart Rhyt hm.
2009;6(2):238-43. Epub 2008 Oct 29. [PMID: 19187918]
Item 18 Answer: C
Educati onal Objecti ve: Evaluate recurrent syncope with an implantable loop recorder.
The t est t hat is most likely t o yield a diagnosis is t he implant able loop recorder. Common causes of syncope include neurocardiogenic (vasovagal) syncope, bradyarrhyt hmia,
t achyarrhyt hmia, out flow t ract obst ruct ion, and seizures. The next st ep in t he evaluat ion of t his pat ient is monit oring for an arrhyt hmia. The gold st andard for diagnosis of
an arrhyt hmic cause of syncope is document at ion of a rhyt hm dist urbance at t he t ime of sympt om occurrence. The choice of monit oring t est should be relat ed t o t he
frequency of t he sympt oms. This pat ient has had recurrent , infrequent event s; t herefore, an implant able loop recorder would be t he most likely t est t o result in a useful
finding (eit her posit ive or negat ive). An implant ed loop recorder records pat ient -act ivat ed event s and aut omat ically records bradycardic and t achycardic event s; it is,
t herefore, significant ly less prone t o acquisit ion errors t han an event monit or.
Ext ernal event monit ors are of t wo t ypes: loop monit ors, which are worn and record cont inuously but only save when t he pat ient act ivat es t he monit or, and hand-held event
monit ors, which must be held t o t he chest t o record. Loop monit ors are useful for syncope because pat ient act ivat ion saves dat a from a short period of t ime (programmable
and varying by company) before t he monit or is act ivat ed by t he pat ient . Hand-held event monit ors are not useful for syncope, since t he pat ient cannot act ivat e t he monit or
when consciousness is lost .
This pat ient has had t hree syncopal event s in 3 years. Neit her a 24-hour ambulat ory monit or nor an event monit or would be a good choice because of t he infrequency of t he
pat ient 's sympt oms. He is highly unlikely t o have an event during t he st andard 24 hours of ambulat ory monit oring or t he st andard event monit or durat ion of 30 days. Event
monit ors are complex enough in t heir use t hat pat ient acquisit ion errors can occur, rendering t he result s less reliable. Since t his pat ient has no prodromal sympt oms, it is
unlikely t hat t he pat ient will be able t o t rigger t he event monit or prior t o t he onset of syncope.
Elect rophysiology st udy is incorrect because t he diagnost ic yield for syncope wit h an ot herwise normal cardiac evaluat ion is ext remely low.
Key Poi nt
The implant able loop recorder has been shown t o have t he great est diagnost ic yield and cost -effect iveness for t he evaluat ion of infrequent syncope.
Bi bl i ography
Gould PA, Krahn AD, Klein GJ, Yee R, Skanes AC, Gula LJ. Invest igat ing syncope: a review. Curr Opin Cardiol. 2006;21(1):34-41. [PMID: 16355027]
Item 19 Answer: B
Educati onal Objecti ve: Treat depression that does not respond to initial therapy by switching to another drug.
The most appropriat e management for t his pat ient is swit ching t o cit alopram. The goal of depression t herapy should not be simply improvement of sympt oms but rat her
remission of depressive sympt oms whenever possible. Pat ient s wit h no response t o full-dose t herapy wit hin 6 weeks should receive anot her medicat ion or referral for
psychot herapy. The STAR*D t rial found t hat 25% of pat ient s wit h major depression who did not respond t o an init ial ant idepressant achieved remission when anot her agent
was subst it ut ed for t he init ial drug. Because t his pat ient has not responded t o an appropriat e dose of sert raline aft er a reasonable period of t ime, changing t o anot her
ant idepressant such as cit alopram is indicat ed. Alt hough bot h cit alopram and sert raline are select ive serot onin reupt ake inhibit ors (SSRIs), t he STAR*D t rial report ed
essent ially ident ical responses when one SSRI was subst it ut ed for anot her or when an SSRI was changed t o an ant idepressant from a different class.
This pat ient has had a complet e lack of response t o sert raline aft er 3 mont hs. Therefore, cont inuing t his agent at t he same dose for anot her 4 weeks is unlikely t o be helpful.
Similarly, augment at ion wit h a second agent might be considered if a part ial response had been achieved wit h sert raline, but t hat is not t he case here. Alt hough several case
report s suggest ed met hylphenidat e might be an effect ive augment er, a randomized, double-blind, placebo-cont rolled t rial found no benefit for met hylphenidat e augment at ion
in t reat ment -resist ant depression.
Elect roconvulsive t herapy is reserved for sit uat ions warrant ing immediat e change and should be considered if profound suicidal ideat ion or psychot ic feat ures are present or if
t he pat ient fails t o respond t o mult iple ant idepressant s. However, a t rial of at least one ot her agent is warrant ed before considering elect roconvulsive t herapy in t he absence
of compelling urgency t o achieve a prompt response.
Key Poi nt
A pat ient wit h major depression who has not responded t o one ant idepressant at an appropriat e dose for an adequat e period should be given a different ant idepressant .
Bi bl i ography
Fancher TL, Kravit z RL. In t he clinic. Depression. Ann Int ern Med. 2010;152(9):ITC51-15; quiz ITC5-16. [PMID: 20439571]
Item 20 Answer: D
Educati onal Objecti ve: Manage a patient with depression with suicidal features with an urgent mental health referral.
This pat ient wit h major depression wit h suicidal ideat ion should be urgent ly referred t o a ment al healt h professional. Major depression is charact erized by t he presence of at
least five of t he nine crit eria for t his disorder, including at least one of t he t wo hallmark feat ures of depressed mood and anhedonia. The nine depressive sympt oms are as
follows: sleep dist urbance, psychomot or agit at ion or ret ardat ion, appet it e dist urbance, concent rat ion impairment , low energy level, depressed mood, lost int erest in act ivit ies,
guilt or wort hlessness, and suicidal ideat ion. This pat ient describes five of t hese sympt oms (poor concent rat ion, depressed mood, lack of int erest , guilt , suicidal ideat ion).
Urgent referral t o a psychiat rist is appropriat e for pat ient s wit h suicidal ideat ion and a plan. In evaluat ing a pat ient wit h major depression, previous suicide at t empt s should be
considered t he best predict or of complet ed suicide.
Pat ient s wit h suicidal ideat ion can be furt her risk st rat ified by assessing t he level of social support . Pat ient s wit h good social support can likely be safely referred t o a
psychiat rist for management .
Reassurance and careful follow-up is an insufficient course of act ion for a pat ient wit h suicidal ideat ion and a plan, part icularly if t here is no planned t herapeut ic int ervent ion.
Speaking wit h her fiance is similarly inadequat e.
Init iat ion of an ant idepressant wit h follow-up in 2 weeks would be an accept able approach for moderat e depression, but not for a pat ient wit h significant suicidal or homicidal
ideat ion or psychot ic feat ures.
Key Poi nt
Pat ient s wit h suicidal ideat ion and a plan should be eit her urgent ly referred t o a psychiat rist or hospit alized for psychiat ric assessment .
Bi bl i ography
Item 21 Answer: B
Educati onal Objecti ve: Manage bereavement-associated depression.
The most appropriat e management opt ion for t his pat ient is t o init iat e an ant idepressant , such as mirt azapine. Bet ween 20% and 30% of spouses experience depression or
complicat ed grief aft er t he loss of a loved one. Most negat ive sympt oms of bereavement peak before 6 mont hs, and most family members are able t o resume social act ivit ies
and ot her act ivit ies of daily living by 6 mont hs aft er t heir loved one's loss. Pat ient s who have sympt oms of major depression for at least 2 consecut ive weeks 8 or more
weeks aft er t heir loved one's deat h are candidat es for pharmacologic t herapy.
Major depression in t he set t ing of bereavement cannot be diagnosed unless t he sympt oms persist for more t han 2 mont hs or include subst ant ive funct ional impairment ,
morbid preoccupat ion wit h wort hlessness, suicidal ideat ion, psychot ic sympt oms, or psychomot or ret ardat ion. In t his pat ient , t he sympt oms have persist ed for more t han 2
mont hs, and t herapy is indicat ed. Mirt azapine would be an appropriat e init ial choice in t his pat ient because it is an effect ive ant idepressant and has a side effect of sedat ion.
Also, weight gain somet imes occurs wit h mirt azapine, which may be advant ageous in a depressed pat ient wit h weight loss.
Psychost imulant s such as dext roamphet amine have been st udied as an init ial t reat ment of depression but wit h inconsist ent efficacy result s. Treat ing t he insomnia wit h
zolpidem would not t reat t he underlying cause of t he insomnia. Reassuring t he pat ient does not adequat ely address t he underlying problem, for which t here is effect ive
t reat ment .
Key Poi nt
Pat ient s who meet sympt oms of major depression for at least 2 consecut ive weeks 8 or more weeks aft er t heir loved one's deat h are candidat es for pharmacologic t herapy.
Bi bl i ography
Fancher TL, Kravit z RL. In t he clinic. Depression. Ann Int ern Med. 2010;152(9):ITC51-15. [PMID: 20439571]
Item 22 Answer: B
Educati onal Objecti ve: Diagnose bipolar disorder.
This pat ient most likely has bipolar disorder. Alt hough she present s wit h sympt oms of depression, her hist ory includes episodes of mania or hypomania. Diagnost ic crit eria
for mania include a dist inct period of abnormally and persist ent ly elevat ed, expansive, or irrit able mood last ing at least 1 week. Typical sympt oms include inflat ed self-est eem
or grandiosit y, decreased need for sleep, dist ract ibilit y, increased goal-direct ed behavior, and excessive involvement in pleasurable act ivit ies t hat have a high pot ent ial for
consequences (unrest rained buying sprees, sexual indiscret ions). It is import ant t o ask depressed pat ient s about a personal and family hist ory of manic sympt oms in order t o
select an appropriat e t herapy.
The diagnosis of at t ent ion-deficit /hyperact ivit y disorder (ADHD) requires document at ion of mult iple sympt oms of inat t ent ion or hyperact ivit y and impulsivit y dat ing back
t o at least age 7 years. There is no hist ory provided t o indicat e eit her t hese sympt oms or relat ed impairment in t wo or more set t ings, such as school and home, so ADHD
appears an unlikely diagnosis.
There is also no hist ory provided of self-harm, dysfunct ional relat ionships, or int ense anger t o suggest borderline personalit y disorder. Alt hough t he impulsive sexual behavior
could be a manifest at ion of borderline personalit y disorder, it can also be charact erist ic of mania or hypomania, and t he overall present at ion is more consist ent wit h bipolar
disorder. While t here is overlap bet ween depression and generalized anxiet y disorder (GAD), wit h impaired concent rat ion, sleep dist urbance, and fat igue being common t o
bot h, t his pat ient report s depression as a prominent sympt om and has a hist ory of depression as well as a hist ory of prior manic or hypomanic periods. Thus, a diagnosis of
bipolar disorder is much more apt t han GAD.
Key Poi nt
Diagnost ic crit eria for mania include a dist inct period of abnormally and persist ent ly elevat ed, expansive, or irrit able mood last ing at least 1 week.
Bi bl i ography
Item 23 Answer: D
Educati onal Objecti ve: Prevent seizures in acute alcohol withdrawal syndrome.
Lorazepam should be administ ered now. Clinicians should ident ify t he severit y of alcohol wit hdrawal and fact ors t hat may predict t he onset of serious complicat ions. The 10-
it em Clinical Inst it ut e Wit hdrawal Assessment Scale for Alcohol, Revised, can be used t o measure sympt om severit y and t o help provide guidance in t he course of t reat ment .
Pat ient s scoring more t han 10 point s usually need addit ional medicat ion for wit hdrawal, and pat ient s scoring more t han 15 point s are t ypically hospit alized t o manage
alcohol wit hdrawal sympt oms. Benzodiazepines, such as lorazepam, are first -line t herapy for pat ient s who require pharmacologic prophylaxis or t reat ment for alcohol
wit hdrawal. Pat ient s wit h t he alcohol wit hdrawal syndrome who are t reat ed wit h benzodiazepines have fewer complicat ions, including delirium t remens and alcohol-wit hdrawal
seizures. Alt hough short er act ing agent s such as lorazepam are more commonly used, longer act ing agent s (chlordiazepoxide or diazepam) may be more effect ive in
prevent ing seizures but can pose a risk for excess sedat ion in older adult s and in pat ient s wit h liver disease. Pat ient s wit h a hist ory of seizures should receive a prophylact ic
benzodiazepine on a fixed schedule, even if asympt omat ic during t he acut e alcohol wit hdrawal period.
-Blockers, such as at enolol, and clonidine can be used t o cont rol t achycardia and hypert ension when needed but are adjunct ive, not primary, t reat ment s for alcohol
wit hdrawal. Haloperidol can be used t o t reat agit at ion and hallucinosis in pat ient s exhibit ing t hese signs. However, -blockers are associat ed wit h a great er incidence of
delirium, and neurolept ics like haloperidol are associat ed wit h a great er incidence of seizures during wit hdrawal. The use of ant iepilept ics, such as phenyt oin, is ineffect ive
compared wit h benzodiazepines in prevent ing alcohol-relat ed seizures.
Key Poi nt
Benzodiazepines are t he drug class of choice for prophylaxis of alcohol wit hdrawal seizures.
Bi bl i ography
Bayard M, McInt yre J, Hill KR, Woodside J Jr. Alcohol wit hdrawal syndrome. Am Fam Physician. 2004;69(6):1443-50. [PMID: 15053409]
Item 24 Answer: B
Educati onal Objecti ve: Manage cocaine intoxication.
This pat ient 's sympat homimet ic syndrome is consist ent wit h cocaine int oxicat ion. Clinical findings oft en include t achycardia, hypert ension, hypert hermia, mydriasis,
agit at ion, and psychosis. Ot her possible complicat ions of cocaine abuse may be difficult t o evaluat e in t he agit at ed pat ient . The init ial t reat ment in t his pat ient should include
sedat ion wit h lorazepam, administ ered int ravenously or int ramuscularly. Cont rol of agit at ion usually brings about a decrease in heart rat e, blood pressure, and t emperat ure.
Int ravenous fluids should be administ ered t o est ablish adequat e urine out put for possible rhabdomyolysis, and an elect rocardiogram should be obt ained t o assess for myocardial
ischemia. Laborat ory st udies should include measurement of serum elect rolyt es and serum creat ine kinase and evaluat ion of liver funct ion. CT scan of t he brain may be
indicat ed t o rule out int racranial injury.
Haloperidol is not init ially indicat ed for cont rol of agit at ion in a pat ient who abuses cocaine. Haloperidol has t he pot ent ial t o lower t he seizure t hreshold and would not be an
init ial t reat ment in t his pat ient , who has already had a seizure. Aft er agit at ion is cont rolled, haloperidol can be considered if t he pat ient manifest s psychot ic feat ures.
Drug-induced seizures, which are usually self-limit ed, do not respond well t o phenyt oin. The t reat ment of choice for drug-induced seizures is benzodiazepines.
Hypert ension is rarely severe in cocaine abuse, and it usually responds t o cont rol of agit at ion. Propranolol and ot her -blockers are not recommended because of t he
pot ent ial concern about worsening of vasoconst rict ion due t o unopposed -blocking effect s.
Key Poi nt
The init ial t reat ment of acut e cocaine int oxicat ion is sedat ion wit h a benzodiazepine.
Bi bl i ography
Glauser J, Queen JR. An overview of non-cardiac cocaine t oxicit y. J Emerg Med. 2007;32:181-6. Epub 2007 Jan 22. [PMID: 17307630]
Item 25 Answer: D
Educati onal Objecti ve: Manage alcohol dependence with naltrexone.
This pat ient present s wit h a hist ory of alcohol dependence. Brief int ervent ions work for pat ient s wit h at -risk alcohol use, but more aggressive t herapy, pot ent ially including
pharmacot herapy, is indicat ed in bot h alcohol abuse and alcohol dependence. Nalt rexone, an opioid recept or ant agonist , has been shown t o be effect ive in short -t erm
t reat ment as well as in decreasing t he frequency of relapse. Benzodiazepines, such as diazepam, would be used in t he acut e det oxificat ion set t ing. Ant idepressant s and
anxiolyt ics may play a role if an underlying psychiat ric disorder is present but is not a primary t reat ment of alcohol dependence. Disulfiram has been used for years and works
by leading t o an accumulat ion of aldehyde if alcohol is consumed, result ing in vomit ing, headache, and anxiet y. However, st udies have been inconclusive on it s efficacy in
enhancing abst inence.
Key Poi nt
Nalt rexone, an opioid recept or ant agonist , has been shown t o be effect ive in short -t erm t reat ment of alcohol dependence as well as in decreasing t he frequency of relapse.
Bi bl i ography
In t he clinic. Alcohol use. Ann Int ern Med. 2009;150:ITC3-1-ITC3-15; quiz ITC3-16. Errat um in: Ann Int ern Med. 2009;150:504. [PMID: 19258556]
Item 26 Answer: C
Educati onal Objecti ve: Manage hypoventilation caused by opioid overdose with naloxone.
The most appropriat e next st ep is int ravenous administ rat ion of naloxone. The pat ient 's acut e vent ilat ory failure is most consist ent wit h hypovent ilat ion result ing from
opioid int oxicat ion. In pure hypovent ilat ion, t he alveolar-art erial difference is normal. Improved alert ness aft er administ rat ion of naloxone confirms opioid int oxicat ion.
Naloxone has a short half-life and is t ypically given as a cont inuous int ravenous infusion. If t he response t o naloxone is inadequat e, endot racheal int ubat ion would be
appropriat e.
Benzodiazepines, such as diazepam, can be used t o t reat cocaine t oxicit y. Acut e cocaine t oxicit y is charact erized by hypert ension, t achycardia, hypert hermia, mydriasis, and
agit at ion. This pat ient 's present at ion is not consist ent wit h acut e cocaine int oxicat ion.
Int ravenous fomepizole is an effect ive t reat ment for et hylene glycol and met hyl alcohol poisoning. These alcohols cause an anion gap met abolic acidosis and an osmolar gap.
This pat ient has an isolat ed acut e respirat ory acidosis t hat is not compat ible wit h et hylene glycol and met hyl alcohol poisoning, and t hus fomepizole is not indicat ed.
Tradit ional t herapy for cyanide poisoning includes inhalat ion of amyl nit rit e followed by t he administ rat ion of int ravenous sodium nit rit e or sodium t hiosulfat e. Cyanide
poisoning result s from inhalat ion of gaseous hydrogen cyanide or t he ingest ion of pot assium or sodium cyanide. Hydrogen cyanide poisoning is also common as a result of
smoke inhalat ion from fires. Ingest ion of cyanide is most oft en associat ed wit h suicides and homicides. Inhalat ion result s in seizures, coma, and cardiopulmonary arrest .
Chronic exposure t o low levels result s in weakness and paralysis. The pat ient 's findings are not compat ible wit h cyanide poisoning.
Key Poi nt
Cont inuous naloxone infusion is used t o t reat opioid int oxicat ion.
Bi bl i ography
St rang J, Kelleher M, Best D, Mayet S, Manning V. Emergency naloxone for heroin overdose. BMJ. 2006;333(7569):614-615. [PMID: 16990298]
Item 27 Answer: B
Educati onal Objecti ve: Screen a patient for alcohol problems.
The CAGE quest ionnaire is t he best choice t o screen for alcohol problems. The CAGE quest ionnaire is a commonly used inst rument t o ident ify alcohol problems:
C - Have you ever felt you should cut down on your drinking?
A - Have people annoyed you by crit icizing your drinking?
G - Have you ever felt bad or guilt y about your drinking?
E - Eye opener: Have you ever had a drink first t hing in t he morning t o st eady your nerves or t o get rid of a hangover?
Wit h a cut off of t wo posit ive answers, t he CAGE quest ionnaire is 77% t o 94% sensit ive and 79% t o 97% specific for det ect ing alcohol abuse or dependence in primary care
set t ings and indicat es t hat furt her assessment is warrant ed. Alcohol abuse may be difficult t o diagnose. Pat ient s oft en present wit h complaint s t hat may be at t ribut able t o
ot her medical condit ions but act ually are caused by alcohol consumpt ion. These problems might include depression, insomnia, injuries, gast roesophageal reflux disease,
uncont rolled hypert ension, and import ant social problems. Ot her pot ent ial clues t o alcohol misuse are recurrent legal or marit al problems, absent eeism or loss of
employment , and commit t ing or being t he vict im of violence. The U.S. Prevent ive Services Task Force (USPSTF) recommends rout ine screening of adult s wit h eit her
direct ed quest ioning or use of a st andardized t ool t o ident ify persons whose alcohol use put s t hem at risk. More likely t o be at risk are t hose wit h prior alcohol problems,
young adult s, and smokers. The USPSTF found good evidence t hat brief behavioral counseling int ervent ions wit h follow-up produce small t o moderat e reduct ions in alcohol
consumpt ion t hat are sust ained over 6- t o 12-mont h periods or longer.
Alt hough t he opt imal int erval for screening is not known, screening at t he t ime of an init ial visit is clearly import ant . There are mult iple screening inst rument s; t he CAGE
quest ionnaire is one of t he most widely used. Two posit ive responses indicat e t hat furt her assessment for alcohol misuse is warrant ed.
The CAGE quest ionnaire has a report ed sensit ivit y ranging from 43% t o 94% and specificit y ranging from 70% t o 97%.
Laborat ory t est s such as an elevat ed mean corpuscular volume (sensit ivit y 63%; specificit y 48%) and an elevat ed aspart at e aminot ransferase/alanine aminot ransferase rat io
(sensit ivit y 12%; specificit y 91%) can be suggest ive but are not diagnost ic of alcohol abuse and dependence. Their relat ively low sensit ivit ies make t hem unsuit ed for
screening.
Because of t he short half-life of et hanol, a random et hanol level should not be used t o screen for alcoholism.
Key Poi nt
Screening inst rument s such as t he CAGE quest ionnaire are effect ive for alcohol misuse screening in t he primary care set t ing.
Bi bl i ography
Sait z R. Clinical pract ice. Unhealt hy alcohol use. N Engl J Med. 2005;352(6):596-607. [PMID: 15703424]
Item 28 Answer: D
Educati onal Objecti ve: Treat lumbar spinal stenosis with surgery.
Back pain and neurologic impairment from spinal st enosis may be t reat ed by surgery. In considering surgical t reat ment for pat ient s wit h back pain from radiculopat hy or
spinal st enosis, guidelines recommend referring pat ient s aft er a minimum of 3 mont hs t o 2 years of failed nonsurgical int ervent ions. Failure is defined as progressive
neurologic deficit s and severe pain t hat is not responsive t o conservat ive t reat ment . This pat ient has t ried conservat ive t herapy wit h first -line medicat ion t reat ment
(NSAIDS and acet aminophen) and physical t herapy, yet her sympt oms have progressed. Therefore, if she is willing t o consider surgical t reat ment , t hen t he next appropriat e
st ep is t o refer t he pat ient for surgical considerat ion. Surgical t reat ment of spinal st enosis is usually elect ive.
Elect romyography and nerve conduct ion st udies are not required for t he diagnosis of lumbar spinal st enosis but may be helpful in pat ient s wit h at ypical sympt oms and when
t he possibilit y of an alt ernat ive diagnosis such as peripheral neuropat hy is considered. There is current ly very lit t le evidence t o support t he use of cort icost eroid inject ions in
t he t reat ment of spinal st enosis. Spinal t ract ion is t he applicat ion of const ant or int ermit t ent pulling force applied t o t he spine t o gradually st ret ch t he spine. Cont inuous or
int ermit t ent spinal t ract ion has not been shown t o be effect ive in pat ient s wit h sciat ica or spinal st enosis.
Key Poi nt
Back pain and neurologic impairment from spinal st enosis may be t reat ed by surgery.
Bi bl i ography
Wilson JF. In t he clinic. Low back pain. Ann Int ern Med. 2008;148(9):ITC5-1-ITC5-16. [PMID: 18458275]
Item 29 Answer: C
Educati onal Objecti ve: Diagnose vertebral osteomyelitis.
The most appropriat e management is urgent spine MRI. "Red flags" in t his pat ient 's present at ion suggest ing a syst emic illness as t he cause of back pain include localized pain,
hist ory of int ravenous drug use, fever, and elevat ed eryt hrocyt e sediment at ion rat e. These findings st rongly suggest t he possibilit y of vert ebral ost eomyelit is, infect ious
diskit is, or spinal epidural abscess. Most pat ient s wit h vert ebral ost eomyelit is have back or neck pain t hat gradually worsens over weeks or mont hs; fever is present in only
50% of pat ient s and leukocyt osis is t ypically absent , but t he eryt hrocyt e sediment at ion rat e is oft en great er t hat 100 mm/h. Tenderness t o palpat ion over t he involved
port ion of t he spine is common. Vert ebral ost eomyelit is is most oft en disseminat ed hemat ogenously. Segment al art eries supply blood t o t he vert ebrae, wit h bifurcat ing
art eries supplying blood t o t he inferior margin of one end plat e and t he superior margin of t he adjacent end plat e. Consequent ly, when infect ion occurs, it generally follows
t his vascular pat t ern, involving bone in t wo adjacent vert ebral bodies wit h invasion int o t heir int ervert ebral disk (diskit is). Pot ent ial sources of hemat ogenous ost eomyelit is
include skin (inject ion drug users), urinary t ract , or respirat ory t ract infect ion; endocardit is; or int ravascular cat het er-relat ed infect ion. Pat ient s wit h infect ious diskit is are at
risk for spinal epidural abscess. Because blood cult ures are posit ive in up t o 75% of pat ient s wit h vert ebral ost eomyelit is, t hey should be obt ained for all pat ient s in whom t his
condit ion is suspect ed. In pat ient s wit h suspect ed vert ebral ost eomyelit is, diskit is, or spinal epidural abscess, urgent evaluat ion wit h imaging is warrant ed. MRI is t he preferred
imaging modalit y, because scans show changes of acut e ost eomyelit is wit hin days of infect ion and are superior t o and more sensit ive (90%) and specific (80%) t han plain
films and CT scans; can det ect soft t issue abscesses and epidural, paravert ebral, or psoas abscesses possibly requiring surgical drainage; and can delineat e anat omy before
surgery. Nonet heless, false-posit ive MRI result s may occur in pat ient s wit h noninfect ious condit ions such as fract ures, t umors, and healed ost eomyelit is.
Ant ibiot ic t herapy, wit h or wit hout surgery, is t ypically required t o t reat spine and relat ed soft t issue infect ion. However, ant ibiot ic t herapy should be guided, whenever
possible, by blood cult ure result s; empiric ant ibiot ic t herapy wit hout an at t empt t o confirm t he underlying cause of t he pat ient 's pain and source of infect ion is inappropriat e.
Key Poi nt
MRI is t he preferred imaging modalit y for suspect ed vert ebral ost eomyelit is, because scans show changes of acut e ost eomyelit is wit hin days of infect ion and are superior t o
plain films and CT scans.
Bi bl i ography
Wilson JF. In t he clinic. Low back pain. Ann Int ern Med. 2008;148:ITC5-1-ITC5-16. [PMID: 18458275]
Item 30 Answer: A
Educati onal Objecti ve: Manage acute nonspecific low back pain with acetaminophen.
The best init ial management opt ion for t his pat ient is acet aminophen. This pat ient has acut e low back pain result ing from a recent injury. He has no signs of neurologic
compromise or pot ent ially serious underlying condit ions. Guidelines published by t he American College of Physicians and t he American Pain Societ y recommend
acet aminophen or NSAIDs for first -line t reat ment of acut e nonspecific low back pain. An opioid analgesic or t ramadol is an opt ion when used judiciously in pat ient s wit h
severe, disabling acut e low back pain t hat is not cont rolled (or is unlikely t o be cont rolled) wit h acet aminophen or NSAIDs. Pat ient s should be informed t hat t he prognosis for
acut e low back pain is generally good and t hat most pat ient s improve wit hin 1 mont h.
The pat ient has no signs of neurologic compromise or feat ures suggest ing a pot ent ially serious condit ion; t herefore, MRI would not be necessary. Even if t here were signs of
disk herniat ion (a posit ive st raight leg raising t est ), an MRI would not be necessary unless t he pat ient had evidence of mot or impairment , had not responded t o t herapy, or
sympt oms were increasing.
Lumbar plain radiographs are generally not recommended in t he evaluat ion of low back pain because t here is no evidence t hat rout ine plain radiography in pat ient s wit h
nonspecific low back pain is associat ed wit h a great er improvement in pat ient out comes t han select ive imaging. Plain radiographs would be appropriat e if a vert ebral
compression fract ure is suspect ed.
St udies have not demonst rat ed t hat bed rest is helpful in acut e low back pain, and it may impair recovery t ime.
Key Poi nt
Acet aminophen or NSAIDs are first -line t herapy for acut e nonspecific low back pain.
Bi bl i ography
Wilson JF. In t he clinic. Low back pain. Ann Int ern Med. 2008;148(9):ITC5-1-ITC5-16. [PMID: 18458275]
Item 31 Answer: C
Educati onal Objecti ve: Diagnose spinal cord compression due to bone metastases with MRI scan.
The next diagnost ic st udy should be an MRI scan of t he t horacolumbar spine. This pat ient most likely has spinal cord compression due t o bone met ast ases from recurrent
prost at e cancer. The t hree most common malignancies responsible for spinal cord compression are prost at e, breast , and lung cancer. His signs and sympt oms are consist ent
wit h spinal cord compression. The init ial sympt om in pat ient s wit h epidural spinal cord compression due t o t umor usually is spinal or radicular pain t hat may precede t he
onset of neurologic sympt oms, which may include weakness, numbness, or sphinct er dist urbances. Spinal cord compression is an oncologic emergency, and MRI of t he
t horacolumbar spine is needed t o confirm t he diagnosis and assist in t reat ment planning. Clinicians should have a low t hreshold of suspicion for spinal cord compression in a
pat ient wit h known cancer or a risk for recurrent cancer. The absence of neurologic findings should not alt er t hat st rat egy. Pat ient s whose cord compression is discovered
aft er developing neurologic deficit s are more likely t o remain funct ionally impaired aft er int ervent ion.
Radionuclide bone scanning is very sensit ive for det ect ing bone met ast ases and has t he advant age of visualizing t he ent ire skelet on, but it has a high false-posit ive rat e and
provides no informat ion about t hecal sac compression. Because a bone scan cannot confirm a diagnosis of spinal cord compression, it is an inappropriat e diagnost ic t est in
t his emergent set t ing.
The clinical feat ure of bilat eral lower ext remit y weakness accompanied by hyperreflexia localizes t he process t o t he spinal cord. An MRI of t he brain would t herefore be an
inappropriat e diagnost ic t est .
Plain radiographs are used t o diagnose compression fract ures of t he t horacic spine but cannot direct ly visualize spinal cord compression. In a pat ient such as t his, major
vert ebral body collapse or pedicle erosion is approximat ely 80% predict ive of spinal cord compression, but a false-negat ive result occurs in nearly 20% of pat ient s wit h spinal
cord compression. Therefore, plain radiography is not t he best diagnost ic t est for t his pat ient .
Key Poi nt
The t riad of back pain, muscle weakness, and loss of bowel or bladder cont rol is suggest ive of spinal cord compression.
Bi bl i ography
Cole JS, Pat chell RA. Met ast at ic epidural spinal cord compression. Lancet Neurol. 2008;7(5):459-66. [PMID: 18420159]
Item 32 Answer: E
Educati onal Objecti ve: Diagnose cough-variant asthma with a trial of inhaled albuterol.
A t rial of inhaled albut erol could help cont rol t he pat ient 's sympt oms and confirm t he diagnosis of cough-variant ast hma. The most common causes of chronic cough are
ast hma, post nasal drip syndrome (chronic sinusit is-rhinit is), and gast roesophageal reflux disease (GERD). Bronchoscopy and chest CT play no role in diagnosing cough due t o
t hese t hree causes. The diagnosis of cough-variant ast hma is suggest ed by t he presence of airway hyperresponsiveness and confirmed when cough resolves wit h ast hma
t herapy.
The pat ient does not have post nasal drip, purulent nasal secret ions, sinus congest ion, or ot her sympt oms suggest ive of chronic or recurrent sinusit is and has not responded t o
t reat ment . Therefore, CT of t he sinuses is not necessary. If t he pat ient does not respond t o albut erol, eosinophilic bronchit is should be considered as t he cause of chronic
cough, and bronchoscopy wit h biopsy should be performed t o confirm t hat diagnosis. Ot herwise, bronchoscopy is not a first -line diagnost ic t est in t his pat ient .
There is lit t le about t he charact er and t iming of chronic cough due t o GERD t hat dist inguishes it from ot her condit ions; in addit ion, it oft en can be "silent " from a
gast roint est inal st andpoint . However, t he pat ient did not benefit from 3 mont hs of empiric gast ric acid suppression t herapy for GERD. Therefore, it is reasonable t o rule out
cough-variant ast hma before pursuing 24-hour esophageal pH monit oring.
Key Poi nt
The diagnosis of cough-variant ast hma is suggest ed by t he presence of airway hyperresponsiveness and confirmed when cough resolves wit h a t rial of inhaled albut erol.
Bi bl i ography
Abouzgheib W, Prat t er MR, Bart t er T. Cough and ast hma. Curr Opin Pulm Med. 2007;13(1):44-48. [PMID: 17133124]
Item 33 Answer: A
Educati onal Objecti ve: Initiate empiric management for chronic cough with antihistamine/decongestant combination.
The most appropriat e t reat ment for t his pat ient is a t rial of an ant ihist amine/decongest ant combinat ion. The init ial approach in pat ient s wit h chronic cough (>8 weeks in
durat ion) is t o conduct a hist ory and physical examinat ion looking for ident ifiable causes, det ermine whet her t he pat ient is t aking an angiot ensin-convert ing enzyme (ACE)
inhibit or, and obt ain a chest radiograph. In t he populat ion of pat ient s who do not smoke, do not t ake an ACE inhibit or, and have a normal chest radiograph, upper airway
cough syndrome (UACS) (previously t ermed postnasal drip), ast hma, and gast roesophageal reflux disease (GERD) are responsible for approximat ely 99% of cases of chronic
cough. When t he cause of a chronic cough is unclear, t he American College of Chest Physicians recommends init ial t reat ment wit h a first -generat ion
ant ihist amine/decongest ant combinat ion t o t reat UACS. This is t rue even in t he absence of evidence of a post nasal drip. The diagnosis of chronic cough is oft en based upon
t he pat ient 's response t o empiric t herapy, and it may t ake weeks or even mont hs for t he cough t o resolve wit h appropriat e t herapy.
In a nonsmoking pat ient wit h a normal chest radiograph and no syst emic sympt oms, CT scan of t he chest is not indicat ed.
Ast hma is a common cause for a chronic cough and may present only wit h a cough (cough-variant ast hma). However, pursuing pulmonary funct ion t est ing or init iat ing
empiric -agonist t herapy or an inhaled cort icost eroid such as flut icasone for ast hma is premat ure unless t he pat ient fails t o respond t o empiric t reat ment of UACS.
In t he absence of GERD sympt oms, prot on-pump inhibit ors should be reserved for pat ient s wit h chronic cough who have a normal chest radiograph, are not t aking an ACE
inhibit or, do not smoke, and who have failed t o improve wit h t reat ment for UACS, ast hma, and nonallergic eosinophilic bronchit is.
In pat ient s wit h chronic cough who have normal chest radiograph findings, normal spiromet ry, and a negat ive met hacholine challenge t est , t he diagnosis of nonast hmat ic
eosinophilic bronchit is (NAEB) should be considered. This diagnosis is oft en considered aft er pat ient s fail t o respond t o t reat ment s direct ed at UACS, GERD, and ast hma.
Alt hough confirmat ion of NAEB requires a bronchial biopsy, t he response t o empirically administ ered inhaled cort icost eroids is oft en used t o est ablish t he diagnosis.
Key Poi nt
Empiric t reat ment of chronic cough in a nonsmoking pat ient not t aking an angiot ensin-convert ing enzyme inhibit or who has a normal chest radiograph begins wit h an
ant ihist amine/decongest ant combinat ion.
Bi bl i ography
Pavord ID, Chung KF. Management of chronic cough. Lancet . 2008;371(9621):1375-1384. [PMID: 18424326]
Item 34 Answer: A
Educati onal Objecti ve: Diagnose angiotensin-converting enzyme inhibitor chronic cough.
The most appropriat e management opt ion for t his pat ient is t o discont inue t he angiot ensin-convert ing enzyme (ACE) inhibit or, lisinopril. This pat ient present s wit h a
cough of longer t han 8 weeks' durat ion and t hus meet s t he definit ion for chronic cough. According t o American College of Chest Physicians guidelines, t he init ial evaluat ion
includes a hist ory and physical examinat ion t o det ermine likely et iologies, followed by a chest radiograph t o ident ify obvious abnormalit ies. If t he chest radiograph is normal,
one should recommend discont inuing ACE inhibit ors and smoking, if t hese fact ors are ident ified in t he hist ory, or pursue empiric management of chronic cough if t he pat ient
is a nonsmoker and is not t aking an ACE inhibit or. In some est imat es, up t o 20% of pat ient s t aking an ACE inhibit or develop a chronic cough. There may be no obvious
t emporal relat ionship bet ween t he init iat ion of ACE inhibit or t herapy and t he onset of cough. The median t ime t o resolut ion is 26 days from wit hdrawal of t he ACE
inhibit or.
In pat ient s wit h chronic cough and a normal chest radiograph, a chest CT is only indicat ed for t hose at high risk for lung cancer.
Upper airway cough syndrome (UACS) is a common cause of chronic cough. A t rial of a first -generat ion ant ihist amine/decongest ant combinat ion for several weeks is
appropriat e t reat ment for UACS. In a nonsmoking pat ient who is t aking an ACE inhibit or, however, t he ACE inhibit or should be discont inued for several weeks before
t reat ing for UACS.
Ast hma and nonallergic eosinophilic bronchit is may present wit hout any sympt oms ot her t han cough. Spiromet ry would be indicat ed in t he evaluat ion of chronic cough t hat
has not resolved aft er t he init ial management measures (hist ory, physical examinat ion, chest radiograph, cessat ion of ACE inhibit or, t reat ment for upper airway cough
syndrome).
Alt hough empiric t herapy for gast roesophageal reflux disease (GERD) is appropriat e if prominent sympt oms of GERD accompany t he cough or if init ial management
measures fail, discont inuing t he ACE inhibit or always should precede empiric t herapy for GERD.
Key Poi nt
In pat ient s t aking an angiot ensin-convert ing enzyme inhibit or who present wit h a chronic cough and a normal chest radiograph, discont inuing t he angiot ensin-convert ing
enzyme inhibit or may be bot h diagnost ic and t herapeut ic.
Bi bl i ography
Irwin RS, Baumann MH, Bolser DC, et al; American College of Chest Physicians (ACCP). Diagnosis and management of cough execut ive summary: ACCP evidence-based
clinical pract ice guidelines. Chest . 2006;129(1 suppl):1S-23S. [PMID: 16428686]
Item 35 Answer: A
Educati onal Objecti ve: Use chest CT to evaluate a patient with hemoptysis for lung cancer.
The most appropriat e next st ep in t he management of t his pat ient is chest CT. The most commonly encount ered causes of hemopt ysis in ambulat ory pat ient s are infect ion
(bronchit is or pneumonia) and malignancy. All pat ient s wit h hemopt ysis should have a chest radiograph. Risk fact ors t hat increase t he risk of malignancy include male sex,
age older t han 40 years, a smoking hist ory of more t han 40 pack-years, and sympt oms last ing for more t han 1 week. These pat ient s should be referred for chest CT and
fiberopt ic bronchoscopy even if t he chest radiograph is normal.
Sput um cyt ology examinat ion alone is not effect ive in early diagnosis of lung cancer because of low sensit ivit y. Alt hough pulmonary funct ion t est ing can det ermine if t he
pat ient has chronic obst ruct ive pulmonary disease and whet her t he pat ient is a surgical candidat e, it is not indicat ed t o est ablish a diagnosis of lung cancer. Follow up in 6
mont hs is not an advisable st rat egy for a pat ient at high risk for lung cancer such as t his pat ient ; delayed diagnosis may result in subopt imal out come.
Key Poi nt
All pat ient s wit h hemopt ysis should have a chest radiograph; pat ient s at high risk for lung cancer should be referred for chest CT and fiberopt ic bronchoscopy even if t he
chest radiograph is normal.
Bi bl i ography
Dudha M, Lehrman S, Aronow WS, Rosa J. Hemopt ysis: diagnosis and t reat ment . Compr Ther. 2009;35(3-4):139-49. [PMID: 20043609]
Item 36 Answer: E
Educati onal Objecti ve: Treat acute bronchitis with symptomatic measures.
The best management for t his pat ient is sympt omat ic t reat ment . Treat ment of acut e bronchit is is usually sympt omat ic. There is no evidence t o support t he use of most
over-t he-count er and prescript ion ant it ussive medicat ions. However, some st udies have shown t hat NSAIDs, wit h or wit hout an ant ihist amine, decrease cough severit y. A t rial
of ibuprofen may be reasonable for t his pat ient , provided t here are no cont raindicat ions.
Albut erol in a met ered-dose inhaler may help t o decrease cough severit y and durat ion in adult s wit h acut e bronchit is when t here is evidence of wheezing. However, -agonist
inhalers have not been shown t o be helpful in t he absence of wheezing and, t herefore, probably would not benefit t his pat ient .
Approximat ely 50% of pat ient s wit h acut e bronchit is have purulent sput um, but t his is not a reliable predict or of bact erial infect ion. Most st udies fail t o show t hat
administ rat ion of ant ibiot ics, such as azit hromycin, significant ly improves out comes, including sympt om resolut ion and early ret urn t o work, in pat ient s wit h acut e
bronchit is. In pat ient s wit h an acut e exacerbat ion of chronic obst ruct ive pulmonary disease, ant ibiot ic t herapy is most likely t o be helpful in t hose wit h at least t wo of t he
following: increased sput um purulence (change in sput um color), increased sput um volume, or increased dyspnea. Ant ibiot ics are appropriat e for pat ient s wit h pert ussis in
order t o decrease disease t ransmission, alt hough t hese agent s have a limit ed effect on sympt oms. Pert ussis should be suspect ed when a communit y out break has been report ed.
Sympt oms may include coughing paroxysms and post t ussive vomit ing but are not reliable indicat ors of infect ion.
A chest radiograph is not indicat ed in a pat ient wit h acut e bronchit is who does not have signs or sympt oms of pneumonia, such as fever, dyspnea, and pleurit ic chest pain.
Cough t hat persist s for more t han 3 weeks is at ypical for acut e bronchit is, and a chest radiograph is generally indicat ed as t he init ial diagnost ic t est .
Influenza virus cult ure is not needed in a pat ient wit hout fever, myalgia, or malaise because t he probabilit y of influenza virus infect ion is very low.
Key Poi nt
Ant ibiot ics are not beneficial for pat ient s wit h acut e bronchit is.
Bi bl i ography
Wenzel RP, Fowler AA 3rd. Clinical Pract ice. Acut e bronchit is. N Engl J Med. 2006;355(20):2125-2130. [PMID: 17108344]
Item 37 Answer: A
Educati onal Objecti ve: Treat chronic obstructive pulmonary disease with smoking cessation.
Smoking cessat ion is t he single most effect ive int ervent ion t o reduce t he risk of developing chronic obst ruct ive pulmonary disease and t o st op it s progression. Short -t erm
t obacco dependence t reat ment is effect ive, and every t obacco user should be offered counseling and nicot ine replacement (pat ch, gum, inhaler, and nasal spray) at every visit .
Counseling should focus on est ablishing a quit dat e, emphasizing abst inence, using ot her family members, and avoiding alcohol and ot her drugs. Several effect ive
pharmacot herapies for t obacco dependency are available and at least one of t hese medicat ions should be added t o counseling unless cont raindicat ed. Dat a from t he Nat ional
Inst it ut es of Healt h Lung Healt h St udy revealed t hat more part icipant s in t he smoking int ervent ion group quit compared wit h usual and cust omary t herapy (year 1: 34.4% vs.
9.0%; year 5: 37.4% vs. 21.9%). The annual rat e of decline in FEV
1
over 4 years for quit t ers was half t hat for cont inuing smokers.
This pat ient is already on t herapeut ic doses of a long-act ing bronchodilat or, an inhaled cort icost eroid, iprat ropium, and a short -act ing -agonist , and she does not exhibit
oxyhemoglobin desat urat ion wit h exert ion. Therefore, she does not need any changes in her inhaled medicat ions or require supplement al oxygen t herapy.
Key Poi nt
Smoking cessat ion is t he single most effect ive int ervent ion t o reduce t he risk of developing chronic obst ruct ive pulmonary disease and t o st op it s progression.
Bi bl i ography
Wilson JF. In t he clinic. Smoking cessat ion. Ann Int ern Med. 2007;146:ITC2-1-ICT2-16. [PMID: 17283345]
Item 38 Answer: A
Educati onal Objecti ve: Know the effects of smoking cessation on lung function.
This pat ient likely has chronic obst ruct ive pulmonary disease (COPD), based on her clinical findings and pulmonary funct ion result s (FEV
1
<80% and FEV
1
/FCV <0.7). In t he
Lung Healt h St udy, 6000 smokers wit h mild t o moderat e COPD were randomized t o receive smoking int ervent ion plus iprat ropium bromide, smoking int ervent ion plus
placebo, or no int ervent ion. Lung funct ion was monit ored for 5 years. The smoking int ervent ion arms were bot h associat ed wit h a decreased rat e of decline in lung funct ion.
The use of a bronchodilat or had a small beneficial effect on lung funct ion. The benefit did not persist aft er pat ient s st opped using t he bronchodilat or. In a subsequent st udy,
t he Lung Healt h St udy II, inhaled cort icost eroids did not improve t he rat e of decline in lung funct ion.
Among t hose who quit smoking, lung funct ion improved during t he first year by an average of 2%. Women who successfully quit smoking improved by 3.7%, compared wit h
men, who improved by 1.6%. In t he smoking int ervent ion group, among t hose who quit smoking, t he subsequent rat e of decline in lung funct ion was 31 mL per year, a
normal value, compared wit h cont inuing smokers, whose lung funct ion declined at a rat e of 63 mL per year.
Key Poi nt
Smoking cessat ion is associat ed wit h a decreased rat e of decline in lung funct ion.
Bi bl i ography
Wilson JF. In t he clinic. Smoking cessat ion. Ann Int ern Med. 2007;146(3):ITC2-1-ICT2-16. [PMID: 17283345]
Item 39 Answer: B
Educati onal Objecti ve: Counsel the patient on smoking cessation to reduce the risk of cardiovascular disease.
Smoking cessat ion will have t he great est impact on reducing t his pat ient 's risk of fut ure cardiovascular disease. This woman has several risk fact ors for cardiovascular disease,
including obesit y (BMI >30), her family hist ory, her sedent ary lifest yle, and her smoking st at us. When faced wit h t he possibilit y of mult iple int ervent ions for cardiovascular
disease risk fact or management , it is oft en import ant t o counsel t he pat ient regarding t he relat ive benefit of each int ervent ion and t o address t he risk fact ors and
int ervent ions sequent ially. However, t here are also dat a t o suggest t hat addressing mult iple risk fact ors sequent ially is not superior t o a simult aneous approach. Women who
are current smokers have a t hreefold higher risk of cardiovascular disease compared wit h women who have st opped smoking or have never smoked. Surprisingly, t he durat ion
of smoking does not correlat e wit h risk of fut ure cardiovascular disease. (It does, however, correlat e wit h risk of smoking-relat ed cancers and lung disease.) In addit ion, t he
risk of cardiovascular disease drops rapidly aft er smoking cessat ion, wit h t he great est relat ive reduct ion occurring in t he first 5 years aft er st opping. Therefore, alt hough t his
pat ient has a 32-pack-year hist ory of smoking, smoking cessat ion now will immediat ely and significant ly reduce her risk of cardiovascular disease. Wit h regard t o her risk of
having a cardiovascular event , t he Framingham risk est imat e is calculat ed t o be 3% over t he next 10 years (low risk) compared wit h less t han 1% if she were a nonsmoker.
Ot her import ant lifest yle considerat ions include regular exercise, a healt hy diet , and maint aining a healt hy weight . While t hese int ervent ions have been shown t o reduce t he
risk of hypert ension and diabet es, t hey have not conclusively been shown t o reduce t he risk of cardiovascular event s.
Key Poi nt
The risk of a cardiovascular event is reduced rapidly (wit hin 5 years) of smoking cessat ion in women.
Bi bl i ography
Kenfield SA, St ampfer MJ, Rosner BA, Coldit z GA. Smoking and smoking cessat ion in relat ion t o mort alit y in women. JAMA. 2008;299(17):2037-2047. [PMID: 18460664]
Item 40 Answer: D
Educati onal Objecti ve: Treat smoking addiction with varenicline.
The most appropriat e pharmacologic t herapy for t his pat ient is varenicline. The U.S. Public Healt h Service has recommended brief smoking cessat ion counseling
int ervent ions for smokers int erest ed in quit t ing. Pot ent ial quit t ers should be warned of wit hdrawal sympt oms (which will improve in several weeks), plan a coping st rat egy for
cravings (such as chewing gum), avoid high-risk smoking sit uat ions, and ant icipat e some weight gain.
For t his pat ient who would like t o t ry an alt ernat ive t o nicot ine replacement t herapy, varenicline would be t he best opt ion. Syst emat ic reviews have addressed a number of
pharmacologic approaches t o smoking cessat ion t reat ment . Varenicline for 12 weeks increased t he odds of long-t erm smoking cessat ion approximat ely t hreefold compared
wit h placebo. When compared direct ly wit h bupropion, varenicline was t he more effect ive drug. The main side effect was nausea, which usually subsided over t ime. Two t rials
t est ed varenicline for an addit ional 12 weeks wit hout adverse effect s. One randomized, open label t rial found a modest effect of varenicline compared t o nicot ine replacement
t herapy. Generally, nicot ine replacement t herapy should not be combined wit h varenicline, since t he combinat ion may increase t he risk of nausea, vomit ing, headache,
dizziness, and ot her adverse effect s. In 2009, t he FDA required boxed warnings on varenicline and bupropion not ing t he risk for serious neuropsychiat ric sympt oms including
changes in behavior, host ilit y, agit at ion, depressed mood, suicidal t hought s and behaviors, and at t empt ed suicide.
When used as sole pharmacot herapy, bupropion and nort ript yline doubled t he odds of cessat ion compared wit h placebo. However, alt hough bupropion and nort ript yline
appear t o be equally effect ive and of similar efficacy t o nicot ine replacement t herapy, t hey appear t o be less effect ive t han varenicline. There is a risk of 1 in 1000 of
seizures associat ed wit h bupropion use, making bupropion a poor choice for t his pat ient . Adverse effect s of bupropion include insomnia, dry mout h, nausea and serious
psychiat ric sympt oms (as not ed above); t hose of nort ript yline include dry mout h, const ipat ion, nausea, and sedat ion.
Trials of select ive serot onin reupt ake inhibit ors, including sert raline, have shown no evidence of significant benefit for smoking cessat ion.
Key Poi nt
For smoking cessat ion, bupropion and nort ript yline appear t o be equally effect ive and of similar efficacy t o nicot ine replacement t herapy but less effect ive t han varenicline.
Bi bl i ography
Wilson JF. In t he clinic. Smoking cessat ion. Ann Int ern Med. 2007;146(3):ITC2-1-ICT2-16. [PMID: 17283345]
Item 41 Answer: B
Educati onal Objecti ve: Treat obesity with bariatric surgery.
Surgical t reat ment should be considered for pat ient s wit h BMI of 35 or great er and serious obesit y-relat ed medical comorbidit ies (such as hypert ension, diabet es, dyslipidemia,
coronary art ery disease, or sleep apnea) or BMI of 40 or great er wit hout comorbidit ies in whom at t empt s at weight loss, including drug t herapy, were unsuccessful. Surgery
produces long-t erm weight loss t hat can be more t han 25% of body weight at 1 year, and lost weight is regained slowly, if at all. Surgery may also be recommended t o persons
wit h progressive obesit y, such as cont inuing weight increases of more t han 5 kg/year before age 30 years. Aft er bariat ric surgery, many pat ient s have significant improvement
or resolut ion of obesit y-relat ed diseases, including diabet es, hypert ension, sleep apnea, and hyperlipidemia, and recent st udies suggest decreased overall mort alit y.
Low carbohydrat e diet s produce slight ly more weight loss t han ot her diet s, and may have a slight ly more favorable effect on lipid panel and blood pressure. Unfort unat ely,
t his pat ient has had cont inued weight gain despit e her diet at t empt s and a t rial of a different diet is unlikely t o produce different result s.
Increasing physical act ivit y increases energy expendit ure. Recommending exercise for 30 t o 60 minut es 5 or more days a week by increasing walking or ot her comparable
act ivit ies is useful. Exercise is part icularly helpful in maint aining a lower weight once achieved. Reducing calories, however, is essent ial for weight loss. Exercise alone is rarely
a successful weight loss program.
Key Poi nt
Surgical t reat ment should be considered for pat ient s wit h BMI of 35 or great er and serious obesit y-relat ed medical comorbidit ies or BMI of 40 or great er wit hout comorbidit ies
in whom at t empt s at weight loss, including drug t herapy, were unsuccessful.
Bi bl i ography
Bray GA, Wilson JF. In t he clinic. Obesit y. Ann Int ern Med. 2008;149(7):ITC4-1-ITC4-15. [PMID: 18838723]
Item 42 Answer: C
Educati onal Objecti ve: Screen for obesity-related complications.
The most appropriat e evaluat ion for t his pat ient includes fast ing blood glucose, lipid panel, and serum creat inine evaluat ion. Abnormal waist circumference (>102 cm [40 in]
for males or >88 cm [35 in] for females) is a measure for cent ral obesit y, a surrogat e est imat e for visceral fat . Visceral fat is a more met abolically act ive fat t hat releases free
fat t y acids int o t he port al syst em, which cont ribut es t o hyperlipidemia, hyperinsulinemia, and at herogenesis. BMI has a good correlat ion wit h risks associat ed wit h obesit y
and body fat , such as diabet es mellit us, heart disease, ost eoart hrit is, gallbladder disease, gast roesophageal reflux, and cert ain t ypes of cancer (e.g., breast , endomet rium,
prost at e, colon, kidney, and gallbladder). In adult s wit h a BMI of 25 t o 34.9, an abnormal waist circumference is associat ed wit h a great er risk t han t hat det ermined by BMI
alone. Pat ient s ident ified as overweight (BMI, 25-29.9), obese (BMI, 30), or having an abnormal waist circumference are assessed for obesit y-associat ed condit ions such as
hypert ension, met abolic syndrome, endocrinopat hies (i.e., hypot hyroidism, diabet es, and Cushing syndrome), and reproduct ive disorders such as polycyst ic ovary disease. In
all pat ient s wit h a BMI great er t han 25, obt ain a blood glucose level, serum creat inine level, and fast ing lipid profile (HDL cholest erol, t riglycerides, and LDL cholest erol) t o
assess for comorbidit ies.
Screening asympt omat ic pat ient s wit h complet e blood count and serum elect rolyt es (in t he absence of condit ions known t o alt er elect rolyt es) does not provide measureable
healt h care benefit s. Screening elect rocardiograms are not recommended in asympt omat ic pat ient s because abnormalit ies of t he rest ing elect rocardiogram are rare, are not
specific for coronary art ery disease, and do not predict subsequent mort alit y from coronary disease. Similarly, screening chest x-rays are not helpful in asympt omat ic persons.
A sleep st udy may be indicat ed t o confirm sleep apnea in pat ient s wit h dayt ime fat igue, somnolence, hypert ension, or hist ory of snoring, but t his pat ient is asympt omat ic and
does not require a sleep st udy or pulse oximet ry t o det ermine oxygen sat urat ion.
Key Poi nt
In all pat ient s wit h a BMI great er t han 25, obt ain a blood glucose level, serum creat inine level, and fast ing lipid profile (HDL cholest erol, t riglycerides, and LDL cholest erol)
t o assess for comorbidit ies.
Bi bl i ography
Bray GA, Wilson JF. In t he clinic. Obesit y. Ann Int ern Med. 2008;149(7):ITC4-1-ITC4-15. [PMID: 18838723]
Item 43 Answer: A
Educati onal Objecti ve: Treat obesity with orlistat.
The best management opt ion for t his pat ient is t o add a weight loss medicat ion such as orlist at wit h meals, wit h cont inued encouragement of diet and exercise. A met a-
analysis of orlist at t rials demonst rat ed an average weight loss of 2.9 kg (6.4 lb) compared wit h placebo. Repeat ed at t empt s at diet ary modificat ion and exercise have failed t o
t reat t his pat ient 's obesit y, which is likely a cont ribut ing fact or t o her hyperlipidemia, hypert ension, and t ype 2 diabet es mellit us. According t o t he American College of
Physicians clinical guideline, drug t herapy can be offered t o obese pat ient s who have failed t o achieve t heir weight loss goals t hrough diet and exercise alone. Before init iat ing
drug t herapy, it is import ant t o have a frank discussion wit h t he pat ient regarding t he drugs' side effect s, safet y dat a, and t he t emporary nat ure of t he weight loss achieved
wit h medicat ions.
Sibut ramine is a sympat homimet ic agent t hat suppresses appet it e and food int ake. Like orlist at , it is an effect ive drug for weight loss. However, sibut ramine increases syst olic
blood pressure and pulse. It is also associat ed wit h in increase in nonfat al myocardial infarct ion and st roke in pat ient s wit h preexist ing cardiac disease. In Oct ober 2010,
sibut ramine was volunt arily wit hdrawn from t he U.S. and Canadian market s for safet y concerns.
Medicat ions are a common cont ribut ing fact or t o obesit y, and sulfonylureas such as glipizide have been associat ed wit h weight gain. However, insulin is also associat ed wit h
weight gain, and swit ching t he pat ient 's medicat ion from glipizide t o insulin is unlikely t o be of benefit .
Referring t he pat ient for bariat ric surgery is not indicat ed, as t he pat ient does not meet commonly est ablished referral guidelines (BMI 40 or BMI 35 wit h medical
comorbidit ies such as sleep apnea, obesit y-relat ed cardiomyopat hy, severe art hrit is, hyperlipidemia, diabet es, or glucose int olerance).
Key Poi nt
Pharmacologic t reat ment may be considered when obese pat ient s fail t o lose weight aft er an adequat e t rial of diet and exercise and t reat ment of any cont ribut ing
comorbidit ies.
Bi bl i ography
Bray GA, Wilson JF. In t he clinic. Obesit y. Ann Int ern Med. 2008;149(7):ITC4-1-15; quiz ITC4-16. [PMID: 18838723]
Item 44 Answer: D
Educati onal Objecti ve: Diagnose a stomal stenosis after gastric bypass surgery.
The pat ient should undergo upper endoscopy t o rule out a complicat ion from her recent laparoscopic gast ric bypass surgery, especially st omal st enosis (a st rict ure at t he
anast omosis of t he gast ric pouch and jejunum) or marginal ulcerat ions or erosions. If a st rict ure is diagnosed at t he t ime of endoscopy, dilat ion of t he st rict ure endoscopically
oft en result s in relief of sympt oms wit hout t he need for repeat surgery.
St omal st enosis t ypically present s wit h sympt oms of nausea, vomit ing, and inabilit y t o eat . Eit her barium swallow or upper endoscopy can est ablish t he diagnosis. Endoscopy
may be more appropriat e t han barium swallow in t his pat ient because of t he possibilit y of st omal erosion, which is more difficult t o diagnose wit h barium radiography.
Because t he pat ient has not had ot her signs of upper gast roint est inal bleeding or anemia wit h her persist ent sympt oms, st rict ure is more likely. However, t he pat ient t akes
naproxen, and t herefore, ulcerat ion at t he anast omot ic sit e should also be excluded.
Marginal erosions or ulcerat ions can be t reat ed wit h prot on pump inhibit ors, such as omeprazole, and cessat ion of t he NSAID in most pat ient s. However, t his t herapy is not
indicat ed unt il a diagnosis is est ablished.
A right upper quadrant ult rasound would be useful for t he diagnosis of biliary colic. Gallst ones are very common aft er gast ric bypass surgery wit h rapid weight loss. However,
t he close proximit y t o t he surgery, normal hepat ic enzyme levels, and t he prominent recurrent vomit ing (rat her t han pain) associat ed wit h t his pat ient 's sympt oms argue
against t his diagnosis.
Surgical laparot omy should not be performed unless endoscopy fails t o diagnose a t reat able cause of her sympt oms t hat can be managed less invasively.
Key Poi nt
St omal st enosis is a cause of persist ent nausea and vomit ing occurring wit hin t he first few mont hs aft er gast ric bypass surgery.
Bi bl i ography
Schneider BE, Villegas L, Blackburn GL, Mun EC, Crit chlow JF, Jones DB. Laparoscopic gast ric bypass surgery: out comes. J Laparoendosc Adv Surg Tech A. 2003;13(4):247-
255. [PMID: 14561253]
Item 45 Answer: E
Educati onal Objecti ve: Manage involuntary weight loss.
The most appropriat e management st ep is t o re-evaluat e t he pat ient in 6 mont hs. Among pat ient s wit h involunt ary weight loss, approximat ely 50% will have a physical
cause for t he weight loss, and a significant proport ion of t hose wit h a physical cause have a malignancy. However, among pat ient s who have an init ial normal laborat ory
evaluat ion, normal chest x-ray, normal abdominal ult rasound, and no focal sympt oms t o guide furt her t est ing, t he proport ion who are ult imat ely diagnosed wit h an occult
malignancy is ext remely low, perhaps less t han 1%. In t hese pat ient s, cont inued ext ensive t est ing is unlikely t o yield a diagnosis, leads t o significant pat ient inconvenience,
and is not cost effect ive. In part icular, CT scanning has part icularly low yield aft er an init ial negat ive evaluat ion. A wat chful wait ing st rat egy is t he preferred approach.
This pat ient does not have focal sympt oms, abnormal laborat ory st udies, or radiographic screening t o suggest upper endoscopy, chest CT, or measurement of ant inuclear
ant ibodies are indicat ed. No evidence indicat es diet ary supplement s improve qualit y of life or mort alit y in t his populat ion.
Key Poi nt
Among pat ient s wit h involunt ary weight loss, lack of focal sympt oms and a negat ive baseline evaluat ion predict t he absence of malignancy.
Bi bl i ography
Met alidis C, Knockaert DC, Bobbaers H, Vanderschueren S. Involunt ary weight loss. Does a negat ive baseline evaluat ion provide adequat e reassurance? Eur J Int ern Med.
2008;19(5):345-9. [PMID: 18549937]
Item 46 Answer: B
Educati onal Objecti ve: Diagnose depression as a cause of weight loss.
The most likely cause of t his pat ient 's weight loss is depression. Among communit y-dwelling pat ient s wit h involunt ary weight loss, approximat ely 10% t o 20% will have a
psychiat ric disorder as t he cause. This proport ion may be as high as 60% among nursing home resident s. This pat ient 's loss of int erest in his previous act ivit ies represent s
anhedonia; t his paired wit h his sleep difficult y, in t he set t ing of a major life st ressor (unemployment ), may be a sign of major depression and warrant furt her evaluat ion.
Unexplained weight loss of 5% or more in 1 mont h is one of t he diagnost ic crit eria for major depression, alt hough some pat ient s present wit h weight gain due t o a decline in
physical act ivit y and increase in appet it e.
Alt hough prost at e cancer can rarely cause weight loss in t he absence of ot her sympt oms, it is a much less likely cause t han is depression, part icularly in a pat ient wit h
anhedonia and sleep dist urbance. This pat ient does not have polyuria or polydipsia t o suggest a diagnosis of t ype 2 diabet es, and t he fast ing blood glucose level is normal. Age-
appropriat e cancer screening, which would include a colonoscopy in t his age group, was normal 6 mont hs ago, making colon cancer unlikely as well.
Key Poi nt
Psychiat ric disorders are common causes of involunt ary weight loss among pat ient s who do not have a physical cause for weight loss.
Bi bl i ography
Vanderschueren S, Geens E, Knockaert D, Bobbaers H. The diagnost ic spect rum of unint ent ional weight loss. Eur J Int ern Med. 2005;16:160-164. [PMID: 15967329]
Item 47 Answer: B
Educati onal Objecti ve: Manage unintentional weight loss by stopping bupropion.
The most appropriat e next st ep in t he management of t his pat ient 's unint ended weight loss is t o st op bupropion. Many medicines can cause involunt ary weight loss by
inducing anorexia, dysgeusia, gast roint est inal sympt oms, dry mout h, confusion or inat t ent ion, or a movement disorder. The pat ient 's medicat ion list should be reviewed wit h
special at t ent ion t o t he presence of ant icholinergic agent s, ant iparkinsonian agent s, digoxin, iron and pot assium supplement s, aspirin and NSAIDs, opiat es, cert ain
ant idepressant s (bupropion and fluoxet ine), t hyroid hormone supplement at ion, and cert ain hypoglycemic agent s (met formin and exenat ide). In t his pat ient , t here is a
possible t emporal relat ionship bet ween t he init iat ion of bupropion and t he onset of anorexia and weight loss. Because she has no ot her findings t o suggest anot her cause of
weight loss, st opping t he bupropion and carefully observing t he pat ient is t he most reasonable opt ion. Most expert s recommend maint enance wit h an ant idepressant drug for
4 t o 9 mont hs aft er remission of sympt oms. This pat ient has been t reat ed for 7 mont hs, so it is not unreasonable t o discont inue t herapy wit h careful follow up.
Body imaging of t he t horax and abdomen wit h CT or MRI in t he absence of hist orical informat ion or physical examinat ion findings point ing t o t he t horax or abdomen has
not been shown t o help det ermine t he cause of involunt ary weight loss. In st udies in which a cause of involunt ary weight loss was aggressively pursued, a t horough hist ory and
physical examinat ion and basic laborat ory t est ing, rat her t han advanced imaging, provided t he diagnosis in nearly all pat ient s. Similarly, in t he absence of sympt oms, upper
endoscopy is unlikely t o reveal a cause of unint ent ional weight loss and is not indicat ed.
Appet it e st imulant t herapy for involunt ary weight loss wit h megest rol acet at e or similar agent s has been st udied mainly in pat ient s wit h AIDS or cancer cachexia. In t hese
pat ient s, cert ain agent s have been shown t o promot e weight gain; however, a survival advant age has not been shown. Furt hermore, t he use of an appet it e st imulat e does not
address t he underlying cause of weight loss.
Key Poi nt
Medicat ions can be a cause of involunt ary weight loss in elderly pat ient s.
Bi bl i ography
Alibhai SM, Greenwood C, Payet t e H. An approach t o t he management of unint ent ional weight loss in elderly people. CMAJ. 2005;172(6):773-780. [PMID: 15767612]
Item 48 Answer: C
Educati onal Objecti ve: Diagnose chronic obstructive pulmonary disease as a cause of weight loss.
Severe chronic obst ruct ive pulmonary disease (COPD) can cause syst emic effect s, including unexplained weight loss, skelet al muscle dysfunct ion, increased cardiovascular
morbidit y and mort alit y, increased risk for t ype 2 diabet es mellit us, ost eoporosis, fract ures, and depression. Unexplained weight loss occurs in approximat ely half of t he
pat ient s wit h severe COPD, most ly because of t he loss of skelet al muscle mass. Unexplained weight loss carries a poor prognosis in COPD independent of ot her indicat ors,
such as FEV
1
or PCO
2
. The mechanisms underlying t hese syst emic effect s are unclear but are probably int errelat ed and mult ifact orial, including inact ivit y, syst emic
inflammat ion, t issue hypoxia, and oxidat ive st ress. Increases in concent rat ions of inflammat ory mediat ors indicat ing peripheral blood cell act ivat ion also have been found
t hroughout t he body and may mediat e some of t hese syst emic effect s.
Alt hough t he weight loss of malignancy is a possibilit y in t his pat ient , t he absence of gast roint est inal sympt oms or ot her localizing sympt oms, t he normal cancer screening
t est result s wit hin t he last year, and t he pat ient 's hist ory of severe COPD make t he cachexia of COPD, not cancer, t he most likely cause in t his pat ient . The pat ient 's
spiromet ry indicat es severe COPD, and aggressive management of COPD is necessary. Evaluat ion for depression is also indicat ed.
Key Poi nt
Severe chronic obst ruct ive pulmonary disease can cause syst emic effect s, including unint ent ional weight loss, skelet al muscle dysfunct ion, and increased risk of cardiovascular
disease, ost eoporosis, and depression.
Bi bl i ography
Agust i A, Soriano JB. COPD as a syst emic disease. COPD. 2008;5(2):133-138. [PMID: 18415812]
Item 49 Answer: D
Educati onal Objecti ve: Treat heavy menstrual bleeding with oral medroxyprogesterone.
The most appropriat e next management st ep is oral medroxyprogest erone acet at e. In pat ient s who present wit h menorrhagia (heavy menst rual bleeding) wit h a known
et iology, several t herapeut ic agent s can decrease bleeding. For moderat e bleeding t hat can be managed on an out pat ient basis, a progest at ional agent such as
medroxyprogest erone acet at e can be given for 10 t o 21 days. The progest erone will t ypically act t o st abilize t he endomet rium and st op ut erine blood flow. Alt ernat ively, a
monophasic oral cont racept ive may be dosed four t imes a day for 5 t o 7 days, and subsequent ly reduced t o daily dosing for 3 weeks, followed by wit hdrawal bleeding.
Nonst eroidal ant i-inflammat ory drugs act by inhibit ing prost aglandin synt hesis and may decrease mild bleeding by approximat ely 30%. Once daily oral cont racept ives are
effect ive in decreasing menst rual blood loss by 50%; however, in bleeding t hat is as heavy as t his case, neit her of t hese medicat ions would be as effect ive as
medroxyprogest erone.
If t he pat ient were ort host at ic or dizzy from blood loss, int ravenous est rogen would be appropriat e. Parent eral conjugat ed est rogens are approximat ely 70% effect ive in
st opping t he bleeding ent irely. Pulmonary embolism and venous t hrombosis are complicat ions of int ravenous est rogen t herapy.
Surgical opt ions are reserved for cases when medical t reat ment fails, but it is likely in t his case t hat medical t reat ment can provide a bridge unt il her scheduled surgical
procedure. Monit oring her for a week will not be helpful, because it is likely she will sust ain a great deal of addit ional blood loss during t his t ime.
Key Poi nt
Medroxyprogest erone acet at e for 10 t o 21 days is effect ive t reat ment for moderat e menst rual bleeding.
Bi bl i ography
Fazio SB, Ship AN. Abnormal ut erine bleeding. Sout h Med J. 2007;100(4):376-82; quiz 383, 402. [PMID: 17458397]
Item 50 Answer: C
Educati onal Objecti ve: Diagnose polycystic ovary syndrome.
This pat ient has classic polycyst ic ovary syndrome (PCOS). PCOS affect s 6% of women of child-bearing age and t ypically present s wit h oligomenorrhea and signs of
androgen excess (hirsut ism, acne, and occasionally alopecia). Insulin resist ance is a major feat ure of t he disorder, as are overweight and obesit y, alt hough only 50% of affect ed
women are obese. Typically, t here is a mild elevat ion in t est ost erone and dehydroepiandrost erone sulfat e levels and a lut einizing hormone t o follicle-st imulat ing hormone
rat io of great er t han 2:1. Diagnosis requires t wo of t he t hree following feat ures: (1) ovulat ory dysfunct ion, (2) laborat ory or clinical evidence of hyperandrogenism, and (3)
ult rasonographic evidence of polycyst ic ovaries. This pat ient has ovulat ory dysfunct ion and clinical evidence of hyperandrogenism.
This pat ient 's t ot al t est ost erone level (84 ng/dL [2.9 nmol/L]), alt hough somewhat high, is not high enough t o raise concerns about a t umor. Typically, t he serum
t est ost erone level in pat ient s wit h PCOS rarely exceeds 150 ng/dL (5.2 nmol/L); higher levels warrant a search for an adrenal or ovarian t umor. In addit ion t he pat ient lacks
any signs of virilism t hat is commonly associat ed wit h androgen secret ing t umors such as sudden onset of menst rual irregularit y, hirsut ism, acne, deepening of t he voice,
front al (or crown) balding, increased muscle mass, or clit oromegaly.
The absence of galact orrhea and normal prolact in level eliminat es a pit uit ary prolact inoma as t he cause of t he pat ient 's oligomenorrhea. Addit ionally, hyperprolact inemia
does not cause hirsut ism.
Key Poi nt
Polycyst ic ovary syndrome t ypically present s wit h oligomenorrhea and signs of androgen excess including hirsut ism, acne, and occasionally alopecia.
Bi bl i ography
Wilson JF. The polycyst ic ovary syndrome. Ann Int ern Med. 2011;154(3):ITC21. [PMID: 21282692]
Item 51 Answer: B
Educati onal Objecti ve: Treat perimenopausal symptoms with estrogen replacement therapy.
The most appropriat e t reat ment for t his pat ient is est rogen replacement t herapy (ERT). ERT provides significant relief for hot flushes associat ed wit h menopause in 50% t o
90% of pat ient s. There is no clear benefit of one est rogen-cont aining product over anot her. Relief of hot flushes is t he primary (arguably t he only) indicat ion for ERT,
alt hough it also reduces t he rat e of post menopausal bone densit y loss. However, t he benefit s of ERT must be weighed against t he risks, which include pot ent ial increased rat es
of breast cancer, t hromboembolic event s, and cardiac event s.
Cont raindicat ions t o est rogen use include undiagnosed vaginal bleeding, breast cancer, ot her est rogen-sensit ive cancers, current or previous hist ory of venous or art erial
t hrombosis, and liver dysfunct ion or disease. The U.S. Food and Drug Administ rat ion recommends use of t he smallest effect ive dose of hormone replacement t herapy for t he
short est durat ion possible t o t reat menopausal sympt oms.
Alt hough some st udies have report ed posit ive result s wit h black cohosh, report s have been inconsist ent , and t he met hodologically st rongest st udies have found no evidence of
benefit . Conclusive evidence is similarly lacking for ot her alt ernat ive medicines such as soy prot eins and red clover.
Prescript ion t reat ment s for which t here is some evidence of benefit in pat ient s wit h hot flushes include t he select ive serot onin and norepinephrine reupt ake inhibit ors
venlafaxine and select ive serot onin reupt ake inhibit ors such as cit alopram, paroxet ine, fluvoxamine, and fluoxet ine. These can be considered as second-line agent s, especially
in women who also have some sympt oms of mood or anxiet y disorders. It is hypot hesized t hat hot flushes are pat hophysiologically associat ed wit h increased noradrenergic
act ivit y and decreased serot onergic act ivit y, so it is likely t hat t he blockage of serot onin reupt ake is responsible for t he benefit s wit h t hese agent s. Ot her agent s t hat may
relieve hot flushes include mirt azapine and gabapent in.
Raloxifene is a select ive est rogen recept or modulat or t hat is approved for t he prevent ion of post menopausal bone mass loss, but it does not help wit h hot flushes or ot her
post menopausal sympt oms, and may even worsen t hem.
Key Poi nt
Est rogen replacement t herapy provides effect ive relief of hot flushes, but it s use must be weighed against t he pot ent ial adverse effect s.
Bi bl i ography
Col NF, Fairfield KM, Ewan-Whyt e C, Miller H. In t he clinic. Menopause. Ann Int ern Med. 2009;150(7):ITC4-1-15; quiz ITC4-16. [PMID: 19349628]
Item 52 Answer: D
Educati onal Objecti ve: Evaluate secondary amenorrhea with a progestin withdrawal challenge.
The next st ep in t he evaluat ion of t his pat ient wit h secondary amenorrhea aft er st opping her oral cont racept ive pill is a progest in wit hdrawal challenge. This pat ient has an
unremarkable personal and family medical hist ory and no evidence of androgen excess. Result s of her screening laborat ory st udies are negat ive for t hyroid disorders, ovarian
dysfunct ion, and hyperprolact inemia. Given t hese dat a, t he different ial diagnosis of t his pat ient 's secondary amenorrhea includes anat omic defect s and chronic anovulat ion,
wit h or wit hout est rogen. The different ial diagnosis can be narrowed most effect ively wit h a progest in wit hdrawal challenge. Menses aft er challenge excludes anat omic defect s
and chronic anovulat ion wit hout est rogen. Therefore, a progest in wit hdrawal challenge is t he most appropriat e next st ep.
Polycyst ic ovary syndrome (PCOS) affect s 6% of women of childbearing age and t ypically present s wit h oligomenorrhea and signs of androgen excess (hirsut ism, acne, and
occasionally alopecia). Insulin resist ance is a major feat ure of t he disorder, as is overweight and obesit y (alt hough only 50% of women wit h PCOS are obese). Typically,
t est ost erone and dehydroepiandrost erone sulfat e levels are mildly elevat ed, and t he lut einizing hormone t o follicle-st imulat ing hormone rat io is great er t han 2:1.
Measurement of dehydroepiandrost erone sulfat e is rarely clinically useful.
Posit ive wit hdrawal bleeding aft er t he progest in wit hdrawal challenge suggest s an est radiol level of great er t han 40 pg/mL (146.8 pmol/L) and t hus obviat es t he need for
measurement of serum est radiol levels.
An MRI of t he pit uit ary gland is unnecessary at t his point because her follicle-st imulat ing hormone, prolact in, and t hyroid levels are all normal.
Key Poi nt
Menst rual flow on progest in wit hdrawal indicat es relat ively normal est rogen product ion and a pat ent out flow t ract , which limit s t he different ial diagnosis of secondary
amenorrhea t o chronic anovulat ion wit h est rogen present .
Bi bl i ography
Pract ice Commit t ee of t he American Societ y for Reproduct ive Medicine. Current evaluat ion of amenorrhea. Fert il St eril. 2006;86(5 Suppl 1):S148-S155. [PMID: 17055812]
Item 53 Answer: B
Educati onal Objecti ve: Evaluate secondary amenorrhea with measurement of serum follicle stimulating hormone and prolactin levels.
This pat ient 's serum follicle-st imulat ing hormone (FSH) and prolact in levels should be measured. Secondary amenorrhea is defined by t he absence of menses for 3 or more
consecut ive mont hs in a woman who has menst ruat ed previously. Menst rual failure can be complet e amenorrhea or varying degrees of oligomenorrhea, t he lat t er being much
more common. Pregnancy should be excluded in all pat ient s prior t o ot her evaluat ions. Polycyst ic ovary syndrome is t he most common cause of secondary amenorrhea, and
hypogonadot ropic hypogonadism (low FSH and low est rogen) is most commonly caused by hyperprolact inemia (elevat ed serum prolact in). In young women, secondary
amenorrhea may be associat ed wit h hypergonat rophic hypogonadism. This group includes primary ovarian failure (oft en due t o Turner syndrome mosaicism and aut oimmune
disorders) and in cancer survivors can be t raced t o chemot herapy or radiat ion t reat ment s.
Laborat ory evaluat ion is first direct ed t oward ovarian failure, hyperprolact inemia, and t hyroid disease. Therefore, FSH, prolact in, t hyroid-st imulat ing hormone, and free
t hyroxine (T
4
) levels are generally measured. An FSH great er t han 20 mU/mL (20 U/L) suggest s ovarian failure.
If serum FSH and prolact in levels are normal on laborat ory st udies, t he next st ep in t he evaluat ion is a progest in wit hdrawal challenge. If t he progest in challenge does not
result in wit hdrawal bleeding, t hen assessment of t he pelvic anat omy wit h ult rasonography or MRI would be appropriat e. A high serum prolact in level requires addit ional
pit uit ary evaluat ion, including MRI. Obt aining an MRI before t his pat ient 's serum prolact in level has been det ermined, however, is premat ure.
This pat ient has no sympt oms of hyperandrogenemia. Therefore, measurement of her t ot al serum t est ost erone level is of lit t le value.
Key Poi nt
Aft er pregnancy is excluded, t he init ial evaluat ion of secondary amenorrhea includes measurement of follicle-st imulat ing hormone, t hyroid-st imulat ing hormone, and
prolact in levels.
Bi bl i ography
Pract ice Commit t ee of t he American Societ y for Reproduct ive Medicine. Current evaluat ion of amenorrhea. Fert il St eril. 2006;86(5 suppl 1):S148-S155. [PMID: 17055812]
Item 54 Answer: D
Educati onal Objecti ve: Diagnose abnormal uterine bleeding with an endometrial biopsy.
The most appropriat e next st ep in t he management of t his pat ient wit h abnormal ut erine bleeding is t o obt ain an endomet rial biopsy. Abnormal ut erine bleeding can t ake
many forms, including infrequent menses, excessive flow, prolonged durat ion of menses, int ermenst rual bleeding, and post menopausal bleeding. In all pat ient s wit h abnormal
bleeding, physical examinat ion should include a pelvic examinat ion and Pap smear. In pre- or perimenopausal pat ient s, a urine pregnancy t est is also appropriat e. Furt her
laborat ory t est ing depends on t he findings of t he hist ory and physical examinat ion and may include cult ures for gonorrhea and Chlamydia trachomatis, complet e blood count ,
t hyroid funct ion t est s, plasma glucose measurement , prolact in levels, and coagulat ion st udies. Aft er performing appropriat e laborat ory st udies, an assessment of t he
endomet rial lining wit h an endomet rial biopsy is appropriat e t o rule out endomet rial cancer or hyperplasia in pat ient s older t han 35 years of age wit h abnormal ut erine
bleeding.
Lut einizing hormone and follicle-st imulat ing hormone levels may be able t o confirm t he menopausal st at e, but t hese t est s cannot exclude t he possibilit y of endomet rial
carcinoma.
In pat ient s wit h anovulat ory bleeding, init iat ion of oral cont racept ives or cyclic progest ins can help t o maint ain regular cycles. However, t his int ervent ion would be
inappropriat e wit hout first eliminat ing t he possibilit y of endomet rial cancer as t he cause of t he abnormal ut erine bleeding in t his pat ient .
Est rogen is t he most effect ive t reat ment for t he relief of hot flushes, wit h a 50% t o 90% response rat e, and evidence shows t hat even low doses provide effect ive sympt om
relief. Relief of hot flushes is now considered t he primary reason for init iat ing est rogen replacement t herapy. Est rogen replacement t herapy is not indicat ed in t he
management of abnormal ut erine bleeding and would be harmful if t he bleeding is caused by an endomet rial cancer.
Key Poi nt
An assessment of t he endomet rial lining wit h an endomet rial biopsy is appropriat e t o rule out endomet rial cancer or hyperplasia in pat ient s older t han 35 years wit h
abnormal ut erine bleeding.
Bi bl i ography
Fazio SB, Ship AN. Abnormal ut erine bleeding. Sout h Med J. 2007;100(4):376-382. [PMID: 17458397]
Item 55 Answer: C
Educati onal Objecti ve: Diagnose cellulitis.
This pat ient has cellulit is. Cellulit is is a rapidly spreading, deep (dermis), subcut aneous-based infect ion most frequent ly caused by Staphylococcus aureus or group A
st rept ococci. It is charact erized by a well-demarcat ed area of warmt h, swelling, t enderness, and eryt hema t hat may be accompanied by lymphat ic st reaking and/or fever and
chills. Risk fact ors for lower-ext remit y cellulit is include inflammat ion (eczema), t inea pedis, onychomycosis, skin t rauma, chronic leg ulcerat ions, t ype 2 diabet es mellit us,
and edema. Cellulit is is a clinical diagnosis; cult ures are usually not necessary and are seldom posit ive. Treat ment is based on t he risk of met hicillin-resist ant S. aureus (MRSA)
infect ion and t he severit y of illness and generally consist s of oral ant ibiot ics and analgesics; int ravenous ant ibiot ics may be necessary for unsuccessful out pat ient t reat ment , in
some pat ient s wit h diabet es, or if signs of syst emic t oxicit y are present .
Allergic cont act dermat it is (ACD) is a delayed-t ype hypersensit ivit y react ion in which t he skin is it chy, red, edemat ous, weepy, and crust ed, somet imes wit h vesicles or bullae.
Cont act dermat it is can usually be different iat ed from cellulit is by t he presence of prurit us and t he absence of fever. At opic dermat it is, when acut e, result s in poorly
demarcat ed, eczemat ous, crust ed, eryt hemat ous papulovesicular plaques and excoriat ions t hat charact erist ically are prurit ic and involve t he ant ecubit al and poplit eal fossae
and flexural wrist s. Venous st asis dermat it is affect s t he skin on t he lower legs, part icularly around t he medial malleoli, and result s from venous hypert ension, edema, chronic
inflammat ion, and microangiopat hy. Bilat eral involvement , absence of fever or leukocyt osis, hyperpigment at ion due t o hemosiderin deposit ion, and minimal pain help
dist inguish venous st asis dermat it is from cellulit is.
Key Poi nt
The hallmark of cellulit is is a well-demarcat ed, rapidly spreading area of warmt h, swelling, t enderness, and eryt hema t hat may be accompanied by fever.
Bi bl i ography
Daum RS. Clinical pract ice. Skin and soft -t issue infect ions caused by met hicillin-resist ant Staphylococcus aureus. N Engl J Med. 2007;357(4):380-90. [PMID: 17652653]
Item 56 Answer: C
Educati onal Objecti ve: Diagnose seborrheic dermatitis
This pat ient has seborrheic dermat it is. Seborrheic dermat it is affect s areas of t he scalp (dandruff) and face t hat are rich in sebaceous glands and is dist inguished from ot her
dermat oses primarily by it s dist ribut ion. Lesions are eryt hemat ous, wit h dry or greasy scales and crust s, and may be prurit ic. Common areas of involvement include t he
nasolabial folds, cheeks, eyebrows, eyelids, and t he ext ernal audit ory canals. Frequent remissions and exacerbat ions are common. Treat ment consist s of low-pot ency
cort icost eroids (face), ket oconazole cream (face), and medicat ed shampoos t hat cont ain t ar, ket oconazole, or selenium sulfide (scalp).
Pat ient s wit h syst emic lupus eryt hemat osus (SLE) almost exclusively develop acut e cut aneous lupus eryt hemat osus (LE), which is t ypically precipit at ed by sunlight . Acut e
cut aneous LE can present as t he classic "but t erfly rash," charact erized by confluent malar eryt hema, or as generalized, red, papular or urt icarial lesions on t he sun-exposed
skin. Ot her sympt oms of SLE may be present .
Rosacea is a chronic inflammat ory skin disorder of unknown et iology affect ing t he face, t ypically t he cheeks and nose, and usually occurring aft er t he age of 30 years.
Eryt hema wit h t elangiect asias, pust ules, and papules wit hout comedones are found on physical examinat ion. Rosacea can be different iat ed from seborrheic dermat it is by t he
presence of pust ules. In early st ages, rosacea can present wit h only facial eryt hema and resemble t he but t erfly rash of SLE; however, acut e cut aneous LE t ypically spares t he
nasal labial folds and areas under t he nose and lower lip.
Dermat omyosit is is a condit ion wit h charact erist ic cut aneous manifest at ions combined wit h proximal inflammat ory muscle weakness; cut aneous disease may somet imes be
t he only manifest at ion. The dist inct ive cut aneous feat ures are t he heliot rope rash charact erized by a violaceous t o dusky eryt hemat ous periorbit al rash and Got t ron papules
appearing as slight ly elevat ed, scaly, violaceous papules and plaques over bony prominences, part icularly t he small joint s of t he hands.
Key Poi nt
Seborrheic dermat it is affect s t he scalp and face and is recognized by eryt hemat ous, dry, or greasy scales and crust s.
Bi bl i ography
Naldi L, Rebora A. Clinical pract ice. Seborrheic dermat it is. N Engl J Med. 2009;360(4):387-96. [PMID: 19164189]
Item 57 Answer: D
Educati onal Objecti ve: Diagnose tinea cruris.
This pat ient has t inea cruris. Superficial fungal infect ions, or t inea, are classified by body part . Tinea cruris is a subacut e and chronic dermat ophyt e infect ion of t he skin,
involving t he groin, pubic region, and inner t highs; in cont rast t o candidiasis, t he scrot um is rarely involved. The condit ion is recognized as light pink t o red papules and t hin
plaques wit h scaling borders. Occasionally t he lesions may have an arciform or polycyclic pat t ern. The lesion has an "act ive border," meaning t hat t he border has more
redness and scaling t han t he inner port ion of t he lesion, which may have cent ral clearing. The presence of fungi can be confirmed wit h a pot assium hydroxide (KOH) slide
preparat ion.
Cut aneous candidiasis is a superficial infect ion t hat occurs most frequent ly in warm, moist skin areas. Many pat ient s wit h t his infect ion have alt ered local immunit y, such as
increased moist ure at t he sit e of infect ion, diabet es, or alt ered syst emic immunit y. The infect ion begins wit h pust ules on a red base t hat become eroded and confluent .
Event ually, t he rash evolves int o a sharply demarcat ed, bright red pat ch (or pat ches), wit h small, pust ular lesions at t he periphery (sat ellit e lesions).
Psoriasis can present on t he t runk wit h red t o salmon-colored papules and plaques t hat are covered wit h a heavy silver-whit e scale.
The lesions of seborrheic dermat it is are ill defined (lack a dist inct border), are yellowish-red, vary in size, and are usually associat ed wit h a greasy or dandruff-like scale.
Seborrheic dermat it is most commonly occurs on t he scalp, cent ral face, upper mid-chest , and ot her oily areas of t he body.
Key Poi nt
Tinea is recognized as light pink t o red papules and t hin plaques wit h scaling, "act ive" borders and cent ral clearing.
Bi bl i ography
Schwart z RA. Superficial fungal infect ions. Lancet . 2004;364:1173-82. [PMID: 15451228]
Item 58 Answer: D
Educati onal Objecti ve: Diagnose Stevens-Johnson syndrome.
This pat ient has St evens-Johnson syndrome, which is charact erized by fever followed by t he onset of eryt hemat ous macules and plaques t hat progress t o epidermal necrosis
and sloughing. Involvement is limit ed t o less t han 10% of t he body surface area. Mucous membranes are affect ed in most pat ient s, and ocular, oral, and genit al surfaces may
be involved. Toxic epidermal necrolysis is t he more severe variant of t his condit ion, and is defined as epidermal necrosis and sloughing involving more t han 30% of t he body
surface area. A sulfonamide is t he most likely causat ive drug, but St evens-Johnson syndrome can be caused by ot her ant ibiot ics, ant i-epilept ic drugs, and allopurinol, as well as
cert ain syst emic diseases.
Allergic cont act dermat it is is a delayed-t ype hypersensit ivit y react ion. The first react ion t o an ant igen may occur several weeks aft er exposure, but subsequent react ions
usually develop wit hin 24 t o 48 hours of reexposure. Allergic cont act dermat it is is usually int ensely it chy. In acut e react ions, t he skin is red, edemat ous, weepy, and crust ed,
and t here may be vesicles or bullae. This pat ient 's erupt ion, which involves many part s of his body (including t he soft palat e) and includes t he presence of urt icarial t arget oid
lesions, is not consist ent wit h t he diagnosis of allergic cont act dermat it is.
Cellulit is is a rapidly spreading, deep, subcut aneous-based infect ion charact erized by a well-demarcat ed area of warmt h, swelling, t enderness, and eryt hema t hat may be
accompanied by lymphat ic st reaking and/or fever and chills. It is not charact erized by urt icarial t arget oid lesions or involvement of t he oral mucosa.
The "red man syndrome" is t he most common adverse react ion t o vancomycin. This react ion does not appear t o be ant ibody relat ed and is charact erized by flushing,
eryt hema, and prurit us involving primarily t he upper body, neck, and face. This pat ient has none of t he clinical findings charact erist ic of red man syndrome and was not
exposed t o vancomycin, making t his an unlikely diagnosis.
Key Poi nt
St evens-Johnson syndrome is an acut e severe cut aneous react ion charact erized by fever followed by t he onset of eryt hemat ous macules and plaques t hat progress t o epidermal
necrosis and sloughing; involvement is limit ed t o less t han 10% of t he body surface area.
Bi bl i ography
Greenberger PA. 8. Drug allergy. J Allergy Clin Immunol. 2006;117(2 Suppl Mini-Primer):S464-S470. [PMID: 16455348]
Item 59 Answer: A
Educati onal Objecti ve: Diagnose erythema multiforme.
The most likely diagnosis is eryt hema mult iforme. Eryt hema mult iforme is a mucocut aneous react ion charact erized by t arget oid lesions and, in most cases, bot h skin and
mucosal involvement . The majorit y (up t o 90%) of recurrent cases of eryt hema mult iforme have been associat ed wit h infect ions, t he most common of which is herpes
simplex virus (bot h HSV-1 and HSV-2). It may also be idiopat hic or drug relat ed. No virus is rout inely recovered wit h cult ure, and t reat ment wit h ant iviral agent s does not
affect t he out come of an acut e out break. Suppressive ant iviral t herapy, however, may minimize t he number of eryt hema mult iforme recurrences. It is import ant t o recognize
t hat recurrences of eryt hema mult iforme can occur in t he absence of apparent clinical react ivat ion of HSV; pat ient s may not be aware t hat t hey are infect ed wit h HSV.
Eryt hema migrans (also called eryt hema chronicum migrans) is t he hallmark cut aneous lesion of early Lyme disease. A cent rifugally spreading ring of eryt hema t hat
resembles a bull's eye usually develops at t he sit e of infect ion 3 t o 30 days aft er a t ick bit e. Eryt hema migrans lesions are most t ypically found near t he axilla, inguinal region,
poplit eal fossa, or at t he belt line, and palmar involvement is rare, if it occurs at all. Lesions slowly expand over days or weeks, wit h cent ral clearing producing a t arget or
bull's-eye appearance, and increase in size t o 20 cm or more. Eryt hema migrans is dist inguished from eryt hema mult iforme by t he lesion size, it s locat ion, and lack of
associat ed mucosal involvement .
Rocky Mount ain spot t ed fever (RMSF) is a t ick-borne disease caused by Rickettsia rickettsii. RMSF may present wit h subt le, fine, pink, blanching macules and papules on t he
wrist s and ankles t hat t hen spread cent ripet ally and t o t he palms and soles. As t he rash spreads, t he charact erist ic pet echial and purpuric "spot s" appear. Most pat ient s have
fever, severe headache, and myalgia.
St rept ococcal infect ions have been associat ed wit h eryt hema nodosum, flares of psoriasis, and several skin infect ions, including perianal cellulit is and blist ering dist al
dact ylit is; however, t hey are not commonly associat ed wit h eryt hema mult iforme.
Key Poi nt
Eryt hema mult iforme is a mucocut aneous react ion charact erized by t arget oid lesions and, in most cases, bot h skin and mucosal involvement .
Bi bl i ography
Aurelian L, Ono F, Burnet t J. Herpes simplex virus (HSV)-associat ed eryt hema mult iforme (HAEM): a viral disease wit h an aut oimmune component . Dermat ol Online J.
2003;9(1):1. [PMID: 12639459]
Item 60 Answer: C
Educati onal Objecti ve: Treat acute herpes zoster infection with oral famciclovir.
The most appropriat e t reat ment for t his pat ient is oral famciclovir. This pat ient has acut e herpes zost er. When given wit hin 72 hours of t he onset of t he herpet ic rash,
ant iviral t herapy wit h oral acyclovir, valacyclovir, or famciclovir decreases acut e pain severit y and durat ion, promot es more rapid healing of t he lesions, and possibly
decreases post herpet ic neuralgia incidence and severit y. These benefit s appear t o be great est in pat ient s older t han 50 years. This pat ient 's pain began more t han 72 hours
ago, but t he rash has been present for just 24 hours. Therefore, ant iviral t herapy will likely be beneficial. Because of t heir improved bioavailabilit y, valacyclovir and
famciclovir are preferred t o acyclovir, which is poorly absorbed and requires more pills daily.
Adding cort icost eroids may help accelerat e healing of lesions, decrease t he t ime t o acut e pain resolut ion, decrease insomnia incidence, help pat ient s ret urn t o normal daily
act ivit ies sooner, and decrease analgesic pain medicat ion needs. However, cort icost eroids do not appear t o decrease post herpet ic neuralgia incidence. Therefore, if
cort icost eroids are given, t hey should be used only as an adjunct t o ant iviral agent s, never as t he sole t herapy.
The bioavailabilit y of oral valacyclovir and famciclovir is excellent , so t reat ment of cut aneous herpes zost er infect ion wit h int ravenous acyclovir is not necessary. It is
reasonable t o consider beginning t herapy wit h int ravenous acyclovir for pat ient s wit h severe herpes zost er opht halmicus or for t hose who develop cent ral nervous syst emic
complicat ions of herpes zost er, but t his pat ient does not meet any of t hese crit eria.
There is no role for ant iviral t opical creams or oint ment s, including t opical acyclovir or penciclovir, in t he management of herpes zost er because t hey are not as effect ive as
syst emic ant iviral t reat ment , and t heir addit ion t o syst emic ant iviral t reat ment does not enhance healing compared wit h syst emic t reat ment alone.
Key Poi nt
In pat ient s wit h herpes zost er, administ rat ion of oral acyclovir, valacyclovir, or famciclovir wit hin 72 hours of t he development of t he rash decreases acut e pain severit y and
durat ion, promot es more rapid healing of t he lesions, and possibly decreases post herpet ic neuralgia incidence and severit y.
Bi bl i ography
Wilson JF. Herpes zost er. Ann Int ern Med. 2011;154(5):ITC31. [PMID:21357905]
Item 61 Answer: C
Educati onal Objecti ve: Diagnose rosacea.
This pat ient has rosacea, which is an inflammat ory dermat it is charact erized by eryt hema, t elangiect asias, papules, pust ules, and sebaceous hyperplasia t hat develops on t he
cent ral face, including t he nasolabial folds. Rhinophyma, or t he presence of a bulbous, red nose, is a variant of t his condit ion. Recurrent flushing in response t o st imuli such as
spicy food or alcohol is a common manifest at ion.
Dermat omyosit is may be associat ed wit h various skin manifest at ions. Periungual eryt hema and malar eryt hema, consist ing of a light purple (heliot rope) edemat ous
discolorat ion of t he upper eyelids and periorbit al t issues, are t he most common present at ions. Dermat omyosit is also may cause an eryt hemat ous, papular erupt ion t hat
develops in a V-shaped pat t ern along t he neck and upper t orso; in a shawl-shaped pat t ern along t he upper arms; and on t he elbows, knees, ankles, and ot her sun-exposed
areas. Involvement of t he hands may include scaly, slight ly raised, purplish papules and plaques t hat develop in periart icular areas of t he met acarpal and int erphalangeal joint s
and ot her bony prominences (Got t ron sign or Got t ron papules) and scaly, rough, dry, darkened, cracked, horizont al lines on t he palmar and lat eral aspect s of t he fingers
(mechanic's hands).
Psoriasis usually involves t he scalp, elbows, or ot her ext ensor areas but does manifest as an isolat ed facial rash. Charact erist ic findings of psoriasis include an eryt hemat ous
plaque wit h an adherent , variably t hick, silvery scale.
Seborrheic dermat it is causes whit e, scaling macules and papules on yellowish-red skin and may be greasy or dry. St icky crust s and fissures oft en develop behind t he ears, and
significant dandruff or scaling of t he scalp frequent ly occurs. Seborrheic dermat it is may develop in a "but t erfly"-shaped pat t ern but also may involve t he nasolabial folds,
eyebrows, and forehead. This condit ion usually improves during t he summer and worsens in t he fall and wint er.
Dist inguishing rosacea from syst emic lupus eryt hemat osus can be difficult and is frequent ly a reason t hat pat ient s are referred t o a dermat ologist . Syst emic lupus
eryt hemat osus is unlikely in t his pat ient because t he malar rash associat ed wit h t his condit ion is usually phot osensit ive and oft en spares t he nasolabial folds and t he areas
below t he nares and lower lip (areas relat ively prot ect ed from t he sun). Finally, t he pat ient has no ot her support ing sympt oms or signs of syst emic lupus eryt hemat osus.
Key Poi nt
Rosacea is an inflammat ory dermat it is charact erized by eryt hema, t elangiect asias, papules, pust ules, and sebaceous hyperplasia t hat affect s t he cent ral face, including t he
nasolabial folds.
Bi bl i ography
Powell FC. Clinical pract ice. Rosacea. N Engl J Med. 2005;352(8):793-803. [PMID: 15728812]
Item 62 Answer: C
Educati onal Objecti ve: Diagnose seborrheic keratoses.
This pat ient has seborrheic kerat oses, a benign skin condit ion. These lesions are common in adult s and increase in number wit h age. They are charact erized by sharply
demarcat ed, t an t o dark brown, wart y papules, plaques, and nodules t hat have a waxy t ext ure and appear t o be "st uck on" t he skin. While t hey can arise on any area of t he
skin, t hey are frequent ly locat ed in t he scalp and on t he back and chest .
Skin cancers t end t o occur on t he sun-exposed part s of t he body. Basal cell carcinoma is a pearly or t ranslucent papule or nodule wit h associat ed t elangiect asias. Melanomas,
like seborrheic kerat oses, are pigment ed, but do not classically have a waxy, wart y surface. Melanomas oft en have irregular borders, whereas seborrheic kerat oses are usually
well demarcat ed. Dist inguishing bet ween t he t wo can be difficult , however, and a biopsy may be necessary if t he diagnosis is in quest ion. Squamous cell carcinoma present s as a
scaly, hyperkerat ot ic, red or pink papule, pat ch, or plaque. It is not brown, t an, or black and does not have a wart y appearance like seborrheic kerat oses.
Key Poi nt
Seborrheic kerat oses are common, benign neoplasms t hat present as brown t o black, well-demarcat ed, "st uck-on"-appearing papules wit h waxy surfaces.
Bi bl i ography
Luba MC, Bangs SA, Mohler AM, St ulberg DL. Common benign skin t umors. Am Fam Physician. 2003;67(4):729-738. [PMID: 12613727]
Item 63 Answer: A
Educati onal Objecti ve: Treat inflammatory acne with oral antibiotics.
This pat ient has cyst ic and pust ular acne and should be t reat ed wit h oral ant ibiot ics. Acne is classified by severit y and t ype as noninflammat ory and inflammat ory acne.
Noninflammat ory acne consist s of open comedos ("blackheads") or closed comedones ("whit eheads"). Subsequent inflammat ory papules, pust ules, or nodules may develop.
Acne lesions most commonly develop in areas t hat have a high concent rat ion of sebaceous glands, including t he face, neck, chest , upper arms, and back. Exacerbat ing fact ors
are mechanical obst ruct ions (such as clot hing) and medicat ions (anabolic st eroids such as danazol and t est ost erone, cort icost eroids, isoniazid, lit hium, and phenyt oin).
Noninflammat ory acne can be t reat ed wit h t opical comedolyt ic agent s such as benzoyl peroxide, salicylic acid, azelaic acid, and ret inoids. Mild inflammat ory acne consist ing
of comedones and a few papules and pust ules can be t reat ed wit h t opical comedolyt ic agent s combined wit h a t opical ant ibiot ic. If t opical t herapy is ineffect ive, oral
ant ibiot ic t herapy is indicat ed. Oral ant ibiot ic t herapy may be t he first line of t herapy in cases where t he cyst ic and pust ular acne lesions are ext ensive and t opical applicat ion
would be impract ical or in cases where t he disease is so severe t hat t here would be a high likelihood of failure wit h t opical t reat ment alone, as in t his pat ient . Isot ret inoin is
t he only medicat ion t hat alt ers t he nat ural hist ory of acne, and it is indicat ed for cyst ic and pust ular acne t hat is unresponsive t o ant ibiot ics. Isot ret inoin is highly t erat ogenic
and has pot ent ially severe side effect s, including hypert riglyceridemia, pseudot umor cerebri, decreased bone mineral densit y, and possibly depression and psychosis; st rict
at t ent ion t o informed consent and careful monit oring are mandat ory if t his medicat ion is used.
Key Poi nt
Oral ant ibiot ic t herapy is first line in cases where t he cyst ic and pust ular acne lesions are ext ensive and t opical applicat ion would be impract ical or in cases where t he disease is
so severe t hat t here would be a high likelihood of failure wit h t opical t reat ment alone.
Bi bl i ography
Bershad SV. In t he clinic. Acne. Ann Int ern Med. 2008;149:ITC1-1-ITC1-16. [PMID: 18591631]
Item 64 Answer: A
Educati onal Objecti ve: Diagnose acute urticaria.
This pat ient has acut e urt icaria. Urt icaria, also known as hives, is a common skin finding t hat arises from a recurrent , but t ransient , cut aneous swelling wit h sudden eryt hema
caused by vascular ext ravasat ion. This condit ion can signify a complet ely benign, almost evanescent nuisance, or a severe, life-t hreat ening form of urt icaria called
angioedema. The hallmark of urt icaria is t he rapid appearance of t he wheal, a superficial, it chy, somet imes painful, discret e swelling of t he skin. Wheals can be mult iple or
isolat ed and usually involve t he t runk and ext remit ies, sparing t he palms and soles. The hallmark of angioedema is self-limit ed, localized swelling of t he skin or mucosa,
usually t he lips, face, hands, feet , penis, or scrot um. The skin is eit her normal or red in color and it ching is absent unless associat ed wit h urt icarial lesions. Concomit ant
angioedema and urt icaria occur in 40% of pat ient s; 40% have urt icaria alone; and 20% have angioedema but no urt icaria.
The clinical classificat ion of urt icaria depends on sympt om durat ion and precipit at ing fact ors. By definit ion, t he individual lesions of acut e urt icaria last less t han 24 hours.
Lesions can be observed carefully by drawing circles around t hem and observing t heir durat ion. Acut e urt icaria is generally relat ed t o environment al allergens, including drugs,
foods, and occasionally inhalant s. Penicillin, aspirin, NSAIDs, cont rast dyes, and sulfonamides are t he most common drug-relat ed causes of acut e urt icaria. Ot her common
exposures t hat precipit at e acut e urt icaria are lat ex, nut s, fish, eggs, and chocolat e. When chronic urt icaria occurs, pat ient diaries are oft en helpful in det ermining t he cause.
An individual wheal in chronic urt icaria last s more t han 24 hours and may occur several t imes per week for up t o six weeks.
Eryt hema mult iforme is recognized by t he appearance of red papules, vesicles, and bullae dist ribut ed in round, oft en t arget -shaped pat t erns. They oft en have a bullous
component in t he cent er of t he t arget .
Key Poi nt
The hallmark of urt icaria is t he rapid appearance of t he wheal, a superficial, it chy, somet imes painful, discret e swelling of t he skin.
Bi bl i ography
Frigas E, Park MA. Acut e urt icaria and angioedema: diagnost ic and t reat ment considerat ions. Am J Clin Dermat ol. 2009;10(4):239-50. [PMID: 19489657]
Item 65 Answer: D
Educati onal Objecti ve: Diagnose benign lymphadenopathy.
The most appropriat e management for t his pat ient is reassurance and wat chful wait ing. This pat ient has none of t he feat ures t o suggest a serious cause of her generalized
lymphadenopat hy. She is younger t han 40 years of age, and t he lymphadenopat hy is less t han 2 cm, mobile and rubbery in consist ency, and is locat ed in regions t ypical for
benign lymphadenopat hy. Her recent viral-like illness suggest s t hat it is react ive lymphadenopat hy. Usually, an evaluat ion is init iat ed in pat ient s wit h syst emic sympt oms,
progressively enlarging lymph nodes, or persist ent ly enlarged nodes for more t han 2 weeks. Therefore, t his is a sit uat ion in which wat chful wait ing is t he correct course of
act ion.
If she had any signs or sympt oms t o suggest a pat hological cause of lymphadenopat hy (syst emic sympt oms, progressive enlargement , persist ence beyond 3 weeks), t hen a
complet e blood count wit h a different ial and a chest radiograph would be reasonable t est s in addit ion t o t arget ing t he evaluat ion of localized signs or sympt oms. Her illness 2
weeks ago could have been Epst ein-Barr virus (EBV) infect ion or anot her infect ious mononucleosis-like illness, such as cyt omegalovirus infect ion. The early ant igen ant ibody
t est for EBV may not become posit ive unt il a mont h aft er t he illness. The capsid (ant i-VCA) IgM ant ibody becomes posit ive earlier, as does t he het erophile agglut inat ion t est
(monospot ), and t hese are t he usual early t est s ordered for EBV infect ion. No feat ures in t he hist ory or examinat ion suggest a pat hological cause of t he lymphadenopat hy
warrant ing biopsy. Alt hough t he inguinal lymph node was t he largest , it was less t han 2 cm, and furt hermore, inguinal lymph nodes are frequent ly react ive and t hus t he least
preferred for biopsy when ot her enlarged lymph nodes are present .
Key Poi nt
Lymphadenopat hy is usually evaluat ed in pat ient s wit h syst emic sympt oms, progressively enlarging lymph nodes, or persist ent ly enlarged nodes for great er t han 2 weeks.
Bi bl i ography
Habermann TM, St eensma DP. Lymphadenopat hy. Mayo Clin Proc. 2000;75(7):723-32. [PMID: 10907389]
Item 66 Answer: C
Educati onal Objecti ve: Diagnose metastatic breast cancer in a woman with isolated axillary lymphadenopathy.
The most appropriat e init ial st ep in t he evaluat ion of t his pat ient is lymph node biopsy. Alt hough she lacks obvious risk fact ors for breast cancer, t he size, locat ion, and
growt h of t he lymph node are all worrisome for malignancy. Breast cancer would also be t he most likely malignancy given t he locat ion, lack of ot her sympt oms, and her age
and gender; t herefore, she should have a lymph node biopsy as part of her init ial evaluat ion. Pat hologic confirmat ion of malignancy should be performed early in t he
diagnost ic evaluat ion. Opt imal pat hologic evaluat ion, including special st ains t hat might reveal t issue of origin, help t o dist inguish carcinoma from ot her cancer t ypes,
det ermine hist ologic t ype, and ident ify specific t reat ment t arget charact erist ics.
Because t he lymph node is increasing in size and it is already larger t han 2 cm, it does not make sense t o follow it conservat ively wit h a repeat examinat ion. She does have a
hist ory of lat ent t uberculosis, and she received t he appropriat e course of t reat ment . This, in addit ion t o t he absence of any syst emic sympt oms, makes t uberculous
lymphadenit is very unlikely. If suspicion were great er for t uberculous lymphadenit is, t hen a lymph node aspirat e and subsequent st ains and cult ure for Mycobacterium
tuberculosis would be a reasonable init ial t est . Chest x-ray can evaluat e for t he presence of int rat horacic lymphadenopat hy caused by condit ions like sarcoidosis, lung cancer,
and lymphoma, but she does not have any sympt oms t o suggest t hese diagnoses such as fever, night sweat s, weight loss, or cough.
Key Poi nt
Enlarging, firm axillary lymphadenopat hy in a woman older t han 40 years suggest s t he possibilit y of met ast at ic breast cancer.
Bi bl i ography
Habermann TM, St eensma DP. Lymphadenopat hy. Mayo Clin Proc. 2000;75(7):723-32. [PMID: 10907389]
Item 67 Answer: A
Educati onal Objecti ve: Diagnose and treat cystitis as the cause of urinary incontinence.
The best management of t he urinary incont inence is t he init iat ion of ciprofloxacin. Pat ient s wit h new-onset urinary incont inence should first be evaluat ed for t ransient ,
reversible causes, for which t he mnemonic DIAPERS may be useful: Drugs, Infect ion, At rophic vaginit is, Psychological (depression, delirium, dement ia), Endocrine
(hyperglycemia, hypercalcemia), Rest rict ed mobilit y, and St ool impact ion. Urinary t ract infect ion is a very common cause of t ransient incont inence in t he elderly,
part icularly if ot her cont ribut ing fact ors such as cognit ive impairment or impaired mobilit y are present . The presence of significant pyuria in t his set t ing generally just ifies
administ rat ion of empiric ant ibiot ic t herapy pending urine cult ure result s.
Alt hough some medicat ions may induce t ransient incont inence, causat ive agent s are most oft en diuret ics or drugs t hat affect aut onomic nervous syst em or bladder funct ion.
Oral hypoglycemic agent s do not t ypically cause incont inence, and discont inuing t hese agent s in a pat ient wit h diabet es mellit us could precipit at e hyperglycemia and
increased incont inence.
Indwelling cat het erizat ion is a t reat ment of last resort for pat ient s who have chronic incont inence t hat is unresponsive t o ot her t herapy and in whom int ermit t ent
cat het erizat ion is not feasible.
This pat ient 's confusion is more consist ent wit h delirium in an elderly pat ient as a generalized response t o an acut e illness rat her t han a focal neurologic event . CT scan of t he
head is t ypically not helpful in such pat ient s and is unlikely t o provide an explanat ion for t his pat ient 's incont inence.
Key Poi nt
Pat ient s wit h new-onset urinary incont inence should first be evaluat ed for t ransient , reversible causes, for which t he mnemonic DIAPERS may be useful: Drugs, Infect ion,
At rophic vaginit is, Psychological (depression, delirium, dement ia), Endocrine (hyperglycemia, hypercalcemia), Rest rict ed mobilit y, and St ool impact ion.
Bi bl i ography
Goode PS, Burgio KL, Richt er HE, Markland AD. Incont inence in older women. JAMA. 2010;303(21):2172-2181. [PMID: 20516418]
Item 68 Answer: C
Educati onal Objecti ve: Screen for hearing impairment with the whispered voice test.
The best way t o screen for hearing loss is t he whispered voice t est . Screening for hearing loss is import ant in elderly persons because hearing impairment is prevalent but
frequent ly underdiagnosed in t his populat ion. In addit ion, significant hearing loss is st ill possible despit e a pat ient 's denial of having t rouble hearing. A recent syst emat ic
review evaluat ed t he accuracy and precision of office clinical maneuvers for diagnosing hearing impairment . The whispered-voice t est is a quick and easy assessment t ool t hat
has t he best t est charact erist ics among t he office maneuvers. This t est assesses t he abilit y t o hear a whispered voice wit h t he examiner st anding behind t he pat ient 2 feet from
t he pat ient 's ear while occluding and simult aneously rubbing t he opposit e ext ernal audit ory canal and whispering t hree numbers or let t ers. Using a bat t ery-powered handheld
audioscope is an accept able alt ernat ive screening modalit y.
The syst emat ic review also found t hat t he Screening Hearing Handicap Invent ory and t he Weber and Rinne t est s did not perform as well as t he whispered-voice t est in
det ect ing hearing impairment .
Referring pat ient s for formal audiomet ry, alt hough t he gold st andard for evaluat ing hearing loss, is expensive and t ime consuming. It is also unnecessary t o do rout inely, since
a normal result on t he whispered-voice t est effect ively rules out significant hearing loss.
Key Poi nt
Elderly persons should be screened for hearing impairment wit h t he whispered-voice t est or t he handheld audioscopy, even if t hey deny having a hearing problem.
Bi bl i ography
Bagai A, Thavendiranat han P, Det sky AS. Does t his pat ient have hearing impairment ? JAMA. 2006;295(4):416-428. [PMID: 16434632]
Item 69 Answer: B
Educati onal Objecti ve: Evaluate a fall in an elderly patient with the "get up and go" test.
The next diagnost ic st udy for t his pat ient is t he "get up and go t est ." Risk fact ors for falling include lower ext remit y weakness, gait deficit , art hrit is, impaired act ivit ies of
daily living, female sex, and age over 80 years. Ot her risk fact ors for falls include balance deficit s, impaired vision, depression, cognit ive impairment , psychot ropic drug use,
and use of an assist ive device. Because falls oft en have mult iple causes and more t han one predisposing risk fact or, t here is no st andard diagnost ic evaluat ion for pat ient s who
fall or are at risk for falling. However, evaluat ions should begin wit h balance and gait screening, such as t he "get up and go" t est . The "get up and go" t est is appropriat e for
screening because it is a quant it at ive evaluat ion of general funct ional mobilit y. A st rong associat ion exist s bet ween performance on t his t est and a person's funct ional
independence in act ivit ies of daily living. Persons are t imed in t heir abilit y t o rise from a chair, walk 10 feet , t urn, and t hen ret urn t o t he chair. Most adult s can complet e t his
t ask in 10 seconds, and most frail elderly persons, in 11 t o 20 seconds. Those requiring more t han 20 seconds should undergo a fall evaluat ion. Typically, t his consist s of a
focused hist ory and physical examinat ion, much of which has already been performed in t his pat ient . Furt her evaluat ion, including measurement of 25-hydroxyvit amin D
levels, should be direct ed according t o findings of t he evaluat ion. Int ervent ions t o prevent falls should be t ailored t o t he pat ient 's needs.
A CT scan of t he head, 24-hour elect rocardiographic monit oring, and echocardiography are not rout ine st udies for fall evaluat ion and should not be done before balance and
gait screening. A CT scan of t he head is unlikely t o be helpful in t he absence of focal neurologic findings. The diagnost ic value of echocardiography in t he evaluat ion of falls
is low in t he absence of heart failure or murmurs. Elect rocardiographic monit oring is unlikely t o be helpful in a pat ient who falls in t he absence of syncope or ot her cardiac
sympt oms such as palpit at ions.
Key Poi nt
For elderly persons t he "get up and go" t est is a good screening t est for gait and balance problems t hat may warrant furt her evaluat ion.
Bi bl i ography
Tinet t i ME, Kumar C. The pat ient who falls: "It 's always a t rade-off". JAMA. 2010;303(3):258-266. [PMID: 20085954]
Item 70 Answer: C
Educati onal Objecti ve: Treat urge urinary incontinence with oxybutynin.
The most appropriat e medicat ion for t his pat ient is oxybut ynin. This pat ient 's sympt oms are most consist ent wit h urge urinary incont inence (overact ive bladder), which is
manifest ed by involunt ary leakage of large amount s of urine. The incont inence is frequent ly preceded by a sense of urgency but an inabilit y t o get t o t he bat hroom in t ime.
This pat ient 's memory loss and findings on t he Mini-Ment al St at e Examinat ion could indicat e early dement ia, which is a risk fact or for urge incont inence.
An ant icholinergic agent such as oxybut ynin is effect ive in reducing episodes of urge incont inence. Tolt erodine is an alt ernat ive agent in t he same drug class wit h similar
efficacy. Alt hough t his pat ient has no signs or sympt oms of benign prost at ic hyperplasia, he should be monit ored for difficult y urinat ing or urinary ret ent ion following
init iat ion of any ant icholinergic agent . Oxybut ynin appears t o be safe in pat ient s wit h mild t o severe dement ia.
Doxazosin, like ot her -adrenergic blockers, is effect ive for t he urinary sympt oms associat ed wit h benign prost at ic hyperplasia, such as slow urinary st ream, urinary
hesit ancy, and noct uria. However, doxazosin is not indicat ed for t he t reat ment of urge incont inence.
Alt hough t ricyclic ant idepressant s such as imipramine have been used t o t reat urge incont inence, t here is no st rong evidence from clinical t rials support ing t heir effect iveness
in t his set t ing.
Adrenergic drugs (phenylpropanolamine, norepinephrine, clenbut erol) have been principally st udied for t reat ment of st ress urinary incont inence in women, but have not
proved superior t o placebo or pelvic floor muscle t raining.
Key Poi nt
Tolt erodine and oxybut ynin are ant icholinergic agent s t hat are effect ive for t reat ing urge urinary incont inence.
Bi bl i ography
Goode PS, Burgio KL, Richt er HE, Markland AD. Incont inence in older women. JAMA. 2010;303(21):2172-2181. [PMID: 20516418]
Item 71 Answer: C
Educati onal Objecti ve: Screen an older patient for depression.
This asympt omat ic elderly man should be screened for depression. Depression is common in lat er life. Risk fact ors include older age, neurologic condit ions including st roke
and Parkinson disease, st ressful life event s, a personal or family hist ory of depression, and ot her medical illnesses. The U.S. Prevent ive Services Task Force (USPSTF) has
document ed t hat screening adult s in primary care set t ings leads t o accurat e ident ificat ion of depression, a disorder for which t reat ment is oft en effect ive. The USPSTF
recommends t hat screening be rest rict ed t o primary care set t ings in which an accurat e diagnosis of depression can be made, effect ive t reat ment can be provided, and follow-up
care is available. Screening should be considered in pat ient s wit h t he risk fact ors list ed above (such as t he st ressful life event s in t he pat ient discussed here) and in t hose wit h
unexplained or unrelat ed somat ic sympt oms; ot her psychological condit ions, such as anxiet y or subst ance abuse; chronic pain; or lack of response t o usually effect ive
t reat ment of ot her medical condit ions.
A t wo-it em screening inst rument has a sensit ivit y of 96% and specificit y of 57% for diagnosing depression. A "yes" response t o eit her of t he following quest ions const it ut es a
posit ive screen: "Over the past 2 weeks have you felt down, depressed, or hopeless?" and "Over the past 2 weeks have you felt little interest or pleasure in doing things?" A
posit ive result on eit her of t hese screening measures should be followed by a full diagnost ic int erview t o det ermine t he presence of a depressive disorder.
Alt hough t he USPSTF recommends one-t ime ult rasonographic screening for abdominal aort ic aneurysm in men 65 t o 75 years of age who are current or former smokers, it
does not ext end t his recommendat ion t o never-smokers because of t he lower risk of large aneurysms in t his populat ion.
The USPSTF does not recommend for or against screening for t he diagnosis of peripheral art erial disease (such as det erminat ion of t he ankle-brachial index) because t here is
lit t le evidence t hat t reat ment , ot her t han t herapy based on st andard cardiovascular risk fact or assessment , is beneficial during t he asympt omat ic phase of t his disease.
The USPSTF does not recommend for or against screening for dement ia wit h inst rument s such as t he Mini-Ment al St at e Examinat ion because of t he pot ent ial harm of
inaccurat e diagnosis and t he modest benefit s of drug t herapy for t his disorder.
Key Poi nt
Screening adult s for depressive disorders in t he primary care set t ing is recommended by t he U.S. Prevent ive Services Task Force.
Bi bl i ography
Williams JW Jr, No'l PH, Cordes JA, Ramirez G, Pignone M. Is t his pat ient clinically depressed? JAMA. 2002;287(9):1160-1170. [PMID: 11879114]
Item 72 Answer: C
Educati onal Objecti ve: Manage multifactorial dizziness in a geriatric patient with physical therapy.
Physical t herapy is t he best management opt ion for t his pat ient . Disequilibrium in t he elderly is oft en described as a vague sense of unst eadiness, most oft en occurring while
st anding or walking. It is different from ort host at ic hypot ension in t hat sympt oms are not always t emporally relat ed t o moving from a seat ed t o a st anding posit ion and are
not associat ed wit h a drop in blood pressure. Disequilibrium in t he elderly is oft en mult ifact orial, wit h cont ribut ors including peripheral neuropat hy, visual loss, decline in
bilat eral vest ibular funct ion, decondit ioning, aut onomic neuropat hy, and medicat ion side effect s. Treat ment of disequilibrium involves reducing polypharmacy, inst alling
safet y feat ures in pat ient s' homes, providing assist ive devices such as walkers and canes, correct ing eyesight and hearing if possible, and inst it ut ing physical t herapy t o
improve muscle st rengt h.
Neuroimaging should usually be reserved for pat ient s wit h signs suggest ing cerebellar or focal neurologic sympt oms or vert ical nyst agmus. There is no evidence t hat t his
pat ient has a new neurologic lesion.
Meclizine can be of use in pat ient s wit h prolonged or sust ained vert igo such as in acut e viral labyrint hit is; however, for int ermit t ent episodes of unst eadiness, it is not likely t o
be of benefit and will add t o her polypharmacy.
The combinat ion of aspirin and dipyridamole is an effect ive st rat egy for t he secondary prevent ion of ischemic st roke. There is no evidence, however, t hat such t reat ment
improves disequilibrium in t he elderly.
Key Poi nt
Dizziness in geriat ric pat ient s is oft en mult ifact orial and caused by deficit s in mult iple sensory syst ems and medicat ion side effect s.
Bi bl i ography
Eat on DA, Roland PS. Dizziness in t he older adult , Part 2. Treat ment s for causes of t he four most common sympt oms. Geriat rics. 2003;58(4):46,49-52. [PMID: 12708155]
Item 73 Answer: D
Educati onal Objecti ve: Manage hypertension in a young patient with lifestyle modifications.
Lifest yle modificat ions are recommended for all pat ient s wit h hypert ension, including prehypert ension. The Diet ary Approaches t o St op Hypert ension (DASH) st udy showed
t hat 8 weeks of a diet of fruit s, veget ables, low-fat dairy product s, whole grains, poult ry, fish, and nut s, along wit h a reduct ion in int ake of fat s, red meat , and sweet s, caused an
11.4-mm Hg decrease in syst olic pressure and a 5.5-mm Hg decrease in diast olic pressure. In addit ion, pat ient s using t he DASH diet who consumed less t han 100 mmol/d of
sodium had a syst olic pressure 3 mm Hg and a diast olic pressure 1.6 mm Hg less t han t hose who consumed high amount s of sodium.
Weight reduct ion in a pat ient whose weight is 10% above ideal body weight lowers blood pressure by an average of 5 t o 7 mm Hg. Alcohol consumpt ion should be limit ed t o
t wo drinks daily for men and one for women because excess amount s of alcohol may cont ribut e t o hypert ension and resist ance t o ant ihypert ensive medicat ions. Regular
aerobic exercise also modest ly decreases blood pressure. In addit ion, t his pat ient should be counseled about smoking cessat ion.
In pat ient s wit h st age 1 hypert ension (syst olic pressure bet ween 140 and 159 mm Hg or diast olic pressure bet ween 90 and 99 mm Hg), lifest yle modificat ions should be t ried
before ant ihypert ensive medicat ion is init iat ed. In pat ient s wit h st age 1 hypert ension who do not have evidence of cardiovascular disease or t arget organ damage, t herapeut ic
lifest yle changes can be t ried for 6 t o 12 mont hs before init iat ing drug t herapy.
Key Poi nt
In young pat ient s wit h st age 1 hypert ension, lifest yle modificat ions should be t ried before ant ihypert ensive medicat ion is init iat ed.
Bi bl i ography
American College of Physicians. In t he clinic. Hypert ension. Ann Int ern Med. 2008;149(11):ITC6(1-15). [PMID: 19047024]
Item 74 Answer: A
Educati onal Objecti ve: Treat hypertension in an elderly patient with the addition of hydrochlorothiazide.
The most appropriat e next st ep in t his pat ient 's management is t he addit ion of low-dose chlort halidone and follow-up in 1 week. Ant ihypert ensive t herapy has been shown
t o benefit pat ient s age 60 t o 80 years. Furt hermore, ant ihypert ensive t herapy in pat ient s older t han 80 years is associat ed wit h a decrease in st roke and cardiovascular
mort alit y.
Diuret ics enhance t he ant ihypert ensive efficacy of mult idrug regimens and are inexpensive. According t o t he Sevent h Report of t he Joint Nat ional Commit t ee on
Prevent ion, Det ect ion, Evaluat ion, and Treat ment of High Blood Pressure (JNC 7), t hiazide diuret ics should be used as init ial t herapy for most pat ient s wit h hypert ension,
eit her alone or in combinat ion wit h one of t he ot her classes of ant ihypert ensive agent s. JNC 7 also recommends t hat older pat ient s wit h hypert ension should follow t he same
principles out lined for t he general care of hypert ension in younger pat ient s. Because older pat ient s wit h hypert ension are more likely t o be salt sensit ive and responsive t o a
diuret ic, low-dose chlort halidone is appropriat e for t his pat ient . Follow-up evaluat ion in 1 week also is indicat ed t o assess for elect rolyt e abnormalit ies or azot emia.
Adding an angiot ensin-convert ing enzyme inhibit or (such as lisinopril), an angiot ensin recept or blocker (such as losart an), or an -blocker (such as t erazosin) would be less
likely t han a diuret ic t o benefit an elderly pat ient .
Key Poi nt
Low-dose diuret ic t herapy is appropriat e in older pat ient s wit h hypert ension because t hese pat ient s are more likely t o be salt sensit ive.
Bi bl i ography
Item 75 Answer: C
Educati onal Objecti ve: Identify the maximum blood pressure in a patient with diabetes as less than 130/80 mm Hg.
The maximum t arget blood pressure for t his pat ient is less t han 130/80 mm Hg. The Sevent h Report of t he Joint Nat ional Commit t ee on Prevent ion, Det ect ion, Evaluat ion,
and Treat ment of High Blood Pressure (JNC 7) defines normal blood pressure as less t han 120/80 mm Hg. Cardiovascular risk correlat es direct ly wit h blood pressure st age,
beginning at 115/75 mm Hg and doubling wit h each 20/10 mm Hg increment .
The goal of ant ihypert ensive t reat ment in pat ient s wit h essent ial hypert ension is t o reduce blood pressure t o less t han 140/90 mm Hg. However, pat ient s wit h diabet es
mellit us have an increased risk for cardiovascular morbidit y and mort alit y. Therefore, t he t arget blood pressure goal for t hese pat ient s is less t han 130/80 mm Hg, which is
associat ed wit h a lower rat e of cardiovascular out comes.
A similar blood pressure t arget is appropriat e for pat ient s wit h chronic nondiabet ic kidney disease not associat ed wit h significant prot einuria. A t arget blood pressure of less
t han 125/75 mm Hg is recommended for pat ient s wit h kidney disease accompanied by a urine prot ein-creat inine rat io above 1 mg/mg. However, t his level of blood pressure
cont rol is not indicat ed in t his pat ient , because he does not meet t he prot einuria crit eria on t he basis of his urine albumin-creat inine rat io.
Key Poi nt
The t arget blood pressure in pat ient s wit h t ype 2 diabet es mellit us and nondiabet ic chronic kidney disease in t he absence of prot einuria is less t han 130/80 mm Hg.
Bi bl i ography
Kidney Disease Out comes Qualit y Init iat ive (K/DOQI). K/DOQI clinical pract ice guidelines on hypert ension and ant ihypert ensive agent s in chronic kidney disease. Am J
Kidney Dis. 2004;43(5 Suppl 1):S1-S290. [PMID: 15114537]
Item 76 Answer: A
Educati onal Objecti ve: Diagnose coarctation of the aorta.
This pat ient has classic feat ures of aort ic coarct at ion. He has a pulse delay bet ween t he upper and lower ext remit ies (radial art ery t o femoral art ery delay). The blood pressure
in t he lower ext remit ies, when measured, will be lower t han t he blood pressure not ed in t he upper ext remit ies. The pat ient also has an eject ion click and an early syst olic
murmur consist ent wit h a bicuspid aort ic valve, which is present in more t han 50% of pat ient s wit h aort ic coarct at ion. The syst olic and diast olic murmurs not ed over t he
back are relat ed t o collat eral vessels, which also cause t he sign of rib not ching, seen on t his pat ient 's chest radiograph on t he inferior surface of t he post erior upper t horacic
ribs bilat erally. Also, indent at ion of t he aort ic wall at t he sit e of coarct at ion combined wit h pre- and post -coarct at ion dilat at ion produces t he "3" sign.
Essent ial hypert ension is t he most common cause of syst emic hypert ension, but t he physical examinat ion feat ures of t his pat ient are not explained by t his diagnosis. In
addit ion, a family hist ory of hypert ension is common in pat ient s wit h essent ial hypert ension.
Pheochromocyt oma causes paroxysmal hypert ension in about half of affect ed pat ient s; ot her pheochromocyt omas present similarly t o essent ial hypert ension. The signs and
sympt oms of pheochromocyt oma are variable. The classic t riad of sudden severe headaches, diaphoresis, and palpit at ions carries a high degree of specificit y (94%) and
sensit ivit y (91%) for pheochromocyt oma in hypert ensive pat ient s. The absence of all t hree sympt oms reliably excludes t he condit ion. Finally, t he physical examinat ion
feat ures in t his pat ient do not reflect t his diagnosis.
Renovascular hypert ension due t o fibromuscular disease of t he renal art eries usually present s in pat ient s younger t han 35 years of age. At herosclerot ic renovascular disease is
more common in older pat ient s and is frequent ly associat ed wit h vascular disease in ot her vessels (carot id or coronary art eries and peripheral vessels). Azot emia is oft en
observed in pat ient s wit h at herosclerot ic renovascular hypert ension. Renal art ery st enosis cannot explain t his pat ient 's cardiac and peripheral vascular examinat ion findings.
Key Poi nt
Coarct at ion of t he aort a should be suspect ed in a young pat ient present ing wit h syst emic hypert ension, radial t o femoral art ery delay, and rib not ching on chest radiography.
Bi bl i ography
Tanous D, Benson LN, Horlick EM. Coarct at ion of t he aort a: evaluat ion and management . Curr Opin Cardiol. 2009. [Epub ahead of print ] [PMID: 19667980]
Item 77 Answer: B
Educati onal Objecti ve: Treat stage 2 hypertension with two-drug therapy.
The most appropriat e next st ep in management for t his pat ient is init iat ion of lisinopril and hydrochlorot hiazide. This pat ient has st age 2 hypert ension (syst olic blood
pressure 160 mm Hg or diast olic blood pressure 100 mm Hg), and bot h lifest yle modificat ions and ant ihypert ensive t herapy are indicat ed. The guidelines proposed by t he
Sevent h Report of t he Joint Nat ional Commit t ee on Prevent ion, Det ect ion, Evaluat ion, and Treat ment of High Blood Pressure (JNC 7) recommend init iat ing t reat ment wit h
t wo medicat ions in pat ient s wit h st age 2 hypert ension or t hose whose blood pressure is great er t han 20 mm Hg syst olic or 10 mm Hg diast olic above t arget . Low-dose
hydrochlorot hiazide and an angiot ensin-convert ing enzyme (ACE) inhibit or, such as lisinopril, would be reasonable in t his pat ient t o ensure adequat e blood pressure cont rol.
Careful follow-up and monit oring for signs of impaired fast ing glucose or glucose int olerance also are recommended.
Monot herapy wit h hydrochlorot hiazide, met oprolol, or t erazosin would not be appropriat e in a pat ient wit h st age 2 hypert ension. Furt hermore, evidence suggest s t hat -
blockers do not perform as well as comparat or drugs, part icularly in prevent ing st roke, and t hus t hey are no longer universally recommended as first -line single agent s in t he
absence of a compelling indicat ion, which may include a hist ory of myocardial infarct ion and heart failure. Finally, t hiazide diuret ics appear t o be superior t o -blockers (such
as t erazosin), ACE inhibit ors, and calcium channel blockers as init ial t herapy for reducing cardiovascular and kidney risk in pat ient s wit h hypert ension.
Key Poi nt
Current guidelines recommend init iat ing t reat ment wit h t wo medicat ions in pat ient s wit h st age 2 hypert ension or t hose whose blood pressure is great er t han 20 mm Hg
syst olic or 10 mm Hg diast olic above t arget .
Bi bl i ography
Item 78 Answer: C
Educati onal Objecti ve: Treat prehypertension with lifestyle modification.
The most appropriat e next st ep in management is lifest yle modificat ion. This pat ient has prehypert ension, defined by t he Sevent h Report of t he Joint Nat ional Commit t ee
on Prevent ion, Det ect ion, Evaluat ion, and Treat ment of High Blood Pressure (JNC 7) guidelines as a blood pressure of 120 t o 139/80 t o 89 mm Hg. Lifest yle modificat ion
consist s of adhering t o a Diet ary Approaches t o St op Hypert ension (DASH) diet , reducing sodium int ake, regular aerobic exercise, and moderat ing alcohol int ake. Lifest yle
modificat ions can lower blood pressure, modify addit ional cardiovascular risk fact ors, and decrease t he incidence of overt hypert ension in pat ient s wit h prehypert ension.
Ambulat ory blood pressure monit oring is primarily indicat ed for pat ient s wit h whit e coat hypert ension. Alt hough no overall agreement exist s about t he diagnost ic crit eria,
some expert s define whit e coat hypert ension as at least t hree separat e office blood pressure measurement s above 140/90 mm Hg wit h at least t wo set s of measurement s below
140/90 mm Hg obt ained in non-office set t ings.
Current dat a do not support pharmacologic t reat ment in pat ient s wit h prehypert ension wit h no ot her major risk fact ors for hypert ension, such as diabet es mellit us, kidney
disease, or evidence of t arget organ damage. Therefore, administ rat ion of hydrochlorot hiazide or lisinopril is inappropriat e.
Key Poi nt
Lifest yle modificat ions, such as maint aining a normal body weight , regular aerobic physical act ivit y, adhering t o a Diet ary Approaches t o St op Hypert ension (DASH) diet ,
reducing sodium int ake, and moderat ing alcohol int ake, are indicat ed for pat ient s wit h prehypert ension who do not have ot her major risk fact ors for hypert ension.
Bi bl i ography
Secti on 5. Hematol ogy
Questi ons
Item 1 [Advanced]
A 50-year-old woman is evaluat ed for met hot rexat e t herapy for her new-onset rheumat oid art hrit is. She had a mild anemia at t ribut ed t o rheumat oid art hrit is. Low-dose
met hot rexat e and folic acid t herapy are init iat ed.
Five mont hs lat er, her art hrit is sympt oms are improved, but her anemia has worsened. She feels well wit hout fat igue. She cont inues t o have menses every 28 days, wit h flow
last ing 5 days. She has no ot her source of blood loss.
5 Mont hs Ago Today
Hemoglobin 10.8 g/dL (108 g/L) 9.7 g/dL (97 g/L)
Ret iculocyt e count 0.7% 0.8%
Mean corpuscular volume 92 fL 93 fL
Serum iron 36 g/dL (6.4 mol/L) 15 g/dL (2.7 mol/L)
Tot al iron-binding capacit y (calculat ed) 394 g/dL (70.5 mol/L) 394 g/dL (70.5 mol/L)
Serum ferrit in 36 ng/mL (36 g/L)
Serum creat inine Normal
Serum hapt oglobin Normal
Serum lact at e dehydrogenase Normal
Vit amin B
12
Normal
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s for her anemi a?
(A) Iron deficiency
(B) Anemia of inflammat ion
(C) Anemia of inflammat ion plus iron deficiency
(D) Megaloblast ic anemia
Item 2 [Basic]
A 28-year-old woman has a 3-mont h hist ory of easy bruising and bleeding gums. She feels ot herwise well. Medical and family hist ories are unremarkable, and she t akes no
medicat ions.
On physical examinat ion, vit al signs are normal. Pet echiae are present on t he buccal mucosa and pret ibial areas, and ecchymoses are not ed on t he upper t highs. There is no
lymphadenopat hy or splenomegaly.
9
/L)
Absolut e neut rophil count 1200/L (1.2 10
9
/L) (normal >1500/L [1.5 10
9
/L])
9
/L)
Ret iculocyt e count 0.9% of eryt hrocyt es
Direct ant iglobulin (Coombs) t est Negat ive
A peripheral blood smear shows no circulat ing blast s. The plat elet s are decreased in number but ot herwise normal. Bone marrow examinat ion shows hypoplast ic marrow
(<20% cellularit y) wit h normal mat urat ion of all cellular element s and normal iron st ores. There are no findings suggest ing an infilt rat ive disease and no fibrosis.
(A) Aplast ic anemia
(B) Aut oimmune hemolyt ic anemia
(C) Immune t hrombocyt openic purpura
(D) Iron deficiency anemia
Item 3 [Basic]
A 64-year-old man is evaluat ed in t he office for a gradual decrease in exercise t olerance over t he past 2 mont hs. He has ost eart hrit is of t he right knee but no ot her medical
problems. His only medicat ion is over-t he-count er ibuprofen. Result s of rout ine screening colonoscopy 4 mont hs ago were normal.
On physical examinat ion, heart rat e is 90/min, respirat ion rat e is 20/min, and blood pressure is 140/80 mm Hg.
Laborat ory st udy findings include a hemoglobin level of 9.6 g/dL (96 g/L) and mean corpuscular volume of 76 fL. Result s of rout ine serum chemist ry analysis are normal.
Serum iron, serum ferrit in, and t ransferrin sat urat ion levels are all low, and t he t ot al iron-binding capacit y is elevat ed. St ool is posit ive for occult blood.
Upper endoscopy reveals chronic gast rit is, and t he ibuprofen is st opped.
Whi ch of the fol l owi ng i s the most appropri ate treatment for thi s pati ent's anemi a?
(A) Blood t ransfusion
(B) Eryt hropoiet in
(C) Int ravenous iron
(D) Oral iron
Item 4 [Advanced]
A 27-year-old man is evaluat ed in t he office for dark urine. Four days ago, t he pat ient began t aking t rimet hoprim-sulfamet hoxazole for bact erial sinusit is. He has a brot her
who developed hemolyt ic anemia when exposed t o a sulfa-cont aining drug.
On physical examinat ion, t emperat ure is 37.8C (100.2F), blood pressure is 127/66 mm Hg, pulse rat e is 112/min, and respirat ion rat e is 25/min. Scleral ict erus is not ed.
Tachycardia is heard on cardiac auscult at ion, but cardiac examinat ion is ot herwise unremarkable. Abdominal examinat ion discloses no hepat osplenomegaly.
Ret iculocyt e count 11% of eryt hrocyt es
Bilirubin
Tot al 5.1 mg/dL (87.2 mol/L)
Indirect 4.6 mg/dL (78.7 mol/L)
Urinalysis 3+ bilirubin
A peripheral blood smear is shown (Plat e 11).
(A) Glucose 6-phosphat e dehydrogenase deficiency
(B) Heredit ary spherocyt osis
(C) Microangiopat hic hemolyt ic anemia
(D) Warm ant ibody-mediat ed hemolyt ic anemia
Item 5 [Advanced]
A 14-year-old boy undergoing a rout ine evaluat ion is found t o have mild microcyt ic anemia. His hist ory and physical examinat ion findings are normal.
Hemoglobin level is 10 g/dL (100 g/L), eryt hrocyt e count is 5.9 10
6
/L (5.9 10
12
/L), and mean corpuscular volume is 76 fL. The serum iron and ferrit in levels are
normal.
The peripheral blood smear is shown (Plat e 12).
(A) Heredit ary spherocyt osis
(B) Iron deficiency anemia
(C) Sickle cell anemia
(D) Thalassemia minor
Item 6 [Advanced]
An 86-year-old woman is evaluat ed for a 6-mont h hist ory of increasing fat igue and parest hesias of t he t oes. Medical hist ory is ot herwise noncont ribut ory. Her only
medicat ion is a daily aspirin.
On physical examinat ion, vit al signs are normal. Neurologic examinat ion shows decreased vibrat ory sense and propriocept ion in t he t oes and fingers. Findings from t he
remainder of t he neurologic and general physical examinat ion are normal.
Mean corpuscular volume 106 fL
9
/L)
Vit amin B
12
220 pg/mL (162.4 pmol/L)
Folat e (serum) 22 ng/mL (49.8 nmol/L)
A peripheral blood smear shows macro-ovalocyt es but no ot her abnormalit y.
(A) Bone marrow biopsy
(B) Eryt hrocyt e folat e measurement
(C) Met hylmalonic acid and homocyst eine measurement s
(D) Pariet al cell ant ibody assay
Item 7 [Basic]
A 56-year-old woman is evaluat ed during a rout ine follow-up examinat ion. Six mont hs ago, she underwent aort ic valve replacement wit h a mechanical prost hesis. Her init ial
post operat ive course has been unevent ful, and she has no sympt oms. Her hemat ocrit at discharge was 40%. Her only medicat ion is warfarin.
On physical examinat ion, vit al signs are normal. Her cardiac examinat ion reveals a normal S
1
and mechanical S
2
wit hout an S
3
or S
4
. There is a nonradiat ing grade 2/6
midpeaking syst olic murmur heard best at t he lower left st ernal border. Ot her physical examinat ion findings are normal.
Hapt oglobin 8 mg/dL (80 mg/L)
Hemat ocrit 31%
INR 2.6
9
/L)
The blood smear shows normocyt ic eryt hrocyt es wit h schist ocyt es.
Whi ch of the fol l owi ng i s the most l i kel y cause of her anemi a?
(A) Aut oimmune hemolyt ic anemia
(B) Disseminat ed int ravascular coagulat ion
(C) Hemolyt ic anemia due t o mechanical heart valve
(D) Thrombot ic t hrombocyt openic purpura
Item 8 [Basic]
A previously healt hy 65-year-old man is evaluat ed for easy fat igabilit y. He has no significant medical hist ory, has never had a screening colonoscopy or ot her colon cancer
screening, and does not drink alcohol. The pat ient t akes no medicat ions. His hemoglobin level 1 year ago was 14.3 g/dL (143 g/L).
Result s of physical examinat ion are normal except for t he finding of pallor. Laborat ory examinat ion reveals a hemoglobin level of 8.6 g/dL (86 g/L). Test ing of st ool for
occult blood is negat ive. A peripheral blood smear is shown (Plat e 13).
(C) Sickle cell anemia
Item 9 [Basic]
A 57-year-old woman wit h chronic lymphocyt ic leukemia (CLL) is evaluat ed in t he emergency depart ment because of a 2-week hist ory of increasing malaise, decreased
exercise t olerance, and darkened urine. Her CLL was last t reat ed 2 mont hs ago wit h chemot herapy.
On physical examinat ion, t he pat ient has scleral ict erus. Temperat ure is 37.3C (99.2F), blood pressure is 142/82 mm Hg, pulse rat e is 117/min, and respirat ion rat e is
18/min. Cardiopulmonary examinat ion discloses a regular t achycardia. Splenomegaly is present .
9
/L)
9
/L)
Bilirubin
Tot al 6.3 mg/dL (107.7 mol/L)
Direct 0.5 mg/dL (8.6 mol/L)
Direct ant iglobulin (Coombs) t est Posit ive for IgG
(A) Aut oimmune hemolyt ic anemia
(B) Heredit ary spherocyt osis
(C) Microangiopat hic hemolyt ic anemia
(D) -Thalassemia
Item 10 [Advanced]
A 60-year-old man is evaluat ed in t he hospit al for esophageal variceal bleeding and easy bruising. He was admit t ed 2 hours ago and was init ially st abilized wit h int ravenous
fluids and endoscopic band ligat ion, but he cont inues t o bleed. He has a long hist ory of alcohol abuse, is t aking no medicat ions, and has not recent ly consumed aspirin or
nonst eroidal ant i-inflammat ory (NSAIDs) medicat ions. There is no family hist ory of bleeding. One year ago, he successfully underwent a part ial colect omy for recurrent
divert iculit is wit hout excessive bleeding.
The pat ient is alert but t remulous. On physical examinat ion, blood pressure is 90/60 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 14/min. Cardiopulmonary
examinat ion is normal. Abdominal palpat ion reveals minimal t enderness. The spleen is palpable. Large ecchymoses are present at previous phlebot omy sit es. No pet echiae
are present .
Serum creat inine 1.5 mg/dL (132.6 mmol/L)
9
/L)
Prot hrombin t ime 16.1 s
Act ivat ed part ial t hromboplast in t ime 40 s
Mixing st udy Correct s t o near normal
Whi ch of the fol l owi ng i s the most l i kel y cause of hi s bl eedi ng di sorder?
(A) Acquired fact or deficiency
(B) Acquired fact or inhibit or
(C) Acquired plat elet dysfunct ion
(D) Thrombocyt openia
Item 11 [Basic]
A 79-year-old woman is evaluat ed in t he hospit al for sepsis secondary t o pyelonephrit is. The pat ient was well before t his illness and has no ot her medical problems.
On physical examinat ion, t emperat ure is 38.9C (102.0F), blood pressure is 90/50 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 18/min. She has bleeding at
phlebot omy sit es and around her int ravenous access insert ion and many ecchymoses on her arms and legs.
Hemoglobin 9 mg/dL (90 g/L)
9
/L)
Prot hrombin t ime 15 s
Act ivat ed part ial t hromboplast in t ime 30 s
D-dimer Elevat ed
Fibrinogen Reduced
Examinat ion of t he peripheral blood smear shows many fragment ed eryt hrocyt es and diminished plat elet s.
Whi ch of the fol l owi ng i s the most l i kel y cause of her bl eedi ng di sorder?
(A) Disseminat ed int ravascular coagulat ion
(B) Hemolyt ic uremic syndrome
(C) Immune t hrombocyt openic purpura
Item 12 [Basic]
An 18-year-old man is evaluat ed for excessive bleeding. Aft er a rout ine t oot h ext ract ion, he had 5 hours of bleeding t hat t he dent ist was able t o cont rol. The pat ient is
healt hy and t akes no medicat ions, including aspirin or NSAIDs. Medical hist ory includes easy bruisabilit y and occasional nose bleeds t hat are easily cont rollable. The pat ient
was circumcised at birt h, and his mot her recalls t hat he had more bleeding t han expect ed from t he circumcision sit e. His fat her also has easy bruisabilit y.
Physical examinat ion is normal, wit h no evidence of pet echiae, ecchymoses, or abnormal vasculat ure.
9
/L)
INR 1.1
Act ivat ed part ial t hromboplast in t ime (aPTT) 41 s
aPTT mixing st udy Correct s t o normal
Thrombin t ime 16 s (cont rol, 15 s)
Fibrinogen Normal
D-dimer assay Negat ive
Bleeding t ime 10 min (prolonged)
Fact or VIII act ivit y 60% (normal, 65%-120%)
(A) Hemophilia A (fact or VIII deficiency)
(B) Presence of a lupus inhibit or
(C) Vit amin K deficiency
(D) von Willebrand disease
Item 13 [Basic]
A 55-year-old woman undergoes preoperat ive evaluat ion before elect ive laparoscopic cholecyst ect omy. Medical hist ory includes t hree pregnancies and full-t erm deliveries
wit h no complicat ions or healt h problems. She has had no previous surgeries. Physical examinat ion findings are normal.
Whi ch of the fol l owi ng i s the best screeni ng approach to detect any bl eedi ng di sorders i n thi s pati ent?
(A) Clinical hist ory
(B) INR
(C) INR, prot hrombin t ime (PT), and part ial t hromboplast in t ime (PTT)
(D) INR, PT, PTT, and bleeding t est
Item 14 [Advanced]
A 19-year-old man wit h sickle cell disease develops severe weakness and dyspnea. He has not had rash, fever, new joint or abdominal sympt oms, bleeding from his mucous
membranes, hemopt ysis, hemat emesis, or hemat uria.
On physical examinat ion, vit al signs are normal except for a pulse rat e of 148/min. His conjunct ivae are very pale. There is no t hrush or lymphadenopat hy. A st ool
specimen is negat ive for occult blood. Hemat ocrit is 16% wit h no ret iculocyt es compared wit h his usual hemat ocrit of approximat ely 25% wit h 15% ret iculocyt es. The
leukocyt e and plat elet count s are normal.
(A) Acut e myeloblast ic leukemia
(B) Bleeding pept ic ulcer
(C) Epst ein-Barr virus infect ion
(D) Parvovirus B19 infect ion
Item 15 [Advanced]
A 46-year-old man is evaluat ed in t he emergency depart ment for swelling of t he feet and ankles and a 2-mont h hist ory of worsening dyspnea. The pat ient has homozygous
sickle cell disease and a hist ory of acut e chest syndrome. Current medicat ions are hydroxyurea and folic acid.
On physical examinat ion, t emperat ure is normal, blood pressure is 145/85 mm Hg, pulse rat e is 98/min, and respirat ion rat e is 28/min. Jugular venous pressure is elevat ed and
is associat ed wit h large a and v waves. On cardiac examinat ion, t here is a heave, fixed split t ing of S
2
wit h a palpable P
2
, and a syst olic murmur at t he lower left st ernal border
t hat increases wit h respirat ion. The lungs are clear. Examinat ion of t he lower ext remit ies shows 2+ edema bilat erally.
A chest radiograph shows enlargement of t he cent ral pulmonary art eries wit h clear lung fields. Echocardiographic findings include a normal left vent ricular eject ion fract ion,
right vent ricular enlargement and hypert rophy, right at rial enlargement , and t ricuspid regurgit at ion.
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's fi ndi ngs?
(B) Hypert rophic cardiomyopat hy
(C) Ischemic heart disease
(D) Pulmonary hypert ension
Item 16 [Advanced]
A 31-year-old man wit h sickle cell disease is hospit alized because of right -sided pleurit ic chest pain, a nonproduct ive cough, fever, and pain in his upper legs and pelvis.
On physical examinat ion, t emperat ure is 38.6C (101.5F), blood pressure is 130/85 mm Hg, pulse rat e is 95/min, and respirat ory rat e is 20/min. Crackles and rhonchi are
heard over t he right lower lung field. There is no t enderness over t he joint s or bones. Hemoglobin is 6.7 g/dL (67 g/L), ret iculocyt e count is 18%, and leukocyt e count is
17,000/L (17 10
9
/L) wit h 65% neut rophils. No neut rophils are seen on a sput um smear. A chest radiograph shows a large infilt rat e in t he right lower lobe. His art erial PO
2
is 60 mm Hg (8 kPa) on ambient air. The pat ient is st art ed on ant ibiot ics and supplement al oxygen.
Whi ch of the fol l owi ng shoul d be performed next?
(A) Eryt hropoiet in init iat ion
(B) Hydroxyurea init iat ion
(C) Red blood cell exchange t ransfusion
(D) Red blood cell t ransfusion
Item 17 [Advanced]
A 34-year-old woman wit h sickle cell disease is evaluat ed for a 2-week hist ory of increasingly severe left groin pain. The pain awakens her at night and causes subst ant ial
difficult y in walking. There is no hist ory of t rauma, but she t ypically has 1 t o 2 hospit alizat ions per year for t reat ment of sickle cell painful crisis. Her only medicat ion is a
folic acid supplement .
On physical examinat ion, she has an obvious left leg limp. Vit al signs are normal. There is rest rict ed flexion and int ernal rot at ion of t he left hip due t o pain locat ed in t he
groin. No t enderness t o palpat ion over t he lat eral hip, sacroiliac joint s, or sciat ic not ch is not ed. There is no evidence of ot her joint involvement .
Plain radiographs of t he pelvic region and hips are normal.
Whi ch of the fol l owi ng i s the best test to eval uate the hi p pai n?
(A) Art hrocent esis
(B) Bone densit omet ry
(C) MRI
(D) Radionuclide bone scan
Item 18 [Basic]
A 13-year-old girl is hospit alized because of t he sudden development of left hemiparesis and aphasia. A peripheral blood smear is shown (Plat e 15).
(C) Sickle cell disease
Item 19 [Advanced]
A 67-year-old woman is admit t ed t o t he hospit al because of a deep venous t hrombosis involving t he left leg t hat developed during a 12-hour car t rip. Medical hist ory is
significant for a 2-day hospit alizat ion 14 weeks ago for a non-ST elevat ion myocardial infarct ion; she underwent cardiac cat het erizat ion at t hat t ime and was t reat ed wit h
low-molecular-weight heparin. Her current medicat ions include aspirin, clopidogrel, pravast at in, and lisinopril.
On physical examinat ion, vit al signs are normal. The left leg is swollen and slight ly t ender t o palpat ion. A complet e blood count , elect rolyt e levels, and liver chemist ry t est
findings are normal on laborat ory st udies; t he plat elet count is 150,000/L (150 10
9
/L).
Unfract ionat ed heparin is administ ered. Twelve hours lat er, t he pat ient 's plat elet count is 87,000/L (87 10
9
/L).
Whi ch of the fol l owi ng i s the most appropri ate next step i n treatment?
(A) Cont inue heparin and administ er a plat elet t ransfusion
(B) Cont inue heparin and init iat e high-dose cort icost eroid t herapy
(C) St op heparin and init iat e argat roban
(D) St op heparin and init iat e warfarin
Item 20 [Advanced]
A 27-year-old woman is evaluat ed in t he emergency depart ment for a 2-day hist ory of diffuse headache, fat igue, and gingival bleeding on brushing her t eet h. She is ot herwise
healt hy and t akes no mediat ions.
On physical examinat ion, she is alert and orient ed but in considerable dist ress from t he headache. Funduscopic examinat ion is normal. A few scleral hemorrhages and mild
ict erus are not ed. Pet echiae are visible on t he lower ext remit ies. Cardiopulmonary and abdominal examinat ion findings are normal.
9
/L)
Prot hrombin t ime Normal
Act ivat ed part ial t hromboplast in t ime Normal
Thrombin t ime Normal
Serum creat inine Normal
(A) Aut oimmune hemolyt ic anemia and t hrombocyt openia
(B) Heparin-induced t hrombocyt openia
(C) Immune t hrombocyt openia
(D) Thrombot ic t hrombocyt openia purpura
Item 21 [Advanced]
A 28-year-old woman in t he t hird t rimest er of an uncomplicat ed pregnancy has a complet e blood count performed during a rout ine visit . She feels well and has no evidence of
bleeding.
On physical examinat ion, all findings are consist ent wit h a normal seven mont h gest at ion.
9
/L)
9
/L)
(A) Gest at ional t hrombocyt openia
(B) Immune t hrombocyt openic purpura
(C) Pseudot hrombocyt openia
Item 22 [Advanced]
A 29-year-old woman is evaluat ed for a pet echial rash of t he lower ext remit ies of 3 weeks' durat ion. The pat ient report s no bleeding problems except for recent , occasional
bleeding from her gums aft er brushing her t eet h. Medical hist ory is ot herwise unremarkable, and she t akes no medicat ions.
Physical examinat ion reveals pet echiae limit ed mainly t o bot h lower ext remit ies, wit h a few similar spot s not ed on her forearms and abdomen. Ot her examinat ion findings
are normal.
9
/L)
9
/L)
Ant inuclear ant ibody assay Negat ive
HIV ant ibody Negat ive
(A) Admit for urgent splenect omy
(B) Init iat e cort icost eroids
(C) Init iat e plat elet t ransfusion
(D) Perform a bone marrow biopsy
Item 23 [Advanced]
A 27-year-old woman undergoes follow-up evaluat ion 5 mont hs aft er diagnosis of an idiopat hic pulmonary embolism for which she was prescribed a 6-mont h course of
warfarin. Family hist ory includes a mat ernal grandmot her, a mot her, and an older brot her wit h a hist ory of deep venous t hrombosis, which was diagnosed in all t hree relat ives
before t hey were aged 50 years. The pat ient t akes no oral cont racept ives or ot her medicat ions and is ot herwise healt hy. The complet e blood count is normal, and t he INR is
3.0.
Whi ch of the fol l owi ng i s the most appropri ate next step i n the eval uati on of thi s pati ent?
(A) Immediat e t hrombophilic screening
(B) JAK2 mut at ion analysis
(C) Thrombophilic screening 2 weeks aft er st opping warfarin
(D) No furt her evaluat ion needed
Item 24 [Advanced]
A 42-year-old woman is evaluat ed for swelling and discomfort of t he right leg wit hout an obvious precipit at ing event . She has no ot her medical problems.
On physical examinat ion, vit al signs are normal. Examinat ion of t he right lower ext remit y shows mild eryt hema, swelling, warmt h, and t enderness t o deep palpat ion of t he
calf. Cardiopulmonary and abdominal examinat ion findings are normal.
Laborat ory st udies indicat e a moderat ely elevat ed IgG ant icardiolipin ant ibody level and t he presence of a lupus inhibit or on coagulat ion t est ing.
An ult rasound shows a right proximal lower ext remit y deep venous t hrombosis.
The pat ient is t reat ed wit h ant icoagulat ion t herapy. Repeat ant icardiolipin ant ibody t est ing 12 weeks lat er confirms t he previous result .
Whi ch of the fol l owi ng i s the most appropri ate anti coagul ati on management for thi s pati ent?
(A) Ant icoagulat ion t herapy indefinit ely
(B) Ant icoagulat ion t herapy for a t ot al of 12 mont hs
(C) Ant icoagulat ion t herapy for a t ot al of 6 mont hs
(D) Cessat ion of ant icoagulat ion t herapy at 3 mont hs
Item 25 [Advanced]
A 33-year-old woman who has been t rying t o become pregnant for 8 years is evaluat ed aft er receiving posit ive pregnancy t est result s. Medical hist ory is significant for t hree
miscarriages occurring 6 years ago, 3 years ago, and 1 year ago, each of which occurred early in her pregnancy. She had an unprovoked venous t hromboembolism 18 mont hs
ago. Her last menst rual period was approximat ely 5 weeks ago.
Result s of physical examinat ion, including vit al signs and abdominal examinat ion, are normal.
Result s of laborat ory st udies show a prolonged act ivat ed part ial t hromboplast in t ime (aPTT). A mixing st udy does not correct t he aPTT
Testi ng for whi ch of the fol l owi ng i s the most appropri ate next step?
(A) Fact or V Leiden mut at ion
(B) Homocyst eine level
(C) Lupus inhibit or and ant iphospholipid ant ibody
(D) Prot hrombin G20210A mut at ion
Item 26 [Basic]
A 70-year-old woman is evaluat ed because of malaise and anorexia for 1 week. She has hypert ension t reat ed wit h hydrochlorot hiazide.
On physical examinat ion, t he supine blood pressure is 150/95 mm Hg, pulse rat e is 80/min, respirat ion rat e is 20/min, and t emperat ure is 37.4C (99.3F). The blood pressure
is 125/80 mm Hg and t he pulse rat e 96/min while st anding. The remainder of t he examinat ion is unremarkable.
Hemat ocrit 29%
Serum creat inine 4.6 mg/dL (406.6 mol/L)
Serum sodium 134 meq/L (134 mmol/L)
Serum pot assium 5.0 meq/L (5.0 mmol/L)
Serum chloride 114 meq/L (114 mmol/L)
Serum bicarbonat e 15 meq/L (15 mmol/L)
Serum calcium 12.5 mg/dL (3.1 mmol/L)
Serum phosphat e 8.5 mg/dL (2.7 mmol/L)
Urinalysis Specific gravit y 1.007; t race prot einuria; no glucosuria or ket onuria
(A) Hypercalcemia secondary t o hydrochlorot hiazide t herapy
(B) Milk-alkali syndrome
(C) Mult iple myeloma
(D) Primary hyperparat hyroidism
Item 27 [Basic]
A 59-year-old man is evaluat ed for a 4-day hist ory of progressively worsening fat igue, forget fulness, const ipat ion, excessive t hirst , and increased urinat ion. He has no pain.
His only significant medical hist ory is a diagnosis of right lower lobe pneumonia due t o Streptococcus pneumoniae 3 mont hs ago.
On physical examinat ion, he appears somnolent but is arousable. Temperat ure is 37.1C (98.8F), blood pressure is 110/70 mm Hg, pulse rat e is 120/min, and respirat ion rat e
is 17/min. The oral mucosa is dry, and t he conjunct ivae are pale. The lungs are clear.
9
/L)
9
/L)
Prot ein
Tot al 7.6 g/dL (76 g/L)
Urinalysis Negat ive for prot ein
A peripheral blood smear shows normochromic, normocyt ic eryt hrocyt es wit h rouleaux format ion and no evidence of t eardrop eryt hrocyt es or immat ure myeloid and
eryt hroid cells.
A chest radiograph shows ost eopenia of all ribs. No pulmonary parenchymal infilt rat es are seen.
The pat ient is hospit alized and responds t o int ravenous hydrat ion wit h normal saline. The result s of a bone marrow aspirat ion are shown (Plat e 19).
(A) Acut e myeloid leukemia
(B) Chronic lymphocyt ic leukemia
(C) Met ast at ic small cell lung cancer
(D) Mult iple myeloma
Item 28 [Advanced]
A 74-year-old woman is evaluat ed aft er a high serum t ot al prot ein level was found during rout ine laborat ory t est ing. Medical hist ory is noncont ribut ory.
On physical examinat ion, vit al signs are normal and examinat ion findings are unremarkable, wit h no organomegaly or lymphadenopat hy.
9
/L)
9
/L)
Prot ein
Tot al 10.1 g/dL (101 g/L)
Serum prot ein elect rophoresis shows a monoclonal spike of 1.8 g/dL (18 g/L), which is furt her ident ified as IgG-K by serum immunofixat ion. A bone marrow aspirat e reveals
6% plasma cells. A skelet al survey does not show any lyt ic lesions.
(A) AL (light chain) amyloidosis
(B) Lymphoplasmacyt ic lymphoma (Waldenst rom macroglobulinemia)
(C) Monoclonal gammopat hy of undet ermined significance (MGUS)
(D) Mult iple myeloma
Item 29 [Basic]
A 60-year-old man comes t o t he office for follow-up evaluat ion 1 mont h aft er being seen for sympt oms of an upper respirat ory t ract infect ion. Physical examinat ion
findings at his init ial visit were normal; laborat ory st udy result s showed a leukocyt e count of 18,000/L (18 10
9
/L), wit h 60% lymphocyt es. The pat ient 's upper respirat ory
t ract infect ion sympt oms have since resolved complet ely, and he not es no ot her medical problems or sympt oms.
Physical examinat ion findings during t his visit are again normal, wit h no evidence of lymphadenopat hy or splenomegaly. The repeat ed leukocyt e count remains t he same,
and t he comprehensive met abolic profile and lact at e dehydrogenase concent rat ion are normal. Peripheral blood smear reveals morphologically mat ure-appearing
lymphocyt es.
(A) Acut e lymphocyt ic leukemia
(B) Acut e myeloid leukemia
(C) Chronic lymphocyt ic leukemia
(D) Chronic myeloid leukemia
Item 30 [Basic]
A 57-year-old woman is evaluat ed in t he emergency depart ment for fever and shaking chills of 8 hours' durat ion. The pat ient has a 1-year hist ory of myelodysplast ic
syndrome t reat ed wit h azacit idine.
On physical examinat ion, t emperat ure is 39.2C (102.6F), blood pressure is 100/70 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 20/min. Physical examinat ion
findings are ot herwise unremarkable, wit h no rash, lymphadenopat hy, cost overt ebral angle t enderness, abdominal t enderness, or splenomegaly.
9
/L)
9
/L)
Urinalysis Normal
A chest radiograph is normal.
(A) Acut e lymphoblast ic leukemia
(C) Acut e promyelocyt ic leukemia
Item 31 [Advanced]
A 58-year-old man is evaluat ed for increasing fat igue of 2 mont hs' durat ion. He has no ot her medical problems and is not t aking any medicat ions.
On physical examinat ion, vit al signs are normal. There is no lymphadenopat hy or peripheral edema. The spleen is palpable 4 cm below t he left cost al margin.
9
/L)
9
/L)
A peripheral blood smear shows an increased number of granulocyt ic cells in all phases of development but wit h a marked left shift and no Auer rods in t he blast s. Bone
marrow examinat ion shows hypercellular marrow (80% cellularit y) wit h marked granulocyt ic hyperplasia, a left shift in t he granulocyt es, and 3% myeloblast s. Cyt ogenet ic
t est ing reveals a BCR/ABL t ranslocat ion.
(A) Acut e lymphoblast ic leukemia
(C) Acut e promyelocyt ic leukemia
Item 1 Answer: C
Educati onal Objecti ve: Diagnose iron deficiency in the setting of inflammatory anemia.
This pat ient has anemia of inflammat ion and iron deficiency. She has rheumat oid art hrit is, a cause of inflammat ory anemia. Inflammat ory cyt okines block iron ut ilizat ion,
decrease t ransferrin (and t ot al iron-binding capacit y [TIBC]) levels, and increase ferrit in levels. In cont rast , t he physiologic response t o iron deficiency is t o increase
t ransferrin (and TIBC) levels and decrease ferrit in levels. When inflammat ion accompanies iron deficiency, inflammat ory cyt okines always confound t he expect ed pat t ern of
serum iron chemist ries for iron deficiency alone.
This pat ient 's init ial serum iron chemist ries demonst rat e a serum iron-t o-TIBC rat io of 12%. Repeat serum iron chemist ries 5 mont hs lat er show an even lower iron-t o-TIBC
rat io of 4.7%, and her ferrit in level is low-normal. Virt ually all pat ient s wit h serum ferrit in levels lower t han 10 t o 15 ng/mL (10-15 g/L) are iron deficient ; however, 25%
of menst ruat ing women wit h absent st ainable bone marrow iron have ferrit in levels higher t han 15 ng/mL (15 g/L). Assuming absence of inflammat ion, higher ferrit in cut off
limit s of 30 t o 41 ng/mL (30-41 g/L) improve t he efficiency of diagnosing iron deficiency in women during t heir reproduct ive years. Because t his pat ient also has
rheumat oid art hrit is, serum ferrit in levels are expect ed t o rise (by as much as t hreefold) owing t o t he effect s of inflammat ory cyt okines. Therefore, t his pat ient 's serum
ferrit in level of 36 ng/mL (36 g/L) support s a diagnosis of iron deficiency, part icularly in t he set t ing of her inflammat ory illness. As a rule of t humb, serum ferrit in levels
lower t han 100 t o 120 ng/mL (100-120 g/L) may reflect iron deficiency in pat ient s wit h inflammat ory st at es.
Alt hough mont hly physiologic blood loss wit h menst ruat ion is t he most likely cause of iron deficiency in t his pat ient , she should have age-appropriat e cancer screening wit h
colonoscopy (at a minimum) t o exclude gast roint est inal causes of occult blood loss.
Met hot rexat e is an ant imet abolit e t hat inhibit s dihydrofolat e reduct ase and causes megaloblast ic mat urat ion; however, low-dose met hot rexat e is unlikely t o cause significant
megaloblast ic anemia, whereas higher doses may do so wit h a significant rise in mean corpuscular volume (MCV). This pat ient 's MCV is unchanged wit h low-dose
met hot rexat e. Hence, megaloblast ic anemia due t o met hot rexat e is not a likely cont ribut or t o t his pat ient 's anemia.
Key Poi nt
Serum ferrit in levels lower t han 100 t o 120 ng/mL (100-120 g/L) may reflect iron deficiency in pat ient s wit h inflammat ory st at es.
Bi bl i ography
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011-23. [PMID: 15758012]
Item 2 Answer: A
Educati onal Objecti ve: Diagnose aplastic anemia.
This pat ient has aplast ic anemia. Pat ient s wit h t his disorder have pancyt openia, a low ret iculocyt e count , and a hypoplast ic bone marrow (<20% cellularit y) wit h normal
mat urat ion of all cell lines. Aplast ic anemia is a fat al disorder in which myeloid progenit or cells and st em cells are severely diminished or absent in t he bone marrow because
of eit her an int rinsic defect of t he st em cells or immune-mediat ed st em cell dest ruct ion, which leads t o t ransfusion-dependent anemia, t hrombocyt openia, and severe
neut ropenia. In approximat ely 50% of cases of aplast ic anemia, t here is no obvious cause; chemicals, drugs, viral infect ions, collagen vascular diseases, and t hymoma can be
implicat ed in t he remaining cases. Int erferon-act ivat ed T lymphocyt es are involved in aut oimmune dest ruct ion of st em cells in a significant proport ion of pat ient s wit h t he
idiopat hic or t he acquired form of t he disease; t his fact explains why immunosuppressive t herapy is effect ive in some pat ient s. Init ial management involves wit hdrawal of any
pot ent ially causat ive agent s and a CT scan of t he chest t o rule out an associat ed t hymoma.
Pat ient s wit h immune t hrombocyt openic purpura (ITP) have pet echiae and ecchymoses but do not have a decreased leukocyt e count . Most pat ient s wit h ITP do not have
anemia, but some of t hem may have an associat ed aut oimmune hemolyt ic anemia or iron deficiency anemia due t o bleeding. However, t his pat ient 's direct ant iglobulin
(Coombs) t est was negat ive, and she had a low ret iculocyt e count , which t oget her rule out hemolyt ic anemia. Finally, t his pat ient does not have a clinical hist ory of bleeding,
and her iron st ores are normal, which suggest s t hat blood loss and iron deficiency is not t he cause of her anemia.
Key Poi nt
Pat ient s wit h aplast ic anemia have pancyt openia, a low ret iculocyt e count , and hypoplast ic bone marrow.
Bi bl i ography
Young NS, Scheinberg P, Calado RT. Aplast ic anemia. Curr Opin Hemat ol. 2008;15(3):162-168. [PMID: 18391779]
Item 3 Answer: D
Educati onal Objecti ve: Treat iron deficiency anemia with oral iron.
The most appropriat e t reat ment for t his pat ient is oral iron. This pat ient has iron deficiency anemia, as confirmed by t he low mean corpuscular volume, low serum iron
level, elevat ed t ot al iron-binding capacit y (TIBC), and low t ransferrin sat urat ion (iron/TIBC). Iron deficiency is best t reat ed by using oral iron salt s; ferrous sulfat e, 325 mg
t hree t imes daily, is t he least expensive preparat ion. Alt hough t here are alt ernat ive preparat ions of oral iron, none has conclusively been shown t o increase oral t olerabilit y
and t hey deliver less element al iron. Iron t herapy is t ypically cont inued several mont hs aft er normalizat ion of t he hemoglobin level. Pat ient s who are unable t o absorb iron
orally (for example, pat ient s wit h Crohn disease, celiac disease, or small bowel resect ion) inst ead may receive parent eral iron.
Because t he pat ient is hemodynamically st able, t here is no indicat ion for a blood t ransfusion. This pat ient 's signs, sympt oms, and laborat ory findings are not suggest ive of
renal disease, which may cause a low eryt hropoiet in level, or of a bone marrow disorder, which would require administ rat ion of supraphysiologic levels of eryt hropoiet in.
Moreover, eryt hropoiet in t herapy would be ineffect ive in t his pat ient unt il iron has become available for eryt hrocyt e product ion. This pat ient has no evidence of
malabsorpt ion t hat would require parent eral administ rat ion of iron.
Key Poi nt
Pat ient s wit h iron deficiency anemia require oral iron replacement t herapy.
Bi bl i ography
Killip S, Bennet t JM, Chambers MD. Iron deficiency anemia. Am Fam Physician. 2007;75(5):671-678. [PMID: 17375513]
Item 4 Answer: A
Educati onal Objecti ve: Diagnose glucose 6-phosphate dehydrogenase deficiency.
This pat ient has glucose 6-phosphat e dehydrogenase (G6PD) deficiency. G6PD deficiency is t he most common disorder of eryt hrocyt e met abolism. G6PD is necessary for
generat ing adequat e nicot inamide adenine dinucleot ide phosphat e-oxidase (NADPH) t o prevent oxidant st ress. G6PD is found on t he X-chromosome, and, t herefore,
deficiency rarely occurs in women. The acut e onset of sympt oms and findings in pat ient s wit h t his deficiency can be precipit at ed by drugs, infect ion, or diabet ic ket oacidosis.
In t his pat ient , hemolysis was likely precipit at ed by t rimet hoprim-sulfamet hoxazole.
At 2 t o 4 days aft er int roduct ion of t he oxidat ive st ress in pat ient s wit h G6PD deficiency, onset of jaundice and dark urine occurs, wit h or wit hout abdominal and back pain.
The hemoglobin level decreases by 3 t o 4 g/dL (30 t o 40 g/L), and t here is an appropriat e increase in ret iculocyt es. The hemolysis spont aneously resolves in approximat ely 1
week as t he older enzyme-deplet ed cells are replaced by new cells wit h sufficient G6PD t o prevent furt her hemolysis. Addit ional laborat ory findings in pat ient s wit h G6PD
deficiency include a negat ive direct and indirect ant iglobulin (Coombs) t est and t he presence of "bit e" or "blist er" cells, produced when accumulat ed oxidized hemoglobin
remains adherent t o t he eryt hrocyt e membrane wit h an adjacent membrane-bound clear zone. Such cells are visible on t his pat ient 's peripheral blood smear. Because
ret iculocyt es can have normal G6PD levels, measuring G6PD levels during an acut e episode may produce a false-negat ive result .
Pat ient s wit h heredit ary spherocyt osis have spherocyt es on t he peripheral blood smear, as do pat ient s wit h warm ant ibody-mediat ed hemolysis. The direct ant iglobulin t est is
posit ive in pat ient s wit h warm ant ibody-mediat ed hemolysis and negat ive in pat ient s wit h heredit ary spherocyt osis. Pat ient s wit h a microangiopat hy have schist ocyt es on t he
peripheral blood smear and, t ypically, a low plat elet count . Neit her of t hese findings is present in t he peripheral blood smear shown.
Key Poi nt
In glucose-6-phosphat e dehydrogenase deficiency, "bit e" or "blist er" cells are produced when accumulat ed oxidized hemoglobin remains adherent t o t he eryt hrocyt e
membrane, which creat es an adjacent membrane-bound clear zone.
Bi bl i ography
Cappellini MD, Fiorelli G. Glucose-6-phosphat e dehydrogenase deficiency. Lancet . 2008;371:64-74. [PMID: 18177777]
Item 5 Answer: D
Educati onal Objecti ve: Diagnose thalassemia minor on the basis of a peripheral blood smear.
The most likely diagnosis is t halassemia minor. Pat ient s wit h t halassemia have a low mean cellular volume and t arget cells on t he peripheral smear. Target cells are
charact erized by a cent ral dense deposit of hemoglobin surrounded by a halo of pallor. This gives t he eryt hrocyt es a "bull's-eye" appearance. In normal eryt hrocyt es, t here is
only cent ral pallor. In t halassemia, t he eryt hrocyt e count is usually normal, or even slight ly elevat ed. Iron st udies are t ypically normal unless t here is a coexist ing iron
deficiency anemia. The degree of poikilocyt osis and anisocyt osis is only modest but t he hypochromia is st riking and helps different iat e t halassemia from iron deficiency
anemia.
Heredit ary spherocyt osis is charact erized by uniformly small spherocyt es t hat lack t he t ypical cent ral pallor of normal eryt hrocyt es, and sickle cell anemia is charact erized
by sickled cells (crescent - or spindle-shaped cells) on t he peripheral blood smear. These findings are absent in t his pat ient 's peripheral blood smear. Iron deficiency anemia is
unlikely given t he normal result s of t he iron st udies. Addit ionally, a more st riking variat ion in red blood cell size and shape would be expect ed wit h t his degree of
hypochromia in iron deficiency anemia.
Key Poi nt
Pat ient s wit h t halassemia have a low mean cellular volume and t arget cells on t he peripheral blood smear and have normal result s on iron st udies.
Bi bl i ography
Rund D, Rachmilewit z E. Bet a-t halassemia. N Engl J Med. 2005;353(11):1135-1146. [PMID: 16162884]
Item 6 Answer: C
Educati onal Objecti ve: Diagnose cobalamin deficiency in a patient with a low-normal vitamin B
12
level with methylmalonic acid and homocysteine measurements.
The most appropriat e next diagnost ic t est is measurement of serum met hylmalonic acid and homocyst eine. This pat ient 's findings of macrocyt ic anemia, t hrombocyt openia,
elevat ed lact at e dehydrogenase level, and neurologic findings are very suggest ive of vit amin B
12
deficiency despit e t he low-normal B
12
level. Levels of met hylmalonic acid and
homocyst eine become elevat ed in pat ient s wit h vit amin B
12
deficiency before serum vit amin B
12
levels decrease below t he normal range. In cont rast , only homocyst eine is
elevat ed in folat e deficiency. Subclinical vit amin B
12
deficiency in pat ient s wit h subt le signs and sympt oms of vit amin B
12
deficiency can be det ect ed by ident ificat ion of
elevat ed met hylmalonic acid levels. This is part icularly t rue for pat ient s whose vit amin B
12
level is in t he "low-normal" range, as t his pat ient 's is.
Alt hough bone marrow biopsy can be suggest ive of vit amin B
12
deficiency, it is not a specific t est for confirming t his disorder because t here are ot her pot ent ial causes of
megaloblast ic marrow, including myelodysplasia.
Eryt hrocyt e folat e levels have been t out ed as a bet t er indicat ion of folat e st ores t han serum folat e levels are, but t hey are subject t o problems of defining normal values and
may not be t hat helpful clinically. Eryt hrocyt e folat e levels can also be depressed in pat ient s wit h vit amin B
12
deficiency. Addit ionally, folat e deficiency would not cause t he
neurologic sympt oms present in t his pat ient .
Pariet al cell ant ibodies are elevat ed in pat ient s wit h pernicious anemia but may not be elevat ed in pat ient s whose vit amin B
12
deficiency is due t o malabsorpt ion, which is a
very common cause of deficiency in t he elderly.
Key Poi nt
Met hylmalonic acid levels become elevat ed before vit amin B
12
levels decrease below t he normal range in pat ient s wit h vit amin B
12
deficiency.
Bi bl i ography
Cravens DD, Nashelsky J, Oh RC. Clinical inquiries. How do we evaluat e a marginally low B
12
level? J Fam Pract . 2007;56(1):62-63. [PMID: 17217902]
Item 7 Answer: C
Educati onal Objecti ve: Diagnose prosthetic valve hemolytic anemia.
The most likely cause of t his pat ient 's anemia is hemolyt ic anemia due t o mechanical dest ruct ion by t he prost het ic heart valve. All pat ient s wit h hemolyt ic anemia have
common findings, which include an increased serum lact at e dehydrogenase level, a decreased serum hapt oglobin level, and ret iculocyt osis. Examinat ion of t he peripheral blood
smear is oft en helpful in ident ifying t he cause of t he hemolyt ic anemia.
This pat ient 's blood smear shows schist ocyt es (fragment ed blood cells), which are found in pat ient s wit h microangiopat hic hemolyt ic anemia (for example, t hrombot ic
t hrombocyt openic purpura, hemolyt ic uremic syndrome, and disseminat ed int ravascular coagulat ion) and wit h mechanical dest ruct ion due t o prost het ic heart valves.
Microangiopat hic hemolyt ic anemia is an unlikely diagnosis for a pat ient who appears well, has no evidence of organ dysfunct ion, and has a normal plat elet count . Pat ient s
wit h aut oimmune hemolyt ic anemia have microspherocyt es on t heir peripheral smear in addit ion t o an increased ret iculocyt e count ; schist ocyt es are not ably absent .
Mild hemolyt ic anemia is common in pat ient s wit h prost het ic heart valves, but t he anemia can be more severe in up t o 20% of pat ient s. Sympt omat ic hemolyt ic anemia can
usually be t reat ed wit h oral iron and folat e replacement , alt hough more severe cases may warrant blood t ransfusion or recombinant human eryt hropoiet in. Rarely, pat ient s
will require valve reoperat ion if hemolysis is due t o significant valve dysfunct ion or progressive paravalvular regurgit at ion.
Key Poi nt
Schist ocyt es (fragment ed blood cells) are associat ed wit h microangiopat hic hemolyt ic anemia (t hrombot ic t hrombocyt openic purpura, hemolyt ic uremic syndrome, and
disseminat ed int ravascular coagulat ion) and wit h mechanical dest ruct ion due t o prost het ic heart valves.
Bi bl i ography
Shapira Y, Vat uri M, Sagie A. Hemolysis associat ed wit h prost het ic heart valves: a review. Cardiol Rev. 2009;17(3):121-124. [PMID: 19384085]
Item 8 Answer: B
Educati onal Objecti ve: Diagnose iron deficiency anemia on the basis of a peripheral blood smear.
The findings on t he peripheral blood smear are suggest ive of iron deficiency anemia. The eryt hrocyt es show hypochromia, anisocyt osis (changes in size), and poikilocyt osis
(changes in shape) and are also likely t o be microcyt ic. If a confirmat ory t est (for example, serum ferrit in det erminat ion) support s t he diagnosis of iron deficiency anemia, a
source of gast roint est inal blood loss should be sought , regardless of whet her t he st ool is posit ive or negat ive for occult blood. A gast roint est inal lesion, such as colon cancer or
gast rit is, is far more likely t han diet ary inadequacies or malabsorpt ion in an ot herwise healt hy adult .
Heredit ary spherocyt osis, anot her cause of microcyt osis, is associat ed wit h spherocyt es (small cells wit h loss of t he normal cent ral pallor) and an enlarged spleen, and would
be unlikely t o present in a 65-year-old man. Sickle cell anemia would be associat ed wit h sickled cells (spindle- or crescent -shaped cells) on t he peripheral blood smear, which
are not present . Alt hough t he t halassemias are associat ed wit h hypochromic, microcyt ic eryt hrocyt es, t he diagnosis is unlikely in a pat ient who had a normal hemoglobin
level 1 year ago. In addit ion, eryt hrocyt es in t halassemia show less hypochromia, anisocyt osis, and poikilocyt osis and more t arget cells. Target cells are charact erized by a
concent rat ion of dense hemoglobin in t he cent er of t he cell surrounded by a rim of pallor creat ing a "bull's-eye" appearance. Normal eryt hrocyt es have an area of cent ral
pallor.
Key Poi nt
Peripheral blood smear findings suggest ive of iron deficiency anemia include microcyt osis, hypochromia, anisocyt osis (changes in size), and poikilocyt osis (changes in shape).
Bi bl i ography
Clark SF. Iron deficiency anemia: diagnosis and management . Curr Opin Gast roent erol. 2009;25(2):122-128. [PMID: 19262200]
Item 9 Answer: A
Educati onal Objecti ve: Diagnose autoimmune hemolytic anemia.
This pat ient has aut oimmune hemolyt ic anemia (AIHA). The hemolyt ic anemias are charact erized by increased dest ruct ion of eryt hrocyt es associat ed wit h ret iculocyt osis.
Elevat ed levels of unconjugat ed bilirubin, lact at e dehydrogenase, and uric acid and depressed levels of hapt oglobin are charact erist ic of hemolysis. AIHA may be idiopat hic or
result from drugs, lymphoproliferat ive disorders, collagen vascular diseases, or malignancies. Warm ant ibody-mediat ed hemolyt ic anemia, t he most common t ype of AIHA, is
diagnosed by t he direct ant iglobulin (Coombs) t est , which det ect s IgG or complement on t he cell surface, and t he presence of spherocyt es on t he peripheral blood smear. In
t his condit ion, IgG ant ibodies bind t o Rh-t ype ant igens on t he eryt hrocyt e surface at 37.0C (98.6F).
Heredit ary spherocyt osis is a congenit al hemolyt ic anemia caused by abnormalit ies in eryt hrocyt e membrane prot eins and is charact erized by spherocyt ic eryt hrocyt es wit h
increased osmot ic fragilit y due t o t heir large volume/surface area rat io. It would be very unusual for a congent ial hemolyt ic anemia t o be first diagnosed at t his pat ient 's age.
Addit ionally, heredit ary spherocyt osis is not associat ed wit h posit ive result s on a Coombs t est . Spherocyt es are small round cells t hat lack t he t ypical cent ral pallor of normal
eryt hrocyt es.
Microangiopat hic hemolyt ic anemia is a nonimmune hemolyt ic anemia. As wit h ot her hemolyt ic anemias, it is charact erized by ret iculocyt osis, elevat ed levels of
unconjugat ed bilirubin, lact at e dehydrogenase, and depressed levels of hapt oglobin. Microangiopat hic hemolysis may be associat ed wit h t hrombocyt openia. Anot her
dist inguishing charact erist ic of microangiopat hic hemolyt ic anemia is t he presence of schist ocyt es on t he peripheral blood smear. This finding was lacking on t his pat ient 's
peripheral blood smear.
-Thalassemia is a congenit al hemolyt ic anemia. Pat ient s wit h a t wo--gene defect have t arget cells and an absence of spherocyt es on t he peripheral blood smear and do not
have posit ive result s on a direct ant iglobulin t est .
Key Poi nt
Warm ant ibody-mediat ed hemolyt ic anemia, a common complicat ion of lymphoid malignancies, is charact erized by spherocyt es on t he peripheral blood smear.
Bi bl i ography
Hauswirt h AW, Skrabs C, Schut zinger C, Gaiger A, Lechner K, Jager U. Aut oimmune hemolyt ic anemias, Evans' syndromes, and pure red cell aplasia in non-Hodgkin
lymphomas. Leuk Lymphoma. 2007;48(6):1139-1149. [PMID: 17577777]
Item 10 Answer: A
Educati onal Objecti ve: Diagnose an acquired coagulation factor deficiency.
The pat ient most likely has an acquired coagulat ion fact or deficiency. All coagulat ion fact ors are synt hesized in t he liver, and severe hepat ic impairment leads t o various
fact or deficiencies, and vit amin K deficiency may furt her increase t he risk for deficient coagulat ion fact ors. Pat ient s wit h liver disease, especially cirrhosis, have an enlarged
spleen and a moderat e reduct ion in t he plat elet count (50,000 t o 100,000/L [50-100 10
9
/L]) caused by splenic sequest rat ion (hypersplenism), which may increase t he risk
for bleeding. In addit ion, cirrhosis is oft en associat ed wit h esophageal varices, which also cause gast roint est inal bleeding. Coagulat ion usually does not become impaired unt il
t he cirrhosis is advanced, and t he prot hrombin t ime, act ivat ed part ial t hromboplast in t ime, and t hrombin t ime are all prolonged (as in t his pat ient ). If result s of any of t hese
assays are prolonged and t he diagnosis remains in doubt , an inhibit or mixing st udy should be done. This involves repeat ing t he abnormal assay wit h a 1:1 mixt ure of t he
pat ient 's plasma and normal plasma t o det ect eit her a fact or deficiency or t he presence of an inhibit or (t hat is, an ant ibody direct ed against a fact or). The result s of t he
mixing st udy will normalize in a pat ient wit h a fact or deficiency (as t hey did in t his pat ient ) but will remain abnormal if an inhibit or is present .
The pat ient 's plat elet count is not low enough t o cause significant bleeding. Acquired qualit at ive plat elet disorders are most commonly caused by drugs, especially aspirin and
NSAIDs. Ot her ant iplat elet agent s used t o t reat cardiovascular disease may also cause plat elet disorders (for example, abciximab, ept ifibat ide, clopidogrel). Uremia is anot her
common cause of a qualit at ive plat elet disorder. The plat elet defect in uremia has been at t ribut ed t o impaired plat elet -vessel wall adhesion. The pat ient is t aking no
medicat ions and t he serum creat inine is 1.5 mg/dL (132.6 mmol/L), making an acquired plat elet funct ion disorder unlikely.
Key Poi nt
Al l coagul ati on factors are synthesi zed i n the l i ver, and severe hepati c i mpai rment l eads to vari ous factor defi ci enci es.
Bi bl i ography
Caldwell SH, Sanyal AJ. Coagulat ion disorders and bleeding in liver disease: fut ure direct ions. Clin Liver Dis. 2009;13(1):155-7. [PMID: 19150319]
Item 11 Answer: A
Educati onal Objecti ve: Diagnose disseminated intravascular coagulation.
The most likely diagnosis is disseminat ed int ravascular coagulat ion (DIC). DIC is t he result of widespread act ivat ion of coagulat ion t hat leads t o format ion of fibrin clot s.
Some pat ient s have a t hrombot ic disorder, but in most pat ient s, secondary fibrinolysis dissolves t he fibrin clot and consumpt ion of plat elet s and coagulat ion fact ors causes
t hrombocyt openia, clot t ing fact or deficiencies, bleeding, and vascular injuries. Eryt hrocyt e consumpt ion is manifest ed by a microangiopat hic hemolyt ic anemia wit h
fragment ed eryt hrocyt es seen on a peripheral blood smear. DIC most commonly occurs in pat ient s wit h infect ions, cancer, and obst et rical complicat ions. Gram-negat ive
sepsis is t he most common infect ion associat ed wit h DIC. The diagnosis of DIC is based on a prolonged prot hrombin t ime, act ivat ed part ial t hromboplast in t ime, and
t hrombin t ime; a high D-dimer t it er; a reduced serum fibrinogen level and plat elet count ; and microangiopat hic hemolyt ic anemia. The degree of t hese abnormalit ies depends
on t he ext ent of consumpt ion of plat elet s and coagulat ion fact ors and t he abilit y of t he pat ient t o compensat e for t hese findings.
Two t hrombot ic microangiopat hies in t he different ial diagnosis of DIC are t hrombot ic t hrombocyt openic purpura (TTP) and hemolyt ic uremic syndrome (HUS). The t wo
syndromes overlap, and it is oft en difficult t o dist inguish bet ween t hem. The pent ad of TTP includes t hrombocyt openia, microangiopat hic hemolyt ic anemia, neurologic
deficit s, renal impairment , and fever. All five findings do not need t o be present for t he diagnosis t o be est ablished. HUS is a condit ion primarily of children and mainly
affect s t he kidneys as a result of int rarenal plat elet -fibrin t hrombi. Neit her TTP nor HUS is associat ed wit h elevat ions of t he prot hrombin or part ial t hromboplast in t ime or
t he D-dimer or depression of t he fibrinogen level.
Immune t hrombocyt openic purpura (ITP) may be aut oimmune mediat ed or drug induced. The diagnosis is based on excluding ot her causes of t hrombocyt openia, ot her
syst emic illnesses, and medicat ions. The only laborat ory disorder associat ed wit h ITP is t hrombocyt openia.
Key Poi nt
The di agnosi s of di ssemi nated i ntravascul ar coagul ati on i s based on a prol onged prothrombi n ti me, acti vated parti al thrombopl asti n ti me, and thrombi n
ti me; a hi gh D-di mer ti ter; a reduced serum fi bri nogen l evel and pl atel et count; and mi croangi opathi c hemol yti c anemi a.
Bi bl i ography
Levi M, Toh CH, Thachil J, Wat son HG. Guidelines for t he diagnosis and management of disseminat ed int ravascular coagulat ion. Brit ish Commit t ee for St andards in
Haemat ology. Br J Haemat ol. 2009;145(1):24-33. [PMID: 19222477]
Item 12 Answer: D
Educati onal Objecti ve: Diagnose von Willebrand disease.
The most likely diagnosis is von Willebrand disease. This pat ient has abnormal bleeding on t oot h ext ract ion, a hist ory suggest ive of a bleeding t endency, and a family hist ory
of a pot ent ial bleeding problem. His laborat ory st udies support bot h a qualit at ive plat elet defect (prolonged bleeding t ime) and a mild coagulopat hy (borderline elevat ed
act ivat ed part ial t hromboplast in t ime [aPTT] and low fact or VIII level). These findings are suggest ive of t he most common inherit ed hemost at ic disorder, namely, von
Willebrand disease. von Willebrand disease is one of t he few hemost at ic disorders charact erized by bot h a plat elet and coagulat ion defect due t o a reduct ion or defect in von
Willebrand fact or (vWF), which support s plat elet adhesion and also serves as a carrier prot ein for fact or VIII. The diagnosis is confirmed by measuring t he vWF ant igen level
and act ivit y.
Hemophilia A (fact or VIII deficiency) is not associat ed wit h a prolonged bleeding t ime, nor is it t ransmit t ed from fat her t o son (X-linked inherit ance). The presence of a
lupus inhibit or is generally associat ed wit h a t hrombot ic, not a bleeding, disorder; is an acquired disorder; does not prolong t he bleeding t ime; and is not associat ed wit h
decreased levels of fact or VIII. Vit amin K deficiency can occur in pat ient s receiving t ot al parent eral nut rit ion or long-t erm ant ibiot ics and in t hose who are malnourished,
part icularly in t he set t ing of warfarin administ rat ion. This condit ion is charact erized by a progressively prolonged prot hrombin t ime (PT) and aPTT (wit h t he PT
proport ionat ely more prolonged t han t he aPTT) and a normal t hrombin t ime, findings not consist ent wit h t hose in t his pat ient .
Key Poi nt
von Willebrand disease is an aut osomal dominant disorder charact erized by a personal and family hist ory of a bleeding t endency, a prolonged bleeding t ime, a borderline-
elevat ed act ivat ed part ial t hromboplast in t ime, and a low fact or VIII level.
Bi bl i ography
Kessler CM. Diagnosis and t reat ment of von Willebrand disease: new perspect ives and nuances [errat um in Haemophilia. 2008;14(3):669]. Haemophilia. 2007;13 Suppl 5:3-
14. [PMID: 18078392]
Item 13 Answer: A
Educati onal Objecti ve: Screen for bleeding disorders with a clinical history.
The best screening approach t o det ect bleeding disorders is by t aking a t horough clinical hist ory. The clinical hist ory should focus on t he presence of any syst emic illnesses
and previous bleeding. If bleeding is report ed, it s severit y should be det ermined, as should whet her t he bleeding is spont aneous or is an excessive response t o normal bleeding
aft er injury, surgery, or dent al procedures; whet her t he bleeding pat t ern is lifelong or recent ly acquired; and whet her t he bleeding suggest s a plat elet or a coagulat ion defect .
Plat elet -relat ed bleeding t ends t o occur immediat ely aft er injury and oft en affect s t he mucous membranes or t he skin in t he form of pet echiae. Coagulat ion-relat ed bleeding
may be delayed in onset , is manifest ed more by deep t issue bruises (ecchymoses), and may produce hemart hroses in pat ient s wit h congenit al deficiencies. Women should be
asked about t he pat t ern of menst rual bleeding or, if post menopausal, about whet her any abnormal bleeding has occurred. Obt aining a det ailed medicat ion hist ory and a family
hist ory of any bleeding disorders is imperat ive.
In t he absence of a personal or family hist ory of abnormal bleeding, liver disease, significant alcohol use, malabsorpt ion, or ant icoagulat ion t herapy, t he likelihood of a
bleeding disorder is low, and no furt her preoperat ive t est ing is required. Pat ient s wit h any of t hese risk fact ors should be screened furt her by obt aining a prot hrombin t ime
(PT/INR), an act ivat ed part ial t hromboplast in t ime, and a plat elet count . In addit ion, plasma fibrinogen measurement and von Willebrand fact or t est ing should be considered
in pat ient s wit h a hist ory of bleeding problems.
Key Poi nt
In t he absence of a personal or family hist ory of abnormal bleeding, liver disease, significant alcohol use, malabsorpt ion, or ant icoagulat ion t herapy, t he likelihood of a
bleeding disorder is low, and no furt her preoperat ive t est ing is required.
Bi bl i ography
Smet ana GW, Macpherson DS. The case against rout ine preoperat ive laborat ory t est ing. Med Clin Nort h Am. 2003;87(1):7-40. [PMID: 12575882]
Item 14 Answer: D
Educati onal Objecti ve: Diagnose parvovirus B19 infection as the cause of aplastic crisis in sickle cell disease.
Transient aplast ic crisis in a pat ient wit h chronic hemolyt ic anemia is usually due t o acut e infect ion wit h parvovirus B19, a single-st randed DNA virus. The propensit y of t his
virus t o infect bone marrow eryt hroid progenit or cells can cause profound anemia in someone who is dependent on rapid eryt hrocyt e product ion. Acut e infect ion can be
diagnosed by finding serum IgM ant ibodies against parvovirus B19. Recovery usually occurs spont aneously in days t o weeks.
Parvovirus B19 infect ion also causes eryt hema infect iosum (fift h disease), a common childhood illness charact erized by a "slapped-cheek" appearance of t he face followed by
a lacy red rash on t he t runk and limbs. This virus can also cause polyart hrit is in adult s (oft en aft er exposure t o a child wit h eryt hema infect iosum), hydrops fet alis if infect ion
occurs early during pregnancy, and chronic infect ion in immunocompromised persons, including pat ient s infect ed wit h HIV.
Alt hough leukemia may cause severe anemia, ot her hemat opoiet ic lineages are also oft en involved, which was not evident in t his pat ient . A bleeding ulcer should st imulat e
eryt hrocyt e product ion and not depress ret iculocyt e product ion and most likely would be associat ed wit h melena or st ool samples posit ive for occult blood. Epst ein-Barr virus
infect ion is unlikely t o cause red cell aplasia. This viral infect ion may be associat ed wit h hemolyt ic anemia and ret iculocyt osis, lymphadenopat hy, splenomegaly, hepat it is,
and a variet y of lymphoproliferat ive disorders.
Key Poi nt
Transient aplast ic crisis in pat ient s wit h chronic hemolyt ic anemia is usually due t o acut e infect ion wit h parvovirus B19.
Bi bl i ography
Servey JT, Reamy BV, Hodge J. Clinical present at ions of parvovirus B19 infect ion. Am Fam Physician. 2007;75(3):373-376. [PMID: 17304869]
Item 15 Answer: D
Educati onal Objecti ve: Diagnose pulmonary hypertension in a patient with sickle cell anemia.
The most likely diagnosis is pulmonary hypert ension. Pulmonary hypert ension is a newly recognized cause of morbidit y and mort alit y in pat ient s wit h homozygous sickle
cell disease. Various st udies suggest a prevalence of 20% t o 60%. The present at ion of pulmonary hypert ension is charact erized by right -sided heart failure wit h peripheral
edema, abnormal venous waveforms, fixed split t ing of S
2
, loud or palpable pulmonic valve closure, t ricuspid regurgit at ion, a right vent ricular heave, and clear lungs. This
pat ient 's echocardiographic result s are consist ent wit h pulmonary hypert ension.
The cardinal sympt oms of aort ic st enosis are angina, syncope, and dyspnea. The murmur of aort ic st enosis is a midsyst olic crescendo-decrescendo murmur heard best at t he
second right int ercost al space; t he murmur radiat es t oward t he carot id art eries. The murmur does not vary wit h respirat ion and is not associat ed wit h fixed split t ing of S
2
; in
aort ic st enosis, split t ing is oft en absent or reversed (heard during exhalat ion, not inspirat ion).
Most pat ient s wit h hypert rophic cardiomyopat hy are relat ively asympt omat ic; however, some may develop sympt oms of pulmonary congest ion (exert ional dyspnea,
ort hopnea, and paroxysmal noct urnal dyspnea), chest pain, fat igue, palpit at ions, dizziness, and syncope. In affect ed pat ient s, physical examinat ion in t he presence of left
vent ricular out flow obst ruct ion shows a variable and dynamic syst olic murmur t hat is increased by t he Valsalva maneuver. There is no change in t he murmur wit h respirat ion.
Echocardiography in pat ient s wit h hypert rophic cardiomyopat hy delineat es a pat t ern of left vent ricular or sept al hypert rophy, which is absent in t his pat ient .
Ischemic heart disease can cause left vent ricular dysfunct ion and signs of heart failure wit hout chest pain. However, t his pat ient 's findings are most compat ible wit h right -sided
heart failure (peripheral edema and clear lungs) due t o pulmonary hypert ension, not left vent ricular dysfunct ion (elevat ed cent ral venous pressure, an S
3
, and pulmonary
crackles). Finally, t he echocardiogram shows normal left vent ricular funct ion.
Key Poi nt
Pulmonary hypert ension is a common cause of morbidit y and mort alit y in pat ient s wit h sickle cell disease.
Bi bl i ography
Gladwin MT, Vichinsky E. Pulmonary complicat ions of sickle cell disease. N Engl J Med. 2008;359(21):2254-2265. [PMID: 19020327]
Item 16 Answer: C
Educati onal Objecti ve: Diagnose and treat acute chest syndrome.
Acut e chest syndrome in pat ient s wit h sickle cell anemia should be managed by exchange t ransfusion. Red blood cell exchange t ransfusions are performed t o increase t he
hemoglobin A level t o at least 50% and t hereby decrease t he percent age of abnormal sickle cells and prevent hemoglobin S polymerizat ion and sickling. In adolescent s and
adult s, pulmonary crises usually st art wit h infarct ions t hat may become secondarily infect ed. Wit h t ime, mult iple infarct ions predominat e, and pulmonary congest ion and
int rapulmonary shunt ing develop and lead t o more hypoxia and sickling.
Eryt hropoiet in administ rat ion has a limit ed role in pat ient s wit h sickle cell disease. Eryt hropoiet in has been used t o accelerat e recovery from aplast ic crises in some pat ient s.
However, t his pat ient has a brisk ret iculocyt e response, which indicat es t hat eryt hropoiesis is likely already under int ense eryt hropoiet in st imulat ion; t he addit ion of ext ra
exogenous eryt hropoiet in is unlikely t o be helpful. Hydroxyurea may reduce t he frequency of painful crises and acut e chest syndrome but is not used in t he acut e t reat ment of
t he sickling process. The drug works by increasing hemoglobin F product ion, which helps prevent hemoglobin S polymerizat ion and sickling. Because of t he increased blood
volume result ing from red blood cell t ransfusions, it is not possible t o increase t he hemoglobin A t o more t han 50% wit hout inducing volume overload; t herefore, exchange
t ransfusions are required.
Key Poi nt
In pat ient s wit h sickle cell disease, acut e chest syndrome should be managed by exchange t ransfusion.
Bi bl i ography
Swerdlow PS. Red cell exchange in sickle cell disease. Hemat ology Am Soc Hemat ol Educ Program. 2006:48-53. [PMID: 17124039]
Item 17 Answer: C
Educati onal Objecti ve: Diagnose osteonecrosis of the hip with MRI.
The best t est t o evaluat e t he pat ient 's hip pain is MRI. This pat ient most likely has ost eonecrosis of t he hip. Ost eonecrosis (previously called avascular necrosis) of t he
femoral head in adult s is oft en associat ed wit h t rauma, sickle cell disease, alcohol abuse, gout , cort icost eroid use, and hypercoagulable st at es; it can also be idiopat hic. Pain is
t he most common sympt om and is usually locat ed in t he groin; t high and but t ock pain is also common. Plain film radiography is oft en t he init ial diagnost ic t est , and early
findings may include increased densit y, reflect ing marrow infarct ion and calcificat ion. However, changes on plain film radiography may t ake weeks t o mont hs t o appear, and
radiography is insensit ive in t he diagnosis of early ost eonecrosis. MRI has a report ed sensit ivit y for ost eonecrosis t hat exceeds 90% and is posit ive when ot her st udies are
negat ive. It is t he preferred imaging modalit y, part icularly if init ial plain radiographs are normal.
Sept ic art hrit is should always be considered in a pat ient wit h acut e monoart icular art hrit is. However, in t he absence of previous hip disease or prost hesis, sept ic art hrit is of t he
hip is relat ively rare. An art hrocent esis is t hus not indicat ed at t his t ime.
Localized ost eoporosis may occur in pat ient s wit h injuries and is a prominent feat ure of complex regional pain syndrome (reflex sympat het ic dyst rophy), which is
charact erized by pain in t he ext remit ies associat ed wit h swelling, limit ed range of mot ion, vasomot or inst abilit y, and skin changes. Bone densit omet ry is not indicat ed in t his
pat ient because she has no hist ory of injury and none of t he sympt oms charact erist ic of complex regional pain syndrome.
A radionuclide bone scan is more sensit ive t han plain radiographs but not as sensit ive as MRI in t he diagnosis of ost eonecrosis. A radionuclide bone scan is t ypically reserved
for pat ient s who have a cont raindicat ion for MRI (for example, met al implant s).
Key Poi nt
MRI is more t han 90% sensit ive in t he diagnosis of ost eonecrosis and is t he preferred imaging procedure when plain radiographs are normal.
Bi bl i ography
Jones LC, Hungerford DS. Ost eonecrosis: et iology, diagnosis, and t reat ment . Curr Opin Rheumat ol. 2004;16(4):443-449. [PMID: 15201609]
Item 18 Answer: C
Educati onal Objecti ve: Diagnose sickle cell disease on the basis of a peripheral blood smear.
It is highly likely t hat t his adolescent has homozygous sickle cell disease and has had occlusion of a major vessel in t he dist ribut ion of t he left middle cerebral art ery causing
right hemiparesis and aphasia. The peripheral blood smear shows charact erist ic sickle cells (elongat ed crescent - and spindle-shaped cells). Pat ient s wit h sickle cell disease
commonly have t arget cells charact erized by a cent ral dense area of hemoglobin surrounded by a rim of pallor, giving it a "bull's-eye" appearance. Normal eryt hrocyt es have
an area of cent ral pallor. St rokes due t o occlusion of a large vessel are not uncommon in pat ient s wit h sickle cell disease and are an indicat ion for chronic blood t ransfusion
t herapy t o maint ain t he peripheral blood hemoglobin S level below 50%.
Heredit ary spherocyt osis, iron deficiency anemia, and t halassemia all cause microcyt osis but are not associat ed wit h elongat ed sickled cells. Heredit ary spherocyt osis is
associat ed wit h uniformly small eryt hrocyt es t hat lack t he normal cent ral pallor. Iron deficiency anemia usually is associat ed wit h eryt hrocyt es t hat have increased cent ral
pallor and variat ion in size (anisocyt osis) and shape (poikilocyt osis). Thalassemia minor is associat ed wit h many t arget cells on t he peripheral blood smear.
Key Poi nt
Sickle cell disease is charact erized by a peripheral blood smear showing elongat ed crescent - and spindle-shaped cells (sickle cells) and t arget cells.
Bi bl i ography
Inat i A, Koussa S, Taher A, Perrine S. Sickle cell disease: new insight s int o pat hophysiology and t reat ment . Pediat r Ann. 2008;37(5):311-321. [PMID: 18543542]
Item 19 Answer: C
Educati onal Objecti ve: Treat a patient with heparin-induced thrombocytopenia.
The most appropriat e next st ep is t o st op heparin and administ er argat roban. Up t o 2% of pat ient s t reat ed wit h heparin (eit her unfract ionat ed or low molecular weight
heparin) develop heparin-induced t hrombocyt openia (HIT), and approximat ely 30% of pat ient s wit h HIT also develop t hrombosis (HIT/T). HIT/T should be considered in
any pat ient wit h an ot herwise unexplained decrease in t he plat elet count and/or a new t hrombot ic event 5 t o 10 days aft er init iat ion of heparin t herapy. However, in pat ient s
wit h recent exposure t o heparin (such as t his pat ient ), t he onset of HIT may be rapid (median t ime, 10.5 hours), and a syndrome of delayed-onset HIT t hat develops as lat e
as 3 weeks aft er discont inuat ion of heparin has also been recognized. Almost all pat ient s wit h HIT/T have circulat ing ant ibodies t o complexes cont aining plat elet fact or 4
(PF4) and heparin. Laborat ory t est ing for HIT/T is considered confirmat ory t o clinical evaluat ion findings. Test s for t he diagnosis of HIT/T rely on plat elet act ivat ion or
measure binding of ant ibodies t o PF4/heparin complexes. The
14
C-serot onin release assay (SRA) is considered t he "gold st andard" for diagnosis, wit h a posit ive predict ive
value approaching 100% and a negat ive predict ive value of approximat ely 20%; t herefore, a negat ive SRA does not exclude HIT/T. Heparin must be discont inued prompt ly
aft er t he diagnosis of HIT is suspect ed and alt ernat ive ant icoagulat ion init iat ed. Lepirudin and argat roban are direct t hrombin inhibit ors t hat have emerged as t he agent s of
choice for t reat ment of HIT or HIT/T in t he Unit ed St at es. Fondaparinux and bivalirudin have also been used.
Plat elet t ransfusions are cont raindicat ed in pat ient s in whom t hrombocyt openia is caused by a consumpt ive process, unless t here is life-t hreat ening bleeding. Cort icost eroids
would only be appropriat e if t he t hrombocyt openia were t hought t o be t ypical for immune t hrombocyt openic purpura, which is not likely in t his pat ient given t he
relat ionship bet ween t he reexposure t o heparin and t he rapid development of t hrombocyt openia. Warfarin should not be init iat ed in t he absence of a concurrent ly
administ ered parent eral ant icoagulant because warfarin alone can pot ent iat e a hypercoagulable st at e early in t reat ment .
Key Poi nt
Heparin-induced t hrombocyt openia and t hrombosis should be considered in any pat ient wit h an ot herwise unexplained decrease in t he plat elet count and/or a new t hrombot ic
event 5 t o 10 days aft er init iat ion of heparin t herapy.
Bi bl i ography
Prechel M, Walenga JM. The laborat ory diagnosis and clinical management of pat ient s wit h heparin-induced t hrombocyt openia: an updat e. Semin Thromb Hemost .
2008;34(1):86-96. [PMID: 18393145]
Item 20 Answer: D
Educati onal Objecti ve: Diagnose thrombotic thrombocytopenic purpura.
The most likely diagnosis is t hrombot ic t hrombocyt openic purpura (TTP). This pat ient has t he principal t riad of TTP: microangiopat hic hemolyt ic anemia (schist ocyt es, or
eryt hrocyt e fragment s, on t he peripheral blood smear); t hrombocyt openia wit h normal coagulat ion; and cent ral nervous syst em sympt oms. The presence of renal failure and
fever compose t he pent ad of TTP findings. Classic TTP occurs mainly in adult s, and it s pat hogenesis appears t o be relat ed t o deficient von Willebrand fact or (vWF)
cleavage. Pat ient s wit h TTP oft en have increased levels of ult ralarge vWF mult imers (ULvWF), which are part icularly act ive in binding t o plat elet s and inducing plat elet
agglut inat ion. Under normal condit ions, ULvWF are not present in t he circulat ion because of cleavage of vWF monomers by ADAMTS13, t he vWF cleaving prot ease. A
severe deficiency of ADAMTS13 has been shown in most pat ient s wit h TTP. Plasma exchange is t he principal t reat ment modalit y for TTP and should be init iat ed as soon as
possible t o decrease pat ient morbidit y.
Idiopat hic t hrombocyt openic purpura is an immune-mediat ed disorder of plat elet dest ruct ion. At present at ion, affect ed pat ient s t ypically have isolat ed t hrombocyt openia,
generally wit hout splenomegaly or adenopat hy. The peripheral blood smear in idiopat hic t hrombocyt openic purpura shows only decreased numbers of plat elet s wit h normal
eryt hrocyt e and leukocyt e morphology. The presence of severe microangiopat hic hemolyt ic anemia seen in t his pat ient 's blood smear is inconsist ent wit h immune
t hrombocyt openic purpura.
Evans syndrome refers t o t he combinat ion of Coombs-posit ive warm aut oimmune hemolyt ic anemia and immune t hrombocyt openic purpura. However, pat ient s wit h
aut oimmune hemolyt ic anemia have microspherocyt es on t heir peripheral smear (in addit ion t o an increased ret iculocyt e count ) rat her t han schist ocyt es, such as t his pat ient
has.
Heparin-induced t hrombocyt openia (HIT) should be considered in any pat ient wit h an ot herwise unexplained decrease in t he plat elet count of at least 50% and/or a new
t hrombot ic event 5 t o 10 days aft er init iat ion of heparin t herapy. However, t his pat ient has no hist ory of heparin exposure, and HIT is not associat ed wit h microangiopat hic
hemolyt ic anemia.
Key Poi nt
Microangiopat hic hemolyt ic anemia, t hrombocyt openia wit h normal coagulat ion, and cent ral nervous syst em sympt oms are t he principal t riad of t hrombot ic
t hrombocyt openic purpura; renal failure and fever compose t he pent ad of sympt oms.
Bi bl i ography
George JN. Clinical pract ice. Thrombot ic t hrombocyt openic purpura. N Engl J Med. 2006;354(18):1927-1935. [PMID: 16672704]
Item 21 Answer: C
Educati onal Objecti ve: Diagnose pseudothrombocytopenia.
This pat ient most likely has pseudot hrombocyt openia, a condit ion in which plat elet s agglut inat e and t he clumped plat elet s are not recognized as such by aut omat ed blood
count ers. The diagnosis is suspect ed by finding large plat elet clumps on t he st ained blood film. These clumps occasionally adhere t o neut rophils but may also be unassociat ed
wit h any ot her cell t ypes. If plat elet clumping is observed, t he plat elet count is repeat ed using an alt ernat ive ant icoagulant t o EDTA, such as heparin or sodium cit rat e.
Gest at ional t hrombocyt openia is t he most common cause of pregnancy-associat ed t hrombocyt openia. Most pregnant women who do have a mild t hrombocyt openia have
plat elet count s ranging bet ween 70,000/L (70 10
9
/L) and 150,000/L (150 10
9
/L). This occurs in approximat ely 5% of pregnancies and appears in lat e gest at ion. The
cause of gest at ional t hrombocyt openia is unknown, alt hough it is not believed t o have an immune basis. Specific t herapy is not required. The diagnosis of gest at ional
t hrombocyt openia cannot be confirmed or excluded unt il a reliable plat elet count is obt ained.
Immune t hrombocyt openic purpura is a disorder caused by ant ibodies react ive wit h plat elet glycoprot eins (part icularly glycoprot ein IIb-IIIa), t he plat elet fibrinogen recept or,
and glycoprot ein Ib. At present at ion, affect ed pat ient s have isolat ed t hrombocyt openia, generally wit hout splenomegaly or adenopat hy. The peripheral blood smear shows
only decreased numbers of plat elet s wit h normal eryt hrocyt e and leukocyt e morphology; occasionally, large (immat ure) plat elet s are seen. In t his pat ient t he diagnosis of
ITP cannot be confirmed or excluded unt il t he plat elet count is repeat ed wit h an alt ernat ive ant icoagulant t o eliminat e plat elet clumping.
Microangiopat hic hemolyt ic anemia, t hrombocyt openia wit h normal coagulat ion, and cent ral nervous syst em sympt oms are t he principal t riad of t hrombot ic
t hrombocyt openic purpura; renal failure and fever compose t he pent ad of sympt oms. Microangiopat hic hemolyt ic anemia is suggest ed by t he presence of schist ocyt es
(eryt hrocyt e fragment s) on t he peripheral blood smear, ret iculocyt osis, and an elevat ed lact at e dehydrogenase level. These findings are not present .
Key Poi nt
Pseudot hrombocyt openia, in which plat elet s agglut inat e and t he clumped plat elet s are not count ed by aut omat ed blood count ers, is an art ifact ual cause of t hrombocyt openia.
Bi bl i ography
Sekhon SS, Roy V. Thrombocyt openia in adult s: a pract ical approach t o evaluat ion and management . Sout h Med J. 2006;99(5):491-498. [PMID: 16711312]
Item 22 Answer: B
Educati onal Objecti ve: Initiate corticosteroids to manage immune thrombocytopenic purpura.
The most appropriat e next st ep in management is t he init iat ion of cort icost eroids. This healt hy young woman has pet echiae caused by her very low plat elet count . Alt hough
most of her remaining laborat ory st udies are normal, her peripheral blood smear showing few, but large, plat elet s support s t he presence of a young populat ion of plat elet s,
consist ent wit h increased t urnover. These findings are suggest ive of immune t hrombocyt openic purpura (ITP), and a bone marrow examinat ion is not essent ial. Inst ead, a
presumpt ive diagnosis of ITP should be est ablished, and t he pat ient should receive high-dose cort icost eroids. Cort icost eroids are generally indicat ed in pat ient s wit h ITP who
have sympt omat ic bleeding and plat elet count s below 50,000/L (50 10
9
/L) or in t hose wit h severe t hrombocyt openia and plat elet count s below 15,000/L (15 10
9
/L).
Splenect omy is not indicat ed as first -line t herapy for ITP but may be considered when ot her less-invasive t herapies have failed. Plat elet t ransfusions would not be indicat ed in
t his pat ient unless serious, life-t hreat ening bleeding was present . A bone marrow biopsy also is not necessary in t his set t ing given t he absence of any ot her signs of a bone
marrow st em cell disorder, such as leukopenia or t he presence of nucleat ed eryt hrocyt es; early myeloid forms suggest a myelopht hisic process, which occurs in neoplast ic and
met ast at ic disease, lymphoma, granulomat ous disease, and infect ions of t he bone marrow.
Key Poi nt
Cort icost eroids are t he first -line t reat ment for pat ient s wit h immune t hrombocyt openic purpura.
Bi bl i ography
St asi R, Evangelist a ML, St ipa E, Buccisano F, Vendit t i A, Amadori S. Idiopat hic t hrombocyt openic purpura: current concept s in pat hophysiology and management . Thromb
Haemost . 2008;99(1):4-13. [PMID: 18217129]
Item 23 Answer: C
Educati onal Objecti ve: Evaluate a patient for thrombophilia after completion of a course of warfarin.
The most appropriat e next st ep in t he evaluat ion of t his pat ient is t hrombophilic screening at least 2 weeks aft er she complet es t he 6-mont h course of warfarin. This pat ient
wit h an idiopat hic pulmonary embolism and a st rong family hist ory of venous t hromboembolism has a high likelihood of having an underlying t hrombophilic condit ion.
Therefore, she should undergo t est ing for act ivat ed prot ein C resist ance, t he prot hrombin gene mut at ion, ant iphospholipid ant ibodies, fact or V Leiden, ant it hrombin
deficiency, prot ein C deficiency, prot ein S deficiency, and t he lupus inhibit or. Screening for t hrombophilia should not be performed during ant icoagulant t herapy because bot h
heparin and warfarin will influence t he result s of cert ain t est s. Neit her should it be done during t he acut e present ing episode before ant icoagulant s are init iat ed because t he
t hrombosis it self may influence t he result s of cert ain t est s. Thus, t hrombophilia t est ing is best done at least a few weeks aft er a course of t herapy is complet ed.
Polycyt hemia vera and essent ial t hrombocyt hemia predispose pat ient s t o venous and art erial t hrombot ic event s, part icularly when t he red blood cell mass or plat elet count is
not cont rolled. Alt hough t he JAK2 mut at ion is found in almost all pat ient s who have polycyt hemia vera and in approximat ely 50% of pat ient s wit h essent ial
t hrombocyt hemia, rout ine screening for t his mut at ion is not recommended, except in pat ient s in whom a myeloproliferat ive disease is suspect ed. Because t his pat ient has a
normal complet e blood count , screening for t he JAK2 mut at ion would be inappropriat e.
Performing no furt her t est ing in t his pat ient , given her recent idiopat hic pulmonary embolism and family hist ory of t hrombot ic issues, would be inappropriat e because t he
risk of recurrent venous t hromboembolism and need for cont inued ant icoagulat ion cannot be est imat ed wit hout screening for inherit ed t hrombophilia.
Key Poi nt
Thrombophilic screening should be performed not at t he onset of a t hrombot ic event or during ant icoagulant t herapy but rat her a few weeks aft er complet ion of t herapy.
Bi bl i ography
Dalen JE. Should pat ient s wit h venous t hromboembolism be screened for t hrombophilia? Am J Med. 2008;121(6):458-463. [PMID: 18501222]
Item 24 Answer: A
Educati onal Objecti ve: Treat a patient with antiphospholipid antibodies after a first deep venous thrombosis with anticoagulation indefinitely.
The most appropriat e ant icoagulat ion management for t his pat ient is ant icoagulat ion t herapy indefinit ely. The absolut e risk of new venous t hromboembolism (VTE) in
pat ient s wit h ant iphospholipid ant ibodies is low (less t han 1% per year). However, t his risk may be increased t o up t o 10% per year in women wit h ant iphospholipid
ant ibodies or ant iphospholipid ant ibody syndrome and recurrent fet al loss and t o more t han 10% per year in pat ient s wit h ant iphospholipid ant ibodies and previous VTE who
have discont inued ant icoagulant s wit hin 6 mont hs. Current recommendat ions are t o t reat t hese pat ient s wit h ant icoagulat ion indefinit ely. The benefit of VTE prevent ion
wit h long-t erm ant icoagulat ion in t hese high-risk pat ient s may out weigh t he risk for bleeding complicat ions.
Posit ive result s for ant icardiolipin ant ibody or lupus inhibit or assay should be confirmed over t ime t o ensure t hat t hey are not t ransient , which can occur aft er viral
infect ions. Ideally, at least t wo posit ive laborat ory t est s (ant icardiolipin ant ibody or lupus inhibit or assay) at least 12 weeks apart should be document ed t o confirm t he
presence of an ant iphospholipid ant ibody syndrome before a pat ient is commit t ed t o lifelong ant icoagulat ion.
Key Poi nt
Pat ient s wit h an ant iphospholipid ant ibody syndrome and deep venous t hrombosis have a high risk for recurrence once ant icoagulat ion t herapy is discont inued and t hus
require ant icoagulat ion t herapy indefinit ely.
Bi bl i ography
Giannakopoulos B, Krilis SA. How I t reat t he ant iphospholipid syndrome. Blood. 2009;114(10):2020-2030. Epub 2009 Jul 8. [PMID: 19587374]
Item 25 Answer: C
Educati onal Objecti ve: Diagnose lupus inhibitor and antiphospholipid antibody syndrome.
The most appropriat e next diagnost ic st ep is t est ing for t he lupus inhibit or and ant iphospholipid ant ibody. The ant iphospholipid ant ibody somet imes int erferes wit h t he
coagulat ion cascade as measured by t he act ivat ed part ial t hromboplast in t ime or prot hrombin t ime and causes a prolongat ion t hat is not correct ed wit h a corresponding mix
t hat includes normal plasma. These ant ibodies, alt hough t hey prolong in vit ro coagulat ion t est s, are associat ed wit h an increased risk of venous (approximat ely t wo t hirds)
and art erial t hromboembolism. There also is a st rong correlat ion bet ween t hese ant ibodies and pregnancy loss, presumably due t o placent al insufficiency in affect ed pat ient s
secondary t o t hrombosis. The diagnosis of ant iphospholipid ant ibody syndrome requires a hist ory of a t hrombot ic event (including recurrent fet al loss) in associat ion wit h a
persist ent lupus ant icoagulant or persist ent ly elevat ed levels of IgG ant icardiolipin or
2
-glycoprot ein I ant ibodies. Lupus ant icoagulant s or elevat ed levels of ant iphospholipid
ant ibodies are frequent ly present in pat ient s wit h syst emic lupus eryt hemat osus; t hey also occur in pat ient s wit h cancer or infect ions (such as HIV) and in associat ion wit h t he
use of cert ain drugs (for example, hydralazine, procainamide, or phenot hiazines); t he lat t er cases are oft en associat ed wit h IgM ant ibodies and do not result in a
hypercoagulable st at e.
The fact or V Leiden mut at ion result s in resist ance t o act ivat ed prot ein C. In het erozygot es wit h t he prot hrombin G20210A mut at ion, prot hrombin ant igen and act ivit y
measurement s are elevat ed by approximat ely 30% over t hose of normal persons. Among unselect ed whit e pat ient s present ing wit h an init ial sympt omat ic episode of deep
venous t hrombosis, 12% t o 20% are het erozygous for t he fact or V Leiden mut at ion and 6% het erozygous for t he prot hrombin G20210A mut at ion, compared wit h 6% and
2%, respect ively, in asympt omat ic cont rol populat ions. Neit her t he fact or V Leiden mut at ion nor t he prot hrombin G20210A mut at ion is associat ed wit h increased fet al loss.
Hyperhomocyst einemia is associat ed wit h an increased risk of venous and art erial t hrombosis. Plasma homocyst eine levels are det ermined by genet ic and environment al
fact ors, t he lat t er including primarily diet ary int ake of folic acid, vit amin B
12
, and vit amin B
6
. Administ rat ion of t hese B vit amins can lower plasma homocyst eine levels, but
t his int ervent ion has not yet been shown t o reduce t he risk of recurrent vascular event s. Hyperhomocyst einemia is not associat ed wit h recurrent fet al loss.
Key Poi nt
Ant iphospholipid ant ibody syndrome consist s of a hist ory of a t hrombot ic event (including recurrent fet al loss) in associat ion wit h a persist ent lupus ant icoagulant or
persist ent ly elevat ed levels of ant icardiolipin or
2
-glycoprot ein I ant ibodies.
Bi bl i ography
George D, Erkan D. Ant iphospholipid syndrome. Prog Cardiovasc Dis. 2009;52(2):115-125. [PMID: 19732604]
Item 26 Answer: C
Educati onal Objecti ve: Diagnose multiple myeloma as the cause of renal failure, anemia, low-anion gap, and hypercalcemia.
The decreased anion gap in t he presence of anemia, prot einuria, hypercalcemia, and renal failure suggest s mult iple myeloma. Acut e kidney injury is t he init ial present at ion in
as many as one half of pat ient s wit h mult iple myeloma. Except in mult iple myeloma, hypercalcemia in t he presence of acut e kidney injury is relat ively unusual because
hyperphosphat emia and a decrease in renal 1- hydroxylat ion of 25-hydroxycholecalciferol bot h act t o predispose t o hypocalcemia. Hypercalcemia may cause renal
insufficiency t hrough several mechanisms, including hemodynamic effect s of vasoconst rict ion t hat mediat e renal sodium and wat er ret ent ion, and direct effect s on renal
t ubular sodium and wat er handling, result ing in prerenal azot emia secondary t o volume deplet ion. Normally, t he anion gap is approximat ely 12 2 meq/L (12 2 mmol/L).
Most unmeasured anions consist of albumin. Therefore, t he presence of eit her a low albumin level or an unmeasured cat ionic light chain, which occurs in mult iple myeloma,
result s in a low anion gap.
Alt hough hydrochlorot hiazide t oxicit y can present wit h volume deplet ion and prerenal azot emia, t he presence of hemat ologic and met abolic complicat ions makes t his less
likely as a unifying diagnosis. The hypercalcemia t hat charact erizes t he milk-alkali syndrome is not associat ed wit h anemia or prot einuria and is usually associat ed wit h
met abolic alkalosis. Primary hyperparat hyroidism should be associat ed wit h hypophosphat emia and not anemia or prot einuria.
Key Poi nt
A decreased anion gap in t he presence of anemia, prot einuria, hypercalcemia, and renal failure suggest s mult iple myeloma.
Bi bl i ography
Raab MS, Podar K, Breit kreut z I, Richardson PG, Anderson KC. Mult iple myeloma. Lancet . 2009;374:324-339. [PMID: 19541364]
Item 27 Answer: D
Educati onal Objecti ve: Diagnose multiple myeloma in a patient with hypercalcemia.
This pat ient has hypercalcemia, diffuse ost eopenia, anemia, leukopenia, renal insufficiency, and a hist ory of encapsulat ed organism-relat ed pneumonia, which is a
charact erist ic present at ion of mult iple myeloma. The diagnosis is support ed by t he bone marrow aspirat e, which shows clust ers of plasma cells. These cells can easily be
dist inguished from megaloblast oid eryt hrocyt es by t heir dispersed chromat in pat t ern and perinuclear halo (Golgi apparat us).
Acut e myeloid leukemia rarely causes hypercalcemia. In addit ion, more severe bone marrow failure and a decreased plat elet count would be likely, and t he bone marrow
aspirat e would show leukemic blast s. Chronic lymphocyt ic leukemia (CLL) only rarely causes hypercalcemia and renal insufficiency; an elevat ed leukocyt e count is t ypical.
Moreover, t he increased number of plasma cells in t he bone marrow aspirat e in t his pat ient rules out a diagnosis of CLL. Met ast at ic small cell lung cancer in t he bone marrow
may cause cyt openia and hypercalcemia. However, t he peripheral blood smear would show leukoeryt hroblast ic feat ures wit h t eardrop eryt hrocyt es and immat ure myeloid and
eryt hroid cells. Furt hermore, t he morphologic findings of t he bone marrow aspirat e in t his pat ient , which shows a proliferat ion of plasma cells, is inconsist ent wit h met ast asis
from any ot her cancer.
Key Poi nt
Mult iple myeloma is suggest ed by t he presence of hypercalcemia, ost eopenia, anemia, leukopenia, and renal insufficiency.
Bi bl i ography
Raab MS, Podar K, Breit kreut z I, Richardson PG, Anderson KC. Mult iple myeloma. Lancet . 2009;374(9686):324-339. Epub 2009 Jun 21. [PMID: 19541364]
Item 28 Answer: C
Educati onal Objecti ve: Diagnose monoclonal gammopathy of undetermined significance.
This pat ient has monoclonal gammopat hy of undet ermined significance (MGUS), which is charact erized by t he presence of a low serum monoclonal prot ein (M-prot ein)
level (<3.0 g/dL [30 g/L]), less t han 10% plasma cells in t he bone marrow, and t he absence of lyt ic bone lesions, anemia, hypercalcemia, or renal insufficiency associat ed wit h
a plasma cell proliferat ive process or relat ed B-cell lymphoproliferat ive disorder. The incidence of MGUS increases wit h age, and more t han 5% of persons older t han 80
years may be affect ed. No specific t reat ment is required, except for close follow-up t o ident ify progression t o myeloma or ot her disorders and periodic measurement of serum
M-prot ein levels. The risk of progression correlat es best wit h t he M prot ein level: t he higher t he level, t he great er t he risk.
AL (light -chain) amyloidosis is a monoclonal plasma cell dyscrasia in which secret ed immunoglobulin is deposit ed as fibrils in kidneys, heart , and peripheral nerves, t hereby
producing progressive organ dysfunct ion. Common sympt oms include fat igue, weight loss, and easy bruising. Kidney involvement produces nephrot ic syndrome wit h large
amount s of non-light -chain prot einuria; azot emia develops lat e in t he disease course. Cardiac involvement can be det ect ed as t hickening of t he sept um and leads t o heart
failure and arrhyt hmias. Sensorimot or neuropat hy is t he manifest at ion of peripheral nerve involvement . Det ect ion of monoclonal immunoglobulin in serum, blood, or t issues
different iat es AL amyloidosis from ot her forms of amyloidosis.
Lymphoplasmacyt ic lymphoma is usually associat ed wit h a monoclonal serum paraprot ein of immunoglobulin M t ype (Waldenst rom's macroglobulinemia), not IgG as seen in
t his pat ient . Most pat ient s have bone marrow, lymph node, and splenic involvement , and some may develop hyperviscosit y syndrome.
Major diagnost ic crit eria for mult iple myeloma include t he following: t he finding of a plasmacyt oma on t issue biopsy; great er t han 30% clonal plasma cells in t he bone
marrow; high M-prot ein levels (IgG >3.5 g/dL [35 g/L] and IgA >2.0 g/dL [20 g/L]); and Bence Jones prot einuria (urine prot ein excret ion >1.0 g/24h). Minor crit eria include
10% t o 30% plasma cells in t he bone marrow; M-prot ein level less t han 3.5 g/dL (35 g/L); lyt ic bone lesions; and diminished levels of non-monoclonal prot eins. A diagnosis
is est ablished wit h one major and one minor crit erion or t hree minor crit eria.
Key Poi nt
Monoclonal gammopat hy of undet ermined significance is charact erized by a serum monoclonal prot ein level less t han 3.0 g/dL (30 g/L) wit hout t he overt clinical feat ures of
myeloma and less t han 10% plasma cells in t he bone marrow.
Bi bl i ography
Blade J, Rosinol L, Cibeira MT, de Larrea CF. Pat hogenesis and progression of monoclonal gammopat hy of undet ermined significance. Leukemia. 2008;22(9):1651-1657.
Epub 2008 Jul 31. [PMID: 18668131]
Item 29 Answer: C
Educati onal Objecti ve: Diagnose chronic lymphocytic leukemia.
The most likely diagnosis for t his pat ient is chronic lymphocyt ic leukemia (CLL), which is charact erized by abnormal accumulat ion of morphologically mat ure-appearing
lymphocyt es wit h a charact erist ic immunophenot ype (CD5
+
, CD20
+
, and CD23
+
B cells) in t he blood, bone marrow, or lymphat ic t issues. The diagnosis oft en is est ablished
by flow cyt omet ry t o avoid t he need for bone marrow aspirat ion or biopsy. CLL occurs in pat ient s aft er age 40 years, wit h increasing frequency in successive decades of life.
The disease is oft en found incident ally on rout ine blood workup as a lymphocyt osis wit hout ot her evident disease. Long periods of st abilit y or very slow progression of disease
may occur over many years.
Acut e lymphoblast ic leukemia (ALL) is an ext remely aggressive disease of precursor T or B cells t hat is usually of explosive onset . Rapidly rising levels blast cells in t he blood
and bone marrow, bulky lymphadenopat hy (especially in t he mediast inum), a younger age at onset , and cyt openia secondary t o bone marrow involvement are t he usual
present ing clinical feat ures of ALL.
Acut e myeloid leukemia (AML) t ypically present s wit h severe pancyt openia and circulat ing myeloid blast s. Infect ion and bleeding are common present ing problems of
pat ient s wit h AML.
Chronic myeloid leukemia (CML) is recognized by an elevat ed leukocyt e count and increased numbers of granulocyt ic cells in all phases of development on t he peripheral
blood smear. Very immat ure cells or blast s represent 1% t o 5% of t he granulocyt es, wit h increasing numbers of promyelocyt es, myelocyt es, and met amyelocyt es. CML is
discovered incident ally in many pat ient s.
Key Poi nt
Chronic lymphocyt ic leukemia is charact erized by abnormal accumulat ion of morphologically mat ure-appearing lymphocyt es wit h a charact erist ic immunophenot ype in t he
blood, bone marrow, or lymphat ic t issues.
Bi bl i ography
Yee KW, O'Brien SM. Chronic lymphocyt ic leukemia: diagnosis and t reat ment . Mayo Clin Proc. 2006;81(8):1105-1129. [PMID: 16901035]
Item 30 Answer: B
Educati onal Objecti ve: Diagnose acute myeloid leukemia on the basis of a peripheral blood smear.
The most likely diagnosis is acut e myeloid leukemia (AML). Myelodysplast ic syndromes are clonal disorders of t he hemat opoiet ic st em cells in pat ient s older t han 50 years
and are charact erized by ineffect ive hemat opoiesis and peripheral cyt openia. Alt hough t he nat ural hist ory of dist inct subt ypes of myelodysplasia ranges from indolent
chronic anemia t o rapid deat h from progression t o acut e leukemia, most pat ient s event ually progress t o leukemic syndromes or die from complicat ions of bone marrow
failure. Pat ient s wit h myelodysplast ic syndrome t reat ed wit h azacit idine have significant ly delayed t ransformat ion t o leukemia and improved qualit y of life. Despit e
t reat ment wit h azacit idine, t his pat ient has AML, as indicat ed by t he peripheral blood smear showing a myeloblast wit h Auer rods. Auer rods are clumps of azurophilic,
needle-shaped cryst als made from primary cyt oplasmic granules. They occur most oft en in pat ient s wit h AML and rarely in pat ient s wit h myelodysplasia. Fever in pat ient s
wit h AML is almost always relat ed t o infect ion; t herefore, t his pat ient must be quickly and t horoughly evaluat ed for a source of infect ion and t reat ed empirically wit h broad-
spect rum ant ibiot ics.
Acut e lymphoblast ic leukemia (ALL) is an ext remely aggressive disease of precursor T or B cells, usually of explosive onset . Rapidly rising blast cells in t he blood and bone
marrow, bulky lymphadenopat hy (especially in t he mediast inum), and cyt openia secondary t o bone marrow involvement are t he usual present ing clinical feat ures. Auer rods
do not occur in pat ient s wit h ALL.
Acut e promyelocyt ic leukemia (APL) is a subt ype of AML t hat account s for 10% of pat ient s wit h AML. The disorder is exquisit ely sensit ive t o ant hracycline cyt ot oxic
t herapy. The addit ion of all-trans-ret inoic-acid and arsenic t rioxide t o t he t herapy has result ed in high cure and salvage rat es. Pat ient s wit h APL may have circulat ing blast s,
but t he predominant cell is a large immat ure granulocyt e wit h mult iple granules overlying t he cyt oplasm and nucleus.
Typically, chronic myeloid leukemia (CML) is diagnosed as a result of a rout ine blood count t hat shows leukocyt osis wit h circulat ing myeloid precursors in all st ages of
development . Pat ient s wit h CML may have circulat ing blast s but also will have more mat ure granulocyt es and will not have Auer rods.
Key Poi nt
A peripheral blood smear showing myeloblast s t hat cont ain Auer rods is diagnost ic of acut e myeloid leukemia.
Bi bl i ography
O'Donnell MR, Appelbaum FR, Cout re SE, et al. Acut e myeloid leukemia. J Nat l Compr Canc Net w. 2008;6(10):962-993. [PMID: 19176196]
Item 31 Answer: D
Educati onal Objecti ve: Diagnose chronic myeloid leukemia.
This pat ient has chronic myeloid leukemia (CML). The prot ot ype of t he myeloproliferat ive syndromes, CML result s from a balanced t ranslocat ion bet ween chromosomes 9
and 22 [t (9;22), t he Philadelphia chromosome], which creat es a unique gene designat ed BCR-ABL; t his gene codes a 210-kDa prot ein (p210) t hat funct ions as t yrosine
kinase. A t (9;22) is not only diagnost ic of CML but is also t he causat ive genet ic event and a t herapeut ic t arget . The diagnosis of CML in t his pat ient is based on t he presence
of t he BCR/ABL oncogene, peripheral blood smear findings showing increased granulocyt es wit h a marked left shift , and hypercellular bone marrow wit h marked myeloid
proliferat ion.
Pat ient s wit h acut e lymphoblast ic leukemia (ALL) t ypically have lymphocyt osis, neut ropenia, anemia, t hrombocyt openia, lymphadenopat hy, and hepat osplenomegaly at
present at ion. An increased number of lymphoblast s found on bone marrow examinat ion are suspicious for t he diagnosis. Immunophenot yping is necessary t o confirm t he
diagnosis of AML and det ermine if t he lymphocyt es are B cells, T cells, or biphenot ypic cells wit h markers of bot h lymphoid and myeloid cells.
Acut e myeloid leukemia (AML) should be considered when circulat ing blast s are present in t he peripheral blood smear. The diagnosis of AML is confirmed by a bone marrow
aspirat e showing hypercellular marrow cont aining great er t han 20% t o 30% myeloblast s. Once t he diagnosis of acut e leukemia is est ablished, t he classificat ion is based on t he
morphology of t he immat ure cells. The presence of Auer rods confirms t he myeloid nat ure of t he leukemia.
Acut e promyelocyt ic leukemia (APL) is a subt ype of AML t hat account s for 10% of cases. Pat ient s wit h APL may have circulat ing blast s, but t he predominant cell is a large
immat ure granulocyt e wit h mult iple granules overlying t he cyt oplasm and nucleus.
Key Poi nt
The diagnosis of chronic myeloid leukemia is based on t he presence of t he BCR/ABL oncogene, peripheral blood smear findings showing increased granulocyt es wit h a marked
left shift , and hypercellular bone marrow wit h marked myeloid proliferat ion.
Bi bl i ography
Vardiman JW. Chronic myelogenous leukemia, BCR-ABL1+. Am J Clin Pat hol. 2009;132(2):250-260. [PMID: 19605820]
Secti on 6. Infecti ous Di sease Medi ci ne
Questi ons
Item 1 [Advanced]
A 62-year-old man who lives in At lant a is evaluat ed in July for a 24-hour hist ory of fever, myalgia, and a front al headache. He is ot herwise healt hy and t akes no medicat ions.
Recent t ravel includes a 2-week camping t rip t o t he Blue Ridge Mount ains of Virginia 11 days ago. The pat ient does not recall a specific insect or t ick bit e.
On physical examinat ion, t he pat ient appears mildly ill. Temperat ure is 38.7C (101.6F), blood pressure is 125/65 mm Hg, pulse rat e is 90/min, and respirat ion rat e is
18/min. He has blanching eryt hemat ous macules locat ed around t he wrist s. There is no lymphadenopat hy. Cardiopulmonary and abdominal examinat ions are normal.
Laborat ory t est s, blood cult ures, and chest radiograph are pending.
(A) Babesiosis
(B) Influenza
(C) Lyme disease
(D) Rocky Mount ain spot t ed fever
Item 2 [Advanced]
A 33-year-old woman is evaluat ed for fever, fat igue, myalgia, headaches, dyspnea, and abdominal pain of 1 mont h's durat ion. She has no hist ory of t ravel, camping, or animal
exposure. She t akes no medicat ions.
On physical examinat ion, she appears healt hy. The vit al signs and complet e physical examinat ion are normal.
She is re-evaluat ed for t he same sympt oms 10 days lat er and no changes from her init ial examinat ion are evident .
Laborat ory evaluat ion is normal, including complet e blood count , eryt hrocyt e sediment at ion rat e, comprehensive met abolic profile, and urinalysis. Serologic t est ing for
ant inuclear ant ibody and rheumat oid fact or are negat ive. Test ing for Epst ein-Barr, cyt omegalovirus, and HIV infect ion is negat ive. Urine cult ure and t hree set s of blood
cult ures are negat ive.
CT of t he chest , abdomen, and pelvis is normal.
Review of her fever diary shows nondaily, random spikes t o 40.3C (104.5F) last ing less t han 1 hour. No diurnal t emperat ure variat ion is not ed, and no associat ed chills or
sweat s are report ed.
(A) Fact it ious fever
(B) Familial Medit erranean fever
(C) Infect ive endocardit is
Item 3 [Advanced]
A 65-year-old man is admit t ed t o t he int ensive care unit for gram-negat ive sepsis. The pat ient 's medical hist ory is significant only for hypert hyroidism, for which he t akes
met himazole. On day 2 in t he int ensive care unit , he undergoes int ubat ion following medicat ion wit h propofol and succinylcholine for acut e respirat ory dist ress syndrome.
The pat ient also receives int ermit t ent lorazepam and fent anyl boluses int ravenously for sedat ion. Several hours lat er, t he pat ient becomes febrile (t emperat ure 40C
[104F]), hypert ensive, and t achycardic. On examinat ion, he is diaphoret ic and has muscular rigidit y. Art erial blood gas analysis shows a met abolic and respirat ory acidosis,
and laborat ory result s are significant for an elevat ed serum creat ine kinase level.
Whi ch of the fol l owi ng i s the most l i kel y cause of the fever?
(A) Malignant hypert hermia
(B) Neurolept ic malignant syndrome
(C) Serot onin syndrome
(D) Thyroid st orm
Item 4 [Advanced]
A 23-year-old woman is admit t ed t o t he int ensive care unit wit h sepsis. She report s sust aining a cut on her left leg 4 days ago while hiking. She t akes no medicat ions and has
been ot herwise healt hy.
On physical examinat ion, t emperat ure is 38.5C (101.3F), blood pressure is 95/55 mm Hg, pulse rat e is 115/min, and respirat ion rat e is 22/min. On t he lower left leg is a 3-
cm purulent wound surrounded by 10 cm of marked eryt hema, indurat ion, and crepit us under t he skin. Skin mot t ling is present up t o midt high.
9
/L) and serum creat inine is 1.9 mg/dL (168 mmol/L). Radiograph of t he leg shows subcut aneous air.
Blood and wound cult ure specimens are t aken, and high-volume int ravenous fluid administ rat ion and empiric broad spect rum ant ibiot ics are init iat ed.
Whi ch of the fol l owi ng i s the most appropri ate i mmedi ate next step i n management?
(A) Begin drot recogin alfa (act ivat ed prot ein C)
(B) Begin renal (low-dose) dopamine
(C) Begin norepinephrine
(D) Surgical wound debridement
Item 5 [Basic]
A 71-year-old woman is brought t o t he emergency depart ment from a nursing home because of confusion, fever, and flank pain. Her t emperat ure is 38.5C (101.3F), blood
pressure is 82/48 mm Hg, pulse rat e is 123/min, and respirat ion rat e is 27/min. Mucous membranes are dry, and t here is cost overt ebral angle t enderness, poor skin t urgor, and
no edema. Hemoglobin concent rat ion is 10.5 g/dL (105 g/L) and leukocyt e count is 15,600/L (15.6 10
9
/L); urinalysis reveals 50 t o 100 leukocyt es/hpf and many
bact eria/hpf. The pat ient has an anion gap met abolic acidosis. A cent ral venous cat het er is placed, and ant ibiot ic t herapy is st art ed.
Whi ch of the fol l owi ng i s most l i kel y to i mprove survi val for thi s pati ent?
(A) Aggressive fluid resuscit at ion
(B) Hemodynamic monit oring wit h a pulmonary art ery cat het er
(C) Maint aining hemoglobin concent rat ion above 12 g/dL (120 g/L)
(D) Maint aining PCO
2
below 50 mm Hg (6.7 kPa)
Item 6 [Advanced]
A 67-year-old man is evaluat ed in t he surgical int ensive care unit . He underwent laparot omy and divert ing colost omy for a rupt ured divert iculum 72 hours ago, and now has a
t emperat ure of 40.0C (104.0F) and a heart rat e of 135/min. In t he past 3 hours his mean art erial blood pressure has dropped t o 58 mm Hg despit e t hree 1-L boluses of
normal saline; urine out put was only 15 mL in t he past hour. The pat ient 's oxygen sat urat ion is 85% on 100% oxygen by non-rebreat her mask. Plat elet count is 42,000/L
(42 10
9
/L) and random glucose is 148 mg/dL (8.2 mmol/L).
A port able chest radiograph shows bilat eral alveolar infilt rat es. A cent ral venous cat het er is placed; invasive mechanical vent ilat ion and broad-spect rum ant ibiot ic t herapy are
begun.
Whi ch of the fol l owi ng i s most l i kel y to i mprove survi val of thi s pati ent?
(A) Act ivat ed prot ein C
(B) Colloid fluid infusion
(C) Insulin drip
(D) Low-dose dopamine
Item 7 [Advanced]
A 60-year-old woman is admit t ed t o t he int ensive care unit because of upper abdominal pain, fever, nausea, and vomit ing of 6 hours' durat ion. She has no ot her pert inent
medical hist ory and t akes no medicat ions.
On physical examinat ion, her t emperat ure is 39.1C (102.4F), blood pressure is 70/30 mm Hg, and heart rat e is 120/min. She has right upper quadrant t enderness wit hout
rebound.
Abdominal ult rasonography shows a gallst one obst ruct ing t he common bile duct t hat is ext ract ed during emergency endoscopic ret rograde cholangiopancreat ography. Post -
procedure, her syst olic blood pressure remains below 90 mm Hg despit e t wo int ravenous boluses of 500 mL of normal saline. Ampicillin, gent amicin, and met ronidazole are
begun.
(A) Cent ral venous cat het er placement and aggressive fluid resuscit at ion
(B) Met hylprednisolone, int ravenously
(C) Pulmonary art ery cat het er placement
(D) Recombinant human act ivat ed prot ein C (drot recogin ), int ravenously
Item 8 [Advanced]
A 75-year-old woman is brought t o t he emergency depart ment because of a 2-day hist ory of generalized weakness and fever. The pat ient is a nursing home resident and
requires a chronic indwelling urinary cat het er.
On physical examinat ion, t emperat ure is 38.4C (101.1F), blood pressure is 132/72 mm Hg, pulse rat e is 95/min, and respirat ion rat e is 22/min. Examinat ion findings are
ot herwise normal.
The leukocyt e count is 13,000/L (13 10
9
/L) wit h 11% immat ure band forms. Urinalysis shows 20-25 leukocyt es/hpf. A complet e met abolic profile is normal. Art erial
oxygen sat urat ion is 95% by pulse oximet ry wit h t he pat ient breat hing ambient air. Urine cult ure and t wo set s of blood cult ures obt ained in t he emergency depart ment are
growing Escherichia coli.
Whi ch of the fol l owi ng terms best descri bes thi s pati ent's i l l ness?
(A) Sepsis
(B) Sept ic shock
(C) Severe sepsis
(D) Syst emic inflammat ory response syndrome
Item 9 [Advanced]
A 21-year-old man is evaluat ed for 5 days of sore t hroat , ant erior neck pain and fever. Four days ago he was t reat ed for st rept occocal pharyngit is wit h penicillin. Despit e
ant ibiot ic t herapy, his sympt oms progressed and now he has difficult y swallowing and managing his secret ions. Medical hist ory is ot herwise unremarkable and his only
medicat ion is oral penicillin.
On physical examinat ion his t emperat ure is 38.9C (102F), blood pressure is 140/86 mm Hg, pulse rat e is 110/min and respirat ion rat e is 20/min. He spit s frequent ly and
drools. His oral pharynx is not able for enlarged t onsils, right significant ly great er t han t he left . The right t onsil enlargement crowds t he uvula t o t he left . He has t ender right
cervical lymphadenopat hy.
(A) Add azit hromycin
(B) Change t o clindamycin
(C) Change t o int ramuscular penicillin
(D) Emergency ENT consult at ion
Item 10 [Basic]
A 32-year-old woman is evaluat ed for an upper respirat ory infect ion. She was well unt il 5 days ago when she developed a fever, sore t hroat , nonproduct ive cough, and runny
nose. She has no ear pain or nasal congest ion. Her medical hist ory is ot herwise unremarkable. She has no allergies and t akes no medicat ions. She lives at home wit h her
husband and 8-year-old t win boys.
On physical examinat ion, her vit al signs are normal. Her ears, nose, and oropharynx appear normal. She has no lymphadenopat hy and her lungs are clear t o auscult at ion.
Whi ch of the fol l owi ng i s the best preventi on strategy for her fami l y?
(A) Echinacea
(B) Frequent hand washing
(C) Penicillin G
(D) Surgical facemask
(E) Vit amin C
Item 11 [Basic]
A 45-year-old man is evaluat ed because of t he acut e onset of right ear pain. The pat ient was well unt il 10 days ago, when he developed sympt oms of an upper respirat ory
t ract infect ion, including nasal congest ion and a nonproduct ive cough. Alt hough t hese sympt oms are resolving, pain and some loss of hearing in t he right ear first occurred
last night . He does not have fever, sore t hroat , or drainage from t he ear. Medical hist ory is unremarkable. The pat ient has no allergies and t akes no medicat ions.
On physical examinat ion, vit al signs, including t emperat ure, are normal. The right t ympanic membrane is eryt hemat ous, opacified, and immobile, but t he ext ernal audit ory
canal is normal. The left ear and post erior pharynx are normal. Examinat ion of t he chest is unremarkable.
Whi ch of the fol l owi ng i s the best i ni ti al anti bi oti c choi ce i n thi s pati ent?
(A) Amoxicillin
(B) Amoxicillin-clavulanat e
(C) Azit hromycin
(D) Ceft riaxone
Item 12 [Basic]
A 28-year-old woman has a 3-day hist ory of a sore t hroat , malaise, and fat igue wit hout cough or fever. Medical hist ory is unremarkable. She has no known drug allergies and
t akes no medicat ions.
On physical examinat ion, vit al signs, including t emperat ure, are normal. Bilat eral t onsillar exudat es are present . There is no cervical lymphadenopat hy.
(A) Begin eryt hromycin
(B) Begin penicillin
(C) Obt ain a rapid st rept ococcal ant igen t est
(D) Obt ain a t hroat cult ure
Item 13 [Basic]
A 32-year-old man has a 5-day hist ory of persist ent nasal congest ion and pain in t he right forehead area associat ed wit h a clear nasal discharge and mild cough. The pat ient
report s t hat he has had similar episodes in t he past t hat were helped in 2 t o 3 days by ant ibiot ics. Medical hist ory is ot herwise unremarkable, and he current ly t akes no
medicat ions.
On physical examinat ion, vit al signs, including t emperat ure, are normal. Mild right suborbit al ridge t enderness is present . The nares are pat ent wit h a clear mucoid discharge.
There is no pharyngeal eryt hema or exudat e. The lungs are clear t o auscult at ion.
(A) Amoxicillin
(B) CT scan of t he sinuses
(C) Plain films of sinuses
(D) Sympt omat ic t reat ment
(E) Trimet hoprim-sulfamet hoxazole
Item 14 [Basic]
A 25-year-old woman who is 28 weeks pregnant has asympt omat ic bact eriuria det ect ed during a rout ine prenat al visit . She has not had fever, urinary frequency, or dysuria and
is not t aking any medicat ions ot her t han prenat al vit amins. She has never had a urinary t ract infect ion before and has no medical problems.
On physical examinat ion, vit al signs, including t emperat ure, are normal. There is no cost overt ebral angle t enderness.
(A) Ampicillin
(B) Ciprofloxacin
(C) Trimet hoprim
(D) Observat ion
Item 15 [Advanced]
A 69-year-old man is evaluat ed in t he emergency depart ment for a 2-day hist ory of fever, confusion, vomit ing, dysuria, and lower abdominal and perineal pain. He has a
hist ory of chronic kidney disease, and his last serum creat inine level was 2.5 mg/dL (221 mmol/L).
On physical examinat ion, t emperat ure is 39.9C (103.8F), blood pressure is 88/50 mm Hg, heat rat e is 130/min. Examinat ion shows poor skin t urgor and dry mucous
membranes. The abdomen is soft , but suprapubic t enderness is present . Rect al examinat ion reveals an enlarged and t ender prost at e.
9
/L) wit h 80% segment ed neut rophils and 10% band forms. Blood urea nit rogen is 35 mg/dL (12.5 mmol/L) and creat inine is 3.8
mg/dL (336 mmol/L). Urinalysis shows 150 leukocyt es per high-power field and many bact eria.
Int ravenous fluids and parent eral ciprofloxacin are st art ed. Urine cult ure grows Proteus mirabilis sensit ive t o fluoroquinolones. Aft er 3 days, t he pat ient cont inues t o have
fever, abdominal and perineal pain, and persist ent leukocyt osis.
(A) Discont inue ciprofloxacin and st art gent amicin
(B) Add gent amicin
(C) Insert a cat het er for bladder drainage
(D) Obt ain a t ransrect al ult rasound
Item 16 [Advanced]
A 77-year-old woman is evaluat ed during a rout ine physical examinat ion. She is asympt omat ic and has a hist ory of hypert ension, t ype 2 diabet es mellit us, and
hyperlipidemia. Medicat ions are aspirin, lisinopril, hydrochlorot hiazide, a glyburide, and lovast at in. She has no allergies.
Her physical examinat ion is unremarkable. Laborat ory st udies including serum creat inine, blood urea nit rogen, elect rolyt es, liver funct ion t est s, and a fast ing lipid panel are
normal. Her hemoglobin A
1c
is 6.3%.
Urinalysis shows 15 leukocyt es per high-power field and bact eria; no eryt hrocyt es, prot ein, or glucose are not ed. Urine cult ure grows Escherichia coli of at least 10
5
colony-
forming unit s (cfu)/mL.
Repeat urinalysis and urine cult ure confirm t hese result s.
Whi ch of the fol l owi ng i s the most appropri ate next step i n management of thi s pati ent?
(A) Ciprofloxacin for 3 days
(B) Ciprofloxacin for 7 days
(C) Trimet hoprim-sulfamet hoxazole for 3 days
(D) No t reat ment
Item 17 [Advanced]
A 32-year-old woman is evaluat ed for a 2-day hist ory of fever, urinary frequency, left -sided flank pain, and nausea wit hout vomit ing. She also has diet -cont rolled t ype 2
diabet es mellit us.
On physical examinat ion, t emperat ure is 38.3C (100.9F), blood pressure is 122/82 mm Hg, pulse rat e is 102/min, and respirat ion rat e is 18/min. Left -sided cost overt ebral
angle t enderness is present . Result s of abdominal and pelvic examinat ions are normal.
Leukocyt e count 14,000/L (14 10
9
/L)
Urinalysis Posit ive for leukocyt e est erase and nit rit es
Pregnancy t est Negat ive
Urine cult ure Pending
(A) Ampicillin
(B) Ciprofloxacin
(C) Nit rofurant oin
(D) Trimet hoprim-sulfamet hoxazole
Item 18 [Advanced]
An ot herwise healt hy 28-year-old woman has had t wo episodes of acut e cyst it is wit hin t he past 6 mont hs. The pat ient is sexually act ive and has int ercourse wit h her husband
on average 2 t imes per week and says her cyst it is does not seem t o be int ercourse relat ed. Each t ime, sympt oms remit aft er a single course of t rimet hoprim-
sulfamet hoxazole. The pat ient is current ly asympt omat ic but will be t raveling abroad for t he next 2 mont hs and is concerned about recurrent infect ions. Her only medicat ion
is an oral cont racept ive for birt h cont rol. She report s no allergies.
(A) Ciprofloxacin aft er int ercourse
(B) Ciprofloxacin for 10 days when sympt oms develop
(C) Trimet hoprim chronic suppressive t herapy
(D) Trimet hoprim-sulfamet hoxazole for 3 days when sympt oms develop
Item 19 [Basic]
A 24-year-old woman is evaluat ed during a new pat ient visit . She is not current ly sexually act ive, but has been in t he past ; she has had t wo lifet ime part ners, and has always
used condoms. She has no medical problems and t akes no medicat ions. She was last seen by a physician 3 years ago.
In addi ti on to obtai ni ng a Pap smear, screeni ng for whi ch of the fol l owi ng sexual l y transmi tted di seases shoul d be preformed?
(A) Chlamydia and gonorrhea
(B) Chlamydia, gonorrhea, and HIV
(C) Chlamydia, gonorrhea, and syphilis
(D) Chlamydia, gonorrhea, HIV, and syphilis
(E) HIV and syphilis
Item 20 [Basic]
A 34-year-old woman is evaluat ed for vaginal discharge and int ermenst rual bleeding. She is gravida 4, para 2, wit h one spont aneous pregnancy loss and one t erminat ion. She
had been living int ermit t ent ly wit h t he fat her of her children, t hough recent ly t he t wo have been apart , and she is in t he process of moving out of t own. Her last menst rual
period was 3 weeks ago. She t akes no medicat ions and has no allergies.
Vit al signs are normal. On pelvic examinat ion, a yellow-t inged cervical discharge is not ed, and bleeding is easily induced when obt aining a cult ure from t he os. Bimanual
examinat ion is unremarkable, wit h no adnexal or cervical mot ion t enderness.
Examinat ion of t he discharge under microscopy reveals no pseudohyphae or clue cells, and Gram st ain is unremarkable. Pregnancy t est is negat ive.
Whi ch of the fol l owi ng condi ti ons shoul d recei ve empi ri c anti bi oti c treatment at thi s ti me?
(A) Bact erial vaginosis
(B) Chlamydia
(C) Gonorrhea and chlamydia
(D) Pelvic inflammat ory disease (PID)
Item 21 [Basic]
An 18-year-old woman is evaluat ed in t he emergency depart ment for a 3-day hist ory of fever and rash accompanied by joint pain and swelling t hat init ially involved only t he
left elbow before progressing t o t he left wrist . Medical hist ory is unremarkable. She t akes a depot medroxyprogest erone acet at e inject ion every 12 weeks for cont racept ion.
On physical examinat ion, t emperat ure is 38.1C (100.6C); ot her vit al signs are normal. The left wrist is eryt hemat ous and swollen, and pain is induced wit h act ive range of
mot ion. The left elbow is also swollen and painful. Scat t ered lesions are present on t he left hand and bot h feet . Skin examinat ion findings of t he left hand are shown (Plat e
21).
Appropriat e cult ures are t aken.
(A) Acyclovir
(B) Ceft riaxone
(C) Ciprofloxacin
(D) Gent amicin
Item 22 [Basic]
An 18-year-old woman has a 3-day hist ory of fever, headache, and painful sores in t he genit al area. The pat ient has no previous hist ory of genit al lesions. Medical hist ory is
unremarkable, and her only medicat ion is an oral cont racept ive agent . She does not use condoms.
On physical examinat ion, t emperat ure is 38.1C (100.6F); ot her vit al signs are normal. There are no signs of meningismus. Tender ulcerat ive lesions wit h a yellow crust ed
roof cover t he labia bilat erally and t he vaginal int roit us.
(A) Chancroid
(B) Herpes simplex virus infect ion
(C) Primary syphilis
(D) Vulvovaginal candidiasis
Item 23 [Advanced]
An 18-year-old woman is evaluat ed in t he emergency depart ment because of a 3-day hist ory of lower abdominal pain. She does not have urinary frequency, dysuria, flank
pain, nausea, or vomit ing. Her only medicat ion is an oral cont racept ive agent .
On physical examinat ion, t emperat ure is 38.3C (101.0F), blood pressure is 118/68 mm Hg, pulse rat e is 104/min, and respirat ion rat e is 16/min. Abdominal examinat ion is
normal. There is no flank t enderness. Pelvic examinat ion shows cervical mot ion t enderness, fundal t enderness, and bilat eral adnexal t enderness on bimanual examinat ion.
The leukocyt e count and urinalysis result s are normal. Urine and serum pregnancy t est s are negat ive.
(A) Ampicillin and gent amicin, int ravenously
(B) Azit hromycin, orally
(C) Cefoxit in, int ramuscularly
(D) Ceft riaxone, int ramuscularly, and doxycycline, orally
Item 24 [Advanced]
A 38-year-old man is admit t ed t o t he hospit al wit h a 1-week hist ory of progressive dyspnea, cough, and low-grade fever. He has a hist ory AIDS and has found it difficult t o
t ake all of his medicat ions. His CD4 count measured 6 mont hs ago was 80/L. He has no allergies.
On examinat ion, he appears dyspneic. Temperat ure is 39.2C (102.5F), blood pressure is 110/70 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 32/min. Oxygen
sat urat ion by pulse oximet ry is 82% on ambient air. Cardiopulmonary examinat ion is normal.
Art erial blood gas result s are: pH, 7.41; PO
2
, 58 mm Hg (7.7 kPa); PCO
2
, 32 mm Hg (4.3 kPa); HCO
3
, 20 meq/L (22 mmol/L). Chest x-ray revealed bilat eral int erst it ial
infilt rat es. A silver st ain of induced sput um is posit ive for Pneumocystis jirovecii.
Whi ch of the fol l owi ng i s the best i ni ti al treatment regi men for thi s pati ent?
(A) Dapsone
(B) Dapsone plus cort icost eroids
(C) Trimet hoprim-sulfamet hoxazole
(D) Trimet hoprim-sulfamet hoxazole plus cort icost eroids
Item 25 [Advanced]
A 28-year-old woman is evaluat ed following t he diagnosis of HIV infect ion discovered during a rout ine screening examinat ion.
On examinat ion, t he pat ient appears well. Temperat ure is 37.1C (98.8F), blood pressure is 105/70 mm Hg; pulse rat e is 88/min, and respirat ion rat e is 10/min. The
remainder of her examinat ion is normal.
Her CD4 cell count is 77/L and her HIV-1 RNA level is 200,000/mL. Her t oxoplasma ant ibody is posit ive, and her t uberculin skin t est is negat ive. All of her immunizat ions
are up t o dat e.
The pat ient agrees t o begin ant iret roviral drug t herapy.
Whi ch of the fol l owi ng treatments i s al so i ndi cated at thi s ti me?
(A) Trimet hoprim-sulfamet hoxazole
(B) Trimet hoprim-sulfamet hoxazole plus azit hromycin
(C) Trimet hoprim-sulfamet hoxazole plus fluconazole
(D) Trimet hoprim-sulfamet hoxazole plus isoniazid
(E) Trimet hoprim-sulfamet hoxazole plus valganciclovir
Item 26 [Advanced]
A 37-year-old man is evaluat ed for a 6-day hist ory of a painful erupt ion on his left post erior t horax. He had an episode of shingles 1 year ago t hat was t reat ed wit h
famciclovir. He has a hist ory of alcoholism and int ermit t ent inject ion drug use. He has lost approximat ely 3.0 kg (6.6 lb) over t he past 3 mont hs. He has had increased
fat igue but denies fever, chills, lymphadenopat hy, jaundice, or change in his bowel habit s. He t akes no medicat ions.
On physical examinat ion, t emperat ure is 37.0C (98.6F), and BMI is 28. The skin findings are shown (Plat e 22).
Whi ch of the fol l owi ng i s the most l i kel y underl yi ng di sease?
(A) Cirrhosis
(B) Diabet es mellit us
(C) Hepat it is B
(D) Hepat it is C
(E) HIV infect ion
Item 27 [Advanced]
A 28-year-old man is evaluat ed at a communit y healt h cent er for a 10-day hist ory of sore t hroat , headache, fever, anorexia, and muscle aches. Two days ago, a rash
developed on his t runk and abdomen. He had been previously healt hy and has not had any cont act wit h ill persons. He has had mult iple male and female sexual part ners and
infrequent ly uses condoms. He has been t est ed for HIV infect ion several t imes, most recent ly 8 mont hs ago; all result s were negat ive.
On physical examinat ion, t emperat ure is 38.6C (101.4F). There are several small ulcers on t he t ongue and buccal mucosa and cervical and supraclavicular
lymphadenopat hy. A faint maculopapular rash is present on t he t runk and abdomen.
A rapid plasma reagin t est is ordered.
Whi ch of the fol l owi ng di agnosti c studi es shoul d al so be done at thi s ti me?
(A) CD4 cell count measurement
(B) Epst ein-Barr virus IgG measurement
(C) HIV RNA viral load and HIV ant ibody measurement s
(D) Skin biopsy
Item 28 [Advanced]
A 38-year-old man is evaluat ed for a 3-week hist ory of progressive right -sided weakness of t he upper and lower ext remit ies, difficult y wit h balance, and slurred speech.
Medical hist ory includes syphilis 12 years ago t hat was t reat ed wit h benzat hine penicillin G.
On physical examinat ion, vit al signs are normal. The Mini-Ment al St at e Examinat ion score is 22 (normal >24/30). Speech is dysart hric. There is right -sided hemiparesis wit h
increased muscle t one on t he right . Serologic t est ing for HIV ant ibodies is posit ive. CD4 cell count is 80/L.
MRI of t he brain reveals numerous ring-enhancing lesions in t he basal ganglia and t he cort icomedullary junct ion, predominant ly on t he left side, wit h mass effect .
(A) Crypt ococcal meningit is
(B) Mycobacterium avium complex infect ion
(C) Progressive mult ifocal leukoencephalopat hy
(D) Toxoplasmosis encephalit is
Item 29 [Basic]
A 69-year-old man is admit t ed t o t he cardiac int ensive care unit wit h an exacerbat ion of heart failure.
Not able clinical findings include elevat ed cent ral venous pressure, an S
3
, pulmonary crackles, and pedal edema. Int ravenous furosemide and lisinopril are init iat ed, and a
urinary cat het er is placed t o measure urine out put .
In addi ti on to meti cul ous hand hygi ene, whi ch of the fol l owi ng measures i s most effecti ve i n preventi ng a catheter-associ ated uri nary tract i nfecti on?
(A) Ant ibiot ic prophylaxis
(B) Changing t he urinary cat het er every 72 hours
(C) Minimizing manipulat ion and irrigat ion of t he cat het er
(D) Prompt ly discont inuing urinary cat het er use
(E) Using silver impregnat ed urinary cat het ers
Item 30 [Advanced]
A 36-year-old woman is admit t ed t o t he int ensive care unit from t he emergency depart ment aft er int ent ionally ingest ing an overdose of a long-act ing barbit urat e.
Endot racheal int ubat ion was performed in t he emergency depart ment and t he pat ient was placed on mechanical vent ilat ion. Ot her t han being minimally arousable and
mechanically vent ilat ed, t he pat ient is st able.
Whi ch of the fol l owi ng measures wi l l reduce the ri sk of venti l ator-associ ated pneumoni a?
(A) Changing t he endot racheal t ube every 2 days
(B) Nasal placement of t he endot racheal t ube
(C) Prophylact ic ant ibiot ics
(D) Semi-erect (45) posit ioning in bed
Item 31 [Advanced]
A 68-year-old man is diagnosed wit h Clostridium difficile infect ion 5 days aft er elect ive hip replacement surgery. This hospit al has recent ly report ed a high incidence of C.
difficile infect ions. The pat ient was in a t wo-bed hospit al room.
In addi ti on to bl each for enhanced room cl eani ng, whi ch of the fol l owi ng "bundl ed" measures woul d be most effecti ve i n preventi ng the spread of C.
difficile i n thi s hospi tal setti ng?
(A) Airborne precaut ions and alcohol hand sanit izer
(B) Airborne precaut ions and soap and wat er for hand hygiene
(C) Barrier precaut ions and alcohol hand sanit izer
(D) Barrier precaut ions and soap and wat er for hand hygiene
(E) Droplet precaut ions and soap and wat er for hand hygiene
Item 32 [Advanced]
A 19-year-old female college freshman is evaluat ed for possible meningit is. Cerebrospinal fluid analysis shows a leukocyt e count of 13,259/L (13,259 10
6
/L) wit h 85%
neut rophils, a glucose concent rat ion of 40 mg/dL (2.2 mmol/L) and a prot ein level of 230 mg/dL (2300 mg/L). Gram st ain shows many neut rophils and gram-negat ive
diplococci.
The pat ient is placed in a privat e room and int ravenous ant ibiot ics are init iat ed.
Whi ch of the fol l owi ng i s the most appropri ate next step i n i nfecti on-control management?
(A) Face mask
(B) High-filt er mask
(C) Nonst erile gloves and gown
(D) St erile gloves and gown
Item 33 [Basic]
A 65-year-old man recent ly immigrat ed t o t he Unit ed St at es from Africa. He is evaluat ed in t he emergency depart ment for a 3-week hist ory of cough and dyspnea, now wit h
hemopt ysis. He has also had fevers, night sweat s, and a 13.6-kg (30-lb) weight loss over t he past 3 mont hs.
On physical examinat ion, he is t hin and coughs frequent ly. Temperat ure is 38.3C (101.0F), blood pressure is 100/60 mm Hg, pulse rat e is 101/min, and respirat ion rat e is
30/min. Pulmonary examinat ion reveals crackles over t he right upper lung field.
Whi ch of the fol l owi ng i s the most i mportant i ni ti al i nfecti on-control opti on i n thi s setti ng?
(B) Inst it ut ion of airborne precaut ions
(C) Sput um for acid-fast bacilli st ain and cult ure
(D) Tuberculin skin t est ing
Item 34 [Advanced]
A 45-year-old woman is evaluat ed because of a t uberculin skin t est result of 11-mm indurat ion discovered yest erday following a hospit al pre-employment examinat ion. She is
ot herwise healt hy. Her HIV t est result is negat ive. She relocat ed 3 mont hs ago t o t he Unit ed St at es from El Salvador where she worked as a bank t eller. She feels well and
report s no fever, cough, or weight loss. She t akes no medicat ions.
On physical examinat ion, t he vit al signs and cardiopulmonary examinat ions are normal.
(B) Four-drug ant it uberculous t herapy
(C) Isoniazid t herapy
(D) Clearance for employment
Item 35 [Advanced]
A 32-year-old healt hy female physician is beginning a post graduat e fellowship at a universit y hospit al and must undergo t uberculin skin t est ing. She grew up in Africa and
complet ed medical school and residency t raining in London. She received t he bacille Calmet t e-Guerin (BCG) vaccine at age 6 years.
Tuberculin skin t est ing indicat es a 16-mm area of indurat ion at t he t uberculin skin t est ing sit e.
Physical examinat ion is normal.
(B) Isoniazid, rifampin, pyrazinamide, and et hambut ol
(C) Repeat t uberculin skin t est ing in 2 weeks
(D) No addit ional t herapy or evaluat ion
Item 36 [Basic]
A 32-year-old man is evaluat ed in t he office for a 2-mont h hist ory of fever, night sweat s, weight loss, and cough. He works as a pharmacy t echnician in an ext ended care
facilit y for vet erans.
On physical examinat ion, he has a prominent cough and appears ill. Temperat ure is 38C (100.4F); ot her vit al signs are normal. Fine crackles are auscult at ed over t he right
post erior t horax. The remainder of t he physical examinat ion is normal.
A chest radiograph shows a right upper lobe infilt rat e wit h a small cavit y. A st ained sput um specimen is posit ive for acid-fast organisms; sput um cult ure result s are pending.
HIV t est ing is negat ive.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al therapy for thi s pati ent?
(A) Isoniazid
(B) Isoniazid, pyrazinamide, and et hambut ol
(C) Isoniazid, rifampin, pyrazinamide, and et hambut ol
(D) No t herapy unt il cult ures confirm Mycobacterium tuberculosis
Item 37 [Advanced]
A 39-year-old woman is recent ly diagnosed wit h syst emic lupus eryt hemat osus aft er invest igat ion of a fever, fat igue, art hralgia, a Coombs-posit ive hemolyt ic anemia, and
leukopenia. She requires t reat ment wit h prednisone at an init ial dosage of 1 mg/kg/day. She weighs 60 kg (132 lbs).
Hemoglobin is 7.5 g/dL (750 g/L) and leukocyt e count is 1900/L (1.9 10
9
/L). Chest radiograph is normal. Tuberculin skin t est ing reveals 8 mm of indurat ion.
Whi ch of the fol l owi ng i s the most appropri ate next step i n thi s pati ent's management?
(A) Isoniazid for 9 mont hs
(B) Isoniazid, pyrazinamide, rifampin, and et hambut ol for 12 mont hs
(C) Rifampin for 1 mont h
(D) No ant it uberculous t herapy
Item 38 [Advanced]
A 35-year-old woman is evaluat ed in t he office before t he init iat ion of infliximab for rheumat oid art hrit is. She was diagnosed wit h rheumat oid art hrit is 5 years ago, and her
disease is inadequat ely cont rolled on met hot rexat e and naproxen. She has no ot her complaint s or medical problems and has no risk fact ors for t uberculosis. She has never
been screened for t uberculosis.
Her physical examinat ion is unremarkable except for changes compat ible wit h act ive rheumat oid art hrit is involving her hands and feet . A chest radiograph is normal. Fort y-
eight hours aft er administ ering t he t uberculin skin t est , t here is 7 mm of indurat ion at t he inject ion sit e.
Ini ti ati on of whi ch of the fol l owi ng i s the most appropri ate next step i n thi s pati ent's treatment?
(A) Infliximab
(B) Isoniazid
(C) Isoniazid and infliximab
(D) Isoniazid, rifampin, pyrazinamide, and et hambut ol
Item 39 [Advanced]
A 65-year-old man is evaluat ed during a rout ine examinat ion. Medical hist ory is significant for hypert ension, ast hma, and t ype 2 diabet es mellit us; t hree years ago, he was
admit t ed t o t he hospit al wit h respirat ory failure and was t reat ed for pneumonia. He received pneumococcal immunizat ion upon his hospit al discharge. He is a current smoker
wit h a 50 pack-year hist ory. His medicat ions are lisinopril, met formin, aspirin, and an albut erol inhaler t hat he uses as needed. He has no allergies.
Vit al signs are normal. The result s of t he physical examinat ion are normal.
Whi ch of the fol l owi ng pneumococcal i mmuni zati on strategi es i s the most appropri ate for thi s pati ent?
(A) Administ er one dose of pneumococcal vaccine now
(B) Administ er one dose of pneumococcal vaccine in 2 years
(C) Administ er a dose of pneumococcal vaccine now and every 5 years t hereaft er
(D) No need for addit ional pneumococcal vaccinat ion
Item 40 [Advanced]
A 35-year-old woman is evaluat ed in t he emergency depart ment in December because of fever, confusion, and short ness of breat h. Three days ago, she became ill wit h fever,
sore t hroat , myalgias, and cough. Her sympt oms rapidly worsened. Her medical hist ory is unremarkable. Influenza infect ion has been report ed in t he communit y.
On physical examinat ion, t emperat ure is 40.0C (104.0F), blood pressure is 82/48 mm Hg, heart rat e is 130/min, respirat ion rat e is 36/min, and pulse oximet ry is 86% on
ambient air. Pulmonary examinat ion reveals bilat eral diffuse crackles. The pat ient is int ubat ed and receives mechanical vent ilat ion and is admit t ed t o t he int ensive care unit .
The leukocyt e count is 2200/L (2.2 10
9
/L) wit h 82% segment ed neut rophils and 10% band forms. The chest radiograph shows mult ilobar pneumonia. Sput um and blood
cult ures are sent , and int ravenous fluids are st art ed.
Whi ch of the fol l owi ng i s the most appropri ate empi ri c anti bi oti c therapy for thi s pati ent?
(A) Ceft riaxone and azit hromycin
(B) Clindamycin
(C) Cefot axime, levofloxacin, and vancomycin
(D) Piperacillin-t azobact am
Item 41 [Basic]
A 60-year-old woman is evaluat ed for t he acut e onset of fever, chills, nonproduct ive cough, diarrhea, and alt ered ment al st at us. Medical hist ory is significant for a 10-year
hist ory of t ype 2 diabet es mellit us cont rolled wit h diet and met formin t herapy.
On physical examinat ion, t emperat ure is 39.4 C (103.0 F), blood pressure is 100/56 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 32/min. Crackles are heard at t he
left lung base. On neurologic examinat ion, t he pat ient is orient ed only t o person.
Laborat ory st udies indicat e a hemat ocrit of 34%, a leukocyt e count of 18,000/L (18 10
9
/L), a plat elet count of 149,000/L (149 10
9
/L), and a serum sodium
concent rat ion of 125 meq/L (125 mmol/L). Chest radiograph reveals an alveolar infilt rat e in t he left lower lobe and a small left pleural effusion.
Whi ch of the fol l owi ng studi es i s most l i kel y to be hel pful i n determi ni ng the cause of pneumoni a i n thi s pati ent?
(A) Acid-fast bacilli sput um smear
(B) Blood cult ure
(C) Legionella urinary ant igen t est
(D) Thoracent esis
Item 42 [Basic]
A 22-year-old woman is evaluat ed in Sept ember for t he acut e onset of fever, myalgia, art hralgia, and nonproduct ive cough. Medical hist ory is noncont ribut ory.
On physical examinat ion, t he pat ient is not ill-appearing. Temperat ure is 38.0C (100.5F), blood pressure is 114/62 mm Hg, pulse rat e is 90/min, and respirat ion rat e is
18/min. A few crackles are heard at t he right lung base.
9
/L), and t he remaining laborat ory st udies are normal. Chest radiograph reveals a right middle lobe infilt rat e.
Whi ch of the fol l owi ng oral anti mi crobi al agents shoul d be i ni ti ated?
(A) Azit hromycin
(B) Moxifloxacin
(C) Penicillin
(D) Zanamivir
Item 43 [Advanced]
A 45-year-old woman is evaluat ed for fever, diminished appet it e, weight loss, and cough product ive of foul-smelling sput um of 2 weeks' durat ion. She has a hist ory of chronic
alcoholism and frequent hospit al admissions for alcohol-wit hdrawal seizures, wit h t he most recent episode occurring 3 weeks ago.
On physical examinat ion, t emperat ure is 38.3 C (101.0 F), blood pressure is 130/84 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 18/min. Her breat h is foul smelling
and dent it ion is poor. Pulmonary examinat ion reveals crackles and rhonchi in t he right ant erior chest .
Laborat ory st udies indicat e a leukocyt e count of 12,500/L (12.5 10
9
/L) wit h 8% band forms. The chest radiograph is shown.
Sput um Gram st ain result s indicat e gram-posit ive cocci in chains, gram-negat ive bacilli, and gram-posit ive bacilli.
Whi ch of the fol l owi ng empi ri c anti mi crobi al regi mens shoul d be i ni ti ated?
(A) Ampicillin-sulbact am
(B) Azt reonam
(C) Ceft riaxone
(D) Levofloxacin
(E) Met ronidazole
Item 44 [Advanced]
A 38-year-old man is scheduled t o have a root canal. He has a hist ory of a heart murmur. On physical examinat ion, t here is a normal S
1
, an eject ion sound, and a
physiologically split S
2
. There is a grade 2/6 midsyst olic murmur heard best at t he second right int ercost al space t hat radiat es t o t he right carot id art ery. He has no ot her
pert inent medical hist ory.
A previous t ranst horacic echocardiogram demonst rat ed a bicuspid aort ic valve wit h normal left vent ricular funct ion.
Whi ch of the fol l owi ng i s the most appropri ate anti bi oti c prophyl axi s for thi s pati ent before hi s dental procedure?
(A) Amoxicillin, orally
(B) Ampicillin, orally
(C) Clindamycin, orally
(D) Vancomycin, int ravenously
(E) No ant ibiot ic prophylaxis
Item 45 [Advanced]
A 56-year-old woman is scheduled t o undergo a root canal procedure. Medical hist ory is significant for mit ral valve infect ive endocardit is t reat ed 10 years ago. She has no
ot her known medical problems. She is allergic t o penicillin and developed hypot ension and respirat ory failure t he last t ime she was given t his ant ibiot ic.
Whi ch of the fol l owi ng i s the most appropri ate endocardi ti s prophyl axi s for thi s pati ent?
(A) Amoxicillin, orally
(B) Ampicillin, int ravenously
(C) Cefazolin, int ravenously
(D) Clindamycin, orally
(E) No ant ibiot ic prophylaxis
Item 46 [Basic]
A 26-year-old man is evaluat ed in t he emergency depart ment for t he acut e onset of a nonproduct ive cough and right -sided pleurit ic chest pain of 2 days' durat ion. The
pat ient is an inject ion drug user, wit h his last use approximat ely 4 days ago. Result s of his most recent HIV t est 2 mont hs ago were negat ive. The remainder of t he medical
hist ory is noncont ribut ory, and he t akes no medicat ions.
On physical examinat ion, t emperat ure is 39.4C (103.0 F), blood pressure is 120/80 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 20/min. Cardiopulmonary
examinat ion reveals clear lungs and a grade 3/6 holosyst olic murmur heard best at t he right st ernal border t hat increases on inspirat ion.
Laborat ory st udies indicat e a hemat ocrit of 39%, a leukocyt e count of 17,000/L (17 10
9
/L) wit h 15% band forms, and a plat elet count of 160,000/L (160 10
9
/L).
Chest radiograph reveals small infilt rat es in t he left upper lobe, right upper lobe, and right lower lobe. Blood cult ures are obt ained.
Whi ch of the fol l owi ng empi ri c anti mi crobi al regi mens shoul d be i ni ti ated?
(A) Azit hromycin plus ceft riaxone
(B) Levofloxacin plus clindamycin
(C) Piperacillin/t azobact am plus azt reonam
(D) Trimet hoprim-sulfamet hoxazole plus prednisone
(E) Vancomycin plus cefepime
Item 47 [Basic]
A 54-year-old man is evaluat ed because of fat igue, backache, and int ermit t ent fever of 3 mont hs' durat ion. He has no hist ory of cardiac disease or drug allergies.
On physical examinat ion, t here are no abnormalit ies of his skin. Opht halmologic examinat ion reveals a right conjunct ival hemorrhage. Funduscopic examinat ion is normal.
The lungs are clear. Cardiac examinat ion discloses a new murmur of aort ic insufficiency. The remainder of t he examinat ion is normal.
A t ranst horacic echocardiogram shows a t hickened bicuspid aort ic valve, wit h evidence of mild aort ic insufficiency. A t ransesophageal echocardiogram confirms t hese
findings and also shows an oscillat ing mass on t he aort ic valve. Four set s of blood cult ures grow a microorganism of t he viridans st rept ococci group t hat is sensit ive t o
penicillin.
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al anti bi oti c therapy for thi s pati ent?
(A) Penicillin G
(B) Vancomycin
(C) Vancomycin plus ceft riaxone
(D) Vancomycin plus gent amicin
Item 48 [Basic]
A 29-year-old woman is hospit alized because of a 4-day hist ory of fever, chills, myalgia, and a nonproduct ive cough. The pat ient has a 10-year hist ory of heroin use. Medical
hist ory is ot herwise unremarkable, including no allergies.
Temperat ure is 39.0C (102.0F); ot her vit al signs are normal. Cardiac examinat ion discloses an early grade 2/6 syst olic murmur at t he base. The remainder of t he
An elect rocardiogram is normal, and a t ranst horacic echocardiogram shows changes compat ible wit h a t ricuspid valve veget at ion.
Aft er blood cult ure specimens are obt ained, vancomycin, 1 g int ravenously every 12 hours, is begun. Wit hin 48 hours, all t he init ial blood cult ures are growing Staphylococcus
aureus t hat is suscept ible t o oxacillin, t he cephalosporins, t et racycline, clindamycin, and t he fluoroquinolones and is resist ant t o penicillin G, ampicillin, and eryt hromycin.
Whi ch of the fol l owi ng i s most appropri ate at thi s ti me?
(A) Cont inue vancomycin
(B) Swit ch t o clindamycin
(C) Swit ch t o linezolid
(D) Swit ch t o oxacillin
Item 49 [Advanced]
A 75-year-old man wit h t ype 2 diabet es mellit us is evaluat ed in t he emergency depart ment for a draining chronic ulcer on t he left foot , eryt hema, and fever. Drainage
init ially began 3 weeks ago. Current medicat ions include met formin and glyburide.
On physical examinat ion, he does not appear ill. Temperat ure is 37.9C (100.2F); ot her vit al signs are normal. The left foot is slight ly warm and eryt hemat ous. A plant ar
ulcer t hat is draining purulent mat erial is present over t he fourt h met at arsal joint . A met al probe makes cont act wit h bone. The remainder of t he examinat ion is normal.
The leukocyt e count is normal, and an eryt hrocyt e sediment at ion rat e is 70 mm/h. A plain radiograph of t he foot is normal.
Gram st ain of t he purulent drainage at t he ulcer base shows numerous leukocyt es, gram-posit ive cocci in clust ers, and gram-negat ive rods.
Whi ch of the fol l owi ng i s the most appropri ate management now?
(A) Begin imipenem
(B) Begin vancomycin and ceft azidime
(C) Begin vancomycin and met ronidazole
(D) Perform bone biopsy
Item 50 [Advanced]
A 75-year-old man has a 2-mont h hist ory of gradually increasing severe low back pain t hat is not relat ed t o t rauma. The pat ient oft en feels warm and diaphoret ic. He has no
urine or st ool incont inence. Ten weeks ago, he was discharged from t he hospit al aft er a prolonged int ensive care unit st ay for t he t reat ment of communit y-acquired
pneumonia-associat ed sepsis. During his st ay, he required mechanical vent ilat ion, ent eral nut rit ion, and prolonged cent ral venous access.
On physical examinat ion, t emperat ure is 38.1C (100.5F); ot her vit al signs are normal. There is mild t enderness t o palpat ion over t he lower back wit h no definit ive point of
maximum t enderness. Neurologic examinat ion is normal.
Complet e blood count and urinalysis are normal. Eryt hrocyt e sediment at ion rat e is 90 mm/h. Blood cult ures are drawn.
Whi ch of the fol l owi ng i s the opti mal di agnosti c test?
(A) CT scan of t he lumbar spine
(B) MRI of t he lumbar spine
(C) Plain radiograph of t he lumbar spine
(D) Three-phase bone scint igraphy
Item 51 [Advanced]
A 64-year-old woman is hospit alized because of a nonpainful draining ulcer on t he plant ar aspect of t he left foot . She has a 10-year hist ory of t ype 2 diabet es mellit us. The
ulcer is chronic and nonhealing but over t he past 3 days has begun draining foul-smelling mat erial. Yest erday, t he pat ient developed fever, and t he area around t he ulcer
became eryt hemat ous. Medicat ions include met formin and pioglit azone.
On physical examinat ion, she does not appear ill. Temperat ure is 38.3C (101.0F); ot her vit al signs are normal. A 3-cm by 2-cm deep plant ar ulcer t hat is draining a
purulent green exudat e is present at t he base of t he fourt h met at arsal. The ent ire foot is warm, eryt hemat ous, and edemat ous. Pulses in t he foot are palpable. No bone is
visible or det ect ed wit h a met al probe. A plain radiograph of t he foot shows only soft t issue swelling.
Whi ch of the fol l owi ng i magi ng studi es of the foot shoul d be performed next?
(A) CT scan
(B) Indium-labeled leukocyt e scan
(C) MRI
(D) Triple-phase t echnet ium bone scan
Item 52 [Advanced]
A 65-year-old man is evaluat ed in t he emergency depart ment for a 3-day hist ory of gradually worsening low back pain and fever.
On physical examinat ion, t emperat ure is 38.0C (100.4F); ot her vit al signs are normal. General examinat ion, including neurologic examinat ion, is normal. MRI of t he spine
shows enhancement of t he L3-L4 end plat es and inflammat ion of t he disk space. No epidural enhancement or paravert ebral collect ions are seen. The pat ient is hospit alized.
(A) Begin ceft riaxone
(B) Begin nafcillin
(C) Obt ain blood cult ures
(D) Obt ain bone biopsy
Item 1 Answer: D
Educati onal Objecti ve: Diagnose Rocky Mountain spotted fever.
This pat ient most likely has Rocky Mount ain spot t ed fever (RMSF). He present s wit h a flu-like illness during t he summer. Because of t he nonspecific nat ure of it s sympt oms,
RMSF should be st rongly considered in pat ient s such as t his one wit h a nonspecific febrile illness wit hin 3 weeks of pot ent ial t ick exposure, and immediat e t reat ment wit h
doxycycline should be given pending result s of diagnost ic st udies. Many people wit h t ick-borne infect ion do not recall a specific t ick bit e. Up t o 90% of pat ient s event ually
develop t he charact erist ic blanching eryt hemat ous macules locat ed around t he wrist s and ankles t hat spread cent ripet ally. The most commonly available diagnost ic t est for
RMSF is a convalescent serology.
Babesiosis is caused by Babesia microti, an int racellular prot ozoan parasit e. Babesiosis is t ransmit t ed t o humans by t icks and occurs primarily in t he nort heast ern Unit ed
St at es wit h an epicent er in Cape Cod, Massachuset t s, and t he associat ed islands. Most infect ions are subclinical, but a nonspecific febrile illness can occur. Babesiosis should be
considered in pat ient s who have t raveled t o endemic areas and now have a nonfocal febrile illness wit h chills, sweat s, myalgia, art hralgia, nausea, vomit ing, or fat igue. On
physical examinat ion, fever, splenomegaly, hepat omegaly, and jaundice may be present .
Alt hough t his pat ient 's present at ion is compat ible wit h influenza, t his disease does not generally occur in t emperat e regions of t he world during t he summer.
Most early localized Lyme disease occurs in t he summer and fall and is charact erized by t he eryt hema migrans rash, an expanding eryt hemat ous pat ch appearing 5 t o 14 days
aft er inoculat ion by an infect ed t ick. Early Lyme disease is usually diagnosed clinically because serologic t est result s are oft en negat ive at present at ion.
Key Poi nt
Rocky Mount ain spot t ed fever should be st rongly considered in pat ient s wit h a nonspecific febrile illness wit hin 3 weeks of pot ent ial t ick exposure and blanching
eryt hemat ous macules locat ed around t he wrist s and ankles.
Bi bl i ography
Sext on DJ, Kaye KS. Rocky Mount ain spot t ed fever. Med Clin Nort h Am. 2002;86(2):351-60, vii-viii. [PMID: 11982306]
Item 2 Answer: A
Educati onal Objecti ve: Diagnose factitious fever.
This pat ient most likely has fact it ious fever. Fact it ious fever was t he diagnosis in 9% of a Nat ional Inst it ut e of Healt h cohort of 343 referrals for evaluat ion of fever of
unknown origin (a highly select ed populat ion). Fact it ious fever usually is diagnosed in young women, generally shows unusual fever pat t erns such as very high or brief spikes
and rapid defervescence wit hout chills, and diaphoresis. A fever diary will t ypically demonst rat e a lack of normal diurnal t emperat ure variat ion. Like t his pat ient , physical and
laborat ory findings of infect ion or inflammat ion are lacking during t he febrile illness.
Familial Medit erranean fever is an aut osomal recessive disorder prevalent in people of Jewish, Turkish, Arabic, and Armenian herit age. Most pat ient s have t he onset of illness
before age 10 years, 95% before t he age of 20 years. The key feat ure is short periods of fever (1-3 days) associat ed wit h serosit is; 90% of pat ient s have abdominal pain, and
pleurit is and synovit is are also common. Episodes of fever are accompanied by elevat ed markers of inflammat ion such as leukocyt osis and eryt hrocyt e sediment at ion rat e.
Endocardit is should be suspect ed if an abnormal murmur is heard on examinat ion, part icularly in pat ient s wit h a compelling hist ory or concurrent fever. Endocardit is is
unlikely in t his pat ient wit h normal physical findings and negat ive blood cult ures.
Approximat ely 80% of pat ient s wit h syst emic lupus eryt hemat osus (SLE) have cut aneous involvement at some point in t heir disease course. Most rashes associat ed wit h SLE
occur in areas exposed t o t he sun. More t han 90% of pat ient s wit h SLE develop joint involvement t hat can manifest as art hralgia or t rue art hrit is. Joint pain is oft en
migrat ory and can be oligoart icular or polyart icular, or asymmet ric or symmet ric. More t han 99% of unt reat ed pat ient s wit h SLE have high t it ers of ant inuclear ant ibodies; a
negat ive ant inuclear ant ibody t est effect ively rules out t he diagnosis of SLE.
Key Poi nt
Fact it ious fever usually is diagnosed in young women; generally shows unusual fever pat t erns such as very high or brief spikes, absent diurnal variat ion, and rapid defervescence
wit hout chills; and diaphoresis.
Bi bl i ography
Cunha BA. Fever of unknown origin: focused diagnost ic approach based on clinical clues from t he hist ory, physical examinat ion, and laborat ory t est s. Infect Dis Clin Nort h
Am. 2007;21(4):1137-87, xi. [PMID: 18061092]
Item 3 Answer: A
Educati onal Objecti ve: Diagnose malignant hyperthermia.
This pat ient most likely has malignant hypert hermia, which is an inherit ed skelet al muscle disorder charact erized by a hypermet abolic st at e precipit at ed by exposure t o
volat ile inhalat ional anest het ics (halot hane, isoflurane, enflurane, desflurane, sevoflurane) and t he depolarizing muscle relaxant s succinylcholine and decamet honium. It
usually occurs on exposure t o t he drug but can occur several hours aft er t he init ial exposure and can develop in pat ient s who were previously exposed t o t he drug wit hout
effect . Increased int racellular calcium leads t o sust ained muscle cont ract ions, wit h skelet al muscle rigidit y and masset er muscle spasm, t achycardia, hypercarbia, hypert ension,
hypert hermia, t achypnea, and cardiac arrhyt hmias. Rhabdomyolysis (elevat ed creat ine kinase) and acut e renal failure can develop. Malignant hypert hermia should be
suspect ed in pat ient s wit h a family hist ory of problems during anest hesia.
The neurolept ic malignant syndrome is a life-t hreat ening disorder caused by an idiosyncrat ic react ion t o neurolept ic t ranquilizers (dopamine D
2
-recept or ant agonist s) and
some ant ipsychot ic drugs. The most common offending neurolept ic agent s are haloperidol and fluphenazine. The syndrome occurs wit h all drugs t hat cause cent ral dopamine
recept or blockade, usually soon aft er st art ing a new drug or wit h dose escalat ion. It has been report ed in pat ient s wit h Parkinson disease who abrupt ly discont inue levodopa or
ant icholinergic t herapy. Most pat ient s wit h t he syndrome develop muscle rigidit y, hypert hermia, cognit ive changes, aut onomic inst abilit y, diaphoresis, sialorrhea, seizures,
arrhyt hmias, and rhabdomyolysis wit hin 2 weeks aft er init iat ing t he drug. Because t his pat ient did not receive a neurolept ic agent , neurolept ic malignant syndrome is unlikely.
Like t he neurolept ic malignant syndrome, t he serot onin syndrome present s wit h high fever, muscle rigidit y, and cognit ive changes. Findings unique t o t he serot onin syndrome
are shivering, hyperreflexia, myoclonus, and at axia. The serot onin syndrome is caused by t he use of select ive serot onin reupt ake inhibit ors, a cat egory of drug t hat t his
pat ient has not been exposed t o.
Thyroid st orm is a pot ent ial cause of hypert hermia in hospit alized pat ient s, but t hyroid st orm does not cause muscle rigidit y or elevat ions of t he creat ine kinase level and is
unlikely in a pat ient receiving adequat e t reat ment for hypert hyroidism.
Key Poi nt
Malignant hypert hermia is an inherit ed skelet al muscle disorder charact erized by a hypermet abolic st at e precipit at ed by exposure t o volat ile inhalat ional anest het ics and
depolarizing muscle relaxant s.
Bi bl i ography
Chamorro C, Romera MA, Balandin B. Fever in crit ically ill pat ient s. Crit Care Med. 2008;36(11):3129-3130. [PMID: 18941337]
Item 4 Answer: D
Educati onal Objecti ve: Treat sepsis with infection source identification and control.
In sept ic pat ient s wit h ident ifiable or pot ent ial sources of infect ion, source cont rol, including t he removal of sources of infect ion such as indwelling cat het ers, drainage of
abscesses, and surgical debridement of wounds should be done prompt ly upon diagnosis. In t his pat ient wit h evidence of t issue dest ruct ion and infect ion wit h gas-forming
organisms, early surgical debridement is an urgent necessit y.
Therapy wit h drot recogin alfa (act ivat ed prot ein C) is not indicat ed, because t he pat ient does not meet t he high-risk mort alit y t hreshold det ermined by a severit y-of-illness
scoring syst em such as APACHE (Acut e Physiology and Chronic Healt h Evaluat ion) II wit h a score of great er t han 25 or t he presence of sept ic shock requiring vasopressors,
sepsis-induced acut e respirat ory dist ress syndrome (ARDS) requiring mechanical vent ilat ion, or t wo or more sepsis-induced organ dysfunct ions. Drot recogin alfa has not been
shown t o direct ly neut ralize inflammat ory mediat ors.
Low-dose dopamine is not indicat ed. A randomized cont rolled t rial showed no benefit from "renal doses" of dopamine on renal or ot her clinical out comes in early renal
dysfunct ion. In sepsis, vasopressors can be added as part of early goal-direct ed t herapy if a fluid challenge fails t o achieve a mean art erial pressure (diast olic pressure plus one-
t hird t he pulse pressure) great er t han 65 mm Hg despit e adequat e fluid resuscit at ion. In t his pat ient , vasopressors may be considered aft er a fluid challenge of at least 4 t o 6
lit ers but is premat ure at t his t ime.
Key Poi nt
In sept ic pat ient s wit h ident ified sources of infect ion, effort s should be made t o remove t he source as early as possible
Bi bl i ography
Jimenez MF, Marshall JC; Int ernat ional Sepsis Forum. Source cont rol in t he management of sepsis. Int ensive Care Med. 2001;27(suppl 1):S49-62. [PMID: 11307370]
Item 5 Answer: A
Educati onal Objecti ve: Treat severe sepsis with aggressive fluid resuscitation.
The addit ional int ervent ion t hat is most likely t o improve survival in t his pat ient is aggressive fluid resuscit at ion. The pat ient has severe urosepsis. Aggressive fluid
resuscit at ion wit h resolut ion of lact ic acidosis wit hin 6 hours will have a beneficial effect on t his pat ient 's survival. Fluid resuscit at ion should t arget cent ral venous oxygen
sat urat ion (SCVO
2
) or mixed venous oxygen sat urat ion (SVO
2
) of at least 70%. Ot her reasonable goals include a cent ral venous pressure of 8 t o 12 mm Hg, a mean art erial
pressure of at least 65 mm Hg, and a urine out put of at least 0.5 mL/kg/h. This oft en t ranslat es int o administ rat ion of 5 t o 6 L of fluid over 6 hours. Timing of resuscit at ion
mat t ers t o survival. Early goal-direct ed t herapy t hat includes int ervent ions wit hin t he first 6 hours t o maint ain a SCVO
2
of great er t han 70% and t o resolve lact ic acidosis
result s in higher survival rat es t han more delayed resuscit at ion at t empt s.
Blood t ransfusion may be part of resuscit at ion for anemic pat ient s in shock, but maint aining hemoglobin levels above 12 g/dL (120 g/L) is not support ed by evidence. In
st able pat ient s who are not in shock, a t ransfusion t hreshold of 7 g/dL (70 g/L) is an accept able conservat ive approach. There are no dat a t o support t hat maint aining a lower
PCO
2
or using a pulmonary art ery cat het er would help t o increase survival in t his pat ient .
Key Poi nt
In pat ient s wit h severe sepsis, aggressive fluid resuscit at ion wit h resolut ion of lact ic acidosis wit hin 6 hours has a beneficial effect on survival.
Bi bl i ography
Rivers E, Nguyen B, Havst ad S, et al; Early Goal-Direct ed Therapy Collaborat ive Group. Early goal-direct ed t herapy in t he t reat ment of severe sepsis and sept ic shock. N
Engl J Med. 2001;345(19):1368-1377. [PMID: 11794169]
Item 6 Answer: A
Educati onal Objecti ve: Treat a patient with severe sepsis with activated protein C.
The administ rat ion of act ivat ed prot ein C is t he most appropriat e next st ep. Act ivat ed prot ein C (drot recogin alfa act ivat ed) is a t ime-sensit ive int ervent ion t hat can
improve survival in pat ient s wit h severe sepsis at high risk of deat h. Improved survival has been demonst rat ed in pat ient s wit h severe sepsis who have an APACHE score of
25 or great er. Pat ient s wit h eit her a single failing organ syst em or an APACHE score less t han 25 do not appear t o benefit and are at risk of bleeding complicat ions. Alt hough
act ivat ed prot ein C is an ant icoagulant , when administ ered t o pat ient s wit h a plat elet count bet ween 30,000/L (30 10
9
/L) and 50,000/L (50 10
9
/L), t here was a relat ive
risk reduct ion in mort alit y of more t han 30%. Plat elet count s below 30,000/L (30 10
9
/L) are considered a relat ive cont raindicat ion. The pat ient is more t han 12 hours out
of surgery, wit h no ongoing act ive bleeding, a plat elet count of 42,000/L (42 10
9
/L), and a high risk of deat h; t herefore, act ivat ed prot ein C is an excellent considerat ion.
The goals of fluid resuscit at ion are a cent ral venous pressure of 8 t o 12 mm Hg, mean art erial pressure great er t han 65 mm Hg, urine out put great er t han 0.5 mL/kg/h, and
cent ral venous oxygen sat urat ion great er t han 70%. Randomized cont rolled t rials have shown no benefit t o t he use of colloid compared wit h cryst alloid fluids.
Hyperglycemia is associat ed wit h poor clinical out comes in crit ically ill pat ient s. However, t he benefit of t ight glycemic cont rol (110 mg/dL [6.1 mmol/L]) is cont roversial
in crit ically ill post surgical pat ient s, and no benefit has been shown in crit ically ill medical pat ient s.
Vasopressors are part of early goal-direct ed t herapy if t he mean art erial pressure is less t han 65 mm Hg aft er init ial adequat e fluid resuscit at ion. The most commonly used
vasopressor for sept ic shock is norepinephrine, a pot ent peripheral vasoconst rict or t hat reverses t he endot oxin-induced vasodilat ion t hat is t he hallmark of sept ic shock.
Dopamine is also accept able but is associat ed wit h more t achycardia and arrhyt hmia. Low-dose dopamine, however, is not indicat ed. A randomized cont rolled t rial showed
t hat t here is no benefit from low-dose dopamine on renal or ot her clinical out comes in early renal dysfunct ion.
Key Poi nt
Act ivat ed prot ein C has been shown t o improve survival in pat ient s wit h severe sepsis wit h an APACHE score of 25 or great er.
Bi bl i ography
Toussaint S, Gerlach H. Act ivat ed prot ein C for sepsis. N Engl J Med. 2009;361(27):2646-52. [PMID: 20042756]
Item 7 Answer: A
Educati onal Objecti ve: Treat sepsis with fluid resuscitation.
The placement of a cent ral venous line and aggressive fluid resuscit at ion will have t he great est impact on improving t his pat ient 's chances of survival. Sepsis is known t o
result in t issue hypoperfusion. Most pat ient s need at least 4 t o 6 L of int ravascular volume replacement wit hin t he first 6 hours, and one of t he biggest pit falls of
management is underest imat ing t he int ravascular volume deficit . Vasopressor t herapy wit h norepinephrine, vasopressin, or dopamine may be necessary when appropriat e
fluid challenge fails t o rest ore adequat e t issue perfusion or during life-t hreat ening hypot ension, but no t rials have est ablished a single superior approach t o handling init ial
vasopressor choice.
Replacement -dose hydrocort isone is no longer recommended rout inely for pat ient s wit h sept ic shock who achieve a syst olic blood pressure of at least 90 mm Hg wit h fluids
and vasopressors, alt hough cort icost eroids may be useful for pat ient s wit h more profound, refract ory shock.
Placement of a pulmonary art ery cat het er in a pat ient wit h clinical evidence of sepsis and hypoperfusion has not been shown t o improve out comes.
Drot recogin alfa (act ivat ed prot ein C) is approved by t he U.S. Food and Drug Administ rat ion and int ernat ional regulat ory aut horit ies for pat ient s wit h severe sepsis who are
at high risk for deat h. Drot recogin alfa t herapy increases bleeding risk at rat es similar t o t hose of heparin. Serious bleeding increases by 1.5% t o 2.5% above t hat expect ed
wit h placebo, and int racerebral hemorrhage occurs in 0.6% of t reat ed pat ient s. Drot recogin alfa is cont raindicat ed in t he presence of act ive bleeding, concurrent t herapy wit h
ot her ant icoagulant drugs, and plat elet count s less t han 30,000/L (30 10
9
/L), and in pat ient s wit h risks of uncont rollable or cent ral nervous syst em bleeding. Drot recogin
alfa t herapy should be considered in pat ient s wit h all of t he following crit eria: sept ic shock requiring vasopressors despit e fluid resuscit at ion, sepsis-induced acut e respirat ory
dist ress syndrome (ARDS) requiring mechanical vent ilat ion; and any t wo sepsis-induced dysfunct ional organs. This pat ient does not meet t he crit eria for t reat ment wit h
act ivat ed prot ein C.
Key Poi nt
Most pat ient s wit h sepsis need at least 4 t o 6 L of int ravascular volume replacement wit hin t he first 6 hours.
Bi bl i ography
Rivers E, Nguyen B, Havst ad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-direct ed t herapy in t he t reat ment of severe sepsis and sept ic shock. N Engl J Med.
2001;345:1368-77. [PMID: 11794169]
Item 8 Answer: A
Educati onal Objecti ve: Diagnose sepsis.
The t erm t hat best describes t his pat ient 's illness is sepsis. The diagnost ic crit eria for sepsis include eit her a cult ure-proven infect ion or visual ident ificat ion of an infect ion
(for example, a wound wit h purulent drainage) and at least t wo crit eria fulfilling t he definit ion of a syst emic response t o infect ion (fever, t achycardia, t achypnea, and an
elevat ed leukocyt e count wit h immat ure band forms). She does not have organ dysfunct ion or perfusion abnormalit ies (hypot ension and lact ic acidosis), which occur in
pat ient s wit h severe sepsis or sept ic shock. Therefore, t he t erm t hat best defines her illness is sepsis.
Definit ions of syst emic inflammat ory response syndrome, sepsis, severe sepsis, sept ic shock, and mult iple organ dysfunct ion syndrome are as follows:
Syst emic inflammat ory response syndrome (SIRS): The syst emic inflammat ory response t o a wide variet y of severe clinical insult s, manifest ed by at least t wo of t he
following condit ions: t emperat ure great er t han 38.0C (100.4F) or less t han 36.0C (96.8F), heart rat e great er t han 90/min, respirat ion rat e great er t han 20/min or art erial
blood PCO
2
less t han 32 mm Hg (4.3 kPa), leukocyt e count great er t han 12,000/L (12 10
9
/L) or less t han 4000/L (4 10
9
/L) or wit h great er t han 10% immat ure band
forms.
Sepsis: The syst emic inflammat ory response t o a document ed infect ion. In associat ion wit h infect ion, manifest at ions of sepsis are t he same as t hose described for SIRS.
Severe sepsis: Sepsis associat ed wit h organ dysfunct ion, hypoperfusion, or hypot ension.
Sept ic shock: A subset of severe sepsis, defined as sepsis-induced hypot ension despit e adequat e fluid resuscit at ion plus t he presence of perfusion abnormalit ies. Pat ient s
receiving inot ropic or vasopressor agent s may no longer be hypot ensive by t he t ime t hey develop hypoperfusion abnormalit ies or organ dysfunct ion; however, t hey would
st ill be considered t o have sept ic shock.
Key Poi nt
The diagnost ic crit eria for sepsis include a cult ure-proven infect ion or visual ident ificat ion of an infect ion and evidence of a syst emic response t o infect ion (fever,
t achycardia, t achypnea, and an elevat ed leukocyt e count wit h immat ure band forms).
Bi bl i ography
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001
SCCM/ESICM/ACCP/ATS/SIS Int ernat ional Sepsis Definit ions Conference. Crit Care Med. 2003;31(4):1250-6. [PMID: 12682500]
Item 9 Answer: D
Educati onal Objecti ve: Diagnose and treat peritonsillar abscess.
The most appropriat e management for t his pat ient is emergent ENT consult at ion. The pat ient is not responding t o ant ibiot ics. He most likely has a perit onsillar abscess.
Complicat ions of unt reat ed group A -hemolyt ic st rept ococcal (GABHS) infect ion include perit onsillar abscess ("quinsy"), post st rept ococcal glomerulonephrit is, and
rheumat ic fever. About half of pat ient s wit h perit onsillar abscess present first wit h t his complicat ion rat her t han wit h pharyngit is. Among t hose who present first wit h sore
t hroat and t hen develop perit onsillar abscess, only one quart er have GABHS pharyngit is. Pat ient s who present first wit h sore t hroat , such as t his pat ient , are dist inguished by
worsening sore t hroat despit e ant ibiot ic t herapy, fever dysphagia, pooling of saliva, possible drooling, and muffled voice. On physical examinat ion, t he pat ient is ill-appearing
and oft en has enlarged t onsils wit h deviat ion of t he uvula t o t he unaffect ed side. The more serous complicat ions include airway obst ruct ion, dissect ion of t he infect ion t o t he
parapharyngeal space, spont aneous abscess drainage and aspirat ion of pus (usually while sleeping) and sepsis. Treat ment consist s of needle drainage or surgical incision and
drainage of t he abscess.
Ant ibiot ic select ion is informed by cult ure result s. However, cult ures are not frequent ly obt ained in t his set t ing and are difficult t o int erpret because of t he presence of mout h
flora. Penicillin alone, by any rout e, is unlikely t o be successful due t o t he emergence of penicillin-resist ant oral anaerobes associat ed wit h t his infect ion. Recommended
t reat ment is ampicillin-sulbact am or t he combinat ion of parent eral penicillin G and met ronidazole. Surgical drainage may be necessary. Clindamycin is reserved for penicillin
allergic pat ient s. Azit hromycin does not provide anaerobic coverage and is t herefore not indicat ed in t his infect ion.
Key Poi nt
A serious complicat ion of unt reat ed group A -hemolyt ic st rept ococcal (GABHS) infect ion is perit onsillar abscess.
Bi bl i ography
St eyer TE. Perit onsillar abscess: diagnosis and t reat ment . Am Fam Physician. 2002;65(1):93-6. Errat um in: Am Fam Physician 2002;66(1):30. [PMID: 11804446]
Item 10 Answer: B
Educati onal Objecti ve: Prevent upper respiratory tract infection with hand washing.
Handwashing wit h soap and wat er has proven efficacy in removing viruses from t he hands and helps prevent t he spread of infect ions. Cont act wit h secret ions is probably t he
principle mode of upper respirat ory viral infect ion t ransmission. A met a-analysis of 30 st udies assessing hand hygiene showed a reduct ion in respirat ory illness of 21%.
Alt hough commonly used t o prevent upper respirat ory t ract infect ions, prevent ion st udies using echinacea have failed t o show consist ent benefit and it cannot be
recommended. Ant ibiot ics, such as penicillin G, are ineffect ive in t he t reat ment or prevent ion of viral diseases. In addit ion, t he inappropriat e use of ant ibiot ics increases t he
risk of bact erial resist ance and exposes t he pat ient t o unnecessary risks, such as allergic react ions, and complicat ions, such as vaginal yeast infect ion and gast roint est inal
upset , including t he possibilit y of Clostridium difficile infect ion. Commonly used in Asia t o prevent respirat ory infect ions, t he benefit of face masks is undocument ed. In one
t rial in Japan, use of surgical face masks did not result in a lower incidence of upper respirat ory t ract infect ions but was associat ed wit h a great er incidence of headache.
Prevent ion st udies using vit amin C have failed t o show consist ent benefit in t he general communit y; however, a subgroup of st udies t hat included persons exposed t o
significant cold or physical st ress showed a reduct ion in t he incidence and durat ion of colds. Mult ivit amin and mult imineral supplement at ion are commonly used in men and
women aged 65 years or older; however, prevent ion st udies using daily mult ivit amin and mult imineral supplement at ion in t his populat ion have failed t o show consist ent
benefit on t he incidence of upper respirat ory t ract infect ions.
Key Poi nt
Handwashing wit h soap and wat er has proven efficacy in removing viruses from t he hands and helps prevent t he spread of infect ions.
Bi bl i ography
Prat t er MR. Cough and t he common cold: ACCP evidence-based clinical pract ice guidelines. Chest . 2006;129(1 suppl):72S-74S. [PMID: 16428695]
Item 11 Answer: A
Educati onal Objecti ve: Treat otitis media with amoxicillin.
The best init ial ant ibiot ic for t his pat ient is amoxicillin. Alt hough ot it is media is t he most frequent bact erial infect ion in children, it is much less common in adult s. In most
cases of acut e ot it is media, a viral upper respirat ory t ract infect ion precedes t he ear infect ion. Eust achian t ube obst ruct ion occurs secondary t o inflammat ion. Bact eria
subsequent ly ent er t he middle ear by means of a compliant eust achian t ube, aided by ot her fact ors, including nose blowing, sniffing, and negat ive middle ear pressure. The
microbiology of ot it is media in adult s is similar t o t hat of children: Streptococcus pneumoniae, 21% t o 63%; Haemophilus influenzae, 11% t o 26%; Staphylococcus aureus,
3% t o 12%; and Moraxella catarrhalis, 3%. Thirt y percent of bact erial cult ures of t he middle ear show no growt h.
Ant ibiot ic t herapy should be reserved for pat ient s in whom evidence of purulent ot it is exist s. Guidelines for ant ibiot ic use are t he same in children and adult s. Amoxicillin is
t he recommended init ial ant ibiot ic because of it s proven efficacy, safet y, relat ively low cost , and narrow spect rum of act ivit y. If sympt oms do not improve aft er 48 t o 72
hours of amoxicillin t herapy, init iat ion of amoxicillin-clavulanat e, cefuroxime, or ceft riaxone is recommended. Alt ernat ive agent s for pat ient s wit h penicillin allergy are oral
macrolides (azit hromycin, clarit hromycin). Follow-up of t hese pat ient s is not necessary unless sympt oms persist or progress.
Key Poi nt
Amoxicillin is t he recommended ant ibiot ic for t reat ing acut e ot it is media in adult s because of it s proven efficacy, safet y, relat ively low cost , and narrow spect rum of act ivit y.
Bi bl i ography
Ramakrishnan K, Sparks RA, Berryhill WE. Diagnosis and t reat ment of ot it is media [errat um in Am Fam Physician. 2008;78(1):30]. Am Fam Physician. 2007;76(11):1650-
1658. [PMID: 18092706]
Item 12 Answer: C
Educati onal Objecti ve: Manage acute pharyngitis using the Centor criteria.
The best management st ep is rapid st rept ococcal ant igen t est ing. Managing pat ient s wit h pharyngit is includes est imat ing t he probabilit y of t he presence of group A -
hemolyt ic st rept ococcal (GABHS) infect ion. The four-point Cent or crit eria (fever, t onsillar exudat es, t ender ant erior cervical lymphadenopat hy, and absence of cough) are
oft en used as a predict ion rule in pat ient s wit h suspect ed GABHS infect ion. Pat ient s wit h t wo Cent or crit eria, such as t he pat ient described here, have an int ermediat e
probabilit y for GABHS infect ion, and rapid st rept ococcal ant igen t est ing (sensit ivit y of 88% and specificit y of 94%) is a reasonable st rat egy for t hese pat ient s. Pat ient s wit h
0 or 1 crit erion have a low (<3%) probabilit y of GABHS, and neit her t est ing nor ant ibiot ic t reat ment is recommended. Empiric ant ibiot ic t herapy is recommended for
pat ient s who meet all four Cent or crit eria because t he probabilit y of GABHS is 40% or great er. Opinion differs regarding t he management of pat ient s wit h t hree crit eria, and
eit her empiric ant ibiot ic t reat ment or t est ing and t hen t reat ing only if t est result s are posit ive is accept able. Pat ient s wit h Cent or scores of 3 or 4 who have negat ive rapid
ant igen t est ing should t hen undergo t hroat cult ures t o guide t reat ment decisions. An init ial t hroat cult ure rat her t han a rapid ant igen t est would be unnecessarily expensive.
Ant ibiot ics are not indicat ed for t his pat ient before rapid st rept ococcal ant igen t est ing is done t o det ermine whet her t hey are needed. If t reat ment is indicat ed, t he ant ibiot ic
of choice is penicillin. Macrolide ant ibiot ics and first - and second-generat ion cephalosporins are alt ernat ive choices for penicillin-allergic pat ient s.
Key Poi nt
Rapid st rept ococcal ant igen t est ing is a reasonable st rat egy for pat ient s wit h pharyngit is who have t wo of t he four Cent or crit eria (fever, t onsillar exudat es, t ender ant erior
cervical lymphadenopat hy, and absence of cough).
Bi bl i ography
Wessels MR. Clinical pract ice. St rept ococcal pharyngit is. N Engl J Med. 2011;364(7):648-55. [PMID: 21323542]
Item 13 Answer: D
Educati onal Objecti ve: Treat acute sinusitis with symptomatic measures.
Sympt omat ic management is best for t his pat ient . He most likely has acut e sinusit is. Most cases of acut e sinusit is are caused by a virus; only 0.5% t o 2% are caused by
bact eria. Signs and sympt oms are not reliable for diagnost ic purposes. A met a-analysis found t hat no sympt oms or signs, including unilat eral facial pain, pain in t he t eet h,
pain on bending, or purulent nasal discharge, were precise enough t o est ablish t he diagnosis. In most pat ient s, sympt oms last up t o 2 weeks and resolve wit hout addit ional
diagnost ic st udies or administ rat ion of ant ibiot ics.
Ant ibiot ics are not indicat ed for t his pat ient . Even t hough most pat ient s wit h suspect ed acut e sinusit is do receive ant ibiot ics, t here is lit t le evidence t o support t he
effect iveness of t his pract ice. A randomized t rial found t hat t he durat ion of sympt oms did not differ bet ween pat ient s who did and did not receive ant ibiot ics. A met a-analysis
found t hat alt hough pat ient s wit h more severe sympt oms had a longer period of illness, ant ibiot ics did not decrease sympt om severit y or durat ion of infect ion. However,
some guidelines st ill recommend administ rat ion of ant ibiot ics. If t hese agent s are used, t hey should be limit ed t o pat ient s wit h at least t wo of t he following findings: sympt oms
last ing longer t han 7 days, facial pain, and purulent nasal discharge. The dat a as a whole suggest t hat if ant ibiot ics are t o be used, amoxicillin or doxycycline are adequat e first -
line agent s. Trimet hoprim-sulfamet hoxazole is accept able for -lact am-allergic adult s. The pat ient described here does not meet t he crit eria for ant ibiot ic administ rat ion by
most guidelines.
Imaging st udies, including CT scans or plain films of t he sinuses and sinus aspirat ion, should be considered only in pat ient s wit h predisposing fact ors for at ypical microbial
causes (for example, pseudomonal or fungal infect ion) and in pat ient s wit h AIDS or who are ot herwise immunocompromised.
Key Poi nt
Ant ibiot ics are unlikely t o be effect ive for most pat ient s wit h suspect ed acut e sinusit is.
Bi bl i ography
Wilson JF. Acut e Sinusit is. Ann Int ern Med. 2010;153(5):ITC31. [PMID: 20820036]
Item 14 Answer: A
Educati onal Objecti ve: Treat asymptomatic bacteriuria in a pregnant patient with ampicillin.
The most appropriat e management is t o begin ampicillin. Pregnant women are screened for asympt omat ic bact eriuria, which is associat ed wit h low birt h weight , premat urit y,
and an increased risk for pyelonephrit is. This pregnant woman has asympt omat ic bact eriuria t hat now requires t reat ment . An appropriat e ant ibiot ic for t his pat ient is
ampicillin, amoxicillin, or nit rofurant oin. These ant ibiot ics are Food and Drug Administ rat ion pregnancy risk cat egory B drugs. Ciprofloxacin and t rimet hoprim are bot h
pregnancy risk cat egory C drugs and are t herefore not indicat ed.
Urine cult ures should be obt ained aft er t reat ment in pregnant women wit h asympt omat ic bact eriuria t o confirm eradicat ion of bact eria. Confirming t he st erilit y of t he urine
can be done by repeat ing urine cult ures at int ervals unt il delivery.
Key Poi nt
Asympt omat ic bact eriuria during pregnancy should be t reat ed wit h ampicillin, amoxicillin, or nit rofurant oin.
Bi bl i ography
Drekonja DM, Johnson JR. Urinary t ract infect ions. Prim Care. 2008;35(2):345-367. [PMID: 18486719]
Item 15 Answer: D
Educati onal Objecti ve: Diagnose prostatic abscess.
The most appropriat e management for t his pat ient is a t ransrect al ult rasound. The pat ient present s wit h acut e prost at it is and appropriat ely has int ravenous ciprofloxacin
init iat ed. The failure of clinical improvement aft er 36 t o 72 hours is most likely due t o a complicat ion such as a prost at ic abscess and furt her evaluat ion wit h a t ransrect al
ult rasound (TRUS) or abdominal/pelvic CT is indicat ed. The TRUS might be t he preferred diagnost ic modalit y in t his pat ient because of his chronic kidney disease. Cont rast -
enhanced CT should be avoided in pat ient s wit h reduced kidney funct ion.
Parent eral administ rat ion of empiric ant ibiot ics is appropriat e for a pat ient who present s wit h syst emic signs of illness and requires hospit al admission. Int ravenous ant ibiot ic
t herapy may be changed t o oral when t he pat ient shows clinical improvement and can t olerat e oral int ake. Adding or st art ing an aminoglycoside should be avoided in t his
pat ient wit h reduced kidney funct ion. Also, subst it ut ing aminoglycoside for ciprofloxacin would not be indicat ed. The urine cult ure shows an organism t hat is sensit ive t o
fluoroquinolones. Furt hermore, fluoroquinolones have excellent prost at e penet rat ion, favorable pharmacokinet ic propert ies, a good safet y profile, and a broad spect rum of
ant ibact erial act ivit y against gram-negat ive pat hogens, including Proteus mirabilis.
Transuret hral cat het erizat ion should be avoided in acut e prost at it is. If bladder drainage is necessary, it should be suprapubic t o reduce t he risk of prost at ic abscess and
sept icemia. Furt hermore, t here is no indicat ion for placement of a bladder cat het er such as out flow obst ruct ion.
Key Poi nt
Pat ient s wit h acut e prost at it is who fail t o respond t o appropriat e ant ibiot ic t herapy wit hin 36 t o 72 hours may have a complicat ion such as a prost at ic abscess.
Bi bl i ography
Ramakrishnan K, Salinas RC. Prost at it is: acut e and chronic. Prim Care. 2010;37(3):547-63, viii-ix. [PMID: 20705198]
Item 16 Answer: D
Educati onal Objecti ve: Recognize that asymptomatic bacteriuria does not require treatment.
The most appropriat e management for t his pat ient 's asympt omat ic bact eriuria is no t reat ment . For asympt omat ic women, bact eriuria is defined as 2 consecut ive voided urine
specimens wit h isolat ion of t he same bact erial st rain in quant it at ive count s of at least 10
5
cfu/mL. Escherichia coli remains t he single most common organism isolat ed from
women, but ot her organisms, such as Proteus mirabilis, are more common in men. Treat ment of asympt omat ic bact eriuria in women wit h diabet es is not indicat ed. A
randomized, cont rolled t rial of ant ibiot ic t herapy or no t herapy for women wit h diabet es and asympt omat ic bact eriuria showed ant ibiot ic t herapy did not delay or decrease
t he frequency of sympt omat ic urinary t ract infect ion, nor did it decrease t he number of hospit alizat ions for urinary infect ion or ot her causes. However, women who received
ant ibiot ic t herapy had significant ly more adverse ant imicrobial effect s.
Screening for asympt omat ic bact eriuria is recommended only for pregnant women and before t ransuret hral resect ion of t he prost at e, urinary t ract inst rument at ion involving
biopsy, or ot her t issue t rauma result ing in mucosal bleeding. Women wit h diabet es, premenopausal nonpregnant women, older persons living in t he communit y, elderly
inst it ut ionalized persons, persons wit h spinal cord injury, and pat ient s wit h cat het ers while t he cat het er remains in sit u should not be screened or t reat ed for asympt omat ic
bact eriuria. Screening is also not recommended for simple cat het er placement or cyst oscopy wit hout biopsy. Unless indicat ed, screening and t reat ment for asympt omat ic
bact eriuria should be discouraged.
Key Poi nt
Screening or t reat ment of asympt omat ic bact eriuria is not recommended for most nonpregnant women.
Bi bl i ography
Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hoot on TM; Infect ious Diseases Societ y of America; American Societ y of Nephrology; American Geriat ric Societ y.
Infect ious Diseases Societ y of America guidelines for t he diagnosis and t reat ment of asympt omat ic bact eriuria in adult s [errat um in Clin Infect Dis. 2005;40(10):1556]. Clin
Infect Dis. 2005;40(5):643-54. [PMID: 15714408]
Item 17 Answer: B
Educati onal Objecti ve: Treat pyelonephritis with a fluoroquinolone antibiotic.
This pat ient has pyelonephrit is and should be t reat ed wit h a fluoroquinolone ant ibiot ic, such as ciprofloxacin or levofloxacin. Pyelonephrit is is associat ed wit h t he abrupt
onset of fever, chills, sweat s, nausea, vomit ing, diarrhea, and flank or abdominal pain; hypot ension and sept ic shock may occur in severe cases. The presence of bact eriuria
and pyuria is t he gold st andard for diagnosing pyelonephrit is if t hese findings are associat ed wit h a suggest ive hist ory and physical examinat ion findings. Leukocyt e cast s in
t he urine are suggest ive of pyelonephrit is but are uncommonly det ect ed. Blood cult ures should be obt ained in pat ient s who appear ill. Hypot ensive pat ient s wit h
pyelonephrit is should receive int ravenous fluids.
Treat ment of pyelonephrit is consist s of ant ibiot ics for 7 t o 14 days. Pat ient s who are acut ely ill, nauseat ed, or vomit ing should receive parent eral t herapy init ially and can
begin receiving oral t herapy once oral int ake is t olerat ed. The st andard t herapy in nonpregnant women is a fluoroquinolone. Alt ernat ives t o fluoroquinolone ant ibiot ics
include ext ended-spect rum cephalosporins or penicillins, but oral opt ions may be more limit ed for pat ient s wit h a cont raindicat ion t o fluoroquinolones. Eradicat ion of
bact eriuria in pat ient s t reat ed for pyelonephrit is can be confirmed t hrough repeat urinalysis and urine cult ure. Imaging st udies should be used only if an alt ernat ive diagnosis or
a urologic complicat ion is suspect ed.
Ampicillin and amoxicillin are not used as init ial t herapy of acut e pyelonephrit is because of t he high rat es of resist ance t o t hese agent s. Nit rofurant oin does not achieve
levels sufficient ly high for pyelonephrit is t reat ment .
Unt il recent ly, t rimet hoprim or t he combinat ion of t rimet hoprim-sulfamet hoxazole was highly effect ive for t reat ing acut e pyelonephrit is. The increased frequency of
resist ant st rains of Escherichia coli and ot her gram-negat ive bact eria t o t hese ant imicrobial agent s has led t o a preference for init ial t herapy wit h fluoroquinolones except in
pregnant women, because fluoroquinolone ant ibiot ics are Food and Drug Administ rat ion pregnancy risk cat egory C drugs.
Key Poi nt
St andard out pat ient management for pyelonephrit is in women who are not pregnant is an oral fluoroquinolone.
Bi bl i ography
Item 18 Answer: D
Educati onal Objecti ve: Manage recurrent cystitis with patient-initiated trimethoprim-sulfamethoxazole.
The most appropriat e management is t rimet hoprim-sulfamet hoxazole for 3 days when sympt oms develop. This pat ient most likely has a recurrent urinary t ract infect ion
(UTI). Self-t reat ment wit h t rimet hoprim-sulfamet hoxazole on development of sympt oms is appropriat e. Recurrent UTIs are common in women and are believed t o
represent new infect ion rat her t han a relapse of a previous episode. Alt hough evaluat ion for subt le predisposing fact ors such as anat omic urinary t ract abnormalit ies is seldom
useful, inquiring about behavioral pract ices can be helpful. Sexual int ercourse is a risk fact or for acut e and recurrent UTIs, as is t he use of spermicides or spermicides plus a
diaphragm.
Most women are able t o diagnose a UTI accurat ely and begin ant imicrobial t reat ment wit hout being seen by a physician. Self-t reat ment is highly effect ive in compliant
women. One st udy found t hat women correct ly diagnosed more t han 90% of recurrent infect ions, and t hat self-t reat ment was effect ive in more t han 95% of pat ient s
numbers t hat rival t hose of physician-init iat ed t herapy. Self-management at first onset of sympt oms is a feasible, safe, and convenient opt ion for t his young, ot herwise
healt hy woman wit h recurrent cyst it is. Trimet hoprim-sulfamet hoxazole, 160 mg/800 mg t wice daily for 3 days, is effect ive for t reat ing uncomplicat ed cyst it is. In addit ion,
t he report ed 12% resist ance of Escherichia coli t o t his agent is low enough t hat ot her ant ibiot ics do not need t o be considered.
This pat ient 's recurrent infect ions do not seem t o be relat ed t o sexual int ercourse; t herefore, post coit al prophylact ic ciprofloxacin t herapy would not be indicat ed. A 10-day
course of ciprofloxacin is indicat ed only if pyelonephrit is is document ed. Some sources may recommend chronic suppressive t herapy for pat ient s wit h more t han t wo UTIs
per year; however, t his approach may increase t he risk of infect ion wit h ant ibiot ic-resist ant bact eria.
Key Poi nt
Short -course ant ibiot ic self-t reat ment is appropriat e for young, ot herwise healt hy women wit h recurrent cyst it is.
Bi bl i ography
Item 19 Answer: B
Educati onal Objecti ve: Screen for HIV, chlamydia, and gonorrhea.
According t o Cent ers for Disease Cont rol and Prevent ion (CDC) guidelines, all sexually act ive women aged 24 years and younger should be screened for chlamydial infect ion,
eit her wit h nucleic acid amplificat ion of a cervical swab if a pelvic examinat ion is being performed or of a urine sample, which has a very similar sensit ivit y. The Unit ed
St at es Prevent at ive Services Task Force recommends screening for gonorrhea in high-risk persons, including women who have a hist ory of sexually t ransmit t ed disease (STD)
infect ion, have mult iple sexual part ners, are pregnant , or are under t he age of 25 years, because t his is t he populat ion wit h t he highest prevalence. Gonorrhea t est ing can only
be performed on a cervical swab. The American College of Physicians and t he CDC recommend HIV screening for pat ient s in all healt h care set t ings. They recommend "opt -
out screening," in which t he pat ient is not ified t hat t est ing will be performed unless t he pat ient declines. In addit ion, pregnant women at increased risk or in areas of high
prevalence should have an addit ional HIV t est during t heir t hird t rimest er.
Persons at risk and all pregnant women should be screened for syphilis. Pregnant women are screened during t he first prenat al visit and during t he t hird t rimest er and, for
women at high risk, at t he t ime of delivery. Ot her high-risk persons include commercial sex workers, prisoners, any person diagnosed wit h anot her STD, men who have sex
wit h men, and t hose who engage in ot her high-risk behaviors. Screening is not recommended in t he general populat ion because a posit ive t est result will most likely be a false-
posit ive t est result .
Key Poi nt
Rout inely screen sexually act ive women under t he age of 25 years for chlamydia, gonorrhea, and HIV.
Bi bl i ography
Cent ers for Disease Cont rol and Prevent ion, Workowski KA, Berman SM. Sexually t ransmit t ed diseases t reat ment guidelines, 2006 [errat um in MMWR Recomm Rep.
2006;55(36):997]. MMWR Recomm Rep. 2006;55(RR-11):1-94. [PMID: 16888612]
Item 20 Answer: C
Educati onal Objecti ve: Diagnose and empirically treat cervicitis.
This pat ient has cervicit is and should be t reat ed empirically for gonorrhea and chlamydia. Cervicit is is t he presence of a mucopurulent cervical discharge or endocervical
bleeding easily induced by gent le passage of a cot t on swab t hrough t he cervical os. Cervicit is is commonly caused by eit her gonorrhea or chlamydial infect ion, and alt hough
gonorrhea infect ion is oft en sympt omat ic, eit her may be asympt omat ic or only mildly sympt omat ic. In pat ient s wit h cervicit is, an abnormal vaginal discharge or
int ermenst rual bleeding is not uncommon. The absence of gram-negat ive int racellular diplococci on Gram st ain does not rule out gonorrhea, because it is observed in only
50% of women wit h t his infect ion.
In a woman wit h a high pret est probabilit y for cervicit is who may easily be lost t o follow-up, it is best t o t reat empirically for gonorrhea and chlamydia rat her t han wait for
specific t est ing t o ret urn. Ceft riaxone wit h eit her doxycycline or azit hromycin is an appropriat e regimen. In t he presence of a document ed gonorrhea infect ion by nucleic
acid or cult ure, chlamydia is always t reat ed even in t he absence of posit ive t est result s for chlamydia infect ion.
(PID) includes a spect rum of disorders of t he female upper genit al t ract , including endomet rit is, salpingit is, t ubo-ovarian abscess, and pelvic perit onit is. Diagnosis is
est ablished clinically wit h suggest ive findings, including cervical mot ion t enderness, ut erine t enderness, or adnexal t enderness on pelvic examinat ion.
Bact erial vaginosis is not a sexually t ransmit t ed disease and does not cause cervicit is. On vaginal examinat ion, inflammat ion is not evident , but a homogeneous, whit e,
noninflammat ory discharge coat s t he vaginal walls. The vaginal pH is higher t han 4.5, t he "whiff t est " is posit ive (a fishy odor is present when pot assium hydroxide is added
t o vaginal secret ions), and "clue cells" (squamous epit helial cells covered wit h bact eria obscuring t he edges of t he epit helial cells) are found on wet mount .
Key Poi nt
Cervicit is is defined by eit her t he presence of a mucopurulent cervical discharge or endocervical bleeding and is caused by chlamydial and/or gonococcal infect ion.
Bi bl i ography
Wilson JF. In t he clinic. Vaginit is and cervicit is. Ann Int ern Med. 2009;151(5):ITC3-1-ITC3-15; Quiz ITC3-16. [PMID: 19721016]
Item 21 Answer: B
Educati onal Objecti ve: Treat disseminated gonococcal infection.
This pat ient most likely has disseminat ed gonococcal infect ion (DGI) and init ial t reat ment should include parent eral t herapy wit h ceft riaxone or a comparable t hird-
generat ion cephalosporin.
DGI may cause sept ic or st erile immune-mediat ed art hrit is and t enosynovit is and frequent ly involves t he knees, hips, and wrist s but not t he spine. Dermat it is associat ed wit h
sparse peripheral necrot ic pust ules also is common. A charact erist ic prodrome of migrat ory art hralgia and t enosynovit is may precede t he set t ling of t he synovit is in one or
several joint s.
Genit ourinary sympt oms associat ed wit h DGI usually are absent in women, and genit al infect ion in women may have occurred long before syst emic disseminat ion. Pat ient s
wit h rect al and pharyngeal colonizat ion of Neisseria gonorrhoeae in t he set t ing of DGI are commonly asympt omat ic. In all pat ient s in whom DGI is clinically suspect ed,
rout ine cult ure of t he rect um and pharynx, as well as t he blood and t he joint s, is indicat ed.
On diagnosis of DGI, prompt evaluat ion for addit ional sexually t ransmit t ed diseases, including syphilis and HIV, is indicat ed. Empiric t reat ment for Chlamydia trachomatis
infect ion wit h doxycycline also should be considered, because coinfect ion wit h N. gonorrhoeae and C. trachomatis is common. Pat ient s wit h DGI are frequent ly
asympt omat ic, and t his condit ion can cause infert ilit y if unt reat ed. Sexual part ners of pat ient s wit h DGI also should be t reat ed.
Acyclovir is an effect ive t reat ment for herpes simplex infect ion. However, herpes simplex is most likely t o cause painful vesicular and erosive disease of t he genit alia, not
papules and necrot ic pust ules on t he cut aneous surfaces, and herpes simplex is not associat ed wit h a migrat ory art hrit is.
Fluoroquinolones such as ciprofloxacin are no longer recommended by t he Cent ers for Disease Cont rol and Prevent ion for t he t reat ment of gonorrhea because of t he high
resist ance rat e. Gent amicin is not indicat ed because N. gonorrhoeae is not consist ent ly suscept ible t o t his agent .
Key Poi nt
Disseminat ed gonococcal infect ion may cause art hrit is and t enosynovit is and is oft en associat ed wit h sparse peripheral necrot ic pust ules.
Bi bl i ography
Cent ers for Disease Cont rol and Prevent ion, Workowski KA, Berman SM. Sexually t ransmit t ed diseases t reat ment guidelines, 2006. MMWR Recomm Rep. 2006;55(RR-11).
[PMID: 16888612]
Item 22 Answer: B
Educati onal Objecti ve: Diagnose genital herpes simplex virus infection.
This pat ient has t he classic findings of primary genit al herpes simplex virus (HSV) infect ion. HSV-1 or HSV-2 may cause t he infect ion, but HSV-2 is t he more common
pat hogen. Genit al herpes lesions t ypically begin as vesicles t hat ulcerat e and are quit e painful. The init ial infect ion is oft en t he most severe and can be accompanied by local
lymphadenopat hy and syst emic sympt oms. Recurrences vary in frequency and are t ypically less severe t han t he init ial episode. Many recurrences are subclinical but are
nonet heless cont agious. The diagnosis of genit al herpes is oft en suspect ed on clinical grounds but may be confirmed by viral cult ure or serologic t est ing if t he diagnosis is in
doubt . Viral cult ure for HSV-1 and HSV-2 is a rapid t est , wit h result s oft en available by t he next day. The specificit y of viral cult ure approaches 100%, but t he sensit ivit y
varies wit h t he qualit y of specimen handling and t he age of t he lesion (older, crust ed lesions have lower yield).
Chancroid is a relat ively uncommon sexually t ransmit t ed disease caused by Haemophilus ducreyi. Infect ion is charact erized by t he presences of ragged, purulent , painful ulcers
associat ed wit h t ender lymph nodes t hat may suppurat e. The superficial vesicles and erosions of herpes simplex virus infect ion are not easily mist aken for t he deep, ragged
ulcers of chancroid.
The primary ulcerat ive lesion (chancre) in pat ient s wit h syphilis develops approximat ely 3 weeks aft er infect ion occurs, has a clean appearance wit h heaped-up borders, and
is usually painless and oft en unrecognized, part icularly in women. Mult iple small painful vesicles and erosions argue st rongly against t his diagnosis.
Sympt oms of vulvovaginal candidiasis include prurit us, ext ernal and int ernal eryt hema, and nonodorous, whit e, curd-like discharge. Lack of prurit us makes vulvovaginal
candidiasis less likely, and candidal infect ion does not cause painful genit al ulcers.
Key Poi nt
Primary genit al herpes simplex virus infect ion is charact erized by fever, headache, and painful, ulcerat ed, vesicular lesions.
Bi bl i ography
Cernik C, Gallina K, Brodell RT. The t reat ment of herpes simplex infect ions: an evidence-based review. Arch Int ern Med. 2008;168(11):1137-1144. [PMID: 18541820]
Item 23 Answer: D
Educati onal Objecti ve: Treat a patient with pelvic inflammatory disease with ceftriaxone and doxycycline.
This pat ient 's clinical findings are compat ible wit h pelvic inflammat ory disease (PID), and she should receive int ramuscularly delivered ceft riaxone and oral doxycycline. PID
is a polymicrobial infect ion of t he endomet rium, fallopian t ubes, and ovaries; diagnosis is based on t he presence of abdominal discomfort , ut erine or adnexal t enderness, or
cervical mot ion t enderness. Ot her diagnost ic crit eria include t emperat ure higher t han 38.3C (101.0F), cervical or vaginal mucopurulent discharge, leukocyt es in vaginal
secret ions, and document at ion of gonorrheal or chlamydial infect ion. PID is most likely t o occur wit hin 7 days of t he onset of menses. All women wit h suspect ed PID should
be t est ed for gonorrhea, chlamydia, and HIV infect ion, and undergo pregnancy t est ing. In severe cases, imaging should be performed t o exclude a t ubo-ovarian abscess.
Ambulat ory pat ient s are t reat ed wit h ceft riaxone and doxycycline wit h or wit hout met ronidazole. Durat ion of t reat ment is 14 days. Pat ient s wit h PID should be hospit alized
if t here is (1) no clinical improvement aft er 48 t o 72 hours of ant ibiot ics; (2) an inabilit y t o t olerat e oral ant ibiot ics; (3) severe illness wit h nausea, vomit ing, or high fever;
(4) suspect ed int ra-abdominal abscess; (5) pregnancy; or (6) noncompliance wit h out pat ient t herapy.
Ampicillin and gent amicin do not reliably t reat gonorrhea and chlamydial infect ion and t herefore are not adequat e ant ibiot ic t herapy for a pat ient wit h PID. Azit hromycin
alone is sufficient t reat ment for chlamydial infect ion but is no longer recommended as init ial t reat ment for gonorrheal infect ion owing t o t he high prevalence of gonorrhea
st rains wit h decreased suscept ibilit y. Cefoxit in alone is insufficient t reat ment for PID and combinat ion wit h oral doxycycline is recommended.
Key Poi nt
The t reat ment for ambulat ory pat ient s wit h pelvic inflammat ory disease is int ramuscular ceft riaxone and oral doxycycline.
Bi bl i ography
Cent ers for Disease Cont rol and Prevent ion (CDC). Updat e t o CDC's sexually t ransmit t ed diseases t reat ment guidelines, 2006: fluoroquinolones no longer recommended for
t reat ment of gonococcal infect ions. MMWR Morb Mort al Wkly Rep. 2007;56(14):332-336. [PMID: 17431378]
Item 24 Answer: D
Educati onal Objecti ve: Treat Pneumocysti s ji roveci i pneumonia with trimethoprim-sulfamethoxazole plus corticosteroids.
The best init ial t reat ment regimen for t his pat ient is t rimet hoprim-sulfamet hoxazole plus cort icost eroids. Pneumocystis jirovecii pneumonia remains t he most common
AIDS-defining illness and cause of deat h in pat ient s wit h AIDS. The diagnosis should be considered in any pat ient wit h a CD4 cell count of less t han 200/L who present s wit h
fever, dry cough, and dyspnea developing over several days or weeks. The chest radiograph t ypically shows bilat eral int erst it ial infilt rat es, but findings can vary from a
normal film t o consolidat ion or a pneumot horax. The diagnosis is est ablished by silver st ain examinat ion of induced sput um or a bronchoscopic sample showing charact erist ic
cyst s. A 3-week course of t rimet hoprim-sulfamet hoxazole is t he st andard t reat ment . Cort icost eroids are required for pat ient s wit h evidence of hypoxia (art erial PO
2
<70 mm
Hg [9.3 kPa] or an alveolar-art erial gradient >35 mm Hg [4.7 kPa]) and should be cont inued for t he ent ire course of t reat ment .
Dapsone can be an adjunct ive t reat ment t o t rimet hoprim in acut e Pneumocystis jirovecii and can be used alone as a prophylact ic agent for pat ient s wit h a CD4 count less
t han 200/L in pat ient s who are int olerant of t rimet hoprim-sulfamet hoxazole, but it is not recommended as single drug t herapy for Pneumocystis jirovecii pneumonia.
Key Poi nt
Trimet hoprim-sulfamet hoxazole plus cort icost eroids is t he preferred init ial t reat ment for Pneumocystis jirovecii pneumonia and hypoxia (art erial PO
2
<70 mm Hg [9.3 kPa]
or an alveolar-art erial gradient >35 mm Hg [4.7 kPa]).
Bi bl i ography
Cat herinot E, Lant ernier F, Bougnoux ME, Lecuit M, Couderc LJ, Lort holary O. Pneumocystis jirovecii pneumonia. Infect Dis Clin Nort h Am. 2010;24(1):107-38. [PMID:
20171548]
Item 25 Answer: A
Educati onal Objecti ve: Provide appropriate prophylactic therapy for a patient with HIV infection.
This pat ient should receive t rimet hoprim-sulfamet hoxazole. Several drugs have been shown t o provide effect ive prophylaxis against opport unist ic infect ions in pat ient s wit h
HIV infect ion and t o prolong life in some pat ient s. The CD4 cell count is an indicat or of immune compet ence. Recommendat ions regarding when t o init iat e prophylaxis are
based on CD4 cell count levels. The t hreshold for Pneumocystis and t oxoplasmosis prophylaxis is 200/L and 100/L, respect ively. The pat ient 's CD4 cell count is 77/L,
and she should receive prophylaxis for Pneumocystis and for t oxoplasmosis if her ant ibody t it er is posit ive (demonst rat ing previous infect ion but not immunit y).
Trimet hoprim-sulfamet hoxazole is t he first -line agent for bot h.
Azit hromycin is used for prophylaxis against Mycobacterium avium complex in pat ient s wit h a CD4 cell count less t han 50/L. This pat ient 's CD4 cell count is not at t his
t hreshold and, t herefore, prophylact ic azit hromycin t herapy is not recommended. Fluconazole is not recommended for t he primary prophylaxis of Candida infect ions
despit e it s effect iveness in t his role. The pot ent ial for drug resist ance, numerous pot ent ial drug-drug int eract ions, t he ease and effect iveness of t reat ing infect ion when it does
occur, and lack of survival benefit argue against prophylact ic use. Isoniazid would be indicat ed if t he pat ient were found t o have a posit ive t uberculin skin t est great er t han 5
mm and a negat ive chest x-ray excluding act ive t uberculosis. There is no reason t o provide prophylact ic isoniazid t herapy for pat ient s who have not been exposed t o
Mycobacterium tuberculosis. Alt hough valganciclovir is effect ive in prevent ing cyt omegalovirus (CMV), infect ion, decisions regarding prophylaxis are complex.
Valganciclovir is expensive, a t heoret ical concern about t he development of drug resist ance exist s, it is t oxic t o t he bone marrow, and t reat ment of early infect ion is very
effect ive. Finally, no proven survival benefit is associat ed wit h CMV prophylaxis.
Key Poi nt
In pat ient s wit h HIV infect ion, prophylact ic t herapy for Pneumocystis, t oxoplasmosis, and Mycobacterium avium complex are det ermined by t he CD4 cell count .
Bi bl i ography
Aberg JA, Kaplan JE, Libman H, Emmanuel P, Anderson JR, St one VE, Oleske JM, Currier JS, Gallant JE; HIV Medicine Associat ion of t he Infect ious Diseases Societ y of
America. Primary care guidelines for t he management of persons infect ed wit h human immunodeficiency virus: 2009 updat e by t he HIV medicine Associat ion of t he
Infect ious Diseases Societ y of America. Clin Infect Dis. 2009;49(5):651-81. [PMID: 19640227]
Item 26 Answer: E
Educati onal Objecti ve: Understand the association between recurrent herpes zoster infection and HIV infection.
This pat ient most likely has HIV infect ion. Herpes zost er infect ion is t he react ivat ion of t he varicella virus in a single cut aneous nerve. Recurrence of herpes zost er infect ion
in t he immunocompet ent host is uncommon but does occur. When recurrent disease is present , t he underlying cause is overwhelmingly HIV infect ion. In t his pat ient , t here is
a band of crust s and blist ers on an eryt hemat ous base along a dermat omal dist ribut ion on t he left t horax. There is evidence of scarring in a dermat ome several cent imet ers
above t he current ly involved sit e, represent ing a previous herpes zost er infect ion. Almost half of all herpes zost er episodes diagnosed in pat ient s wit h HIV are recurrences.
The advent of highly act ive ant iret roviral t herapy has not lessened t he incidence of recurrent herpes zost er infect ion in pat ient s wit h HIV infect ion. Pat ient s on
chemot herapy and pat ient s who have undergone organ t ransplant may also develop recurrent herpes zost er.
All pat ient s wit h HIV infect ion and herpes zost er infect ion are t reat ed wit h ant iviral t herapy regardless of t he age of t he zost er lesions. Most pat ient s wit h HIV infect ion can
be t reat ed wit h an oral ant iviral drug wit h good bioavailabilit y, such as valacyclovir or famciclovir, but pat ient s wit h severe disease, evidence of disseminat ion, or
opht halmologic involvement may have bet t er out comes if t reat ed wit h int ravenous acyclovir.
This pat ient 's alcoholism is a risk fact or for cirrhosis but not for recurrent herpes zost er infect ion. A pat ient wit h unexplained weight loss and fat igue may have an underlying
met abolic disease such as diabet es mellit us, but diabet es is not associat ed wit h recurrent herpes zost er. Because of t his pat ient 's inject ion drug use, he is at risk for hepat it is B
and hepat it is C, and screening for t hese infect ions is recommended. However, neit her of t hese infect ions is associat ed wit h recurrent herpes zost er.
Key Poi nt
Recurrent herpes zost er infect ion should t rigger t est ing for possible associat ed HIV infect ion.
Bi bl i ography
Gebo KA, Kalyani R, Moore RD, Polydefkis MJ. The incidence of, risk fact ors for, and sequelae of herpes zost er among HIV pat ient s in t he highly act ive ant iret roviral
t herapy era. J Acquir Immune Defic Syndr. 2005;40(2):169-174. [PMID: 16186734]
Item 27 Answer: C
Educati onal Objecti ve: Diagnose acute HIV infection with HIV RNA viral load measurement.
The most appropriat e addit ional t est is an HIV RNA viral load and HIV ant ibody measurement . This pat ient 's prolonged febrile syndrome in t he set t ing of HIV risk fact ors
should raise concerns for recent infect ion wit h HIV. Det ect ion of HIV RNA is t he most sensit ive t est for det ect ing HIV infect ion during t he acut e sympt omat ic phase. Test s
for HIV-specific ant igens, such as p24, can also det ect t he presence of virus in t he acut e set t ing. Ant ibodies t o HIV do not commonly occur unt il about 6 weeks aft er
infect ion and may t herefore be negat ive during t he acut e sympt omat ic phase. Pat ient s diagnosed wit h acut e HIV infect ion on t he basis of an HIV viral load measurement
should have confirmat ory serologic ant ibody t est ing performed at a subsequent point in t ime.
In addit ion t o t he acut e ret roviral syndrome, t his pat ient must be evaluat ed for secondary syphilis using t he rapid plasma reagin t est . Secondary syphilis and acut e ret roviral
syndrome should always be considered in sexually act ive pat ient s wit h rash, fever, and generalized lymphadenopat hy. Ot her causes of a mononucleosis syndrome (for
example, Ebst ein-Barr virus and cyt omegalovirus infect ions) should also be considered if t hese t est s are inconclusive.
The CD4 cell count may be profoundly depressed in pat ient s wit h acut e HIV infect ion, but t he CD4 cell count can be bot h insensit ive in t he diagnosis of acut e infect ion and
depressed by various ot her, non-HIV-1 infect ious agent s.
Alt hough acut e HIV infect ion can mimic t he signs and sympt oms of mononucleosis, t est ing for Epst ein-Barr virus infect ion is a less immediat e concern in t his pat ient who
has mult iple risk fact ors for HIV infect ion. Furt hermore, acut e infect ion would be det ect ed wit h an elevat ed IgM ant ibody t it er, not IgG.
The hist opat hology of t he rash in acut e HIV infect ion is nonspecific and is not useful in diagnosis; t herefore, a skin biopsy is not indicat ed.
Key Poi nt
The measurement of HIV RNA viral load is t he most sensit ive t est for infect ion during t he acut e st age.
Bi bl i ography
Miles K. Primary HIV infect ion. Communit y Pract . 2005;78(9):331-3. [PMID: 16187668]
Item 28 Answer: D
Educati onal Objecti ve: Diagnose toxoplasmosis encephalitis.
The most likely diagnosis is t oxoplasmosis encephalit is. Toxoplasmosis almost always present s as react ivat ion disease in pat ient s wit h HIV infect ion and t ypically occurs
when t he CD4 cell count is less t han 100/L. Addit ional findings are fever, neurologic deficit s, and an MRI showing ring-enhancing lesions, oft en wit h associat ed edema.
Sulfadiazine plus pyrimet hamine and folinic acid are given init ially. Follow-up MRI is crit ical t o assess t reat ment response. If t here is no t herapeut ic response aft er 14 days,
st ereot act ic brain biopsy is recommended t o rule out ot her causes, especially a primary cent ral nervous syst em lymphoma.
Crypt ococcal meningit is is t he most common form of meningit is in pat ient s wit h AIDS, who t ypically present wit h sympt oms such as headache, irrit abilit y, and nausea t hat
can mimic ot her disorders. Most pat ient s have a CD4 cell count of less t han 100/L. The diagnosis is based on det ect ion of crypt ococcal ant igen in t he cerebrospinal fluid or
cult ure of Cryptococcus neoformans in t he cerebrospinal fluid. Crypt ococcal meningit is is not usually associat ed wit h ring-enhancing lesions on brain MRI.
Disseminat ed Mycobacterium avium complex (MAC) infect ion is common in pat ient s wit h advanced-st age HIV infect ion and a CD4 cell count of less t han 50/L. Sympt oms
include fever, weight loss, hepat osplenomegaly, lymphadenopat hy, malaise, and abdominal pain. The diagnosis is generally confirmed by recovering t he pat hogen from st erile
t issue (usually blood). MAC infect ion is not associat ed wit h ring-enhancing lesions on MRI. This pat ient 's CD4 count also helps exclude t his diagnosis.
Progressive mult ifocal leukoencephalopat hy is a demyelinat ing disease of t he cent ral nervous syst em caused by t he polyomavirus JC virus. It occurs almost exclusively in
severely immunocompromised pat ient s, including t hose wit h advanced HIV-1 infect ion. Clinical findings of progressive mult ifocal leukoencephalopat hy include dement ia,
hemiparesis or paralysis of one ext remit y, at axia, hemianopia, and diplopia. The charact erist ic MRI appearance of t hese lesions is hyperint ense (whit e) areas on T2-weight ed
images and fluid-at t enuat ed inversion recovery (FLAIR) sequences and hypoint ense (dark) areas on T1-weight ed images. There is usually no mass effect .
Key Poi nt
Toxoplasmosis encephalit is t ypically occurs in HIV-infect ed pat ient s when t he CD4 cell count is less t han 100/L and is associat ed wit h ring-enhancing lesions on brain MRI,
oft en wit h mass effect .
Bi bl i ography
Guidelines for prevent ion and t reat ment of opport unist ic infect ions in HIV-infect ed adult s and adolescent s. Available at
[ht t p://aidsinfo.nih.gov/cont ent files/Adult _OI_041009.pdf]. Published April 10, 2009. Accessed on April 26, 2011.
Item 29 Answer: D
Educati onal Objecti ve: Prevent catheter-associated urinary tract infection.
The most effect ive way t o prevent cat het er-associat ed urinary t ract infect ions (UTIs) is t o decrease cat het er use. Devices should be used for specific indicat ions, not for
convenience and should be removed as soon as possible. Examples of appropriat e use include diagnosing pat hologic findings in t he lower urinary t ract or t he cause of urinary
ret ent ion, monit oring fluid st at us in acut ely ill pat ient s when t his direct ly impact s medical t reat ment , and managing pat ient s wit h st age 3 or 4 pressure ulcers on t he but t ocks.
However, urinary cat het ers oft en are used for convenience, which significant ly increases t he risk for UTIs. If t he cat het er is needed, measures are required t o decrease t he risk
of bact eriuria and subsequent infect ion. These include handwashing, using an asept ic t echnique and st erile equipment for cat het er insert ion and care, securing t he cat het er
properly, maint aining unobst ruct ed urine flow and closed st erile drainage, and considering use of ant ibact erial-coat ed cat het ers. Manipulat ion and irrigat ion should be
minimized. Specimens should be collect ed using t he drainage bag valve. Ant ibiot ics should not be used as prophylaxis for t he prevent ion of UTIs because such use promot es
ant ibiot ic resist ance.
Key Poi nt
The most effect ive way t o prevent cat het er-associat ed urinary t ract infect ions is t o decrease cat het er use.
Bi bl i ography
Lo E, Nicolle L, Classen D, et al. St rat egies t o prevent cat het er-associat ed urinary t ract infect ions in acut e care hospit als. Infect Cont rol Hosp Epidemiol. 2008;29(suppl
1):S41-50. [PMID: 18840088]
Item 30 Answer: D
Educati onal Objecti ve: Prevent ventilator-associated pneumonia with semi-erect positioning.
Semi-erect posit ion will most likely reduce t he risk of vent ilat or-associat ed pneumonia (VAP). Even when a cuffed t ube is in place, bact eria from t he st omach can reach t he
lungs and cause pneumonia. Semi-erect posit ioning in bed at 45 is useful because it reduces t he risk of excursion of bact eria from t he st omach int o t he upper airways.
Changing endot racheal t ubes seems logical, but reint ubat ion is associat ed wit h cert ain risks (for example, int ubat ing t he esophagus or precipit at ing hypoxia during t he
procedure). Reint ubat ion may also increase t he risk of nosocomial pneumonia. Careful inspect ion and management of t he t ubing can help reduce infect ions slight ly. Because
t he t ubing has a t endency t o collect wat er, careful drainage of accumulat ed condensat e int o pat ient -specific drainage cont ainers is advocat ed.
Oral placement of endot racheal t ubes is current ly believed t o be superior t o nasal placement because nasogast ric and nasot racheal t ubes cause some degree of obst ruct ion of
t he ost ia in t he nose, which can predispose t o nosocomial sinusit is. Whet her all nasal t ubes should be replaced by oral t ubes is unclear. However, no benefit will be gained by
changing from an orot racheal t ube t o a nasot racheal t ube t o prevent a case of healt h-care associat ed pneumonia.
Reducing t he densit y of gast ric bact eria by use of prophylact ic ant ibiot ics is t empt ing. However, t his approach is ineffect ive and serves t o select for resist ant st rains.
Key Poi nt
Semi-erect posit ioning reduces t he risk of vent ilat or-associat ed pneumonia.
Bi bl i ography
Barsant i MC, Woelt je KF. Infect ion prevent ion in t he int ensive care unit . Infect Dis Clin Nort h Am. 2009;23(3):703-25. [PMID: 19665091]
Item 31 Answer: D
Educati onal Objecti ve: Use barrier precautions and soap and water for hand hygiene to prevent the spread of Cl ostri di um di ffi ci l e infection.
The most effect ive bundled measures t o prevent t he spread of Clostridium difficile infect ion are barrier precaut ions and soap and wat er for hand cleaning. Environment al
cont aminat ion wit h veget at ive C. difficile and C. difficile spores frequent ly occurs. C. difficile is t ransmit t ed t o ot her pat ient s t hrough t he hands and clot hes of healt h care
workers and from common equipment t hat is used on pat ient s wit hout cleaning. A combinat ion of int ervent ions "bundled" t oget her have been shown t o be effect ive at
reducing many hospit al-acquired infect ions. The use of a C. difficile bundle consist ing of barrier precaut ions, enhanced cleaning wit h bleach, and t radit ional soap-and-wat er
hand hygiene is useful in prevent ing t he spread of C. difficile. Soap and wat er are not sporicidal, but t he mechanics of hand washing effect ively removes spores. Alcohol-based
hand hygiene product s do not kill spores and are ineffect ive at removing t hem from hands.
Barrier precaut ions such as wearing nonst erile gloves and a gown and using dedicat ed equipment have been recommended for C. difficile cont rol by t he Cent ers for Disease
Cont rol and Prevent ion and have been shown t o be effect ive.
Airborne precaut ions are recommended for pat ient s wit h known or suspect ed illnesses t ransmit t ed by airborne droplet nuclei, such as t uberculosis, measles, varicella, or
disseminat ed varicella zost er virus infect ion. Pat ient s must be isolat ed in a privat e room wit h negat ive air pressure, t he door must remain closed, and all ent ering persons must
wear masks wit h a filt ering capacit y of 95%. Transport ed pat ient s must wear masks.
Droplet precaut ions are recommended for pat ient s wit h known or suspect ed illnesses t ransmit t ed by large-part icle droplet s, such as Neisseria meningitidis infect ions and
influenza. Pat ient s are isolat ed in privat e rooms, and hospit al personnel wear face masks when wit hin 3 feet of t he pat ient .
Key Poi nt
A Clostridium difficile "bundle" consist ing of barrier precaut ions, enhanced cleaning wit h bleach, and t radit ional soap-and-wat er hand hygiene is useful in prevent ing t he
spread of C. difficile.
Bi bl i ography
Hessen MT. In t he clinic. Clost ridium difficile Infect ion. Ann Int ern Med. 2010;153(7):ITC41-15; quiz ITC416. [PMID: 20921540]
Item 32 Answer: A
Educati onal Objecti ve: Institute infection-control measures in a patient with Nei sseri a meni ngi ti di s meningitis.
The most appropriat e next st ep is t he use of a face mask. This pat ient has Neisseria meningitidis meningit is. Droplet precaut ions should be init iat ed when t his diagnosis is
suspect ed and require t hat healt h care workers wit hin 6 t o 10 feet of t he index pat ient wear a face mask. Appropriat e infect ion cont rol measures for all pat ient s include hand
hygiene and st andard precaut ions.
The human nasopharynx is t he only known reservoir for meningococcal meningit is. Meningococci are spread from person t o person by respirat ory droplet s of infect ed
nasopharyngeal secret ions. Persons wit h significant exposure t o t he index pat ient (same household, day-care cent er, or anyone wit h direct cont act wit h a pat ient 's oral
secret ions) should receive chemoprophylaxis wit h appropriat e ant ibiot ics. Significant healt h care exposure includes personnel wit h pot ent ial for int imat e cont act (wit hin 3
feet ) of t he pat ient 's respirat ory secret ions.
For infect ion spread by direct cont act wit h t he pat ient (for example, vancomycin-resist ant ent erococci), addit ional infect ion cont rol measures include pat ient placement int o
a privat e room or wit h t hose who have a similar infect ion and t he use of nonst erile gloves and gowns for direct cont act wit h t he pat ient or any infect ive mat erial. Airborne
infect ion precaut ions are appropriat e for illnesses t ransmit t ed by airborne droplet nuclei (for example, t uberculosis, measles, and varicella). Addit ional infect ion cont rol
measures include placement int o a privat e room, t ypically in a pressure-negat ive room, and special masks wit h a filt ering capacit y of 95% of part iculat es (N-95 respirat or or
a powered air purifying respirat or [PAPR]).
Key Poi nt
Droplet precaut ions, which require t hat healt h care workers wear a face mask for close cont act wit h infect ious pat ient s and don t he mask on room ent ry, are indicat ed when
meningococcal meningit is is suspect ed.
Bi bl i ography
Siegel JD, Rinehart E, Jackson M, Chiarello L; The Healt hcare Infect ion Cont rol Pract ices Advisory Commit t ee. Guideline for Isolat ion Precaut ions: Prevent ing
Transmission of Infect ious Agent s in Healt hcare Set t ings. www.cdc.gov/ncidod/dhqp/pdf/guidelines/Isolat ion2007.pdf. Published 2007. Accessed on April 28, 2011.
Item 33 Answer: B
Educati onal Objecti ve: Institute airborne precautions in the setting of suspected tuberculosis.
The most import ant infect ion cont rol measure is t he inst it ut ion of airborne precaut ions. This foreign-born pat ient most likely has react ivat ion of pulmonary t uberculosis.
Tuberculosis is a communicable disease and is inhaled int o t he respirat ory syst em via airborne droplet s. A diagnosis of pulmonary t uberculosis should be considered in any
pat ient wit h cough for longer t han 3 weeks, loss of appet it e, unexplained weight loss, night sweat s, hoarseness, fever, fat igue, or chest pain. The index of suspicion should be
subst ant ially high for pat ient s who have spent t ime in developing count ries, geographic areas of t he Unit ed St at es such as Miami or New York Cit y, or in a correct ional
facilit y.
Init ially, t he most import ant management is prot ect ion from pot ent ial t uberculosis exposure wit h airborne precaut ions, including placement of t he pat ient int o a negat ive-
pressure room and use of respirat ory prot ect ion by healt h care workers. Accept able prot ect ion includes a "respirat or," which refers t o an N95 or higher filt ering facepiece
respirat or or a powered air-purifying respirat or. Wit hin healt h care set t ings, t uberculosis airborne precaut ions should be immediat ely init iat ed in pat ient s wit h sympt oms or
signs consist ent wit h t uberculosis or in t hose wit h document ed infect ious t uberculosis who have not complet ed ant it uberculosis t reat ment . Such pat ient s should cont inue t o be
managed wit h airborne precaut ions unt il t hey are det ermined t o be noninfect ious (clinical response t o a st andard mult idrug ant it uberculosis t reat ment regimen or unt il an
alt ernat ive diagnosis is made).
Alt hough chest radiograph and sput um acid-fast bacilli st ain and cult ure would be performed in a set t ing such as t his, t hey would not be done before implement at ion of
effect ive airborne precaut ions t o reduce t he risk for t ransmission of infect ion t o healt h care workers and ot her pat ient s. Performing t uberculin skin t est ing can help t o
est ablish a diagnosis of t uberculosis; however, such t est ing would not different iat e act ive from lat ent t uberculosis and should not be performed before airborne precaut ions are
inst it ut ed.
Key Poi nt
Airborne precaut ions should be immediat ely init iat ed for any pat ient wit h suspect ed t uberculosis t o reduce risk of t ransmission t o healt h care workers and ot her pat ient s.
Bi bl i ography
Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for prevent ing t he t ransmission of Mycobact erium t uberculosis in healt hcare set t ings, 2005. MMWR
Recomm Rep. 2005;54(RR-17):1-141. [PMID: 16382216]
Item 34 Answer: A
Educati onal Objecti ve: Manage latent tuberculosis with a chest radiograph.
The most appropriat e next management st ep is t o obt ain a chest radiograph. The most common t uberculosis t est ing procedure is t he t uberculin skin t est (TST). The
procedure involves inject ing purified prot ein derivat ive (PPD) int radermally and assessing t he skin response t o t he ant igen load. The indurat ionnot t he eryt hema
result ing wit hin 48 t o 72 hours is t hen measured. Various cut off values are used, based on t he pat ient 's risk st at us, t o increase t he specificit y of t he t est result s. Because of her
recent arrival from a high-prevalence area, an indurat ion great er t han10 mm is considered a posit ive t est result and is indicat ive of lat ent or act ive t uberculosis infect ion.
Consequent ly, t his pat ient should receive a chest radiograph t o exclude t he presence of act ive t uberculous disease. If radiographic result s are negat ive, t reat ment for lat ent
t uberculosis infect ion consist ing of isoniazid t herapy wit h vit amin B
6
(pyridoxine) supplement at ion should be offered. A t uberculin skin t est wit h an indurat ion great er t han10
mm is also considered posit ive in t he following high-risk groups: inject ion drug users, resident s or employees of high-risk congregat e set t ings (such as prisons and jails, nursing
and homeless shelt ers), mycobact eriology laborat ory personnel, persons wit h clinical condit ions t hat put t hem at high risk for act ive disease, children younger t han 4 years or
children exposed t o adult s in high-risk cat egories.
St andard t herapy for act ive t uberculosis includes at least 6 mont hs of t hree- t o four-drug t herapy (isoniazid, rifampin, pyrazinamide, and et hambut ol). This t herapy would be
inappropriat e if t he pat ient has a normal chest radiograph and no sympt oms of act ive infect ion.
Treat ment of lat ent t uberculosis infect ion subst ant ially reduces t he risk t hat t uberculosis infect ion will progress t o act ive disease; t herefore, providing no addit ional evaluat ion
or t herapy and clearing t he pat ient for employment would not be appropriat e.
Key Poi nt
A posit ive t uberculin skin t est is defined as an indurat ion great er t han 10 mm for pat ient s who are recent arrivals from high-prevalence count ries.
Bi bl i ography
Escalant e P. In t he clinic. Tuberculosis [errat um in Ann Int ern Med. 2009;151(4):292]. Ann Int ern Med. 2009;150(11):ITC61-614. [PMID: 19487708]
Item 35 Answer: A
Educati onal Objecti ve: Diagnose latent tuberculosis in a patient who received bacille Calmette-Guerin (BCG) vaccination.
This pat ient should receive a chest radiograph. She received bacille Calmet t e-Guerin (BCG) vaccinat ion in Africa more t han 20 years ago. Receipt of t his vaccinat ion should
not influence int erpret at ion of t he t uberculin skin t est . BCG vaccinat ion is used in many count ries wit h a high prevalence of t uberculosis t o prevent childhood t uberculous
meningit is and miliary disease. Tuberculin react ivit y caused by BCG vaccinat ion wanes wit h t he passage of t ime and is unlikely t o persist more t han 10 years aft er vaccinat ion
in t he absence of Mycobacterium tuberculosis infect ion; t herefore, t uberculin skin t est ing react ions in persons vaccinat ed wit h BCG should be int erpret ed using t he same
crit eria as used in t hose who have not received t he vaccine. This pat ient 's t uberculin skin t est ing result should be int erpret ed as posit ive (16 mm) and is indicat ive of lat ent or
act ive t uberculosis infect ion. Consequent ly, she should receive a chest radiograph t o exclude t he presence of act ive t uberculous disease. If radiographic result s are negat ive,
t reat ment for lat ent t uberculosis infect ion consist ing of isoniazid t herapy should be init iat ed. Vit amin B
6
(pyridoxine) supplement at ion should also be considered as 2% of
pat ient s t reat ed wit h isoniazid will develop peripheral neuropat hy t hat is prevent able wit h supplement al pyridoxine t herapy. Supplement al pyridoxine is especially import ant
in pat ient s at high risk for neuropat hy (t hose wit h diabet es, uremia, alcoholism, malnut rit ion, HIV infect ion, pregnancy, or seizure disorders).
Four-drug t herapy (isoniazid, rifampin, pyrazinamide, and et hambut ol), which is appropriat e in pat ient s wit h act ive t uberculosis, is not indicat ed in t his pat ient .
Treat ment of lat ent t uberculosis infect ion subst ant ially reduces t he risk t hat t uberculosis infect ion will progress t o act ive disease; t herefore, providing no addit ional evaluat ion
or t herapy would not be appropriat e. Pat ient s exposed t o t uberculosis in t he dist ant past may have an init ial negat ive skin t est ; performing a second t est 7 t o 21 days aft er
t he first may be helpful in reducing t he false-negat ive response rat e. Such t wo-st ep t est ing oft en "boost s" a negat ive t est result t o posit ive as t he immune syst em recalls it s
previous exposure, t hus divulging a t rue-posit ive result . Two-st ep t est ing may be part icularly helpful in older persons and in dist inguishing new from old exposures in annual
employee-t est ing programs. Because t his pat ient has a posit ive t uberculin skin t est , repeat ing t he t uberculin skin t est is unnecessary and will not alt er management .
Key Poi nt
Tuberculin skin t est ing react ions in persons who received t he bacille Calmet t e-Guerin (BCG) vaccine should be int erpret ed using t he same crit eria as for t hose who have not
received t he vaccine.
Bi bl i ography
Escalant e P. In t he clinic. Tuberculosis. Ann Int ern Med. 2009;150(11):ITC61-614; quiz ITV616. Errat um in: Ann Int ern Med. 2009;151(4):292. [PMID: 19487708]
Item 36 Answer: C
Educati onal Objecti ve: Treat Mycobacteri um tubercul osi s infection with four-drug therapy.
The init ial t reat ment of t his pat ient wit h act ive t uberculosis must include four ant it uberculous drugs. Because of increasing concerns of drug resist ance, all pat ient s wit h
suspect ed or confirmed t uberculosis are t reat ed wit h four-drug t herapy wit h t he first -line agent s isoniazid, rifampin, pyrazinamide, and et hambut ol for 2 mont hs, followed by
de-escalat ion of ant imicrobial t herapy once drug suscept ibilit y of isoniazid and rifampin is est ablished. These agent s are t hen cont inued for 7 mont hs, t ot aling a 9-mont h
t reat ment course.
Lat ent t uberculosis (posit ive t uberculin skin t est result but no evidence of act ive disease) can be t reat ed wit h a 9-mont h course of isoniazid. However, t his pat ient has
sympt oms, an abnormal chest radiograph, and a posit ive sput um st ain for acid-fast organisms, excluding lat ent t uberculosis. Three-drug t herapy wit h isoniazid, pyrazinamide,
and et hambut ol is insufficient t herapy for pot ent ially drug-resist ant t uberculosis. Therapy cannot be delayed unt il a definit ive diagnosis of t uberculosis is made because t his
may t ake weeks, and t he infect ion could worsen or spread t o ot her persons in t he int erim.
Key Poi nt
When init iat ing ant it uberculous t herapy, a four-drug regimen is used init ially.
Bi bl i ography
Escalant e P. In t he clinic. Tuberculosis. Ann Int ern Med. 2009;150:ITC61-614; quiz ITV616. Errat um in: Ann Int ern Med. 2009;151:292. [PMID: 19487708]
Item 37 Answer: A
Educati onal Objecti ve: Treat latent tuberculosis in an immunosuppressed patient.
Isoniazid t herapy for 9 mont hs is recommended for t his pat ient and pyridoxine (vit amin B
6
) is t ypically added t o prevent isoniazid-induced peripheral neuropat hy. This
pat ient was screened for t uberculosis because of concerns regarding immunosuppression due t o her disease and her impending t herapy wit h prednisone. Malnut rit ion,
immunosuppressed st at es, and st ress are risk fact ors for primary progression or react ivat ion of quiescent t uberculosis. Various cut off values are used, based on t he pat ient 's risk
st at us, t o increase t he specificit y of t uberculin skin t est result s. Three cut -point s have been defined for a posit ive t uberculin react ion: 5 mm, 10 mm, and 15 mm of
indurat ion. An indurat ion of 5 mm or more is considered posit ive in persons at highest risk of developing act ive t uberculosis (HIV-infect ed pat ient s, immunosuppressed
pat ient s, persons wit h close cont act wit h anyone wit h act ive t uberculosis, or t hose wit h a chest radiograph consist ent wit h prior t uberculosis). This pat ient is
immunosuppressed, and t he 5-mm t hreshold for init iat ing t herapy for lat ent t uberculosis applies t o her. In addit ion, t he American Thoracic Societ y recommends t hat pat ient s
who use prednisone (15 mg/d) or any ot her immunosuppressive agent and who have a 5 mm or larger area of indurat ion on t uberculin skin t est ing begin prophylact ic t herapy
wit h isoniazid.
An indurat ion of 10 mm or more is considered posit ive in persons who have immigrat ed t o t he Unit ed St at es from high-risk count ries wit hin t he past 5 years; inject ion drug
users; prisoners; healt h care workers; and pat ient s wit h silicosis, diabet es mellit us, chronic renal failure, leukemia or lymphoma, carcinoma of t he head or neck or lung, recent
significant weight loss, or a hist ory of gast rect omy or jejunoileal bypass. Healt hy adolescent s who are exposed t o adult s in high-risk cat egories should also be screened using
t his 10-mm cut -off. A cut -off point of 15 mm is used for all low-risk persons.
Because t his pat ient has no evidence of act ive t uberculosis, four-drug t reat ment for 1 year is not needed. The use of rifampin for t he t reat ment of lat ent t uberculosis has not
been ext ensively st udied. Rifampin for 3 mont hs seems t o be as effect ive as longer t reat ment wit h isoniazid; one mont h of rifampin t herapy is insufficient . No
ant it uberculous t herapy places t he pat ient at risk for react ivat ion t uberculosis because of her immunosuppressed st at e and would not be appropriat e.
Key Poi nt
Prophylact ic isoniazid t herapy is beneficial in pat ient s who use prednisone (15 mg/d) or any ot her immunosuppressive agent and who have 5 mm or more of indurat ion on
t uberculin skin t est ing.
Bi bl i ography
Escalant e P. In t he clinic. Tuberculosis. Ann Int ern Med. 2009;150:ITC61-614; quiz ITV616. Errat um in: Ann Int ern Med. 2009;151:292. [PMID: 19487708]
Item 38 Answer: B
Educati onal Objecti ve: Treat latent tuberculosis with isoniazid prior to the administration of a tumor necrosis factor (TNF-) inhibitor.
The most appropriat e next st ep in t his pat ient 's management is t o init iat e isoniazid. Screening for lat ent t uberculosis is indicat ed in pat ient s prior t o solid organ t ransplant ,
init iat ion of chemot herapy or t umor necrosis fact or (TNF-) inhibit ors, or in t he presence of ot her major immunocompromising condit ions. Adverse effect s of TNF-
inhibit ors include t he risk for serious infect ion. Infliximab, adalimumab, and et anercept are associat ed wit h an increased incidence of react ivat ion t uberculosis, part icularly
ext rapulmonary t uberculosis. Therefore, all pat ient s being considered for such t herapy should undergo screening for lat ent t uberculosis infect ion, which includes a full medical
hist ory, physical examinat ion, and t uberculin skin t est ing wit h purified prot ein derivat ive (PPD) or an int erferon- release assay. If screening is posit ive, appropriat e
t reat ment for lat ent t uberculosis is indicat ed before beginning t herapy wit h a TNF- inhibit or. The Cent ers for Disease Cont rol and Prevent ion recommend t reat ment of
lat ent t uberculosis infect ion for all pat ient s planning t o t ake a TNF- inhibit or who have a PPD result of 5 mm or more of indurat ion or a posit ive int erferon- release assay.
Therefore, t he most appropriat e t reat ment for t his pat ient is isoniazid for 9 mont hs. Alt hough t he most appropriat e durat ion of t reat ment wit h isoniazid before beginning
infliximab is unknown, most expert s recommend at least 2 mont hs of isoniazid t herapy before init iat ing a TNF- inhibit or.
Four-drug ant it uberculous t herapy is indicat ed for act ive t uberculosis when a pat ient 's drug resist ance st at us is unknown but is not appropriat e for t his pat ient , who has no
evidence of act ive t uberculosis.
Key Poi nt
The Cent ers for Disease Cont rol and Prevent ion recommend t reat ment of lat ent t uberculosis infect ion for all pat ient s planning t o t ake a t umor necrosis fact or inhibit or
who have a t uberculin skin t est result of 5 mm or more of indurat ion or a posit ive int erferon- release assay.
Bi bl i ography
Bellofiore B, Mat arese A, Balat o N, Gaudiello F, Scarpa R, At t eno M, Bocchino M, Sanduzzi A. Prevent ion of t uberculosis in pat ient s t aking t umor necrosis fact or-alpha
blockers. J Rheumat ol Suppl. 2009;83:76-7. [PMID: 19661550]
Item 39 Answer: B
Educati onal Objecti ve: Immunize a patient to prevent invasive pneumococcal disease.
This pat ient should receive a repeat pneumococcal vaccinat ion in 2 years. A one-t ime revaccinat ion 5 years aft er t he first dose is recommended for adult s age 65 years and
older who received t heir first dose for any indicat ion when t hey were younger t han age 65 years. This pat ient received his first pneumococcal vaccinat ion when he was 62
years old aft er being hospit alized wit h respirat ory failure due t o severe pneumonia. The Cent ers for Disease Cont rol and Prevent ion (CDC) also recommends one-t ime
revaccinat ion 5 years aft er t he first dose for adult s younger t han age 65 years at highest risk for serious pneumococcal infect ion or who are likely t o have a rapid decline in
ant ibody levels. Persons at highest risk include adult s wit h anat omic or funct ional asplenia (including sickle cell disease), HIV infect ion, leukemia, lymphoma, Hodgkin
disease, mult iple myeloma, generalized malignancy, chronic kidney disease, nephrot ic syndrome, or ot her condit ions associat ed wit h immunosuppression (such as organ or
bone marrow t ransplant at ion), and t hose receiving immunosuppressive chemot herapy, including long-t erm cort icost eroids.
Adult s who receive pneumococcal vaccine at or aft er age 65 years should receive only a single dose. The pneumococcal vaccine is a polysaccharide vaccine t hat does not
boost well, and dat a do not indicat e t hat more t han t wo doses are beneficial. Neit her t he CDC nor t he Advisory Commit t ee on Immunizat ion Pract ices recommends an every-
5-year schedule.
Key Poi nt
Persons who received pneumococcal vaccine before age 65 years for any indicat ion should receive anot her dose of t he vaccine at age 65 years or lat er if at least 5 years have
passed since t heir previous dose.
Bi bl i ography
Cent ers for Disease Cont rol and Prevent ion (CDC); Advisory Commit t ee on Immunizat ion Pract ices. Updat ed recommendat ions for prevent ion of invasive pneumococcal
disease among adult s using t he 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mort al Wkly Rep. 2010;59(34):1102-6. [PMID: 20814406]
Item 40 Answer: C
Educati onal Objecti ve: Treat severe community-acquired pneumonia.
The most appropriat e empiric ant ibiot ic t herapy for t his pat ient is cefot axime, levofloxacin, and vancomycin. Met hicillin-resist ant Staphylococcus aureus (MRSA) should
be suspect ed in persons wit h severe, rapidly progressive pneumonia, especially during influenza season; in t hose wit h cavit ary infilt rat es on t he chest radiograph; or in t hose
wit h a hist ory of MRSA infect ion. Administ ering cefot axime and levofloxacin for a pat ient who is admit t ed t o t he int ensive care unit (ICU) wit h pneumonia and no risk
fact ors for Pseudomonas aeruginosa infect ion (for example, bronchiect asis, cort icost eroid or broad-spect rum ant ibiot ic use in t he previous mont h, malnut rit ion) is
appropriat e. However, if MRSA pneumonia is suspect ed, vancomycin or linezolid should be added t o t his empiric ant ibiot ic regimen. Communit y-acquired MRSA pneumonia
oft en affect s young, ot herwise healt hy persons and can be rapidly fat al.
Empiric t reat ment wit h ceft riaxone and azit hromycin or piperacillin-t azobact am for a pat ient wit h suspect ed MRSA pneumonia is not appropriat e. The majorit y of
communit y-acquired MRSA infect ions t ypically are resist ant t o bet a-lact ams and macrolides. Lit t le informat ion is available about t he use of clindamycin for communit y-
acquired MRSA pneumonia and vancomycin is preferred.
Key Poi nt
Met hicillin-resist ant Staphylococcus aureus communit y-acquired pneumonia should be suspect ed in persons wit h severe, progressive pneumonia, especially during influenza
season.
Bi bl i ography
Cent ers for Disease Cont rol and Prevent ion (CDC). Severe met hicillin-resist ant Staphylococcus aureus communit y-acquired pneumonia associat ed wit h influenzaLouisiana
and Georgia, December 2006-January 2007. MMWR Morb Mort al Wkly Rep. 2007;56(14):325-9. [PMID: 17431376]
Item 41 Answer: C
Educati onal Objecti ve: Diagnose Legi onel l a pneumophi l a pneumonia with Legi onel l a urinary antigen.
The t est most likely t o est ablish a diagnosis is t he Legionella urinary ant igen t est . Risk fact ors for legionnaires disease include smoking, diabet es mellit us, hemat ologic
malignancy, ot her t ypes of cancer, chronic kidney disease, and HIV infect ion. Sympt oms of Legionella pneumonia may include cough wit h nonproduct ive, mildly product ive,
or blood-st reaked sput um and chest pain. Gast roint est inal sympt oms are prominent and oft en include diarrhea, abdominal pain, nausea, and vomit ing. Most pat ient s are
let hargic and have headache, and some may be obt unded. High fever is common, and an oral t emperat ure great er t han 40.0C (104.0F) is suggest ive of legionnaires disease.
Hyponat remia is found more oft en in pat ient s wit h legionnaires disease t han it is in pat ient s wit h pneumonia from ot her causes.
The urinary ant igen t est has a sensit ivit y of 70% t o 90% and a specificit y of nearly 99% for det ect ion of L. pneumophila serogroup 1; t he urine is posit ive on day 1 of
illness and cont inues t o be posit ive for weeks. However, urinary ant igen t est s do not det ect ot her Legionella species. Therefore, a negat ive t est result cannot be used t o
exclude t he diagnosis of Legionella pneumonia.
Legionella species would not be isolat ed from blood cult ures or t horacent esis fluid. While blood cult ures are generally warrant ed in pat ient s hospit alized wit h pneumonia, a
blood cult ure is unlikely t o be diagnost ic in t his pat ient .
Most pat ient s wit h pulmonary t uberculosis present wit h a subacut e or chronic present at ion of cough, weight loss, low-grade fever, mild syst emic sympt oms, and, possibly,
blood-t inged sput um. The radiographic changes of react ivat ion t uberculosis include upper pulmonary lobe infilt rat es, cavit at ion, and volume loss, and pleural effusions may be
indicat ive of pleural t uberculosis. This pat ient 's clinical present at ion and radiographic findings are not consist ent wit h t uberculosis; t herefore acid-fast bacilli t est ing for
t uberculosis would not be appropriat e.
Key Poi nt
Urinary ant igen t est s for det ect ion of Legionella pneumophila serogroup 1 have a sensit ivit y of 70% t o 90% and specificit y of nearly 99%, but t hese t est s do not det ect
ot her Legionella species; t herefore, a negat ive t est cannot be used t o exclude t he diagnosis of Legionella pneumonia.
Bi bl i ography
Murdoch DR. Diagnosis of Legionella infect ion. Clin Infect Dis. 2003;36(1):64-69. [PMID: 12491204]
Item 42 Answer: A
Educati onal Objecti ve: Treat community-acquired pneumonia in a patient with no comorbidities with azithromycin.
Oral azit hromycin should be init iat ed. The most common pat hogens ident ified from recent st udies of pat ient s wit h mild communit y-acquired pneumonia (CAP) were
Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Macrolides have long been commonly prescribed for t reat ment of out pat ient s wit h
CAP, and numerous randomized clinical t rials have demonst rat ed t he efficacy of clarit hromycin or azit hromycin as monot herapy. Eryt hromycin is a less expensive
macrolide but not generally recommended owing t o t he need for more frequent dosing, more gast roint est inal upset , and lack of coverage for Haemophilus influenzae.
The use of fluoroquinolones t o t reat ambulat ory pat ient s wit h CAP wit hout comorbidit ies is discouraged because of t he concern t hat widespread use would lead t o t he
development of resist ance.
Penicillin would not be effect ive in t reat ing M. pneumoniae or C. pneumoniae and is t herefore not appropriat e in t his pat ient .
Influenza virus sympt oms t ypically consist of fever (usually high), headache, ext reme fat igue, nonproduct ive cough, sore t hroat , nasal congest ion, rhinorrhea, myalgia, and,
occasionally, gast roint est inal sympt oms, wit h most cases of influenza occurring from November t hrough April in t he Nort hern Hemisphere. Because t he pat ient 's sympt oms
and findings are more consist ent wit h CAP t han influenza virus infect ion, ant iviral t herapy wit h zanamivir is not indicat ed.
Key Poi nt
Clarit hromycin or azit hromycin are recommended for t reat ment of mild communit y-acquired pneumonia.
Bi bl i ography
Niederman M. In t he clinic. Communit y-acquired pneumonia. Ann Int ern Med. 2009;151(7):ITC4-2-ITC4-14; quiz ITC4-16. [PMID: 19805767]
Item 43 Answer: A
Educati onal Objecti ve: Treat a patient with lung abscess following aspiration with ampicillin-sulbactam.
This pat ient should receive ampicillin-sulbact am. She has a hist ory of alcohol abuse and alcohol-wit hdrawal seizures, which put s her at risk for aspirat ion pneumonia. She now
present s wit h a lung abscess, charact erized radiologically by a cavit y wit h an air-fluid level, which probably occurred as a complicat ion of aspirat ion pneumonia. Lung
abscesses are polymicrobial infect ions caused by anaerobic bact eria t hat are normally present in t he mout h; micro-aerophilic st rept ococci, viridans st rept ococci, and gram-
negat ive ent eric pat hogens have also been implicat ed. In st udies using sample t echniques t hat avoid oral cont aminat ion, anaerobes are found in about 90% of pat ient s wit h
lung abscess and are t he only organisms isolat ed in about half. Possible anaerobes in pat ient s wit h lung abscess as a complicat ion of aspirat ion pneumonia include
Peptostreptococcus species, Fusobacterium nucleatum, Prevotella melaninogenica, and Bacteroides species (including B. fragilis). Of t he choices list ed, only ampicillin-
sulbact am would have a broad enough spect rum t o cover t he likely pat hogens.
Of t he ot her ant imicrobial choices, levofloxacin and azt reonam would not be effect ive in t reat ing oral anaerobes, and ceft riaxone would be effect ive in t reat ing some oral
anaerobic species but not -lact amase-producing st rains.
Alt hough met ronidazole is highly act ive in vit ro against most anaerobes, it is not act ive against micro-aerophilic st rept ococci and some anaerobic cocci.
Key Poi nt
Pat ient s wit h lung abscess as a complicat ion of aspirat ion pneumonia require t reat ment wit h an ant imicrobial agent effect ive against -lact amase-producing st rains of oral
anaerobes, such as ampicillin-sulbact am.
Bi bl i ography
Niederman M. In t he clinic. Communit y-acquired pneumonia. Ann Int ern Med. 2009;151(7):ITC4-2-ITC4-14; quiz ITC4-16. [PMID: 19805767]
Item 44 Answer: E
Educati onal Objecti ve: Appropriately withhold infective endocarditis prophylaxis in a patient with a heart murmur associated with a native valve abnormality.
This pat ient does not require ant ibiot ic prophylaxis prior t o his dent al procedure. Evidence is clear t hat bact eremia result ing from normal, daily act ivit ies is much more likely
t o cause infect ive endocardit is t han bact eremia associat ed wit h dent al procedures, and t hat only an ext remely small number of cases of infect ive endocardit is are prevent ed by
prophylaxis. Therefore, ant ibiot ic prophylaxis is now recommended only for pat ient s wit h underlying condit ions associat ed wit h t he highest risk of adverse out come from
infect ive endocardit is, including pat ient s wit h:
Prost het ic cardiac valves
Hist ory of prior infect ive endocardit is
Unrepaired cyanot ic congenit al heart disease
Complet ely repaired congenit al heart disease for 6 mont hs following repair
Repaired congenit al heart disease wit h residual defect s or abnormalit ies
Cardiac t ransplant at ion recipient s wit h cardiac valvulopat hy
This pat ient meet s none of t he crit eria for ant ibiot ic prophylaxis.
Key Poi nt
Ant ibiot ic prophylaxis t o prevent infect ive endocardit is is now recommended only for pat ient s wit h underlying condit ions associat ed wit h t he highest risk of adverse out come
from infect ive endocardit is; t his does not include heart murmurs associat ed wit h nat ive valve abnormalit ies.
Bi bl i ography
Duval X, Leport C. Prophylaxis of infect ive endocardit is: current t endencies, cont inuing cont roversies. Lancet Infect Dis. 2008;8(4):225-32. [PMID: 18353264]
Item 45 Answer: D
Educati onal Objecti ve: Provide infective endocarditis prophylaxis in a patient who is allergic to penicillin.
The most appropriat e endocardit is prophylaxis for t his pat ient is oral clindamycin. Ant ibiot ic prophylaxis is recommended before cert ain dent al procedures (i.e., t hose
involving perforat ion of t he oral mucosa or manipulat ion of t he periapical region of t he t eet h or gingival t issue) for pat ient s wit h underlying condit ions associat ed wit h t he
highest risk of adverse out come from infect ive endocardit is. These pat ient s include t hose wit h:
Prost het ic cardiac valves
Hist ory of prior infect ive endocardit is
Unrepaired cyanot ic congenit al heart disease
Complet ely repaired congenit al heart disease for 6 mont hs following repair
Repaired congenit al heart disease wit h residual defect s or abnormalit ies
Cardiac t ransplant at ion recipient s wit h cardiac valvulopat hy
The organisms associat ed wit h t he development of infect ive endocardit is in t his set t ing are viridans st rept ococci. For t he non-penicillin-allergic pat ient , oral amoxicillin is
t he recommended prophylact ic regimen administ ered 30 t o 60 minut es before t he procedure. In pat ient s unable t o t ake oral medicat ions, ampicillin, cefazolin, or ceft riaxone
int ramuscularly or int ravenously is recommended. This pat ient , however, has a hist ory of anaphylaxis t o penicillin; t herefore, oral clindamycin, azit hromycin, or
clarit hromycin is recommended.
Key Poi nt
Oral clindamycin, azit hromycin, or clarit hromycin is recommended for infect ive endocardit is prophylaxis in penicillin-allergic pat ient s.
Bi bl i ography
Nishimura RA, Carabello BA, Faxon DP, et al; American College of Cardiology/American Heart Associat ion Task Force. ACC/AHA 2008 guideline updat e on valvular heart
disease: focused updat e on infect ive endocardit is: a report of t he American College of Cardiology/American Heart Associat ion Task Force on Pract ice Guidelines: endorsed by
t he Societ y of Cardiovascular Anest hesiologist s, Societ y for Cardiovascular Angiography and Int ervent ions, and Societ y of Thoracic Surgeons. Circulat ion. 2008;118(8):887-
96. [PMID: 18663090]
Item 46 Answer: E
Educati onal Objecti ve: Treat an injection drug user with tricuspid valve endocarditis and multilobar pneumonia with vancomycin plus cefepime.
The best init ial t reat ment for t his pat ient is vancomycin plus cefepime. He most likely has t ricuspid valve endocardit is as suggest ed by t he right st ernal border syst olic
murmur t hat increases wit h inspirat ion. He has developed sept ic pulmonary emboli t o bot h lung fields leading t o mult ilobar pneumonia. Sept ic pulmonary emboli are common
in t ricuspid endocardit is, occurring in up t o 75% of pat ient s. In t his inst ance, t he most likely infect ing organism is Staphylococcus aureus, and t reat ment of a possible
met hicillin-resist ant st rain must be init iat ed pending cult ure and in vit ro suscept ibilit y result s. Vancomycin plus cefepime provides appropriat e coverage for endocardit is
caused by S. aureus, gram-negat ive bacilli (for example, Pseudomonas aeruginosa), and ot her likely infect ious causes of pneumonia, especially Streptococcus pneumoniae.
Azit hromycin plus ceft riaxone, levofloxacin plus clindamycin, and piperacillin/t azobact am plus azt reonam do not provide appropriat e coverage for met hicillin-resist ant S.
aureus and are t herefore not appropriat e for t his pat ient . Alt hough t rimet hoprim-sulfamet hoxazole plus prednisone would t reat Pneumocystis jirovecii pneumonia, such a
diagnosis is unlikely in t his pat ient given his clinical present at ion. In HIV-infect ed pat ient s, Pneumocystis pneumonia t ypically has a subacut e onset of cough, fever, and
dyspnea. The most common radiographic abnormalit ies are diffuse, bilat eral, int erst it ial infilt rat es. This pat ient 's acut e onset of sympt oms, mult ilobar pneumonia, and
presence of a heart murmur are not compat ible wit h Pneumocystis pneumonia.
Key Poi nt
Treat ment for sept ic pulmonary emboli from an infect ed t ricuspid valve in an inject ion drug user should include empiric t herapy for met hicillin-resist ant Staphylococcus
aureus, such as vancomycin plus cefepime.
Bi bl i ography
Chambers HF, Korzeniowski OM, Sande MA. St aphylococcus aureus endocardit is: clinical manifest at ions in addict s and nonaddict s. Medicine (Balt imore). 1983;62(3):170-
177. [PMID: 6843356]
Item 47 Answer: A
Educati onal Objecti ve: Diagnose and treat native valve endocarditis.
The pat ient meet s all t hree major clinical crit eria for definit e endocardit is. He has a t ypical microorganism grown on t wo blood cult ures, echocardiographic evidence of
endocardial involvement (an oscillat ing int racardiac mass), and a new valvular regurgit at ion murmur. His hist ory also suggest s endocardit is (several mont hs of fever, fat igue
and muscle aches). Also support ing t he diagnosis are t he presence of a bicuspid aort ic valve, fever, and conjunct ival hemorrhage, which fulfill t hree of t he minor clinical
crit eria for endocardit is.
Endocardit is due t o sensit ive viridans st rept ococci on nat ive valves can be t reat ed for 4 weeks wit h penicillin or ceft riaxone or for 2 weeks when eit her agent is combined
wit h synergist ic low-dose gent amicin. In a pat ient wit h uncomplicat ed endocardit is, t he addit ion of gent amicin decreases t he t ot al t reat ment course from 4 weeks t o 2 weeks.
In t he absence of penicillin allergy or penicillin resist ance, vancomycin is inappropriat e.
Key Poi nt
Endocardit is due t o penicillin-sensit ive viridans st rept ococci on nat ive valves can be t reat ed for 4 weeks wit h penicillin or ceft riaxone or for 2 weeks when eit her agent is
combined wit h synergist ic low-dose gent amicin.
Bi bl i ography
Beynon RP, Bahl VK, Prendergast BD. Infect ive endocardit is. BMJ. 2006;333:334-9. [PMID: 16902214]
Item 48 Answer: D
Educati onal Objecti ve: Treat methicillin-susceptible Staphyl ococcus aureus right-sided endocarditis with oxacillin.
The most appropriat e t reat ment as t his t ime is oxacillin. She has bact eremia most likely result ing from right -sided endocardit is. Treat ment requires using t he most effect ive
drug wit h t he fewest side effect s, and vancomycin should t herefore be changed t o oxacillin. Penicillins have never been shown t o be less effect ive t han ot her ant ibiot ics for
t reat ing suscept ible st rains of Staphylococcus aureus, t heir safet y profile is well document ed, and t hey are reasonably inexpensive. In t he rare set t ing in which an isolat e of S.
aureus is suscept ible t o penicillin G, t his would be t he drug of choice.
Bot h vancomycin and dapt omycin have been used t o t reat S. aureus bact eremia and endocardit is. Alt hough bot h are effect ive for t reat ing met hicillin-resist ant S. aureus
(MRSA) st rains, t hey show no clinical superiorit y for t reat ing met hicillin-suscept ible S. aureus (MSSA). Pat ient s wit h MSSA infect ions appear t o have a slower response t o
vancomycin t han t o t he semisynt het ic penicillins such as oxacillin or t o t he cephalosporins, and t his account s for t he preference of -lact am versus vancomycin t herapy in
pat ient s wit h MSSA.
Clindamycin may be effect ive in vit ro; however, t he failure rat e is higher for clindamycin t han for ot her drugs used t o t reat endocardit is, presumably owing t o it s
bact eriost at ic, rat her t han bact ericidal, act ivit y for many st rains of suscept ible S. aureus.
Linezolid has been used wit h some success and some failure in pat ient s wit h st aphylococcal bact eremia. Because of concerns about it s efficacy, it is usually reserved for
pat ient s who do not respond t o first -line t herapy.
Key Poi nt
Synt het ic penicillins, such as oxacillin and nafcillin, are appropriat e for t reat ing pat ient s wit h met hicillin-suscept ible Staphylococcus aureus bact eremia and endocardit is.
Bi bl i ography
Fowler VG Jr., Boucher HW, Corey GR, et al; The S. aureus Endocardit is and Bact eremia St udy Group. Dapt omycin versus st andard t herapy for bact eremia and endocardit is
caused by St aphylococcus aureus. N Engl J Med. 2006;355(7):653-665. [PMID: 16914701]
Item 49 Answer: D
Educati onal Objecti ve: Diagnose osteomyelitis of the foot in a patient with diabetes with a bone biopsy.
The most appropriat e management is t o perform a bone biopsy. Cont act wit h bone (when using a st erile, blunt , st ainless st eel probe) in t he dept h of an infect ed pedal ulcer in
pat ient s wit h diabet es mellit us is st rongly correlat ed wit h t he presence of underlying ost eomyelit is, wit h a posit ive predict ive value of 90%. Pat ient s wit h diabet es require bone
biopsy t o obt ain deep pat hogens, ident ificat ion of which is t he only way t o est ablish a definit ive diagnosis and guide t herapy. Alt hough it may seem int uit ive t hat drainage
from a superficial sit e such as an ulcer or a sinus t ract would cont ain t he causat ive pat hogens, superficial cult ures usually do not include t he deep organisms responsible for t he
infect ion. Failure t o ident ify t he causat ive deep-bone pat hogens may lead t o spread of infect ion t o adjacent bones or soft t issues and t he need for ext ensive debridement or
amput at ion. The one except ion is Staphylococcus aureus, which, if found in superficial cult ures, correlat es well wit h findings on deep cult ures.
This pat ient appears well enough t o wait for t he bone biopsy t o be complet ed before st art ing empiric ant ibiot ic t herapy and adjust ing t he ant ibiot ics based on cult ure result s.
Empiric t herapy should include act ivit y against st rept ococci, met hicillin-resist ant S. aureus (MRSA), aerobic gram-negat ive bacilli, and anaerobes. Therapy wit h imipenem
alone will not adequat ely cover MRSA, vancomycin and ceft azidime will not adequat ely cover anaerobic bact eria, and vancomycin and met ronidazole will not adequat ely
cover gram-negat ive organisms.
Key Poi nt
Cult ures obt ained from a sinus t ract or ulcer base oft en do not reflect t he bact erial et iology of an underlying ost eomyelit is; bone biopsy is indicat ed t o ident ify t he causat ive
pat hogens and guide ant ibiot ic t herapy.
Bi bl i ography
But alia S, Palda VA, Sargeant RJ, Det sky AS, Mourad O. Does t his pat ient wit h diabet es have ost eomyelit is of t he lower ext remit y? JAMA. 2008;299(7):806-13. [PMID:
18285592]
Item 50 Answer: B
Educati onal Objecti ve: Evaluate a patient with vertebral osteomyelitis with a spine MRI.
The next management st ep is MRI of t he lumbar spine. Vert ebral ost eomyelit is is an infect ion of t he spine t hat must be considered in any pat ient wit h new-onset back pain
and fever. Pat ient s wit h acut e hemat ogenous ost eomyelit is are more likely t o present wit h acut e pain and fever t han are pat ient s wit h chronic cont iguous ost eomyelit is (for
example, foot ulcer-associat ed ost eomyelit is). In adult s, hemat ogenous ost eomyelit is most oft en involves t he int ervert ebral disk space and t wo adjacent vert ebrae. Pot ent ial
sources of hemat ogenous infect ion include t he genit ourinary t ract (part icularly following inst rument at ion), skin (inject ion drug use), infect ed int ravascular devices (for
example, a cent ral venous cat het er), and endocardit is, but oft en, t he source of t he infect ion cannot be ident ified. In pat ient s wit h hemat ogenous ost eomyelit is, t he leukocyt e
count is t ypically normal, but t he eryt hrocyt e sediment at ion rat e is elevat ed in 80% t o 90% of pat ient s and is oft en great er t han 100 mm/h.
MRI is t he most appropriat e imaging st udy for pat ient s wit h suspect ed vert ebral ost eomyelit is and is a more sensit ive st udy t han CT scans or plain radiographs. In addit ion,
MRI can det ect an epidural abscess or a paravert ebral or psoas abscess t hat may require surgical drainage. If MRI cannot be performed (for example, in pat ient s wit h
pacemakers or met al prost het ic devices) or if result s are inconclusive, a gallium nuclear st udy is very sensit ive and specific in t his set t ing.
Three-phase bone scint igraphy using labeled t echnet ium can occasionally be helpful in diagnosing ost eomyelit is, but it is associat ed wit h false-posit ive result s in pat ient s wit h
ot her causes of back pain, including fract ure, as well as false-negat ive result s if t he infect ion is early. Three-phase bone scint igraphy is an inferior diagnost ic t est compared t o
MRI scanning but may be appropriat e when t he init ial MRI imaging result is indet erminat e.
Key Poi nt
The diagnosis of vert ebral ost eomyelit is must be considered in any pat ient who present s wit h new-onset back pain and fever.
Bi bl i ography
Zimmerli W. Clinical pract ice. Vert ebral ost eomyelit is. N Engl J Med. 2010;362(11):1022-9. [PMID: 20237348]
Item 51 Answer: C
Educati onal Objecti ve: Evaluate possible osteomyelitis with MRI.
MRI is t he preferred imaging st udy for pat ient s such as t his one wit h foot infect ion. Foot infect ions are a significant cause of morbidit y in pat ient s wit h diabet es mellit us and,
if unt reat ed, can progress t o ost eomyelit is t hat may require amput at ion for cure. Appropriat e assessment of diabet ic foot infect ions is t herefore essent ial. Unless bone is
visible, physical examinat ion findings are oft en inconclusive for diagnosing ost eomyelit is. Plain radiographs are insensit ive and may show soft t issue swelling but no bony
abnormalit ies for 2 or more weeks aft er infect ion has developed. In addit ion, t his pat ient had a negat ive met al-probe t est (a posit ive t est has a predict ive value of 90% for
diagnosing ost eomyelit is). Alt hough her ulcer is limit ed t o t he plant ar surface, t he cellulit is is more diffuse, which implies a more ext ensive process requiring rapid assessment
and t reat ment .
A CT scan is neit her as sensit ive nor specific as MRI and is indicat ed only when MRI cannot be performed (for example, in pat ient s wit h pacemakers or met al prost het ic
devices). Indium-labeled leukocyt e scan and t riple-phase t echnet ium bone scan are very sensit ive but not specific for diagnosing ost eomyelit is and are associat ed wit h high
false-posit ive rat es, especially when an overlying cellulit is or soft t issue infect ion is present .
Key Poi nt
MRI is t he most sensit ive and specific st udy for diagnosing foot infect ion-associat ed ost eomyelit is.
Bi bl i ography
But alia S, Palda VA, Sargeant RJ, Det sky AS, Mourad O. Does t his pat ient wit h diabet es have ost eomyelit is of t he lower ext remit y? JAMA. 2008;299(7):806-13. [PMID:
18285592]
Item 52 Answer: C
Educati onal Objecti ve: Diagnose the cause of vertebral osteomyelitis with blood cultures.
Blood cult ures are t he most appropriat e next st ep. In a pat ient wit h suspect ed vert ebral ost eomyelit is, a microbiologic diagnosis must be est ablished t o guide ant ibiot ic
t herapy. Because t he infect ion is oft en hemat ogenous, blood cult ures should be obt ained init ially in all pat ient s. Cult ures are posit ive in up t o 75% of pat ient s, and
ident ificat ion of Staphylococcus aureus, which is t he most frequent cause of vert ebral ost eomyelit is, may obviat e t he need for a bone biopsy. However, if t he imaging st udies
suggest vert ebral ost eomyelit is but t he blood cult ures are negat ive, CT-guided percut aneous needle biopsy should be performed. Because t his procedure is only about 50%
sensit ive, ant ibiot ics should be wit hheld unt il a microbiologic diagnosis is made.
Empiric ceft riaxone will provide adequat e coverage for most gram-negat ive and st rept ococcal organisms responsible for vert ebral ost eomyelit is but will provide no coverage
for met hicillin-resist ant S. aureus (MRSA). St art ing empiric nafcillin would be a good choice if t he infect ive organism were a suscept ible st aphylococcus; however, nafcillin
will not adequat ely cover infect ions caused by MRSA or gram-negat ive organisms.
Key Poi nt
Blood cult ures are posit ive in 75% of pat ient s wit h vert ebral ost eomyelit is.
Bi bl i ography
Zimmerli W. Clinical pract ice. Vert ebral ost eomyelit is. N Engl J Med. 2010;362(11):1022-9. [PMID: 20237348]
Secti on 7. Nephrol ogy
Questi ons
Item 1 [Advanced]
A 19-year-old man is evaluat ed for prot einuria discovered during a rout ine sport s prepart icipat ion evaluat ion. He has been asympt omat ic, has no ot her medical problems, and
t akes no medicat ions.
On physical examinat ion, t emperat ure is 36.6C (97.8F) blood pressure is 110/72 mm Hg, pulse rat e is 60/min, and respirat ion rat e is 12/min. BMI is 18. The funduscopic,
cardiopulmonary, and skin findings are normal. No peripheral edema is present .
Hemoglobin 15 mg/dL (150 g/L)
Tot al prot ein 6.5 g/dL (65 g/L)
Spot urine prot ein-creat inine rat io 0.8 mg/mg
Urinalysis Urine dipst ick: prot ein, 2+; blood, negat ive; glucose, negat ive. Microscopic: rare hyaline cast , no cells or cryst als.
(A) 24-Hour urine prot ein excret ion
(B) Evaluat e for ort host at ic prot einuria
(C) Kidney biopsy
(D) Prot ein elect rophoresis of t he serum and urine
Item 2 [Advanced]
A 62-year-old woman is evaluat ed for acut e oliguric renal failure. She was admit t ed t o t he hospit al 7 days ago for sepsis due t o met hicillin-sensit ive Staphylococcus aureus;
int ravenous cefazolin was begun and she quickly improved. Today, her urine out put is 10 mL/h.
On physical examinat ion, t emperat ure is 37.5C (99.5F), blood pressure is 138/88 mm Hg, pulse rat e is 78/min, and respirat ion rat e is 12/min. A macular eryt hemat ous rash
is present over her ant erior chest and abdomen. The remainder of t he physical examinat ion is normal.
Day 1 Day 7
Blood urea nit rogen 8 mg/dL (2.9 mmol/L) 20 mg/dL (7.1 mmol/L)
Creat inine 0.6 mg/dL (53.0 mol/L) 1.8 mg/dL (159.1 mol/L)
Urinalysis Normal Dipst ick: pH, 5; prot ein, 1+; blood, negat ive. Microscopic: 15-20 whit e blood cells per high power field; many leukocyt e cast s
Urine cult ure No growt h
Renal ult rasonography shows normal kidney size wit hout hydronephrosis.
(A) Acut e int erst it ial nephrit is
(B) Acut e t ubular necrosis
(C) Cholest erol cryst al embolizat ion
(D) Prerenal azot emia
Item 3 [Advanced]
A 65-year-old man comes for a follow-up office visit . Three weeks ago, he was admit t ed t o t he hospit al for deep venous t hrombosis of t he left leg. He was t reat ed wit h low-
molecular-weight heparin followed by warfarin. He t akes no ot her medicat ions. He has a 30-pack-year hist ory of cigaret t e smoking and current ly smokes t wo packs of
cigaret t es daily.
Vit al signs and physical examinat ion are normal.
Urinalysis 3 weeks ago revealed t race prot ein and 1+ blood.
Laborat ory st udies obt ained t oday:
INR 3.0
Urinalysis Specific gravit y 1.015; no prot ein; 1+ blood; 5-10 non-dysmorphic eryt hrocyt es/hpf; no cast s
On kidney ult rasound, t he right kidney is 10.4 cm and t he left kidney is 9.0 cm. No masses, cyst s, or st ones are ident ified.
(A) Cyst oscopy
(B) Discont inuat ion of warfarin
(C) Kidney biopsy
(D) Repeat urinalysis in 3 mont hs
Item 4 [Basic]
An 18-year-old man is evaluat ed in t he emergency depart ment aft er his mot her found him unconscious in his bed at home. She report ed t hat her son had gone t o a part y 24
hours ago, but she was not sure when he ret urned home. When she checked on him, he was unarousable. He has no significant medical hist ory and t akes no medicat ions.
In t he emergency depart ment , he is afebrile, blood pressure is 110/70 mm Hg, pulse rat e is 50/min, and respirat ion rat e is 6/min; he is int ubat ed.
Creat ine kinase 18,400 U/L
INR 1.2
Complet e blood count , alkaline phosphat ase, bilirubin, and albumin are normal. Urine dipst ick is 4+ posit ive for occult blood, negat ive for eryt hrocyt es. Blood alcohol level is
0.8 g/dL (174 mmol/L). Toxicology t est ing is posit ive for opiat es and cocaine. Bladder cat het erizat ion reveals only 30 mL of brown urine.
Whi ch of the fol l owi ng i s the most l i kel y cause of the acute ki dney i njury?
(A) Hemolyt ic anemia
(B) Hemolyt ic-uremic syndrome
(C) Hepat orenal syndrome
(D) Rhabdomyolysis
Item 5 [Advanced]
A 72-year-old man is evaluat ed in t he emergency depart ment for a 2-day hist ory of suprapubic abdominal pain. He has had difficult y urinat ing for t he last 6 mont hs, including
urinary frequency and difficult y st art ing his urinary st ream. He has noct uria four t o five t imes per night . Medical hist ory is ot herwise nonsignificant , and he t akes no
medicat ions.
On physical examinat ion, t he pat ient is uncomfort able. Temperat ure is 37.0C (98.6F), blood pressure is 162/90 mm Hg, pulse rat e is 92/min, and respirat ion rat e is 12/min.
Suprapubic fullness t o palpat ion is not ed.
Elect rolyt es
Whi ch of the fol l owi ng i s the best di agnosti c test for thi s pati ent?
(A) Kidney art eriography
(B) Kidney biopsy
(C) Kidney ult rasound
(D) Urine dipst ick for prot ein
Item 6 [Advanced]
A 21-year-old woman is evaluat ed in t he emergency depart ment for a 2-day hist ory of abdominal pain and bloody diarrhea. Before t his episode she was healt hy, and she t akes
no medicat ions.
On physical examinat ion, she appears ill and pale; t emperat ure is 38.5C (101.3F), blood pressure is 97/70 mm Hg, pulse rat e is 120/min, and respirat ion rat e is 16/min.
Bowel sounds are hyperact ive, and t he abdomen is t ender wit hout guarding. The remainder of t he examinat ion is normal.
Hemat ocrit 27%
9
/L)
Creat inine 3.2 mg/dL (283 mol/L)
Urinalysis (microscopic and dipst ick) Normal
The peripheral blood smear reveals schist ocyt es.
(C) Hemolyt ic uremic syndrome
(D) Rhabdomyolysis
Item 7 [Basic]
A 29-year-old woman comes for a follow-up office visit . Six mont hs ago, she underwent double-lung t ransplant at ion for cyst ic fibrosis. She was diagnosed wit h Pseudomonas
bronchit is 14 days ago and began oral ciprofloxacin and int ravenous t obramycin at t hat t ime. Today, she st at es t hat her cough has resolved, she has not had fever, and she
feels well. Addit ional medicat ions are acyclovir, mycophenolat e mofet il, prednisone, t acrolimus, and t rimet hoprim-sulfamet hoxazole.
On physical examinat ion, t emperat ure is 36.6C (97.8F), blood pressure is 132/80 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 18/min. Cardiopulmonary
examinat ion is normal. Cut aneous examinat ion is normal. There is no ast erixis. There is no edema.
9
/L)
9
/L)
Serum creat inine 2.3 mg/dL (203.3 mol/L) (1.2 mg/dL [106.1 mol/L] 6 weeks ago)
Urinalysis Specific gravit y 1.011; pH 5.5; 1+ prot ein; no blood; 2-5 eryt hrocyt es/hpf; no leukocyt e est erase
Urine sediment findings are shown.
Kidney ult rasound shows normal-sized kidneys and no hydronephrosis.
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's fi ndi ngs?
(C) Thrombot ic t hrombocyt openic purpura
(D) Urinary t ract obst ruct ion
Item 8 [Basic]
A 56-year-old woman is evaluat ed for a 1-week hist ory of right upper-quadrant abdominal pain, anorexia, nausea, and vomit ing and a 3-day hist ory of increasing let hargy and
weakness. She also has dark-colored urine and a decreased urine out put . One year ago, she was diagnosed wit h st age IV breast cancer t reat ed wit h mast ect omy and hormonal
and chemot herapy. Current medicat ions are t amoxifen and t rast uzumab.
On physical examinat ion, t emperat ure is normal, blood pressure is 90/50 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 18/min. Cardiopulmonary examinat ion is
normal. The mucous membranes are dry. Abdominal examinat ion reveals hepat omegaly. There is no edema.
Uric acid 9.2 mg/dL (0.54 mmol/L)
Serum creat inine 5 mg/dL (442 mol/L) (1 mg/dL [88.4 mol/L] 1 mont h ago)
Urinalysis Specific gravit y 1.022; pH 5; t race prot ein; rare amorphous cryst als
Urine sodium excret ion 4 meq/L (4 mmol/L)
On abdominal ult rasound, t he right kidney is 9.6 cm and t he left kidney is 9.1 cm. There is no hydronephrosis, and no renal calculi or focal solid masses are seen. There is
hepat omegaly wit h mult iple liver met ast ases.
(A) Dialysis
(B) Isot onic saline
(C) Midodrine and oct reot ide
(D) Rasburicase
Item 9 [Basic]
A 65-year-old man wit h a hist ory of st age 4 chronic kidney disease and hypert ension comes for a follow-up examinat ion. Two days ago, he was discharged from t he hospit al
aft er a 4-day st ay for pneumonia. During his hospit alizat ion, his blood pressure averaged 130/70 mm Hg and he was not exposed t o radiocont rast agent s. He was t reat ed wit h
ceft riaxone and azit hromycin; on discharge, t hese agent s were discont inued and he began oral levofloxacin. Since his discharge, he has had nausea, vomit ing, and anorexia. He
believes t hat his urine out put over t he past day has been less t han 500 mL. Addit ional medicat ions are lisinopril, calcium carbonat e, and low-dose aspirin.
On physical examinat ion, t emperat ure is 35.8C (96.4F), blood pressure is 110/50 mm Hg st anding and 100/80 mm Hg supine, pulse rat e is 108/min st anding and 96/min
supine, and respirat ion rat e is 16/min. The remainder of t he examinat ion is normal except for crackles heard at t he base of t he lungs bilat erally.
Serum creat inine 6.0 mg/dL (530.4 mol/L) (2.5 mg/dL [221.0 mol/L] in t he hospit al)
Urinalysis Specific gravit y 1.016; no prot ein or blood; occasional hyaline cast s
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's acute ki dney i njury?
(C) Prerenal azot emia
(D) Renal vein t hrombosis
Item 10 [Basic]
A 55-year-old man wit h a 15-year hist ory of t ype 2 diabet es mellit us and hypert ension is evaluat ed during a new-pat ient visit . He report s no sympt oms ot her t han ankle
edema. A review of his medical records document s t he presence of microalbuminuria 5 years ago. His medicat ions are amlodipine, chlort halidone, simvast at in, met formin, and
glargine insulin.
On physical examinat ion, t emperat ure is 37.1C (97.8F), blood pressure is 150/95 mm Hg, pulse is 80/min, and respirat ion rat e is 12/min. Cardiopulmonary examinat ion is
normal. He has t race pret ibial edema.
Urine prot ein-creat inine rat io 1 mg/mg
The pat ient is prescribed losart an 25 mg/d. He ret urns in 3 weeks for a repeat blood pressure check. The average of t wo blood pressure recordings is 145/88 mm Hg. The
serum pot assium level is 4.4 meq/L (4.4 mmol/L) and t he serum creat inine level is 2.0 mg/dL (177 mol/L).
(A) Add lisinopril
(B) Discont inue losart an
(C) Increase t he dose of losart an
(D) Schedule a renal biopsy
Item 11 [Advanced]
A 60-year-old man is evaluat ed during follow-up for chronic kidney disease secondary t o aut osomal dominant polycyst ic kidney disease. He report s no chest pain, dyspnea,
changes in his ment al st at us, or excessive sleepiness. He has no anorexia, nausea, vomit ing, weight loss, or it ching. His medicat ions are lisinopril, furosemide, low-dose aspirin,
calcit riol, sevelamer, and ferrous sulfat e. He has several family members who are being evaluat ed as pot ent ial kidney donors. Est imat ed glomerular filt rat ion rat e (GFR) 2
mont hs ago was 18 mL/min/1.73 m
2
On physical examinat ion, he is ment ally alert . Temperat ure is 37.0C (98.7F), blood pressure is 125/75 mm Hg, pulse rat e is 75/min, and respirat ion rat e is 14/min. Cardiac
rhyt hm is normal wit hout murmurs, ext ra sounds, or rubs. The est imat ed cent ral venous pressure is 8 cm H
2
O. The lungs are clear t o auscult at ion. His abdominal examinat ion
is significant for large, nont ender bilat eral flank masses. No bleeding, ecchymosis, or pet echiae is evident . He scores 29/30 on t he Mini-Ment al St at e Examinat ion and no
ast erixis is evident . He has 1+ pret ibial edema.
Creat inine 4.9 mg/dL (433.1 micromol/L)
Elect rolyt es
Est imat ed GFR 13 mL/min/1.73 m
2
Whi ch of the fol l owi ng i s the most appropri ate next step i n the management of thi s pati ent's di sease?
(A) Init iat ion of dialysis
(B) Increase t he dose of lisinopril
(C) Ult rasonography of t he abdomen
(D) No change in management
Item 12 [Advanced]
A 35-year-old woman is evaluat ed for a 1-mont h hist ory of progressive bilat eral lower-ext remit y edema. She was diagnosed wit h t ype 1 diabet es mellit us 10 years ago. At her
last office visit 4 mont hs ago, t he urine albumin-creat inine rat io was 40 mg/g. Medicat ions are enalapril, insulin glargine, insulin aspart , and low-dose aspirin.
On physical examinat ion, vit al signs are normal except for a blood pressure of 162/90 mm Hg (baseline 130/70 mm Hg). Cardiopulmonary and funduscopic examinat ions are
normal. There is 3+ pit t ing edema of t he lower ext remit ies t o t he level of t he t highs bilat erally.
Hemoglobin A
1c
6.8%
Albumin 3 g/dL (30 g/L)
Urinalysis 3+ prot ein; 2+ blood; 8-10 dysmorphic eryt hrocyt es/hpf; 2-5 leukocyt es/hpf; few eryt hrocyt e cast s
Urine prot ein-creat inine rat io 5.2 mg/mg
On kidney ult rasound, t he right kidney is 12.2 cm and t he left kidney is 12.7 cm. There is no hydronephrosis, and no kidney masses are seen.
(A) Cyst oscopy
(B) Kidney biopsy
(C) Spiral CT of t he abdomen and pelvis
(D) Observat ion
Item 13 [Advanced]
A 33-year-old woman comes for follow-up examinat ion for a left fibula fract ure due t o a fall 1 week ago. She has hypert ension and st age 5 chronic kidney disease t reat ed wit h
home hemodialysis. Medicat ions are lisinopril, sevelamer, epoet in alfa, paricalcit ol, and mult ivit amins.
On physical examinat ion, t emperat ure is normal, blood pressure is 130/70 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 12/min. BMI is 29. Cardiopulmonary
examinat ion is normal. An art eriovenous fist ula is present in t he left forearm. Except for a cast on her left leg, musculoskelet al examinat ion is normal and reveals no bone
pain.
Parat hyroid hormone 700 pg/mL (700 ng/L)
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's bone di sease?
(A) Adynamic bone disease
(B) Ost eonecrosis
(C) Ost eoporosis
(D) Secondary hyperparat hyroidism
Item 14 [Advanced]
A 55-year-old woman is found in an alleyway by paramedics. She is obt unded, hypot ensive and t achycardic. Her breat h smells of alcohol.
Elect rolyt es
Blood gases
pH 7.08
PCO
2
42 mm Hg (5.6 kPa)
Whi ch of the fol l owi ng aci d-base di sorders i s most l i kel y present?
(A) Met abolic acidosis, met abolic alkalosis, and respirat ory acidosis
(B) Met abolic acidosis and respirat ory alkalosis
(C) Met abolic alkalosis and respirat ory acidosis
(D) Respirat ory acidosis and met abolic acidosis
(E) Simple met abolic acidosis
Item 15 [Advanced]
A 40-year-old woman is evaluat ed in t he hospit al for met abolic acidosis.
Art erial blood gases
pH 7.30
PCO
2
36 mm Hg (4.8 kPa)
Elect rolyt es
Pot assium 3.0 meq/L (3 mmol/L)
Urine elect rolyt es
Pot assium 10 meq/L (10 mmol/L)
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's aci d-base di sorder?
(A) Diabet ic ket oacidosis
(B) Renal t ubular acidosis
(C) Laxat ive abuse
(D) Viral gast roent erit is
Item 16 [Basic]
A 61-year-old man is evaluat ed in t he emergency depart ment because of a 3-day hist ory of cough product ive of yellow sput um. He has chronic obst ruct ive pulmonary disease
and he rout inely uses supplement al oxygen, 2 L/min. He st at es t hat he is now short of breat h at rest .
Physical examinat ion shows t hat he is using accessory muscles of respirat ion and pursed-lipped breat hing. He has prolonged expirat ory-t o-inspirat ory phase on exhalat ion
and scat t ered wheezes. He has t achycardia and bilat eral pit t ing edema of t he ext remit ies.
His oxygen sat urat ion is 91% on supplement al oxygen. Chest radiograph shows changes consist ent wit h emphysema, but is ot herwise unchanged from baseline. His art erial
blood gas values are PO
2
2
, 64 mm Hg (8.5 kPa); and pH, 7.32. Ot her pert inent laborat ory values include sodium, 140 meq/L (140 mmol/L);
chloride, 100 meq/L (100 mmol/L); pot assium, 3.5 meq/L (3.5 mmol/L); and bicarbonat e, 32 meq/L (32 mmol/L).
Whi ch of the fol l owi ng aci d-base di sorders i s most l i kel y present?
(A) Met abolic acidosis
(B) Respirat ory acidosis
(C) Respirat ory acidosis and met abolic acidosis
(D) Respirat ory alkalosis
Item 17 [Basic]
A 28-year-old man is brought t o t he emergency depart ment wit h t he sudden onset of dyspnea following a st ressful int erview at work.
On physical examinat ion, t emperat ure is 36.7C (98F), heart rat e is 99/min, respirat ion rat e is 32/min, and blood pressure is 156/80 mm Hg. He is weak and in moderat e
respirat ory dist ress. Cardiovascular and pulmonary examinat ions are normal.
Art erial blood gas st udies (on ambient air):
pH 7.49
PCO
2
30 mm Hg (4.0 kPa)
Po
2
99 mm Hg (13.2 kPa)
Whi ch of the fol l owi ng best characteri zes the pati ent's aci d-base di sorder?
(A) Mixed anion gap met abolic acidosis and respirat ory alkalosis
(B) Mixed met abolic alkalosis and respirat ory alkalosis
(C) Respirat ory acidosis
(D) Respirat ory alkalosis
Item 18 [Basic]
A 56-year old man wit h a hist ory of alcoholism is found lying on t he st reet . On arrival at t he emergency depart ment , he is confused.
On physical examinat ion, t emperat ure is 36.1C (97.0F), blood pressure is 126/80 mm Hg, and pulse rat e is 70/min. Funduscopic examinat ion shows no papilledema. Cardiac,
pulmonary, and abdominal examinat ions are normal.
Glucose (fast ing) 86 mg/dL (4.8 mmol/L)
Plasma osmolalit y 336 mosm/kg (336 mol/kg)
Urinalysis Calcium oxalat e cryst als
Art erial blood gas st udies (wit h t he pat ient breat hing ambient air)
pH 7.32
PCO
2
29 mm Hg (3.9 kPa)
PO
2
80 mm Hg (10.6 kPa)
(A) Alcoholic ket oacidosis
(B) Diabet ic ket oacidosis
(C) Et hylene glycol poisoning
(D) Lact ic acidosis
Item 19 [Advanced]
A 39-year-old man is evaluat ed in t he emergency depart ment because of severe left flank pain and hemat uria aft er playing soft ball. The pain is sharp and radiat es t o t he
groin. He vomit ed eight t imes before present at ion. He has a nonobst ruct ing, calcium-cont aining kidney st one at t he uret eropelvic junct ion on t he left side.
On init ial evaluat ion, his blood pressure was 130/90 mm Hg, respirat ory rat e was 30/min, and pulse rat e was 110/min.
Serum sodium 141 meq/L (141 mmol/L)
Serum pot assium 4.0 meq/L (4.0 mmol/L)
Serum chloride 100 meq/L (100 mmol/L)
Serum bicarbonat e 34 meq/L (34 mmol/L)
Art erial blood gases pH, 7.60; PCO
2
, 36 mm Hg (4.8 kPa)
Whi ch of the fol l owi ng best descri bes thi s pati ent's aci d-base di sorder?
(A) Met abolic acidosis and respirat ory alkalosis
(B) Met abolic alkalosis
(C) Met abolic alkalosis and respirat ory acidosis
(D) Met abolic and respirat ory alkalosis
(E) Respirat ory alkalosis
Item 20 [Basic]
A 66-year old man is evaluat ed in t he emergency depart ment for a 6-week hist ory of dyspnea on exert ion and a 3-day hist ory of ort hopnea. He report s no chest pain or
palpit at ions. He has a 45-pack-year hist ory of cigaret t e smoking. He t akes no medicat ions.
On physical examinat ion, t emperat ures is 37.2C (99.0F), blood pressure is 150/90 mm Hg, pulse rat e is 108/min, and respirat ion rat e is 26/min. Oxygen sat urat ion by pulse
oximet ry is 88% on ambient air. The pat ient has jugular venous dist ent ion t o t he angle of t he jaw when sit t ing upright . A prominent S
3
and bibasilar crackles are heard on
auscult at ion of t he lungs, and pit t ing edema t o t he knees is present .
Blood urea nit rogen 56 mg/dL (20 mmol/L)
Elect rolyt es
Whi ch of the fol l owi ng best descri bes thi s pati ent's pl asma toni ci ty and serum sodi um status?
(A) Hyperosmolar hyponat remia
(B) Hyposmolar hyponat remia
(C) Normal osmolar hypernat remia
(D) Normal osmolar hyponat remia
(E) Normal osmolar pseudohyponat remia
Item 21 [Advanced]
A 73-year-old woman is brought t o t he emergency depart ment aft er falling at home. Her family st at es t hat she has been very confused and disorient ed over t he past 2 days
and t hat she began t herapy wit h a new medicat ion 4 days ago. She has t ype 2 diabet es mellit us, hypert ension, and glaucoma. A bag cont aining t he pat ient 's medicat ions
includes glyburide, met formin, hydrochlorot hiazide, acet azolamide, and enalapril.
On physical examinat ion, t emperat ure is 37C (98.6F), heart rat e is 68/min, respirat ion rat e is 12/min, and blood pressure is 115/65 mm Hg. She is confused and unable t o
answer quest ions appropriat ely. Cardiac examinat ion is normal. The lungs are clear. There is no edema.
Whi ch of the fol l owi ng drugs i s most l i kel y responsi bl e for the pati ent's fi ndi ngs?
(A) Acet azolamide
(B) Glyburide
(C) Hydrochlorot hiazide
(D) Met formin
Item 22 [Advanced]
A 55-year-old man is seen during a rout ine evaluat ion. He was diagnosed wit h t ype 2 diabet es mellit us 15 years ago. He also has hypert ension and a 1-year hist ory of right
knee ost eoart hrit is t hat is well cont rolled wit h maximal-dose ibuprofen. His ot her medicat ions are losart an, met formin, and pravast at in.
examinat ion is normal. There is bilat eral lower-ext remit y edema t o t he mid shin.
Glucose (nonfast ing) 230 mg/dL (12.8 mmol/L)
Serum creat inine 2.5 mg/dL (221 mol/L)
Urinalysis Specific gravit y 1.015; 3+ prot ein; 2+ glucose; no cast s
Whi ch of the fol l owi ng i s the most appropri ate i ni ti al management step?
(A) Begin hydrochlorot hiazide
(B) Begin spironolact one
(C) Discont inue ibuprofen and begin furosemide
(D) Subst it ut e lisinopril for losart an
Item 23 [Basic]
A 30-year-old man wit h t ype 1 diabet es mellit us and chronic kidney disease (serum creat inine, 5.3 mg/dL [468.5 mol/L]) is evaluat ed in t he emergency depart ment for a 2-
day hist ory of muscle weakness and recent onset of light headedness. An elect rocardiogram t aken in t he emergency depart ment is shown.
Whi ch of the fol l owi ng i s the best i mmedi ate treatment opti on?
(A) Calcium gluconat e, int ravenously
(B) 50% glucose, int ravenously
(C) Hemodialysis
(D) Sodium polyst yrene sulfonat e in sorbit ol, rect ally
Item 24 [Advanced]
A 17-year-old girl is evaluat ed for weakness. On physical examinat ion, t he blood pressure is 124/74 mm Hg wit h no ort host at ic changes, pulse rat e 72/min, and respirat ion
rat e 15/min. BMI is 18. The rest of t he physical examinat ion is unremarkable.
Blood urea nit rogen and serum creat inine are normal. A spot urine pot assium concent rat ion is 8 meq/L (8 mmol/L).
(A) Laxat ive abuse
(B) Primary hyperaldost eronism
(C) Primary hypoaldost eronism
(D) Surrept it ious diuret ic use
Item 25 [Basic]
A 44-year-old man comes t o t he emergency depart ment wit h polyuria and polydipsia. Over t he past 3 days, he has not ed increased urinat ion wit h nearly const ant t hirst .
Physical examinat ion is normal. Admission laborat ory result s included serum sodium of 155 meq/L (155 mmol/L), plasma glucose of 150 mg/dL (8.3 mmol/L), and urine
osmolalit y of 117 mosm/kg (117 mol/kg). He has significant increase in urine osmolalit y (great er t han 50%) wit hin 1 t o 2 hours aft er inject ion of arginine vasopressin.
What i s the most l i kel y cause of the hypernatremi a?
(A) Cent ral diabet es insipidus
(B) Diabet es mellit us
(C) Nephrogenic diabet es insipidus
(D) Primary polydipsia
Item 26 [Advanced]
A 55-year-old woman is evaluat ed in t he emergency depart ment for a 2-day hist ory of severe midepigast ric pain radiat ing t hrough t o her back and of nausea wit h vomit ing.
Before t his, she was well and had no medical problems; she does not t ake any medicat ions or drink alcohol.
On examinat ion, she is in dist ress from pain. Temperat ure is 37.8C (98.9F), blood pressure is 155/97 mm Hg, and pulse rat e is 104/min. BMI is 29. Midepigast ric t enderness
t o palpat ion is marked.
An abdominal ult rasound reveals a dilat ed common bile duct and mult iple gallst ones. Laborat ory evaluat ion reveals elevat ed alkaline phosphat ase, amylase, and lipase levels;
t ot al calcium level is 6.8 mg/dL (1.7 mmol/L).
What of the fol l owi ng i s the most l i kel y cause of the hypocal cemi a?
(A) 1,25-dihydroxy vit amin D deficiency
(B) Aut oimmune hypoparat hyroidism
(C) Calcium chelat ion wit h free fat t y acids
(D) Parat hyroid gland injury
Item 27 [Advanced]
A 45-year-old man wit h st age 1 pulmonary sarcoidosis (hilar lymphadenopat hy) is evaluat ed for abdominal pain and dist ent ion. He has chronic const ipat ion, and his last
bowel movement was 6 days ago.
On physical examinat ion, t emperat ure is 36.8C (98.2F), blood pressure is 152/80 mm Hg, pulse rat e is 78/min, and respirat ion rat e is 12/min. Bowel sounds are present but
diminished. Tenderness t o palpat ion is present and most prominent in t he left lower quadrant wit hout guarding. Rect al examinat ion reveals firm st ool but no masses.
Serum calcium level is 11.6 mg/dL (2.9 mmol/L); t he reminder of t he laborat ory evaluat ion is normal, including t hyroid-st imulat ing hormone level and free t hyroxine. A
plain film of t he abdomen shows marked colonic dist ent ion wit h st ool but no free air under t he diaphragm or evidence of mechanical bowel obst ruct ion. Enemas and laxat ives
are prescribed.
Whi ch of the fol l owi ng i s the most appropri ate addi ti onal treatment for thi s pati ent?
(A) Cinacalcet
(B) Hydrochlorot hiazide
(C) Int ravenous normal saline
(D) Prednisone
Item 28 [Basic]
A 45-year-old man is evaluat ed for a 3-mont h hist ory of fat igue, const ipat ion, and polyuria. He also has a 5-year hist ory of hypert ension. Current medicat ions are losart an
and dilt iazem.
Physical examinat ion findings, including vit al signs, are normal.
Glucose, fast ing 88 mg/dL (4.9 mmol/L)
Measurement of whi ch of the fol l owi ng l evel s shoul d be done next?
(A) Calcit onin
(B) 25-Hydroxy vit amin D
(C) Parat hyroid hormone
(D) Parat hyroid hormone-relat ed prot ein
Item 29 [Advanced]
A 47-year-old man wit h a long-st anding hist ory of alcoholism is hospit alized for acut e pancreat it is. His last drink was 6 days ago. He has lost approximat ely 10% of his body
weight over t he past 4 mont hs due t o drinking alcohol and not eat ing.
On physical examinat ion, he is cachect ic. Vit al signs are normal. BMI is 17. He is not confused or t remulous. There is midepigast ric t enderness wit hout rebound. Neurologic
The pat ient receives t hiamine replacement , folic acid supplement at ion, and a mult ivit amin followed by vigorous int ravenous fluid replacement wit h 5% dext rose and normal
saline and pot assium chloride. Morphine is used t o cont rol pain.
Eight een hours lat er, t he pat ient 's abdominal pain has improved but he becomes rest less, agit at ed, and ext remely weak and is barely able t o raise his ext remit ies against
gravit y.
(A) Hypercalcemia
(B) Hypokalemia
(C) Hyponat remia
(D) Hypophosphat emia
Item 1 Answer: B
Educati onal Objecti ve: Diagnose orthostatic proteinuria.
The most appropriat e next diagnost ic t est is t o evaluat e t he pat ient for ort host at ic prot einuria. This is done by obt aining separat e upright (dayt ime) and supine (overnight )
urine collect ions for prot ein quant it at ion. Ort host at ic prot einuria is defined by an increase in urinary prot ein excret ion only in t he upright posit ion; when supine, t he urinary
prot ein excret ion rat e is normal (<50 mg/8 h). The condit ion is seen most commonly in children or young adult s. The t ot al urine prot ein excret ion rat e is usually less t han 1
g/24 h, and t he urinalysis is ot herwise normal. The et iology of t he condit ion is uncert ain; in some cases, mild alt erat ions in glomerular hist ology have been report ed. An
associat ion of ort host at ic prot einuria wit h ent rapment of t he left renal vein bet ween t he aort a and t he superior mesent eric art ery ("nut cracker syndrome") also has been
report ed. The condit ion is benign; it oft en resolves spont aneously, and long-t erm follow-up st udies in affect ed pat ient s have shown renal funct ion remains normal.
A kidney biopsy is not t he most appropriat e next st ep in t his pat ient 's management . His medical hist ory provides no evidence of significant past or present illness, and his
physical examinat ion and init ial laborat ory st udies do not suggest serious kidney disease. Specifically, he is normot ensive and not edemat ous; t he serum creat inine, albumin,
and cholest erol are normal; and, t he urinalysis is normal.
A single 24-hour urine collect ion would most likely only confirm t he subnephrot ic rat e of urinary prot ein excret ion, which is already evident from t he spot urine prot ein-
creat inine rat io of 0.8 mg/mg. More import ant ly, a single 24-hour urine collect ion would fail t o different iat e t he rat es of upright versus supine prot einuria, which is essent ial
in dist inguishing ort host at ic from persist ent prot einuria.
Given t he pat ient 's age, normal hemoglobin, and serum prot ein, a dysprot einemia is very unlikely, and serum and urine prot ein elect rophoresis st udies are not needed. Should
t he pat ient prove t o have persist ent prot einuria, urine prot ein elect rophoresis and immunofixat ion st udies may be useful in det ermining whet her t he prot einuria reflect s
glomerular or t ubular disease.
Key Poi nt
Orthostati c protei nuri a i s defi ned by an i ncrease i n uri nary protei n excreti on onl y i n the upri ght posi ti on.
Bi bl i ography
Sebest yen JF, Alon US. The t eenager wit h asympt omat ic prot einuria: t hink ort host at ic first . Clin Pediat r. 2011;50(3):179-182. [PMID: 20837623]
Item 2 Answer: A
Educati onal Objecti ve: Diagnose acute interstitial nephritis.
The most likely diagnosis is acut e int erst it ial nephrit is. This pat ient has acut e kidney injury (AKI), as evidenced by t he sudden onset of oliguria and an increase in her blood
urea nit rogen (BUN) and serum creat inine values. Her urine (normal upon admission) is posit ive for leukocyt es and leukocyt e cast s, but t he cult ure is negat ive (st erile pyuria).
This clinical pict ure is most consist ent wit h t ubuloint erst it ial inflammat ion caused by acut e int erst it ial nephrit is. Drugs, part icularly -lact am ant ibiot ics, are t he most
common et iology of acut e int erst it ial nephrit is. Pat ient s may also have fever, rash, and eosinophilia, alt hough only a minorit y of pat ient s will have all t hree feat ures.
Acut e t ubular necrosis (ATN) is t he most common form of int rarenal disease t hat causes acut e kidney injury in hospit alized pat ient s. Onset of t his condit ion usually occurs
aft er a sust ained period of ischemia or exposure t o nephrot oxic agent s. Urinalysis in approximat ely 75% of pat ient s wit h acut e t ubular necrosis reveals muddy brown cast s;
leukocyt es and leukocyt e cast s are not associat ed wit h ATN.
Cholest erol cryst al embolizat ion may cause AKI in pat ient s wit h aort ic at herosclerot ic plaques. This condit ion may occur spont aneously but most oft en develops aft er
coronary or kidney angiography or aort ic surgery. Kidney injury in pat ient s wit h cholest erol cryst al embolizat ion usually has a subacut e onset wit h a st ut t ering course over
several weeks. Cut aneous manifest at ions develop in approximat ely 10% t o 15% of pat ient s and may include livedo ret icularis, skin ulcerat ion, and nodules. Pat ient s wit h
cholest erol cryst al embolizat ion t ypically have a bland urine sediment but may have dysmorphic hemat uria and eryt hrocyt e cast s.
The absence of ort host at ic hypot ension, t achycardia, and t he normal BUN-creat inine rat io of approximat ely 10:1, argue against prerenal azot emia as t he cause of AKI.
Key Poi nt
Acute i ntersti ti al nephri ti s i s characteri zed by acute ki dney i njury, steri l e pyuri a, and l eukocyte casts.
Bi bl i ography
Perazella MA, Markowit z GS. Drug-induced acut e int erst it ial nephrit is. Nat Rev Nephrol. 2010;6(8):461-70. [PMID: 20517290]
Item 3 Answer: A
Educati onal Objecti ve: Evaluate persistent hematuria with cystoscopy.
The most appropriat e next st ep is cyst oscopy. This pat ient has persist ent hemat uria, defined as t he presence of t hree or more eryt hrocyt es/hpf in t he urine det ect ed on t wo
or more samples. Bleeding in pat ient s wit h persist ent hemat uria may originat e anywhere along t he genit ourinary t ract , and different iat ing bet ween glomerular and
nonglomerular hemat uria helps t o guide management . This pat ient 's normal-appearing eryt hrocyt es revealed on urine microscopy and absence of eryt hrocyt e cast s and
prot ein in t he urine are consist ent wit h nonglomerular hemat uria.
One possible cause of persist ent nonglomerular hemat uria is genit ourinary t ract malignancy. Risk fact ors for t hese malignancies include male sex, age great er t han 50 years,
t obacco use, and exposure t o drugs such as cyclophosphamide and benzene and radiat ion. Because t his pat ient has several risk fact ors, cyst oscopy is indicat ed t o exclude a
malignancy.
Hemat uria may develop in pat ient s t aking NSAIDs or ant icoagulant s but should not aut omat ically be at t ribut ed t o t hese agent s; appropriat e evaluat ion for glomerular or
nonglomerular disorders should st ill be performed in t his set t ing. In addit ion, discont inuat ion of warfarin may place him at risk for furt her t hromboembolic disorders.
This pat ient 's slight ly increased serum creat inine level is suggest ive of glomerular disease, which oft en manifest s as a decrease in kidney funct ion. However, glomerular
hemat uria is commonly associat ed wit h dysmorphic eryt hrocyt es and eryt hrocyt e cast s. Glomerular disease also is unlikely in t he absence of prot ein on urinalysis. Therefore,
kidney biopsy, which is oft en used t o evaluat e pat ient s wit h glomerular disease, would not be appropriat e for t his pat ient .
In a pat ient wit h persist ent hemat uria and at high risk for genit ourinary t ract malignancy, repeat ing t he urinalysis in 3 mont hs put s t he pat ient at risk for progressive spread
of cancer and is not an appropriat e management opt ion.
Key Poi nt
In pati ents wi th nongl omerul ar hematuri a, ki dney ul trasonography and cystoscopy are i ndi cated to excl ude a geni touri nary tract mal i gnancy i n
i ndi vi dual s wi th ri sk factors for thi s condi ti on.
Bi bl i ography
Cohen R, Brown S. Microscopic hemat uria. N Engl J Med. 2003;348(23):2330-2338. [PMID: 12788998]
Item 4 Answer: D
Educati onal Objecti ve: Diagnose rhabdomyolysis secondary to narcotic overdose.
This pat ient most likely has rhabdomyolysis, which is caused by skelet al muscle damage t hat leads t o release of int racellular component s int o t he circulat ion. The syndrome
was first ident ified in pat ient s wit h t raumat ic crush injuries, but t here are nont raumat ic causes, such as alcohol (due t o hypophosphat emia), drug use, met abolic disorders, and
infect ions. The classic t riad of findings includes muscle pain, weakness, and dark urine. The diagnosis is based on clinical findings and a hist ory of predisposing fact ors (such as
prolonged immobilizat ion or drug t oxicit y) and confirmed by t he presence of myoglobinuria, an increased serum creat ine kinase level, and, in some cases, hyperkalemia. A
posit ive urine dipst ick for blood in t he absence of eryt hrocyt es also suggest s rhabdomyolysis. The disorder usually resolves wit hin days t o weeks. Treat ment consist s of
aggressive fluid resuscit at ion; fluids should be adjust ed t o maint ain t he hourly urine out put at least 300 mL unt il t he urine is negat ive for myoglobin. Acut e kidney injury
result ing from acut e t ubular necrosis occurs in approximat ely one t hird of pat ient s. Dialysis is somet imes necessary.
Alt hough fulminant hepat ic failure may result in coma, dark urine, and renal failure, ot her t est s of synt het ic liver funct ion in t his pat ient are normal. Hemolyt ic anemia
would not explain t he pat ient 's elevat ed creat ine kinase level and usually does not cause renal failure. Hemolyt ic uremic syndrome is not consist ent wit h t he normal complet e
blood count , clinical findings of polysubst ance overdose or t he laborat ory finding of t he elevat ed serum creat ine kinase level.
Key Poi nt
Rhabdomyolysis is associat ed wit h muscle pain, weakness, and dark urine; laborat ory findings include an elevat ed serum creat ine kinase level and posit ive urine dipst ick for
blood in t he absence of eryt hrocyt es.
Bi bl i ography
Talaie H, Pajouhmand A, Abdollahi M, et al. Rhabdomyolysis among acut e human poisoning cases. Hum Exp Toxicol. 2007:26(7):557-561. [PMID: 17884958]
Item 5 Answer: C
Educati onal Objecti ve: Diagnose obstructive nephropathy as a cause of acute kidney injury.
The best diagnost ic t est for t his pat ient is kidney ult rasound t o evaluat e for urinary obst ruct ion. The pat ient has lower urinary t ract sympt oms wit h difficult y voiding and
suprapubic fullness. This is consist ent wit h bladder out let obst ruct ion from prost at ic hypert rophy. Obst ruct ion can cause int rarenal vasoconst rict ion, ischemic t ubular injury,
and int erst it ial fibrosis t hat may lead t o end-st age kidney disease if uncorrect ed. Alt hough pat ient s wit h complet e obst ruct ion have significant ly decreased urine out put , t hose
wit h part ial obst ruct ion may have polyuria caused by loss of t ubular funct ion or excret ion of excess ret ained solut e. Kidney ult rasound in most pat ient s wit h obst ruct ion
reveals hydronephrosis. Pat ient s wit h acut e kidney injury (AKI) caused by urinary t ract obst ruct ion have a favorable prognosis when obst ruct ion is relieved wit hin 1 week of
onset . A kidney ult rasound would reveal a dist ended bladder and possible hydronephrosis. Insert ion of a Foley cat het er is init ial t reat ment .
Kidney biopsy should be considered when t he diagnosis of AKI remains unclear aft er excluding prerenal and post renal disease. Biopsy is warrant ed t o help guide t herapy or
provide prognost ic informat ion. Ult rasound duplex art eriography, CT art eriography, MRI, and angiot ensin-convert ing enzyme inhibit or renography are used t o evaluat e
renal vasculat ure in t he presence of disrupt ed art erial or venous blood flow. In t his pat ient wit h voiding sympt oms and suprapubic fullness, noninvasive kidney ult rasoundy is
t he diagnost ic t est of choice.
Albumin is t he only prot ein det ect ed on dipst ick urinalysis, and not hing in t he pat ient 's present at ion suggest s he has a primary glomerular disease causing AKI; dipst ick
evaluat ion would add lit t le t o t his case. Quant it at ive measurement s, rat her t han dipst ick met hodology, are recommended t o det ect albumin excret ion less t han 300 mg/24 h.
Key Poi nt
Ki dney ul trasound i s i ndi cated for al l pati ents wi th acute ki dney i njury to defi ne ki dney anatomy and to excl ude hydronephrosi s.
Bi bl i ography
Sharfuddin AA, Sandoval RM, Molit oris BA. Imaging t echniques in acut e kidney injury. Nephron Clin Pract . 2008;109(4):c198-c204. [PMID: 18802368]
Item 6 Answer: C
Educati onal Objecti ve: Diagnose hemolytic uremic syndrome.
The most likely diagnosis is hemolyt ic uremic syndrome (HUS). HUS commonly manifest s as acut e kidney injury (AKI) accompanied by t hrombocyt openia and
microangiopat hic hemolyt ic anemia (schist ocyt es on peripheral blood smear). The t wo most common causes are infect ion by Shiga t oxin-producing Escherichia coli (E. coli
O157:H7 and ot her serot ypes) and familial deficiency of fact or H. The t oxin causes bloody diarrhea and ent ers t he circulat ion and binds t o plat elet s, glomerular capillary
endot helial cells, mesangial cells, and glomerular and t ubular epit helial cells. Shiga t oxin binds t o plat elet s by means of globot riaosylceramide recept ors, which leads t o plat elet
aggregat ion. Shiga t oxin may also st imulat e endot helial cells t o release large von Willebrand fact or mult imers, which can furt her enhance plat elet aggregat ion. Fact or H, a
prot ein in t he complement pat hway, normally prot ect s cells from damage by t he alt ernat ive complement pat hway. A deficiency of fact or H allows C3 t o pot ent iat e
aut oant ibody-mediat ed or immune complex-mediat ed injury t o glomerular cells, leading t o exposure of subendot helium and act ivat ion of bot h plat elet s and coagulat ion.
Acut e int erst it ial nephrit is (AIN) is most commonly caused by a hypersensit ivit y react ion t o a medicat ion or by cert ain infect ions or aut oimmune condit ions. Urinalysis
findings in pat ient s may include leukocyt e cast s and eosinophils. AIN does not cause hemolyt ic anemia or t hrombocyt openia.
Acut e t ubular necrosis (ATN) usually occurs aft er a sust ained period of ischemia or exposure t o nephrot oxic agent s. ATN may resolve in 1 t o 3 weeks or result in permanent
end-st age kidney disease, depending on t he durat ion and severit y of t he ischemic or nephrot oxic insult . Urinalysis usually reveals muddy brown cast s and is not associat ed wit h
microangiopat hic hemolyt ic anemia or t hrombocyt openia.
Rhabdomyolysis develops when muscle injury leads t o t he release of myoglobin and ot her int racellular muscle cont ent s int o t he circulat ion. Myoglobin is known t o cause
nephrot oxicit y by induct ion of kidney ischemia and t ubular obst ruct ion. Rhabdomyolysis most commonly develops aft er exposure t o myot oxic drugs, infect ion, excessive
exert ion, or prolonged immobilizat ion. A diagnosis of rhabdomyolysis should be considered in pat ient s wit h a serum creat ine kinase level great er t han 5000 U/L who
demonst rat e heme posit ivit y on urine dipst ick t est ing in t he absence of hemat uria.
Key Poi nt
Hemol yti c uremi c syndrome commonl y mani fests as acute ki dney i njury accompani ed by thrombocytopeni a and mi croangi opathi c hemol yti c anemi a.
Bi bl i ography
Amirlak I, Amirlak B. Haemolyt ic uraemic syndrome: an overview. Nephrology (Carlt on). 2006;11(3):213-8. [PMID: 16756634]
Item 7 Answer: B
Educati onal Objecti ve: Diagnose acute tubular necrosis-associated acute kidney injury.
This pat ient 's elevat ed serum creat inine level, minimal prot einuria, and muddy brown cast s on urinalysis are most consist ent wit h acut e t ubular necrosis. This condit ion usually
develops aft er a sust ained period of ischemia or exposure t o nephrot oxic agent s such as cisplat in, int ravenous aminoglycosides, or radiocont rast .
Acut e int erst it ial nephrit is most commonly develops aft er exposure t o cert ain medicat ions, including t rimet hoprim. Manifest at ions of t his condit ion may include rash,
prurit us, eosinophilia, and fever. Urine sediment findings include pyuria, leukocyt e cast s, microscopic hemat uria, and t ubular-range prot einuria. These feat ures are absent in
t his pat ient .
Manifest at ions of t he t hrombot ic microangiopat hies, including t hrombot ic t hrombocyt openic purpura, may include acut e kidney injury t hat is usually accompanied by
microangiopat hic hemolyt ic anemia and t hrombocyt openia. Approximat ely 50% of pat ient s have low C3 levels. The urine sediment usually shows minimal or no
abnormalit ies and is nondiagnost ic; rarely, eryt hrocyt e or muddy brown cast s may be seen. This pat ient 's normal hemoglobin concent rat ion and plat elet count exclude a
t hrombot ic microangiopat hy as t he cause of t he acut e kidney injury.
Kidney ult rasonography in most pat ient s wit h obst ruct ion reveals hydronephrosis, which is absent in t his pat ient . Furt hermore, t he urinalysis in pat ient s wit h obst ruct ion is
benign and is not associat ed wit h t he muddy brown cast s found in t his pat ient 's urine.
Key Poi nt
Acut e t ubular necrosis usually develops aft er a sust ained period of ischemia or exposure t o nephrot oxic agent s and is associat ed wit h muddy brown cast s on urinalysis.
Bi bl i ography
Choudhury D, Ahmed Z. Drug-associat ed renal dysfunct ion and injury. Nat Clin Pract Nephrol. 2006;2(2):80-91. [PMID:16932399]
Item 8 Answer: B
Educati onal Objecti ve: Diagnose and treat prerenal azotemia with volume replacement.
This pat ient most likely has prerenal azot emia, and t he most appropriat e next st ep in management is isot onic saline. Acut e kidney injury in pat ient s wit h malignancy is
oft en due t o prerenal disease, obst ruct ion, or use of nephrot oxic agent s. The presence of hypot ension, hyponat remia, and a decreased urine sodium excret ion accompanied by
a bland urine sediment raises suspicion for prerenal azot emia.
Dialysis would be indicat ed if t he azot emia persist ed or worsened aft er correct ion of t he hypovolemia, part icularly if ot her uremic complicat ions such as encephalopat hy or
refract ory hyperkalemia were present . Dialysis is not indicat ed before t his pat ient has undergone a t rial of adequat e volume replacement .
Therapy wit h midodrine and oct reot ide may be effect ive and safe for t he t reat ment of hepat orenal syndrome in some pat ient s. However, t he absence of ascit es or ot her signs
of port al hypert ension are not consist ent wit h hepat orenal syndrome.
Tumor lysis syndrome may manifest as hyperkalemia, hyperphosphat emia, and hyperuricemia. Tumor lysis syndrome most likely occurs in pat ient s wit h ext remely rapidly
progressive lymphoid neoplasms and in t hose who have bulky lymphoid neoplasms t hat respond rapidly t o t reat ment . Rasburicase can be used t o t reat malignancy-relat ed
hyperuricemia in order t o prevent t umor lysis syndrome in high-risk pat ient s or as a component of t herapy for est ablished t umor lysis syndrome and associat ed
hyperuricemia. However, t his pat ient 's serum elect rolyt e, phosphorus, and uric acid level abnormalit ies are most likely a result of hypovolemia and associat ed kidney
dysfunct ion and should improve wit h volume replet ion; t herefore, rasburicase t herapy would not be warrant ed.
Key Poi nt
The presence of hypot ension, hyponat remia, and a decreased urine sodium excret ion accompanied by a bland urine sediment should raise suspicion for prerenal azot emia.
Bi bl i ography
Darmon M, Ciroldi M, Thiery G, Schlemmer B, Azoulay E. Clinical review: specific aspect s of acut e renal failure in cancer pat ient s. Crit Care 2006;10:211.
[PMID:16677413]
Item 9 Answer: C
Educati onal Objecti ve: Diagnose prerenal azotemia in a patient with chronic kidney disease.
The most likely cause of t his pat ient 's acut e kidney injury is prerenal azot emia. Prerenal azot emia develops when aut oregulat ion of kidney blood flow can no longer maint ain
glomerular filt rat ion rat e (GFR). This condit ion generally occurs in pat ient s wit h a mean art erial pressure below 60 mm Hg but may occur at higher pressures in individuals
wit h chronic kidney disease (CKD) or in t hose who t ake medicat ions t hat can alt er local glomerular hemodynamics, such as NSAIDs. Pat ient s wit h prerenal azot emia may
have a hist ory of fluid losses and decreased fluid int ake accompanied by physical examinat ion findings consist ent wit h ext racellular fluid volume deplet ion, such as post ural
hypot ension. However, t hese findings are absent in up t o 50% of pat ient s wit h t his condit ion. Nausea, vomit ing, and anorexia accompanied by relat ively low blood pressure in
t he absence of edema or urine sediment abnormalit ies st rongly suggest prerenal azot emia.
Acut e int erst it ial nephrit is may be caused by use of cert ain drugs, including ant ibiot ics and NSAIDs, and classically manifest s as pyuria, leukocyt e cast s, or eosinophils on
urinalysis. Fever, rash, and blood eosinophilia also may be present . The urine sediment in acut e t ubular necrosis usually shows muddy brown cast s or t ubular epit helial cell
cast s. Renal vein t hrombosis is an uncommon cause of acut e kidney injury associat ed wit h hemat uria and nephrot ic-range prot einuria. This condit ion is most oft en associat ed
wit h membranous nephropat hy, malignancy, t rauma, or hypercoagulable st at es. The normal urinalysis helps exclude acut e int erst it ial nephrit is, acut e t ubular necrosis, and
renal vein t hrombosis as t he cause of t his pat ient 's renal decompensat ion.
Key Poi nt
Prerenal disease is usually associat ed wit h relat ive low blood pressure, oliguria, and normal urinalysis.
Bi bl i ography
Kellum JA. Acut e kidney injury. Crit Care Med. 2008;36(suppl 4):S141-S145. [PMID: 18382185]
Item 10 Answer: C
Educati onal Objecti ve: Treat diabetic nephropathy with an angiotensin receptor blocker.
The most appropriat e next management st ep is t o increase t he dose of t he losart an. Uncont rolled hypert ension and prot einuria are import ant modifiable risk fact ors for
progressive kidney disease. Lowering blood pressure is crit ical regardless of t he underlying disease. For pat ient s wit h chronic kidney disease, guidelines recommend blood
pressure t arget s of less t han 130/80 mm Hg or less t han 125/75 mm Hg when significant prot einuria is present . Angiot ensin-convert ing enzyme inhibit ors, such as lisinopril,
and angiot ensin recept or blockers (ARBs), such as losart an, are t he preferred agent s in chronic kidney disease and slow progression of kidney disease in pat ient s wit h diabet es.
These agent s reduce efferent art eriolar resist ance and lower int raglomerular pressure and, t herefore, may be associat ed wit h increases in serum creat inine in pat ient s wit h a
reduced glomerular filt rat ion rat e. An increase in creat inine of up t o 30% is accept able. In t his pat ient , blood pressure remains elevat ed and he has significant prot einuria. The
most logical next st ep would be t o increase losart an. It is not necessary t o discont inue losart an, because t he increase in creat inine is not unexpect ed and his pot assium remains
at an accept able level.
Result s from a recent st udy, which involved elderly pat ient s at high risk for cardiovascular event s, indicat e t he use of combinat ion ACE inhibit or and ARB t herapy does not
reduce morbidit y and mort alit y and furt hermore increases adverse side effect s compared wit h t he use of ACE inhibit ors alone. Furt her st udies are warrant ed before
combinat ion t herapy can be recommended.
The clinical course and long-st anding diabet es progressing t o microalbuminuria and t hen t o overt prot einuria and loss of kidney funct ion over a period of years st rongly
suggest s diabet ic nephropat hy. Kidney biopsy would be unlikely t o change t he long-t erm management in t his pat ient .
Key Poi nt
In pat ient s wit h prot einuria and chronic kidney disease, angiot ensin-convert ing enzyme inhibit ors or angiot ensin recept or blockers should be used t o lower blood pressure,
decrease prot einuria, and slow disease progression.
Bi bl i ography
Defarrari G, Ravera M, Berrut i V, Leoncini G, Deferrari L. Opt imizing t herapy in t he diabet ic pat ient wit h renal disease: ant ihypert ensive t reat ment . J Am Soc Nephrol.
2004;15(suppl 1):S6-S11. [PMID: 14684664]
Item 11 Answer: D
Educati onal Objecti ve: Know the indications for initiating dialysis in a patient with chronic kidney disease.
At t his t ime, no change in t he management of t his pat ient 's disease is required. Pat ient s wit h st age 5 chronic kidney disease (glomerular filt rat ion rat e [GRF] <15
mL/min/1.73 m
2
or receiving dialysis) oft en develop signs of uremia and require kidney replacement t herapy. Absolut e indicat ions include uncont rollable hyperkalemia,
uncont rollable hypervolemia, alt ered ment al st at us or excess somnolence, pericardit is, or bleeding-diat hesis secondary t o uremic plat elet dysfunct ion. Relat ive indicat ions
include nausea, vomit ing, and poor nut rit ion caused by decreased appet it e; severe met abolic acidosis; mild changes in ment al st at us such as let hargy and malaise; ast erixis; and
worsening of kidney funct ion wit h GFR less t han 15 mL/min/1.73 m
2
. However, t he t iming of hemodialysis in pat ient s wit hout fluid overload, hyperkalemia, met abolic
acidosis, or uremic sympt oms, such as t his pat ient , is unclear. A recent st udy suggest s early init iat ion of hemodialysis does not improve pat ient out comes. Kidney
t ransplant at ion is t he t reat ment of choice for uremia. Transplant at ion in pat ient s who have not yet been t reat ed wit h hemodialysis is associat ed wit h bet t er pat ient and
allograft out comes. This pat ient has several family members who are willing kidney donors, and it is possible t hat he could receive a t ransplant in t he near fut ure; t herefore,
t he best course of act ion would be t o follow t he pat ient closely t o ensure he does not develop uremic signs or sympt oms or ot her indicat ions for dialysis and st rive for
t ransplant at ion rat her t han dialysis.
No indicat ion exist s for increasing t he lisinopril, especially wit h cont rolled blood pressure and a borderline high serum pot assium level. Likewise, no reason exist s t o perform
an abdominal ult rasound, because t he bilat eral flank masses are expect ed physical findings in a pat ient wit h enlarged kidneys secondary t o polycyst ic kidney disease and are
current ly asympt omat ic.
Key Poi nt
Kidney replacement t herapy for pat ient s wit h st age 5 chronic kidney disease who are not hypervolemic, hyperkalemic, acidot ic, or uremic may be delayed.
Bi bl i ography
Cooper BA, Branley P, Bulfone L, et al; IDEAL St udy. A randomized, cont rolled t rial of early versus lat e init iat ion of dialysis. N Engl J Med. 2010;363(7):609-19. [PMID:
20581422]
Item 12 Answer: B
Educati onal Objecti ve: Evaluate a patient with nondiabetic kidney disease with a kidney biopsy.
Kidney biopsy would be appropriat e for t his pat ient . This st udy is recommended in pat ient s wit h feat ures of nondiabet ic kidney disease in order t o est ablish a diagnosis and
det ermine t he most appropriat e t reat ment . Diabet ic nephropat hy is charact erized by prot einuria, hypert ension, and a decline in t he glomerular filt rat ion rat e in pat ient s wit h
a long-st anding hist ory of t ype 1 diabet es or a 5- t o 10-year hist ory of t ype 2 diabet es. This condit ion usually progresses from microalbuminuria t o macroalbuminuria t o an
elevat ed serum creat inine level over a number of years. Alt hough t his pat ient 's long-st anding hist ory of diabet es and prot einuria is suggest ive of diabet ic nephropat hy, t he
presence of glomerular hemat uria (dysmorphic eryt hrocyt es and eryt hrocyt e cast s) and t he rapid onset of sympt omat ic nephrot ic syndrome are not consist ent wit h diabet ic
nephropat hy. These findings raise suspicion for primary glomerular disease. Furt hermore, pat ient s wit h diabet ic nephropat hy oft en have diabet ic ret inopat hy, which is absent
in t his pat ient .
Cyst oscopy would be considered in an adult wit h hemat uria of uncert ain origin in order t o exclude bladder cancer. Similarly, imaging st udies may help t o evaluat e urinary t ract
obst ruct ion, kidney st ones, kidney cyst s or masses, renal vascular diseases, and vesicouret eral reflux. However, cyst oscopy or a spiral CT would not be warrant ed in a pat ient
wit h eryt hrocyt e cast s seen on urinalysis and dysmorphic eryt hrocyt es, which suggest s glomerular hemat uria.
Observat ion alone would place t his pat ient at risk for progressive kidney injury if her condit ion remains undiagnosed and unt reat ed.
Key Poi nt
Kidney biopsy is recommended in pat ient s wit h diabet es mellit us who have feat ures of nondiabet ic kidney disease.
Bi bl i ography
Lin YL, Peng SJ, Ferng SH, Tzen CY, Yang CS. Clinical indicat ors which necessit at e renal biopsy in t ype 2 diabet es mellit us pat ient s wit h renal disease. Int J Clin Pract .
2009;63(8):1167-1176. [PMID:18422591]
Item 13 Answer: D
Educati onal Objecti ve: Diagnose bone disease due to secondary hyperparathyroidism in a patient with end-stage kidney disease.
The most likely cause of t his pat ient 's bone disease is secondary hyperparat hyroidism. Chronic kidney disease (CKD) is associat ed wit h progressive alt erat ions in mineral and
bone met abolism t hat can cause bone disease. In pat ient s wit h end-st age kidney disease (ESKD), t he kidney's inabilit y t o excret e phosphorus leads t o hyperphosphat emia.
Loss of kidney funct ion also is associat ed wit h 1,25-dihydroxyvit amin D deficiency. Hyperphosphat emia along wit h decreased 1,25 dihydroxyvit amin D levels result in
hypocalcemia, which leads t o direct st imulat ion of parat hyroid hormone secret ion. Furt hermore, decreased 1,25 dihydroxyvit amin D levels cause increased product ion of
parat hyroid hormone. Therefore, bone disease due t o secondary hyperparat hyroidism, t he most common bone pat hologic finding seen in pat ient s wit h ESKD, develops. This
pat ient 's hyperphosphat emia, hypocalcemia, and elevat ed serum parat hyroid hormone and alkaline phosphat ase levels are consist ent wit h secondary hyperparat hyroidism.
Adynamic bone disease commonly occurs in pat ient s wit h ESKD and may cause fract ures. However, unlike bone disease associat ed wit h secondary hyperparat hyroidism,
adynamic bone disease is oft en associat ed wit h hypoparat hyroidism caused by excess vit amin D int ake and/or calcium loading. This condit ion usually manifest s as bone pain
accompanied by a serum parat hyroid hormone level below 100 pg/mL (100 ng/L) and a normal alkaline phosphat ase level.
Ost eoporosis is defined by low bone mass, which is associat ed wit h reduced bone st rengt h and an increased risk of fract ures. Ost eoporosis occurs most commonly in
post menopausal women but may develop secondary t o drugs such as cort icost eroids and ant iconvulsant s. Ost eoporosis does not affect t he concent rat ions of serum calcium,
phosphorus, parat hyroid hormone, or alkaline phosphat ase.
Ost eonecrosis is caused by t ransient or permanent lack of blood supply t o bone, which causes deat h of bone and bone marrow infarct ion t hat result s in mechanical failure.
Pat ient s t ypically present wit h chronic bone pain, not fract ure, and normal concent rat ions of calcium, phosphorus, and parat hyroid hormone.
Key Poi nt
Bone disease due t o secondary hyperparat hyroidism commonly occurs in pat ient s wit h end-st age kidney disease and may be associat ed wit h elevat ed serum parat hyroid
hormone and alkaline phosphat ase levels, hyperphosphat emia, and hypocalcemia.
Bi bl i ography
Abboud H, Henrich WL. Clinical pract ice. St age IV chronic kidney disease. N Engl J Med. 2010;362(1):56-65. [PMID: 20054047]
Item 14 Answer: A
Educati onal Objecti ve: Diagnose a mixed acid-base disorder.
The most likely acid-base disorder is met abolic acidosis, met abolic alkalosis, and respirat ory acidosis. The low pH defines acidosis; t he finding of a low carbon dioxide level
furt her defines t he acidosis as met abolic acidosis. The increased anion gap cat egorizes t he met abolic acidosis as an increased anion-gap acidosis. The PCO
2
measurement
det ermines if respirat ory compensat ion is appropriat e for t he degree of met abolic acidosis. The adequacy of respirat ory compensat ion can be checked using Wint er formula:
Expect ed PCO
2
= (1.5 [HCO
3
-
] + 8) 2 = 24 2
This formula confirms t he measured PCO
2
is elevat ed for t he degree of met abolic acidosis, est ablishing t he diagnosis of respirat ory acidosis. Finally, t he correct ed carbon
dioxide level is calculat ed t o det ermine if a complicat ing met abolic dist urbance is present :
Correct ed [HCO
3
-
] = measured [HCO
3
-
] + (measured anion gap - 12)
Using t his formula, t he correct ed carbon dioxide level (t he expect ed carbon dioxide concent rat ion if no ot her acid-base dist urbances were present ) is 31 meq/L (31 mmol/L),
est ablishing t he diagnosis of a complicat ing met abolic alkalosis.
Key Poi nt
To diagnose a mixed acid-base disorder, it is necessary t o evaluat e t he pH, anion gap, expect ed PCO
2
, bicarbonat e and correct ed bicarbonat e levels.
Bi bl i ography
Kraut JA, Madias NE. Approach t o pat ient s wit h acid-base disorders. Respir Care. 2001;46(4):392-403. [PMID: 11262558]
Item 15 Answer: B
Educati onal Objecti ve: Diagnose renal tubular acidosis.
The pat ient 's low pH indicat es an acidosis. The low carbon dioxide level confirms t hat it is a met abolic acidosis. The normal anion-gap calculat ion furt her classifies t he
acidosis as normal anion-gap acidosis. Normal anion-gap met abolic acidosis can be of kidney or ext rarenal origin. Met abolic acidosis of kidney origin, such as renal t ubular
acidosis (RTA), is caused by abnormalit ies in t ubular hydrogen t ransport . Met abolic acidosis of ext rarenal origin is most commonly caused by gast roint est inal losses of carbon
dioxide; ot her ext rarenal causes include t he ext ernal loss of biliary and pancreat ic secret ions and uret eral diversion procedures. The clinical hist ory usually helps t o dist inguish
bet ween kidney and ext rarenal causes of met abolic acidosis, but measuring t he urine ammonium excret ion can confirm t he cause of t his condit ion. Ext rarenal causes of
met abolic acidosis are associat ed wit h an appropriat e increase in net acid excret ion primarily reflect ed by high levels of urine ammonium excret ion, whereas kidney causes of
t his condit ion are associat ed wit h low net acid excret ion and decreased urine ammonium levels.
Urine ammonium measurement is not a commonly available st udy, but t his value can be indirect ly assessed by calculat ing t he urine anion gap (UAG) using t he following
formula:
Urine anion gap = ([urine sodium] + [urine pot assium]) - [urine chloride]
The UAG is normally bet ween 30 and 50 meq/L (30 t o 50 mmol/L). Met abolic acidosis of ext rarenal origin is suggest ed by a large, negat ive UAG caused by significant ly
increased urine ammonium excret ion. Conversely, met abolic acidosis of kidney origin is suggest ed by a posit ive UAG relat ed t o minimal urine ammonium excret ion. This
pat ient 's UAG is 20 meq/L (20 mmol/L); alt hough it is wit hin t he normal range, it is inappropriat ely low for t he degree of t he pat ient 's acidosis. This t ype of acidosis is
compat ible wit h renal t ubular acidosis. It is not compat ible wit h gast roent erit is or laxat ive abuse, bot h causes of ext rarenal normal anion-gap acidosis. Diabet ic ket oacidosis
causes an increased anion-gap acidosis and is not compat ible wit h t his pat ient 's laborat ory findings.
Key Poi nt
Normal anion-gap met abolic acidosis of ext rarenal origin is suggest ed by a large, negat ive urine anion gap, whereas a posit ive urine anion gap suggest s met abolic acidosis of
kidney origin.
Bi bl i ography
Kraut JA, Madias NE. Approach t o pat ient s wit h acid-base disorders. Respir Care. 2001;46(4):392-403. [PMID: 11262558]
Item 16 Answer: B
Educati onal Objecti ve: Diagnose respiratory acidosis due to chronic obstructive pulmonary disease.
This pat ient 's acid-base disorder is respirat ory acidosis. Respirat ory acidosis is produced by any process associat ed wit h primary ret ent ion of carbon dioxide. In t his pat ient ,
t he pH is less t han 7.38 and t he PCO
2
is >40 mm Hg (5.3 kPa), indicat ing t he presence of a respirat ory acidosis. Renal compensat ory response occurs in respirat ory acidosis.
Persist ent hypercapnia st imulat es t he secret ion of prot ons at t he level of t he dist al nephron. The urinary pH decreases, and excret ion of urinary ammonium, t it rat able acid,
and chloride is enhanced. Consequent ly, t he reabsorpt ion of bicarbonat e t hroughout t he nephron is enhanced. The predict ed increase in serum bicarbonat e is calculat ed as 1
meq/L (1 mmol/L) for each 10 mm Hg (1.3 kPa) increase in PCO
2
(acut e) or 4 meq/L (4 mmol/L) for each 10 mm Hg (1.3 kPa) increase in PCO
2
(chronic). Because t his
pat ient wit h chronic obst ruct ive pulmonary disease probably has chronic ret ent ion of carbon dioxide, an increase in t he serum bicarbonat e by at least 8 meq/L (8 mmol/L) is
expect ed. This is consist ent wit h t he measured serum bicarbonat e level. Therefore, t here is appropriat e compensat ion for t he respirat ory acidosis and no evidence for a
coexist ing met abolic acidosis. Respirat ory alkalosis is not consist ent wit h t he observed decrease in t he serum pH.
Key Poi nt
In respirat ory acidosis, t he predict ed increase in serum bicarbonat e is calculat ed as 1 meq/L (1 mmol/L) for each 10 mm Hg (1.3 kPa) increase in PCO
2
(acut e) or 4 meq/L (4
mmol/L) for each 10 mm Hg (1.3 kPa) increase in PCO
2
(chronic).
Bi bl i ography
Palmer BF. Approach t o fluid and elect rolyt e disorders and acid-base problems. Prim Care. 2008;35:195-213, v. [PMID: 18486713]
Item 17 Answer: D
Educati onal Objecti ve: Diagnose respiratory alkalosis.
This pat ient has a pure respirat ory alkalosis. The presence of an alkaline pH wit h a low PCO
2
is compat ible wit h respirat ory alkalosis. Furt hermore, t here is appropriat e
met abolic compensat ion for t he respirat ory alkalosis. In acut e respirat ory alkalosis, for each 10 mm Hg (1.3 kPa) decline in PCO
2
t he expect ed decline in serum bicarbonat e
is 2 meq/L (2 mmol/L). Since his PCO
2
declined by 10 mm Hg (1.3 kPa) t o 30 mm Hg (4.0 kPa), t he expect ed decline in t he serum bicarbonat e is 2 meq/L (2 mmol/L); t his
mat ches t he measured serum bicarbonat e concent rat ion exact ly. Because t he decline in t he serum bicarbonat e level is appropriat e for t he degree of respirat ory alkalosis t he
pat ient cannot have a met abolic acidosis or met abolic alkalosis. And since his anion gap is normal, t here is no possibilit y t hat t he acid-base dist urbance is an anion-gap
met abolic acidosis. The anion gap is 8, calculat ed as [Na
+
] - ([Cl
-
] + [HCO
3
-
]). Normal anion gap is 12 2.
Because t he PCO
2
is depressed rat her t han elevat ed, t he diagnosis cannot be respirat ory acidosis.
There are many pot ent ial causes of respirat ory alkalosis, and t he physical examinat ion is oft en helpful in ident ifying t he correct diagnosis. Common causes of respirat ory
alkalosis include psychogenic (for example, hypervent ilat ion associat ed wit h anxiet y), normal pregnancy, pulmonary vascular disease (for example, pulmonary hypert ension
or pulmonary embolism), pulmonary parenchymal disease (for example, pneumonia and pulmonary fibrosis), heart failure, sepsis, and cirrhosis.
Key Poi nt
In acut e respirat ory alkalosis, for each 10 mm Hg (1.33 kPa) decline in PCO
2,
t he expect ed decline in serum bicarbonat e is 2 meq/L (2 mmol/L).
Bi bl i ography
Item 18 Answer: C
Educati onal Objecti ve: Diagnose ethylene glycol poisoning.
This pat ient has et hylene glycol poisoning, which may manifest as acut e kidney injury associat ed wit h an increased anion gap met abolic acidosis and an increased osmolal gap.
The osmolal gap is t he difference bet ween t he calculat ed plasma osmolalit y and measured plasma osmolalit y. In t his pat ient , t he osmolalit y is calculat ed using t he following
formula:
2 [Sodium] + [Glucose]/18 + [Blood Urea Nit rogen]/2.8 = 296 mosm/kg (296 mol/kg) Where sodium is meq/L and glucose and blood urea nit rogen are mg/dL.
The difference bet ween t he measured and calculat ed osmolalit y is 40 mosm/kg (40 mol/kg). The normal osmolal gap is approximat ely 10 mosm/kg (10 mol/kg). An
elevat ed osmolal gap suggest s t he presence of an unmeasured osmole t hat is most commonly et hanol but can be et hylene glycol or met hanol. However, only et hylene glycol
is associat ed wit h kidney injury and calcium oxalat e cryst als in t he urine.
Alt hough alcoholic and diabet ic ket oacidosis and lact ic acidosis can cause an anion gap met abolic acidosis, none of t hese condit ions is associat ed wit h an osmolal gap.
Key Poi nt
Et hylene glycol poisoning is associat ed wit h an anion gap met abolic acidosis, an increased osmolal gap, kidney injury, and calcium oxalat e cryst als in t he urine.
Bi bl i ography
Item 19 Answer: D
Educati onal Objecti ve: Diagnose a mixed metabolic and respiratory alkalosis disorder.
Art erial blood gas values demonst rat e a mixed met abolic and respirat ory alkalosis. Met abolic alkalosis is indicat ed by t he high serum bicarbonat e level and a pH great er t han
7.4. Respirat ory compensat ion for t he met abolic alkalosis is not appropriat e; t he PCO
2
would be expect ed t o increase in compensat ion for t he elevat ed serum bicarbonat e
level, but inst ead, t he PCO
2
has decreased t o 36 mm Hg (4.8 kPa), indicat ing t he presence of a respirat ory alkalosis. In most pat ient s, for each 1 meq/L (1 mmol/L) increase
in serum bicarbonat e, t he PCO
2
can be expect ed t o increase by 0.7 mm Hg (0.09 kPa).
The anion gap is 7, calculat ed as (141 - [100 + 34]); t hus, t here is no hidden anion-gap met abolic acidosis (normal anion gap < 12 2). The respirat ory alkalosis is most
likely due t o pain-induced hypervent ilat ion from t he kidney st one, and met abolic alkalosis is probably a result of vomit ing.
Key Poi nt
A mixed met abolic and respirat ory alkalosis is suggest ed by an elevat ed pH and serum bicarbonat e concent rat ion and a PCO
2
concent rat ion t hat is lower t han expect ed for t he
degree of alkalosis.
Bi bl i ography
Item 20 Answer: B
Educati onal Objecti ve: Diagnose hyposmolar hyponatremia in a patient with heart failure.
This pat ient has hyposmolar hyponat remia. Osmolalit y is defined as t he number of solut e part icles per kilogram of solut ion. Plasma osmolalit y can be direct ly measured by
an osmomet er or calculat ed using t he following equat ion:
Plasma osmolalit y (mosm/kg = 2 serum [Na
+
] (meq/L) + blood urea nit rogen (mg/dL)/2.8 + plasma glucose (mg/dL)/18
Using t his formula, t he calculat ed plasma osmolalit y is 252 mosm/kg (normal, 275-295 mosm/kg [275-295 mol/kg]). Therefore, t he pat ient is hyposmolar and
hyponat remic.
Hyponat remia can be caused by a decrease in effect ive art erial blood volume, which result s in barorecept or st imulat ion of ant idiuret ic hormone (ADH) secret ion, which
impairs wat er excret ion. Consequent ly, dist al delivery of filt rat e t o t he t ip of t he loop of Henle decreases. A decrease in effect ive art erial blood volume may be associat ed
wit h low ext racellular fluid volume (hypovolemic hyponat remia) or high ext racellular fluid volume in edemat ous pat ient s (hypervolemic hyponat remia), including heart
failure, cirrhosis, and nephrot ic syndrome.
True hyponat remia may be associat ed wit h an elevat ion in t he plasma concent rat ion of an effect ive osmole, such as glucose. This elevat ion result s in an increase in plasma
osmolalit y (hyperosmolar hyponat remia), which causes wat er t o leave t he cells and result s in a dilut ed serum sodium concent rat ion. Hyponat remia t hat occurs in t he absence
of a hyposmolar st at e (pseudohyponat remia) is generally caused by an increased serum concent rat ion of an effect ive osmole. Common causes of pseudohyponat remia include
hyperglobulinemia and hypert riglyceridemia. Because t hese condit ions are associat ed wit h a decrease of plasma wat er relat ive t o plasma solids in t he blood, t he amount of
sodium in a given volume of blood also decreases.
Key Poi nt
Hyponat remia can be caused by a decrease in effect ive art erial blood volume, which result s in barorecept or st imulat ion of ant idiuret ic hormone (ADH) secret ion.
Bi bl i ography
Kazory A. Hyponat remia in heart failure: revisit ing pat hophysiology and t herapeut ic st rat egies. Clin Cardiol. 2010;33(6):322-9. [PMID:20556801]
Item 21 Answer: C
Educati onal Objecti ve: Diagnose hydrochlorothiazide-induced hyponatremia.
Hydrochlorot hiazide is a common cause of hyponat remia in t he out pat ient set t ing. It is especially common in t he elderly. Early signs of sympt omat ic hyposmolalit y may be
very nonspecific, such as nausea, vomit ing, and headaches (hyponat remic encephalopat hy). Worsening of brain swelling t hen causes decreased ment al st at us and seizures.
Diuret ic-induced hyponat remia most commonly occurs in pat ient s t aking t hiazide diuret ics. Elderly women wit h low body mass indices who t end t o increase fluid int ake aft er
init iat ion of t herapy wit h t hese agent s are oft en affect ed. Thiazide diuret ics work at t he level of t he convolut ed t ubule and collect ing segment . Therefore, t hese agent s
maint ain urinary concent rat ing capacit y but not dilut ing capacit y, which makes t hem prone t o cause hyponat remic encephalopat hy. By inducing relat ive volume deplet ion,
ant idiuret ic hormone secret ion is st imulat ed, which leads t o urine concent rat ion and wat er ret ent ion. Treat ment includes st opping t he diuret ic and infusing normal saline (for
mildly sympt omat ic pat ient s) or 3% saline (for significant ly sympt omat ic pat ient s).
Acet azolamide act s in t he proximal t ubule as a carbonic anhydrase IV inhibit or. Blocking t his enzyme in t he proximal t ubule impairs bicarbonat e reabsorpt ion but not dilut ing
capacit y and is most oft en associat ed wit h hypokalemia and met abolic acidosis. Acet azolamide is not associat ed wit h t he development of hyponat remia. Met formin and
glyburide do not affect fluid and elect rolyt e balance.
Key Poi nt
Hydrochlorot hiazide can cause severe hyponat remia.
Bi bl i ography
Mann SJ. The silent epidemic of t hiazide-induced hyponat remia. J Clin Hypert ens (Greenwich). 2008;10:477-484. [PMID: 18550938]
Item 22 Answer: C
Educati onal Objecti ve: Manage hyperkalemia in a patient with chronic kidney disease.
Discont inuat ion of ibuprofen and init iat ion of furosemide are t he most appropriat e next st eps in t he init ial management of t his pat ient 's chronic kidney disease. This
pat ient 's long-st anding hist ory of diabet es mellit us, hypert ension, prot einuria, and elevat ed serum creat inine level are consist ent wit h diabet ic nephropat hy. Aggressive blood
pressure cont rol, part icularly wit h pharmacologic modulat ors of t he renin-angiot ensin-aldost erone syst em, would help t o slow t he progression of t his pat ient 's disease but will
likely worsen his hyperkalemia.
Unt il t he glomerular filt rat ion rat e decreases t o less t han 15 mL/min/1.73 m
2
, chronic kidney disease usually does not cause hyperkalemia wit hout ot her mit igat ing fact ors.
These fact ors include use of medicat ions t hat int erfere wit h t he renin-angiot ensin-aldost erone syst em and NSAIDs. Use of t he NSAID ibuprofen is most likely cont ribut ing t o
t his pat ient 's hyperkalemia and reduced glomerular filt rat ion rat e and should be discont inued.
However, discont inuing ibuprofen alone would most likely not help t o lower t his pat ient 's blood pressure, cont rol volume overload, or fully correct his hyperkalemia; t he
addit ion of a loop diuret ic is t herefore warrant ed. If needed, addit ional int ervent ions t o help decrease t he risk of hyperkalemia include adherence t o a low-pot assium diet and
use of sodium bicarbonat e.
Thiazide diuret ics are largely ineffect ive in individuals wit h an est imat ed glomerular filt rat ion rat e below 30 mL/min/1.73 m
2
.
The addit ion of losart an would worsen t his pat ient 's hyperkalemia and would not be recommended.
Spironolact one has been shown t o furt her decrease urine prot ein excret ion when added t o eit her angiot ensin-convert ing enzyme inhibit ors or angiot ensin recept or blockers in
pat ient s wit h diabet ic nephropat hy. However, t his agent impairs kidney pot assium excret ion and also would furt her exacerbat e t his pat ient 's hyperkalemia.
Key Poi nt
Discont inuat ion of medicat ions t hat int erfere wit h t he renin-angiot ensin-aldost erone syst em, including NSAIDs and, if needed, angiot ensin-convert ing enzyme inhibit ors and
angiot ensin recept or blockers, is warrant ed t o help correct significant hyperkalemia in t he set t ing of chronic kidney disease.
Bi bl i ography
Palmer BF. Managing hyperkalemia caused by inhibit ors of t he renin-angiot ensin-aldost erone syst em. N Engl J Med. 2004;351(6):585-592. [PMID:15295051]
Item 23 Answer: A
Educati onal Objecti ve: Treat hyperkalemia with intravenous calcium gluconate.
The best immediat e t reat ment opt ion is int ravenous calcium gluconat e. The elect rocardiogram shows spiking of t he T waves and widening of t he QRS complexes, findings
t hat indicat e hyperkalemic cardiot oxicit y in t his pat ient wit h chronic kidney disease. The choice of t reat ment for hyperkalemia and t he aggressiveness of it s implement at ion
depend largely on t he severit y of t he hyperkalemia as well as on elect rocardiographic and neuromuscular manifest at ions. The approximat e relat ionship bet ween
elect rocardiographic changes and t he serum pot assium concent rat ion is subst ant ially modified by changes of ot her cat ions in t he serum and t he acid-base st at us. (For example,
wit h t he simult aneous presence of hyponat remia, hypocalcemia, and acidemia, even modest degrees of hyperkalemia may result in serious and pot ent ially fat al elect rical
dist urbances.)
Urgent t herapy of hyperkalemia consist s of ant agonism of t he membrane effect s of hyperkalemia and induct ion of int racellular pot assium shift . Removing pot assium from
t he body (for example, by sodium polyst yrene sulfonat e, hemodialysis, perit oneal dialysis) is import ant , but t he effect s cannot be accomplished wit h t he necessary urgency.
Therefore, t he first st ep in t reat ing urgent hyperkalemia is t o administ er calcium gluconat e t o ant agonize hyperkalemic cardiac t oxicit y, an effect t hat usually begins wit hin 2
t o 3 minut es of administ rat ion of int ravenous calcium gluconat e. Sodium bicarbonat e and -ant agonist s such as albut erol and glucose (wit h or wit hout insulin) would facilit at e
int racellular pot assium shift . However, t heir effect is slower (10 minut es for sodium bicarbonat e, 15 t o 30 minut es for albut erol, and 30 minut es for glucose and insulin).
Hypert onic glucose should not be administ ered wit hout insulin when t reat ing a pat ient wit h diabet es.
Dialysis, 50% glucose, and sodium polyst yrene sulfonat e are all helpful t herapeut ic st eps in managing urgent hyperkalemia, but none is t he ideal first st ep.
Key Poi nt
The first st ep in t reat ing urgent hyperkalemia is t o administ er calcium gluconat e t o ant agonize hyperkalemic cardiac t oxicit y.
Bi bl i ography
Alfonzo AV, Isles C, Geddes C, Deighan C. Pot assium disorders: clinical spect rum and emergency management . Resuscit at ion. 2006;70(1):10-25. [PMID: 16600469]
Item 24 Answer: A
Educati onal Objecti ve: Diagnose laxative abuse in a patient with hypokalemia.
This pat ient likely has been abusing laxat ives. This is support ed by t he serum elect rolyt e pat t ern suggest ing hypokalemia and a met abolic acidosis. In t he absence of a cellular
shift , a low serum pot assium concent rat ion can be caused by losses via t he gast roint est inal t ract , skin or kidney, or due t o inadequat e diet ary int ake of pot assium. A urine
pot assium concent rat ion of less t han 20 meq/L (20 mmol/L) is suggest ive of ext rarenal losses, whereas a concent rat ion higher t han t his value is suggest ive of kidney losses.
Therefore, t his pat ient has a hypokalemic disorder associat ed nonrenal pot assium loss. Gast roint est inal disorders are t he most common clinical cause of ext rarenal pot assium
losses. Diarrhea leads t o fecal pot assium wast age and is associat ed wit h a normal anion gap acidosis due t o increased gast roint est inal loss of bicarbonat e. Her low serum
bicarbonat e is consist ent wit h met abolic acidosis but wit hout an art erial blood gas, t he acid-base disorder cannot be det ermined. Villous adenoma and laxat ive abuse are t wo
such condit ions t hat can cause gast roint est inal pot assium losses. The fact t hat t he pat ient is an underweight adolescent female, in whom eat ing disorders are common, suggest s
t he possibilit y of surrept it ious laxat ive abuse in an effort t o cont rol weight .
Alt hough primary hyperaldost eronism may result hypokalemia, it is t ypically associat ed wit h hypert ension and high urinary pot assium concent rat ion, bot h of which is absent
in t his pat ient . Hypoaldost eronism is associat ed wit h hyponat remia and hyperkalemia, which are not compat ible wit h t his pat ient 's findings. Surrept it ious diuret ic abuse can
cause of hypokalemia; however, it is associat ed wit h met abolic alkalosis and high urinary pot assium concent rat ion, findings not seen in t his pat ient .
Key Poi nt
In a pat ient wit h hypokalemia, a urine pot assium concent rat ion of less t han 20 meq/L (20 mmol/L) is suggest ive of ext rarenal losses, whereas a concent rat ion higher t han
t his value is suggest ive of kidney losses.
Bi bl i ography
Alfonzo AV, Isles C, Geddes C, Deighan C. Pot assium disorders: clinical spect rum and emergency management . Resuscit at ion. 2006;70(1):10-25. [PMID: 16600469]
Item 25 Answer: A
Educati onal Objecti ve: Diagnose central diabetes insipidus.
The most likely cause of t his pat ient 's hypernat remia is cent ral diabet es insipidus. This pat ient is clearly hyperosmolar, as est imat ed by mult iplying t he serum sodium level by
2 (310 mosm/kg [310 mol/kg]; normal, 275-295 mosm/kg [275-295 mol/kg]). The appropriat e renal response t o hyperosmolalit y is t o maximally concent rat e t he urine
(generally t o great er t han 800 mosm/kg [800 mol/kg]). This response is not seen in t his pat ient . Thus, he has eit her diabet es insipidus or a solut e diuresis. A solut e diuresis is
most oft en caused by hyperglycemia. This pat ient does have a plasma glucose level of 150 mg/dL (8.3 mmol/L); however, t his degree of elevat ion is unlikely t o cause
significant solut e diuresis because t he renal t hreshold for glucose reabsorpt ion in most persons is 200 t o 225 mg/dL (11.1 t o 12.5 mmol/L). Furt hermore, solut e diuresis is
usually charact erized by isot onicit y of t he urine, whereas t his pat ient has a markedly hypot onic urine. Consequent ly, diabet es mellit us is unlikely.
Hyperosmolar pat ient s wit hout glucosuria who have submaximally concent rat ed urine have diabet es insipidus by definit ion. Dist inguishing bet ween cent ral and nephrogenic
diabet es insipidus in a pat ient who is already hyperosmolar can be done by measuring plasma arginine vasopressin (AVP) (pat ient s wit h cent ral diabet es insipidus have an
inappropriat ely low level, whereas pat ient s wit h nephrogenic diabet es insipidus have a normal t o elevat ed level); or by evaluat ing t he response t o administ ered AVP (5 U
subcut aneously) or, preferably, t he select ive AVP V
2
recept or agonist desmopressin (arginine vasopressin, 1 t o 2 g subcut aneously or int ravenously). A significant increase in
urine osmolalit y (great er t han 50%) wit hin 1 t o 2 hours aft er inject ion indicat es insufficient endogenous AVP secret ion, and, t herefore, cent ral diabet es insipidus, whereas a
lack of response indicat es renal resist ance t o t he effect s of AVP and, t herefore, nephrogenic diabet es insipidus.
Pat ient s wit h primary polydipsia also manifest polyuria and polydipsia but do not become hypernat remic and hyperosmolar. These pat ient s may develop hyponat remia and
t ypically have clearly ident ifiable psychiat ric illness.
Key Poi nt
Hyperosmolar pat ient s wit hout glucosuria who have submaximally concent rat ed urine have diabet es insipidus by definit ion.
Bi bl i ography
Loh JA, Verbalis JG. Disorders of wat er and salt met abolism associat ed wit h pit uit ary disease. Endocrinol Met ab Clin Nort h Am. 2008;37:213-234, x. [PMID: 18226738]
Item 26 Answer: C
Educati onal Objecti ve: Diagnose acute pancreatitis as a cause for hypocalcemia.
The most likely cause of t he pat ient 's hypocalcemia is calcium chelat ion wit h free fat t y acids liberat ed by pancreat ic enzymes during an episode of acut e gallst one
pancreat it is. When t he pancreas is injured, t he secret ion of pancreat ic enzymes is blocked, which leads t o an aut odigest ive injury t o t he gland. The pancreat ic enzymes are
t hen released wit hin t he perit oneum and digest fat ; t he generat ed free fat t y acids avidly chelat e insoluble calcium salt s, result ing in hypocalcemia and deposit ion of calcium
salt s in t he pancreat ic bed. This process is known as saponificat ion and can lead t o sympt omat ic hypocalcemia and calcium deposit s ident ifiable on plain films of t he
abdomen. Pancreat ic calcificat ion ident ified by imaging st udies is a diagnost ic sign of chronic pancreat it is.
1,25-hydroxy vit amin D deficiency is most commonly seen in chronic kidney disease and is due t o decreased act ivit y of t he 1-hydroxylase enzyme responsible for
convert ing 25-hydroxy vit amin D t o t he act ive form. This pat ient does not have a hist ory of chronic kidney disease.
This pat ient has no hist ory of previous t hyroid surgery, which is t he most common reason for parat hyroid injury and hypoparat hyroidism and is relat ed t o incident al removal
or vascular injury t o t he parat hyroid glands. Aut oimmune dest ruct ion of t he parat hyroid gland usually occurs in t he set t ing of ot her aut oimmune disorders (polyglandular
aut oimmune syndrome) including adrenal insufficiency and mucocut aneous candidiasis, which are not present in t his pat ient .
Key Poi nt
Acut e pancreat it is can generat e free fat t y acids t hat avidly chelat e insoluble calcium salt s in t he pancreat ic bed, result ing in hypocalcemia.
Bi bl i ography
Juan D. Hypocalcemia. Different ial diagnosis and mechanisms. Arch Int ern Med. 1979;139(10):1166-71. [PMID: 226022]
Item 27 Answer: D
Educati onal Objecti ve: Treat hypercalcemia due to sarcoidosis with corticosteroids.
This man present s wit h severe const ipat ion due t o hypercalcemia in t he set t ing of sarcoidosis. Sarcoidosis is a mult isyst em, granulomat ous, inflammat ory condit ion of
unknown cause t hat occurs in young adult s of bot h sexes. The t emporal pat t ern of disease progression ranges from asympt omat ic t o acut e syst emic present at ions wit h fever,
eryt hema nodosum, polyart hralgia, and hilar lymphadenopat hy (Lofgren syndrome). Approximat ely 90% of pat ient s have pulmonary involvement at t he t ime of
present at ion. Hypercalcemia and hypercalciuria in sarcoidosis are caused by unregulat ed product ion of 1-hydroxylase by act ivat ed macrophages in t he granuloma t issue.
Increased 1-hydroxylase act ivit y increases t he product ion of 1,25 [OH]
2
vit amin D. Increased amount s of vit amin D
3
result in increased gast roint est inal absorpt ion of
calcium, result ing in hypercalcemia. Cort icost eroid t herapy decreases vit amin D
3
product ion by decreasing t he number of act ivat ed macrophages.
Cinacalcet binds t o t he parat hyroid calcium-sensing recept or, leading t o decreased release of parat hyroid hormone. This t herapy is indicat ed only in refract ory secondary
hyperparat hyroidism of chronic kidney disease (low serum calcium and elevat ed parat hyroid hormone levels) or t ert iary hyperparat hyroidism (elevat ed serum calcium and
elevat ed serum parat hyroid hormone levels), neit her of which applies t o t his pat ient .
Hydrochlorot hiazide indirect ly inhibit s calcium excret ion by t he kidney, leading t o calcium ret ent ion, and may cause hypercalcemia. Alt hough t his pat ient 's blood pressure is
elevat ed, it should be remeasured aft er his const ipat ion is relieved and hypercalcemia is resolved; regardless, hydrochlorot hiazide would be an inappropriat e medicat ion because
of it s propensit y t o cause hypercalcemia.
Measures t aken t o t reat acut e sympt omat ic hypercalcemia include increasing urinary excret ion of calcium. Urine calcium excret ion can be at t ained by inhibit ion of proximal
t ubular and loop sodium resorpt ion, which is best achieved by volume expansion using int ravenous normal saline infusion (1-2 L for 1 hour). This t herapy is generally
reserved for sympt omat ic pat ient s wit h moderat e calcium elevat ion (>12 mg/dL [3.0 mmol/L]) and is unnecessary in t his pat ient .
Key Poi nt
Sarcoidosis causes hypercalcemia t hrough increased product ion of 1-hydroxylase and can be t reat ed wit h prednisone.
Bi bl i ography
Iannuzzi MC, Font ana JR. Sarcoidosis: clinical present at ion, immunopat hogenesis, and t herapeut ics. JAMA. 2011;305(4):391-9. [PMID:21266686]
Item 28 Answer: C
Educati onal Objecti ve: Diagnose hyperparathyroidism by measuring the parathyroid hormone level.
This pat ient 's parat hyroid hormone (PTH) level should be det ermined next . Primary hyperparat hyroidism is t he most common cause of hypercalcemia in t he out pat ient
set t ing. The first st ep in t he diagnosis of hypercalcemia is det erminat ion of t he PTH level wit h an assay for int act PTH. If t he PTH level is high or "inappropriat ely"
normal, primary hyperparat hyroidism is t he diagnosis. If t he PTH level is suppressed, a search for ot her ent it ies t hat cause hypercalcemia must be conduct ed.
Calcit onin is secret ed by t hyroid parafollicular C cells. This serum level is elevat ed in pat ient s wit h medullary t hyroid cancer or C-cell hyperplasia. Calcit onin t ends t o lower
t he calcium level by enhancing cellular upt ake, renal excret ion, and bone format ion. The effect of calcit onin on bone met abolism is weak and only relevant in pharmacologic
amount s. Measurement of serum calcit onin is not indicat ed in a pat ient wit h hypercalcemia.
One of t he ways in which PTH increases t he serum calcium level is by up-regulat ion of t he 1-hydroxylase enzyme, which st imulat es conversion of vit amin D t o it s most
act ive form, 1,25-dihydroxy vit amin D. This form of vit amin D increases t he percent age of diet ary calcium absorbed by t he int est ine. Body st ores of vit amin D are assessed
by measuring t he 25-hydroxy vit amin D level, which has a long half-life. Measurement of t his pat ient 's 25-hydroxy vit amin D and 1,25-dihydroxy vit amin D levels may be
appropriat e if t he parat hyroid hormone level is suppressed. At t his t ime, however, such measurement is not indicat ed.
Humoral hypercalcemia of malignancy result s from t he syst emic effect of a circulat ing fact or produced by neoplast ic cells. The hormone most commonly responsible for t his
syndrome is parat hyroid hormone-relat ed prot ein (PTHrP). This pept ide's N-t erminal shares many homologic feat ures wit h PTH and most , if not all, of t he met abolic
effect s of PTH. Tumors t hat elaborat e PTHrP are most commonly squamous cell carcinomas, such as t hose of t he lung, esophagus, and head and neck. This pat ient has no
evidence of cancer. The diagnosis of humoral hypercalcemia of malignancy can oft en be made in t he absence of PTHrP measurement s if a compat ible malignancy,
hypercalcemia, and suppressed PTH level are present .
Key Poi nt
The most common cause of hypercalcemia in t he out pat ient set t ing is hyperparat hyroidism.
Bi bl i ography
Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;35(2):215-237, v-vi. [PMID: 18486714]
Item 29 Answer: D
Educati onal Objecti ve: Diagnose hypophosphatemia in a patient with chronic alcoholism.
This pat ient most likely has hypophosphat emia. Severe hypophosphat emia most oft en develops in pat ient s wit h chronic alcoholism who have poor oral int ake, decreased
int est inal absorpt ion due t o frequent vomit ing and diarrhea, and increased kidney excret ion due t o t he direct effect of et hanol on t he t ubule. Despit e t ot al body phosphorus
deplet ion, t hese pat ient s may have normal serum phosphorus levels on admission t o t he hospit al. Severe hypophosphat emia oft en develops over t he first 12 t o 24 hours
aft er admission, usually because of int ravenous glucose administ rat ion, which st imulat es insulin release and causes phosphat e t o shift int o cells. The sudden development of
hypophosphat emia may cause confusion, rhabdomyolysis, hemolyt ic anemia, and severe muscle weakness t hat can lead t o respirat ory failure. Oral phosphat e is t he preferred
t reat ment in t his set t ing, but int ravenous administ rat ion may be needed if oral t herapy cannot be t olerat ed.
Hypercalcemia may manifest as decreased neuromuscular excit abilit y t hat causes decreased muscular t one. Hypercalcemia is most commonly caused by alt erat ions in calcium
absorpt ion from t he gut and bone resorpt ion due t o primary hyperparat hyroidism, malignancy, and granulomat ous diseases. Primary hyperparat hyroidism and t hiazide
diuret ic use also may cause t his condit ion. The sudden development of hypercalcemia in t his pat ient is unlikely.
Hypokalemia can cause diffuse muscle weakness, gast roint est inal t ract at ony, respirat ory failure, and cardiac arrhyt hmias. In chronic hypokalemia, muscle weakness is unusual
in pat ient s wit h a serum pot assium level above 2.5 meq/L (2.5 mmol/L) and t he risk of profound hypokalemia is low in a pat ient receiving pot assium supplement at ion.
Early signs of hyponat remia t ypically include nausea, vomit ing, and headaches; progressive manifest at ions include impaired ment al st at us and seizures. These sympt oms are
not compat ible wit h t his pat ient 's present at ion. Finally, t he development of acut e hyponat remia would be unlikely in a pat ient receiving int ravenous normal saline.
Key Poi nt
Pat ient s wit h chronic alcoholism may have normal serum phosphorus levels on admission t o t he hospit al but may develop severe hypophosphat emia over t he first 12 t o 24
hours.
Bi bl i ography
Moe S. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;35(2):215-237. [PMID: 18486714]
Secti on 8. Neurol ogy
Questi ons
Item 1 [Basic]
An 80-year old woman living in a nursing home wit h hist ory of dement ia is admit t ed t o t he hospit al wit h pneumonia. In t he emergency depart ment , a peripheral int ravenous
line was insert ed, appropriat e ant ibiot ics were init iat ed, she was given oxygen by nasal cannula, and a urinary cat het er was placed.
On physical examinat ion, t emperat ure is 38.3C (101.0F), blood pressure is 140/88 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 16/min. Pulmonary auscult at ion
reveals left lower lobe crackles. Cardiac examinat ion is normal. Moderat e cognit ive impairment is not ed but no inat t ent ion or focal neurologic deficit s.
She is provided access t o her glasses and hearing aid, and a large clock and night light are in place in her room.
Whi ch of the fol l owi ng addi ti onal steps shoul d be taken to prevent del i ri um i n thi s pati ent?
(A) Administ er benzodiazepine, as needed
(B) Administ er diphenhydramine for sleep
(C) Administ er haloperidol t wice daily
(D) Check vit al signs every 4 hours t hrough t he night
(E) Remove her urinary cat het er
Item 2 [Basic]
A 79-year-old woman was hospit alized 4 days ago aft er sust aining a right hip fract ure in a fall. She underwent surgical repair wit h right hip replacement 3 days ago and did not
fully awake from general anest hesia unt il 12 hours aft er ext ubat ion. As her alert ness has increased, she has become increasingly agit at ed. The pat ient has a 4-year hist ory of
Alzheimer dement ia. She has no ot her pert inent personal or family medical hist ory. Current medicat ions are donepezil, memant ine, and low-molecular-weight heparin.
On physical examinat ion t oday, t emperat ure is 37.2C (99.0F), blood pressure is 100/68 mm Hg, pulse rat e is 100/min and regular, and respirat ion rat e is 18/min. The
pat ient can move all four limbs wit h guarding of t he right lower limb. She is inat t ent ive and disorient ed t o t ime and place and exhibit s combat iveness alt ernat ing wit h
hypersomnolence. The remainder of t he neurologic examinat ion is unremarkable, wit hout evidence of focal findings or meningismus.
(A) Acut e st roke
(B) Acut e worsening of Alzheimer dement ia
(C) Meningit is
(D) Post operat ive delirium
Item 3 [Advanced]
A 75-year-old woman wit h a hist ory of chronic obst ruct ive pulmonary disease is evaluat ed in t he int ensive care unit for delirium. She had a median st ernot omy and repair of
an aort ic dissect ion and was ext ubat ed unevent fully on post operat ive day 4. Two days lat er she developed fluct uat ions in her ment al st at us and inat t ent ion. While st ill in t he
int ensive care unit , she became agit at ed, pulling at her lines, at t empt ing t o climb out of bed, and asking t o leave t he hospit al. Her art erial blood gas values are normal. The
pat ient has no hist ory of alcohol abuse or ot her subst ance abuse. The use of frequent orient at ion cues, calm reassurance, and presence of family members has done lit t le t o
reduce t he pat ient 's agit at ed behavior. Medical evaluat ion ident ifies no focal neurologic deficit s and no evidence of infect ion or met abolic abnormalit y.
Whi ch of the fol l owi ng i s the most appropri ate therapy?
(A) Diphenhydramine
(B) Haloperidol
(C) Lorazepam
(D) Propofol
Item 4 [Basic]
A 36-year-old woman is evaluat ed in t he emergency depart ment for a 3-day hist ory of confusion and falls. The pat ient lives alone and is accompanied by her neighbor who
says t hat t he pat ient 's sympt oms seem t o be get t ing worse. The pat ient has a 10-year hist ory of chronic alcoholism and has had recent weight loss due t o diarrhea. She t akes
no medicat ions.
On physical examinat ion, t emperat ure is 35.6C (96.0F), blood pressure is 142/76 mm Hg, pulse rat e is 90/min, respirat ion rat e is 14/min; BMI is 17. Temporal muscle
wast ing, sunken supraclavicular fossae, and absent adipose st ores are not ed. Abdominal examinat ion findings are normal. On neurologic examinat ion, t he pat ient is confused;
she is unable t o st at e t he dat e and does not know t he name of t he hospit al. Marked horizont al nyst agmus is not ed. There is no nuchal rigidit y or obvious mot or weakness.
Deep t endon reflexes are reduced, and plant ar responses are flexor. The pat ient has a markedly at axic gait .
(A) Elect roencephalography
(B) Haloperidol
(C) Thiamine
(D) Vancomycin, ampicillin, and ceft riaxone
Item 5 [Advanced]
A 73-year-old man is evaluat ed for confusion t hat began 2 weeks ago. He wanders aimlessly in t he house, somet imes not recognizing his wife and mist aking t he newspaper for
his hat . He has visual hallucinat ions and believes he sees mice in t he refrigerat or. His medical hist ory includes t ype 2 diabet es mellit us wit h painful peripheral neuropat hy,
coronary art ery disease, depression, and heart failure. Medicat ions are glyburide, nort ript yline, digoxin, lorazepam, met oprolol, lisinopril, aspirin, and pravast at in. He does
not remember how long he has been t aking t hese medicat ions and if t here have been any recent dosage changes. The pat ient drinks alcohol only occasionally, usually wine
wit h a weekend meal.
On physical examinat ion, t he pat ient has ast erixis. Vit al signs are normal; oxygen sat urat ion is normal wit h t he pat ient breat hing ambient air. He is inat t ent ive and not
orient ed t o t ime or place. His score on t he Mini-Ment al St at e Examinat ion is 13/30 (28/30 6 mont hs ago). Result s of laborat ory st udies, including elect rolyt e levels and liver
chemist ry and renal funct ion st udies, are normal. An MRI of t he brain is normal.
(A) Alcohol hallucinosis
(B) Alzheimer dement ia
(C) Depression
(D) Toxic encephalopat hy (delirium)
Item 6 [Basic]
A 33-year-old woman is evaluat ed in t he emergency depart ment for parest hesia t hat began in t he left face and spread over 30 minut es t o t he left arm and leg, clumsiness of
t he left hand t hat began 30 minut es ago, and a subsequent right -sided t hrobbing headache and nausea. This is t he first t ime she has ever had such sympt oms. She is ot herwise
healt hy but has a family hist ory of migraine. Her only medicat ion is a daily oral cont racept ive pill.
On physical examinat ion, t emperat ure is normal, blood pressure is 140/82 mm Hg, pulse rat e is 110/min, and respirat ion rat e is 20/min. All ot her examinat ion findings are
normal.
Result s of laborat ory st udies and a CT scan of t he head are also normal.
(A) Migraine wit h aura
(B) Mult iple sclerosis
(C) Part ial complex seizure
(D) Transient ischemic at t ack
(E) Trigeminal neuralgia
Item 7 [Basic]
A 24-year-old woman is evaluat ed in t he office for headache t hat occurs once or t wice a week. The pain is a const ant pressure in t he back of t he head. She has no nausea and
can cont inue t o work during t he headaches. She has had t hese headaches since age 13 years and not es t hat t hey now seem t o be more frequent and associat ed wit h less sleep
and increased st ress. When t reat ed wit h ibuprofen or acet aminophen, t he headaches abat e in 30 minut es; unt reat ed, t hey last several hours. She t ypically uses headache
medicat ion four t o six t imes per mont h.
On physical examinat ion, vit al signs are normal. All ot her findings from t he general physical examinat ion findings, including t hose from a neurologic evaluat ion, are normal.
(A) Chronic daily headache
(B) Clust er headache
(C) Migraine headache wit hout aura
(D) Tension-t ype headache
Item 8 [Advanced]
A previously healt hy 42-year-old woman is evaluat ed in t he emergency depart ment for t he sudden onset of a severe occipit al headache during defecat ion 8 hours ago,
followed by t wo episodes of vomit ing. The headache reached maximum int ensit y wit hin seconds. She has never had a headache like t his before. She report s no neck st iffness
or neurologic sympt oms. Her mot her and t wo sist ers have a hist ory of migraine.
On physical examinat ion, t emperat ure is 36.8C (98.2F), blood pressure is 148/88 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 20/min. The pat ient is in significant
dist ress as a result of t he pain. There is no evidence of meningismus, papilledema, or focal neurologic signs.
(A) CT angiography of t he head and neck
(B) Lumbar punct ure
(C) Noncont rast CT of t he head
(D) Subcut aneous administ rat ion of sumat ript an
Item 9 [Basic]
A 32-year-old woman is evaluat ed for a gradual increase in migraine frequency and severit y over t he past 6 mont hs. Migraine at t acks, which formerly occurred t wo or t hree
t imes each mont h, are now occurring approximat ely t hree t imes each week, wit h each at t ack last ing at least 12 hours. She has no ot her medial problems and t akes only
almot ript an as needed for acut e migraine.
On physical examinat ion, vit al signs and result s of a general physical examinat ion, including a neurologic examinat ion, are normal.
An MRI of t he brain shows no abnormalit ies.
(A) Bot ulinum t oxin
(B) Propranolol
(C) Nort ript yline
(D) Sert raline
Item 10 [Basic]
A 75-year-old woman is evaluat ed in t he emergency depart ment aft er she was wit nessed driving errat ically on a cit y st reet . Init ially, t he pat ient was unable t o answer any
quest ions and had difficult y wit h her speech. Twent y minut es lat er, her speech was fluid, and, alt hough she did not have any recollect ion of t he past few hours' event s, she was
able t o provide some det ails of her life, including her husband's name. When her husband arrived, t he pat ient was able t o recognize him, but 10 minut es lat er she did not
recognize him. No evidence of hallucinat ions or delusions exist s.
The husband report s t hat t he pat ient has had a gradual and progressive cognit ive impairment over t he previous 5 years for which she t akes donepezil. She oft en awakens at
night and roams about t he house. She has chronic problems wit h her memory and managing act ivit ies of daily living.
(A) Delirium
(B) Delirium superimposed on dement ia
(C) Dement ia
(D) Psychosis
Item 11 [Basic]
A 68-year-old man is evaluat ed for memory difficult y t hat , according t o his wife, began insidiously 3 or 4 years earlier. He has difficult y remembering recent event s. For
example, he forget s appoint ment s and recent conversat ions and forgot t hat a close relat ive had recent ly died. He is no longer able t o manage his own checkbook or operat e
his car wit hout get t ing lost . Medical hist ory is ot herwise unremarkable.
Physical examinat ion findings, including vit al signs, are normal. Ment al st at us examinat ion shows prominent memory loss and difficult y drawing a complex figure.
Laborat ory st udies show t hat a complet e blood count and rout ine chemist ries are normal. An MRI of t he brain shows only mild cerebral at rophy.
(A) Alzheimer dement ia
(B) Creut zfeldt -Jakob disease
(C) Dement ia wit h Lewy bodies
(D) Front ot emporal dement ia
Item 12 [Advanced]
An 84-year-old man is evaluat ed for t he gradual onset of progressive memory loss over t he past 2 years. In t he past 4 mont hs, he has t wice been unable t o find his way home
aft er going t o t he local supermarket . His wife has assumed responsibilit y for t he household finances aft er t he pat ient overdrew t heir checking account for t he t hird t ime. His
mot her had onset of Alzheimer dement ia at age 79 years and died at age 86 years. His only medicat ion is a daily mult ivit amin.
On physical examinat ion, vit al signs are normal. His level of alert ness, speech, and gait are normal. His score on t he Folst ein Mini-Ment al St at e Examinat ion is 24/30,
including 0/3 on t he recall port ion, which corresponds wit h a diagnosis of mild dement ia.
Result s of laborat ory st udies, including a complet e blood count , serum vit amin B
12
measurement , t hyroid funct ion t est s, and a basic met abolic panel, are normal.
An unenhanced MRI of t he brain shows no abnormalit ies.
Whi ch of the fol l owi ng i s the most appropri ate treatment at thi s ti me?
(A) Donepezil
(B) Ginkgo biloba
(C) Quet iapine
(D) Sert raline
Item 13 [Advanced]
An 81-year-old woman is evaluat ed in t he office for increasing difficult y wit h act ivit ies of daily living, including dressing and feeding herself, over t he past 6 mont hs. She has
had gradually progressive cognit ive decline for t he past 5 years and now needs 24-hour help from a caregiver; Alzheimer dement ia was previously diagnosed. Current
medicat ions are donepezil and a daily mult ivit amin.
On physical examinat ion, vit al signs are normal. Her level of alert ness, speech, and gait are normal. The pat ient scores only 12/30 on t he Folst ein Mini-Ment al St at e
Examinat ion.
Result s of a complet e blood count , a basic met abolic panel, a serum vit amin B
12
measurement , and t hyroid funct ion t est s are normal.
A CT scan of t he head wit hout cont rast shows no evidence of t umor, hemorrhage, or infarct ion.
Whi ch of the fol l owi ng i s the most appropri ate next step i n treatment?
(A) Add memant ine
(B) Add quet iapine
(C) Add sert raline
(D) St op donepezil
Item 14 [Basic]
A 23-year-old man is evaluat ed in t he emergency depart ment because of t he acut e onset of uncont rolled head t urning t o one side and t ongue prot rusion. He was recent ly
diagnosed wit h schizophrenia and had haloperidol t reat ment st art ed 3 days ago. He has no ot her medical problems and t akes no addit ional medicat ions.
On examinat ion, he appears anxious; t emperat ure is normal, blood pressure is 140/80 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 14/min. His head is t urned 40
degrees t o t he right , and he has sust ained t ongue prot rusion. He is unable t o t urn his head back t o midline or ret ract his t ongue back int o his mout h. The remainder of his
neurologic examinat ion is normal.
(A) Drug-induced dyst onia
(B) Hunt ingt on disease
(C) Idiopat hic cervical dyst onia
(D) Neurolept ic malignant syndrome
Item 15 [Advanced]
A 66-year-old man is evaluat ed in t he office for a 6-mont h hist ory of a rest ing right arm t remor. He says t hat his writ ing has got t en smaller during t his t ime and t hat he has
had difficult y but t oning his dress shirt s. The pat ient report s no prior medical problems and is not aware of any neurologic problems in his family. He t akes no medicat ions.
Result s of a general medical examinat ion are normal. Neurologic examinat ion shows a paucit y of facial expression (hypomimia). Cranial nerve funct ion is normal. Mot or
examinat ion shows normal st rengt h but mild left upper limb rigidit y and a 5-Hz rest ing t remor of t he right upper limb. Deep t endon reflexes are normal, as are result s of
sensory examinat ion. There is no t runcal or appendicular at axia. Diminished arm swing is not ed bilat erally but is worse on t he right . A t remor in t he right upper limb is not ed
during ambulat ion. Left upper limb alt ernat ing mot ion rat es are diminished.
(A) Cervical dyst onia
(B) Essent ial t remor
(C) Hunt ingt on disease
(D) Parkinson disease
Item 16 [Basic]
A 62-year-old woman is evaluat ed for a 1-year hist ory of t remor t hat affect s bot h upper ext remit ies. She says t hat her handwrit ing has become sloppier since she first not iced
t he t remor and t hat she occasionally spills her morning coffee because of it . The pat ient is ot herwise healt hy. Her mot her, who died at age 79 years, had a similar t remor. Her
only medicat ion is a daily mult ivit amin.
On examinat ion, she has a mild t remor in t he upper ext remit ies t hat is present wit h t he arms ext ended and during finger-t o-nose t est ing. No rest ing t remor is apparent .
Muscle t one and gait and limb coordinat ion are normal.
Admi ni strati on of whi ch of the fol l owi ng drugs i s the most appropri ate treatment of thi s pati ent?
(A) Carbidopa-levodopa
(B) Pramipexole
(C) Propranolol
(D) Ropinirole
Item 17 [Advanced]
A 45-year-old woman wit h a hist ory of heavy alcohol use is evaluat ed in t he emergency depart ment for a headache and alt ered ment al st at us of 2-day's durat ion. One week
earlier she had a diarrheal illness t hat quickly resolved.
On physical examinat ion, she is let hargic and unable t o follow commands. Temperat ure is 38.8C (101.9F), blood pressure is 110/70 mm Hg, pulse rat e is 105/min, and
respirat ion rat e is 22/min. Jolt accent uat ion of her headache is present .
The leukocyt e count is 14,500/L (14.5 10
9
/L) wit h 44% neut rophils, 42% bands, and 13% lymphocyt es; plat elet count is 146,000/L (146 10
9
/L). The serum albumin is
2.6 mg/dL (26 g/L), t he INR is 1.5, and t he part ial t hromboplast in t ime is 44.1 seconds.
A noncont rast head CT scan is normal. Cerebrospinal fluid (CSF) leukocyt e count is 1500/L (1500 10
6
/L), wit h 60% neut rophils and 40% lymphocyt es; glucose level is 5
mg/dL (0.3 mmol/L); and prot ein level is 328 mg/dL (3280 mg/L). The CSF Gram st ain reveals int racellular gram-posit ive bacilli.
(A) Listeria monocytogenes meningit is
(B) Neisseria meningitidis meningit is
(C) Streptococcus pneumoniae meningit is
(D) Viral meningit is
Item 18 [Advanced]
A 19-year-old-woman who is a sophomore in college is evaluat ed in December for a 24-hour hist ory of fever and headache. She lives in a dormit ory on campus. Her medical
hist ory is unremarkable. She t akes no medicat ions and is up t o dat e wit h all of her immunizat ions, including t he meningococcal vaccine, which she received before ent ering
college. Two cases of meningococcal serogroup B-associat ed meningit is have been report ed on campus.
On physical examinat ion, t he pat ient appears ill. Temperat ure is 39.1C (102.4F), blood pressure is 95/50 mm Hg, pulse rat e is 125/min, and respirat ion rat e is 25/min. A
purpuric rash is appreciat ed over bot h lower ext remit ies. Neck st iffness is present and jolt accent uat ion of t he headache is elicit ed.
A noncont rast CT scan of t he head is normal. The leukocyt e count is 19,500/L (19.5 10
9
/L) wit h 87% neut rophils and 13% lymphocyt es; plat elet count is 110,000/L
(110 10
9
/L). Cerebrospinal fluid (CSF) leukocyt e count is 2000/L (2000 10
6
/L), wit h 95% neut rophils and 5% lymphocyt es; glucose level is 20 mg/dL (1.1 mmol/L); and
prot ein level is 100 mg/dL (1000 mg/L). The CSF Gram st ain reveals gram-negat ive diplococci.
(A) Neisseria meningitidis meningit is
(B) Rocky Mount ain spot t ed fever
(C) Streptococcus pneumoniae meningit is
(D) Vibrio vulnificus meningit is
Item 19 [Advanced]
A 20-year-old female college st udent is evaluat ed in December because of a 12-hour hist ory of fever, myalgia, headache, and a rash. She t akes no medicat ions.
On physical examinat ion, t he pat ient appears ill. Temperat ure is 38.8C (101.8F), blood pressure is 90/45 mm Hg, pulse rat e is 112/min, and respirat ion rat e is 24/min. A
pet echial rash, most prominent on t he lower ext remit ies, is present . Passive neck flexion causes discomfort .
9
/L)
9
/L)
Lumbar punct ure is performed. Opening pressure is 300 mm H
2
O. Cerebrospinal fluid leukocyt e count is 1250/L (1250 10
6
/L) wit h 95% polymorphonuclear cells. Prot ein
level is 100 mg/dL (1000 mg/L) and glucose level is 40 mg/dL (2.2 mmol/L). No organisms are seen Gram st ain.
(A) Listeria monocytogenes meningit is
(B) Neisseria meningitidis meningit is
(C) Rocky Mount ain spot t ed fever
(D) Viral meningit is
Item 20 [Advanced]
A 65-year-old woman is evaluat ed for a 1-day hist ory of fever, headache, and alt ered ment al st at us. Medical hist ory includes t ype 2 diabet es mellit us and hypert ension t reat ed
wit h glipizide and hydrochlorot hiazide. She has no allergies.
On physical examinat ion, t he pat ient is confused. Temperat ure is 38.9C (102.0F), blood pressure is 104/66 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 20/min.
Her neck is supple, and she has no rashes.
9
/L); plat elet count , 90,000/L (90 10
9
/L); and plasma glucose level, 120 mg/dL (6.7 mmol/L). A non-cont rast -enhanced CT
scan of t he head is normal. Cerebrospinal fluid (CSF) analysis shows a leukocyt e count of 1300/L (1300 10
6
/L) wit h 98% neut rophils, a glucose level of 20 mg/dL (1.1
mmol/L), and a prot ein level of 200 mg/dL (2000 mg/L). CSF Gram st ain result s are negat ive for any organisms.
Dexamet hasone is begun.
Whi ch of the fol l owi ng anti mi crobi al regi mens shoul d now be i ni ti ated?
(A) Ceft riaxone
(B) Penicillin G
(C) Vancomycin, ampicillin, and ceft riaxone
(D) Vancomycin plus ceft riaxone
(E) Vancomycin plus t rimet hoprim-sulfamet hoxazole
Item 21 [Advanced]
A 75-year-old woman wit h an 8-hour hist ory of aphasia and right -sided weakness is admit t ed t o t he hospit al. She has a 35-year hist ory of hypert ension t reat ed wit h
chlort halidone and a 10-year hist ory of hyperlipidemia t reat ed wit h simvast at in. Her medical hist ory is ot herwise unremarkable, and she t akes no ot her medicat ions.
On physical examinat ion she is afebrile, blood pressure is 150/90 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 12/min. Oxygen sat urat ion on pulse oximet ry is 96%.
She is alert but has expressive aphasia and dense right hemiplegia. No carot id bruit s are heard, and t he cardiopulmonary examinat ion is normal.
Coagulat ion st udies, serum elect rolyt es, and comprehensive met abolic panel are normal. The elect rocardiogram shows sinus rhyt hm wit hout evidence of ischemia. The CT
scan shows no signs of hemorrhage. Echocardiography is normal wit h an est imat ed eject ion fract ion of 54%.
Whi ch of the fol l owi ng i s the most appropri ate next step i n thi s pati ent's hospi tal management?
(A) Bed rest for t he next 48 hours
(B) Bed rest for t he next week
(C) Begin a mechanical soft diet
(D) Begin physical and occupat ional t herapy
Item 22 [Basic]
A 74-year-old man is brought t o t he emergency depart ment by ambulance 1 hour aft er he had an acut e wit nessed onset of aphasia and right hemiparesis. He has a hist ory of
hypert ension. His current medicat ions are hydrochlorot hiazide and met oprolol.
On physical examinat ion, blood pressure is 178/94 mm Hg and pulse rat e is 80/min and regular. Neurologic examinat ion confirms nonfluent aphasia, a right pronat or drift , a
right leg drift , and an ext ensor plant ar response on t he right .
An elect rocardiogram obt ained on t he pat ient 's arrival at t he emergency depart ment document s sinus rhyt hm. A CT scan of t he head obt ained wit hin 1 hour of his arrival
reveals early ischemic changes.
Whi ch of the fol l owi ng i s the best treatment?
(A) Aspirin
(B) Cont inuous int ravenous heparin
(C) Int ravenous labet alol
(D) Int ravenous recombinant t issue plasminogen act ivat or
Item 23 [Advanced]
A 74-year-old woman is admit t ed t o t he hospit al aft er sust aining a severe left hemispheric ischemic st roke while alone at home. She was last known t o be normal 8 hours ago.
The pat ient has hypert ension for which she t akes enalapril but no hist ory of ischemic heart disease or heart failure.
On physical examinat ion, blood pressure is 190/105 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 16/min. The pat ient has right hemiparesis, right facial droop,
aphasia, and dysart hria. The remainder of t he physical examinat ion, including t he cardiovascular examinat ion, is normal.
Result s of laborat ory st udies, including serum creat inine level, are normal.
A CT scan shows ischemic changes t hat occupy most of t he left middle cerebral art ery t errit ory. An elect rocardiogram and chest radiograph show normal findings.
Whi ch of the fol l owi ng i s the most appropri ate treatment of her hypertensi on at thi s ti me?
(A) Int ravenous labet alol
(B) Int ravenous nicardipine
(C) Oral nifedipine
(D) No t reat ment at t his t ime
Item 24 [Basic]
A 73-year-old ret ired woman is evaluat ed in t he emergency depart ment 6 hours aft er experiencing t he sudden, explosive onset of a severe headache. The pat ient has
hypert ension cont rolled by diet and exercise. There is no relevant family hist ory. She has no allergies and t akes no over-t he-count er medicat ions.
On physical examinat ion, she is in obvious dist ress from t he headache. Temperat ure is normal, blood pressure is 179/108 mm Hg, pulse rat e is 119/min, and respirat ion rat e is
14/min. There is no meningismus. Neurologic examinat ion shows a normal level of consciousness and no focal abnormalit ies.
Result s of laborat ory st udies and a CT scan of t he head wit hout cont rast are normal.
(A) Lumbar punct ure
(B) MRI of t he brain
(C) Observat ion
(D) Sumat ript an, orally
Item 25 [Basic]
A 34-year-old woman is evaluat ed in t he office for right -sided facial paralysis t hat she not iced on awakening 1 hour ago. She has a 10-pack-year smoking hist ory. Personal
and family medical hist ory is noncont ribut ory. Her only medicat ion is a daily oral cont racept ive.
On physical examinat ion, vit al signs are normal. Limb st rengt h, reflexes, and t one are normal bilat erally. Findings from a sensory examinat ion, which included her face, are
also normal. When asked t o raise her eyebrows, t he pat ient does not elevat e t he right side. When asked t o shut her eyes, she cannot close t he right one but t he globe rot at es
upward, part ially covering t he iris. When asked t o smile, t he pat ient does not move t he right side of her face.
(A) Graves opht halmopat hy
(B) Left cerebral infarct ion
(C) Right facial nerve (Bell) palsy
(D) Right t rigeminal neuralgia
Item 26 [Advanced]
A 53-year-old woman is evaluat ed in t he office for a 1-week hist ory of parest hesias t hat began symmet rically in t he feet and progressed t o involve t he dist al legs and, more
recent ly, t he hands. She is unst eady when walking, has lower limb weakness, and has difficult y going upst airs. The pat ient has no hist ory of pain or bowel or bladder
impairment . Personal and family medical hist ory is noncont ribut ory, and she t akes no medicat ions.
On physical examinat ion, vit al signs are normal. Weakness of dist al lower ext remit y muscles is not ed, wit h st ocking-glove sensory loss and areflexia. Deep t endon reflexes
are absent . Plant ar responses are normal, and gait is unst eady. No sensory level is present across t he t horax. Ment al st at us, language, and cranial nerve funct ion are normal.
Complet e blood count result s, eryt hrocyt e sediment at ion rat e, serum creat inine and creat ine kinase levels, and liver chemist ry t est result s are normal.
A chest radiograph shows no abnormalit ies.
(A) Amyot rophic lat eral sclerosis
(B) Diabet ic neuropat hy
(C) Guillain-Barre syndrome
(D) Myelopat hy
Item 27 [Basic]
A 35-year-old woman is evaluat ed in t he office for a 5-mont h hist ory of right -hand numbness and t ingling. She says t hat t hese sympt oms involve t he ent ire hand, seem t o be
worse when she drives or holds a book or newspaper, and have been awakening her at night . She report s no hist ory of neck pain or hand weakness. Personal and family
medical hist ories are noncont ribut ory, and she t akes no medicat ion.
General physical examinat ion reveals no abnormalit ies. Neurologic examinat ion shows normal st rengt h but sensory loss in t he first t hree digit s and t he radial half of t he
fourt h digit in t he right hand.
(A) Carpal t unnel syndrome
(B) de Quervain t enosynovit is
(C) Ganglion cyst s
(D) Ulnar nerve compression (Guyon t unnel syndrome)
Item 28 [Basic]
An obese 66-year-old man has had increasing pain and t ingling in his feet for more t han 8 mont hs. The pat ient has not seen a physician in more t han 20 years. His only
ot her sympt oms are fat igue, blurry vision, and noct uria. He t akes no medicat ions.
On examinat ion, vit al signs are normal; BMI is 30. Result s of skin, opht halmoscopic, cardiopulmonary, and abdominal examinat ions are normal. On neurologic examinat ion,
he has sensory loss in t he feet and dist al legs. Muscle st rengt h and reflexes are normal.
Whi ch of the fol l owi ng tests wi l l most l i kel y di agnose the cause of the neurol ogi c fi ndi ngs?
(A) Creat ine kinase level
(B) Fast ing blood glucose level
(C) Lumbar punct ure and cerebrospinal fluid analysis
(D) Sural nerve biopsy
Item 1 Answer: E
Educati onal Objecti ve: Prevent delirium in patients at high risk.
Elderly pat ient s wit h a hist ory of dement ia are at very high risk for developing delirium during a hospit alizat ion. Delirium is an acut e st at e of confusion t hat may manifest as
a reduced level of consciousness, cognit ive abnormalit ies, percept ual dist urbances, or emot ional dist urbances. Prevent ion involves addressing medical and environment al
issues. Urinary cat het ers are associat ed wit h increased risk of delirium. In t he absence of a medical indicat ion for a cat het er (e.g., relieve urinary ret ent ion, monit or fluid st at us
in acut ely ill pat ient s when t his direct ly impact s medical t reat ment , manage pat ient s wit h st age 3 or 4 pressure ulcers on t he but t ocks), it should be removed.
Benzodiazepines and diphenhydramine have sedat ing effect s but can cause delirium in t he elderly. They should generally be avoided, unless a specific indicat ion is present ed,
such as benzodiazepines for alcohol wit hdrawal or diphenhydramine for an allergic react ion. Alt ernat ive nonpharmacologic met hods for relaxat ion include music, massage,
and medit at ion.
In appropriat e select ed pat ient s wit h severe delirium, low-dose haloperidol may lessen t he severit y and durat ion of delirium, but it is not indicat ed for t he prevent ion of
delirium. The use of ant ipsychot ic medicat ions in elderly pat ient s wit h dement ia is associat ed wit h an increased risk of deat h, primarily due t o infect ion, such as pneumonia. A
normal sleep-wake cycle should be maint ained as much as possible, minimizing int errupt ions or unnecessary t est ing during t he night , and keeping a light on and increasing
st imulat ion during t he day.
Key Poi nt
Access t o hearing aids, glasses, and canes and removal of unnecessary rest raint s and urinary cat het ers are basic procedures t o reduce t he risk of delirium in persons at risk.
Bi bl i ography
Inouye SK. Delirium in older persons. N Engl J Med. 2006;354(11):1157-65. [PMID: 16540616]
Item 2 Answer: D
Educati onal Objecti ve: Diagnose postoperative delirium in a patient with dementia.
The most likely diagnosis is post operat ive delirium. Pat ient s wit h delirium have acut e, fluct uat ing ment al st at us changes, wit h difficult y in focusing or maint aining at t ent ion
and disorganized t hinking. Based on psychomot or act ivit y, t here are four t ypes of delirium: 1) hypoact ive, 2) hyperact ive, 3) mixed delirium wit h hypo- and hyperact ivit y,
and 4) delirium wit hout changes in psychomot or act ivit y. Delirium in elderly pat ient s wit h chronic dement ia usually result s from an acut e medical problem. In addit ion,
pat ient s wit h chronic dement ia from almost any cause are at great er risk for delirium aft er surgery wit h general anest hesia. This pat ient wit h a hip fract ure who underwent
right hip surgery wit h general anest hesia and did not recover from t he anest hesia unt il 12 hours aft er ext ubat ion most likely has post operat ive delirium. Such delirium is
highly predict able and oft en easily managed by ident ificat ion and correct ion of any underlying disorders and t he removal or reduct ion of cont ribut ing fact ors.
The possibilit y of acut e st roke must be considered in a pat ient wit h a change in ment al st at us. However, t his pat ient has no clinical evidence of such an event , which makes
t his diagnosis ext remely unlikely.
Surgery does not exacerbat e Alzheimer dement ia (or dement ia of any ot her cause) but rat her produces a superimposed delirium. Finally, dement ia does not acut ely worsen
over several hours; t he decline is st eadily progressive.
This pat ient has had dement ia for 4 years t hat has abrupt ly got t en worse aft er surgery. Alt hough not impossible, meningit is is highly unlikely in t his set t ing, especially given
t he absence of any support ing physical examinat ion findings, including meningeal irrit at ion.
Key Poi nt
Pat ient s wit h chronic dement ia are at great er risk for delirium aft er surgery wit h general anest hesia.
Bi bl i ography
Rudolph JL, Jones RN, Rasmussen LS, Silverst ein JH, Inouye SK, Marcant onio ER. Independent vascular and cognit ive risk fact ors for post operat ive delirium. Am J Med.
2007;120(9):807-813. [PMID: 17765051]
Item 3 Answer: B
Educati onal Objecti ve: Treat delirium in the intensive care unit with an antipsychotic agent (haloperidol).
The appropriat e t reat ment for t his pat ient is haloperidol. When support ive care is insufficient for prevent ion or t reat ment of delirium, sympt om cont rol wit h medicat ion is
occasionally necessary t o prevent harm or t o allow evaluat ion and t reat ment in t he int ensive care unit . The recommended t herapy for delirium is ant ipsychot ic agent s,
alt hough no drugs are approved by t he U.S. Food and Drug Administ rat ion for t his indicat ion. Ongoing randomized, placebo-cont rolled t rials are invest igat ing different
management st rat egies for int ensive care unit delirium. A recent syst emat ic evidence review found no evidence of superiorit y for second-generat ion ant ipsychot ics compared
wit h haloperidol for delirium. Haloperidol does not cause respirat ory suppression, which is one reason t hat it is oft en used in pat ient s wit h hypovent ilat ory respirat ory failure
who require sedat ion. All ant ipsychot ic agent s, and especially "t ypical" agent s such as haloperidol, pose a risk of t orsades de point es, ext rapyramidal side effect s, and t he
neurolept ic malignant syndrome.
Diphenhydramine and ot her ant ihist amines are a major risk fact or for delirium, especially in older pat ient s. Lorazepam is act ually deliriogenic, and it s use in a delirious
pat ient should be carefully re-evaluat ed, except perhaps in pat ient s experiencing benzodiazepine wit hdrawal or delirium t remens. There is no evidence t hat propofol has any
role in t reat ing delirium.
Key Poi nt
No drug is approved by t he U.S. Food and Drug Administ rat ion for t he t reat ment of delirium, but clinical pract ice guidelines recommend ant ipsychot ic agent s, such as
haloperidol.
Bi bl i ography
Campbell N, Boust ani MA, Ayub A, et al. Pharmacological management of delirium in hospit alized adult sa syst emat ic evidence review. J Gen Int ern Med. 2009;24(7):848-
853. [PMID: 19424763]
Item 4 Answer: C
Educati onal Objecti ve: Diagnose and treat Wernicke encephalopathy due to thiamine deficiency.
This pat ient should receive t hiamine now as t he best init ial management . She has Wernicke encephalopat hy, a syndrome t hat result s from deficiency of vit amin B
1
, an
import ant coenzyme in several biochemical pat hways of t he brain. Typical clinical manifest at ions of t he disorder include ment al st at us changes, nyst agmus, opht halmoplegia,
and unst eady gait , all varying in int ensit y from minor t o severe. When t here is addit ional loss of memory wit h a confabulat ory psychosis, t he condit ion is described as
Wernicke-Korsakoff syndrome. The classical clinical t riad of gait at axia, encephalopat hy, and opht halmoplegia is seen in only 19% of affect ed pat ient s. Condit ions
associat ed wit h Wernicke encephalopat hy include AIDS, alcohol abuse, cancer, hyperemesis gravidarum, prolonged t ot al parent eral nut rit ion, post surgical st at us (part icularly
bariat ric surgeries), and glucose loading (in a predisposed pat ient ).
Because Wernicke encephalopat hy remains a clinical diagnosis, ot her neurologic disorders should be considered in t his pat ient aft er t hiamine has been administ ered.
Elect roencephalography can help exclude a seizure disorder, such as nonconvulsive st at us epilept icus. Infect ions, including encephalit is and meningit is, for which int ravenous
administ rat ion of broad-spect rum ant ibiot ic drugs (such as vancomycin, ampicillin, and ceft riaxone) may be appropriat e also should be part of t he different ial diagnosis and
can be excluded wit h cerebrospinal fluid analysis.
Haloperidol is not indicat ed in t his pat ient , who is confused but has no apparent hist ory of psychosis or agit at ion. Some pat ient s wit h Wernicke encephalopat hy do have
agit at ion, hallucinat ions, and behavioral dist urbances t hat can mimic an acut e psychosis.
Key Poi nt
Wernicke encephalopat hy is caused by t hiamine deficiency and may result in ment al st at us changes, opht halmoplegia, nyst agmus, and unst eady gait ; it is best t reat ed wit h
t hiamine.
Bi bl i ography
Sechi G, Serra A. Wernicke's encephalopat hy: new clinical set t ings and recent advances in diagnosis and management . Lancet Neurol. 2007;6(5):442-455. [PMID: 17434099]
Item 5 Answer: D
Educati onal Objecti ve: Diagnose medication-induced delirium.
The most likely diagnosis is t oxic encephalopat hy present ing as delirium. Delirium is an acut e st at e of confusion t hat may manifest as a reduced level of consciousness,
cognit ive abnormalit ies, percept ual dist urbances, or emot ional dist urbances. The presence of ast erixis suggest s a t oxic/met abolic cause of t his pat ient 's sympt oms. The pat ient
is t aking several medicat ions t hat might impair cognit ion. A prime suspect is nort ript yline; t his drug has ant icholinergic propert ies and is likely t o cause impairment in
pat ient s wit h lat ent cholinergic deficiency (t he elderly or pat ient s wit h mild cognit ive impairment , early dement ia, or Parkinson disease). Digoxin and t he sedat ive-hypnot ic
lorazepam may also cont ribut e t o cognit ive impairment .
Sympt oms of alcohol wit hdrawal most t ypically occur aft er cessat ion of prolonged, sust ained alcohol int ake. However, most people drink in an episodic fashion, as illust rat ed
by t his pat ient , and t his pat t ern of drinking is not associat ed wit h sust ained high blood alcohol levels t hat are requisit e for wit hdrawal sympt oms on abrupt cessat ion.
Alcoholic hallucinosis develops 12 t o 24 hours aft er t he last drink and resolve wit hin 24 t o 48 hours, a sympt omat ic period much short er t han t hat experienced by t his
pat ient . Hallucinat ions are usually visual and are not associat ed wit h clouding of t he sensorium and are not associat ed wit h ast erixis.
In pat ient s wit h early Alzheimer dement ia, delirium is produced more readily by ant icholinergic medicat ions. Alzheimer dement ia cannot be ruled out in t his pat ient , but
est ablishing t he diagnosis would require removal of t he causat ive agent and re-evaluat ion aft er recovery. However, ast erixis, a sign of met abolic encephalopat hy, would be
unusual in t his set t ing and point s st rongly t o a met abolic encephalopat hy and not dement ia.
Depression may cause chronic cognit ive impairment (pseudodement ia) and difficult y concent rat ing, but not ast erixis and an alt ered level of consciousness.
Key Poi nt
Cognit ive impairment accompanied by fluct uat ing let hargy and inat t ent ion, hallucinat ions, and ast erixis most likely result s from a t oxic encephalopat hy.
Bi bl i ography
Inouye SK. Delirium in older persons [errat um in N Engl J Med. 2006;354:1655]. N Engl J Med. 2006;354(11):1157-1165. [PMID: 16540616]
Item 6 Answer: A
Educati onal Objecti ve: Diagnose migraine headache with aura.
This pat ient is most likely experiencing a migraine wit h aura. Approximat ely 15% t o 20% of pat ient s wit h migraine experience aura wit hin 1 hour of or during headache.
Aura const it ut es neurologic abnormalit ies, including visual loss, hallucinat ions, numbness, t ingling, weakness, or confusion. Aura is caused by spreading cort ical depressiona
wave of abnormal elect rical discharges t hat t ravel slowly across t he brain's surface and essent ially short -circuit t he brain. Typically, aura last s a few minut es but may last up t o
1 hour per sympt om. Addit ional clinical clues support ing a diagnosis of migraine are t he pat ient 's young age, t he absence of vascular risk fact ors, and t he family hist ory of
migraine. In addit ion, t he diffuseness of t his pat ient 's sympt oms and t heir progression are more compat ible wit h migraine t han a focal vascular process, such as a t ransient
ischemic at t ack.
Alt hough mult iple sclerosis (MS) should be in t he different ial diagnosis of neurological sympt oms in a young woman, t his pat ient is less likely t o have MS t han a migraine or
st roke because her present at ion was more acut e t han would be t ypical in MS, and MS is not t ypically associat ed wit h a t hrobbing headache.
Part ial seizures in which t he pat ient maint ains full awareness are classified as simple part ial, whereas t hose involving an alt erat ion of consciousness are classified as part ial
complex. Part ial seizures t hat originat e in t he t emporal lobe oft en begin wit h an aura, which may consist of a feeling of deja vu, a rising epigast ric sensat ion, or aut onomic
dist urbances. Aut omat isms, such as lip smacking, are also suggest ive of part ial complex seizures, but a t hrobbing headache wit h nausea is not .
Trigeminal neuralgia is associat ed wit h pain occurring in paroxysms t hat involves one or more divisions of t he t rigeminal nerve. Each episode may persist bet ween a few
seconds and 2 minut es, and pain may be int ensely sharp or st abbing. Behavior such as face washing or t ouching, t oot h brushing, or chewing may t rigger an event . The
pat ient 's sympt oms are not consist ent wit h t rigeminal neuralgia.
Key Poi nt
Bet ween 15% and 20% of pat ient s wit h migraine experience aura wit hin 1 hour of or during headache charact erized by a variet y of neurologic sympt oms, including visual loss,
hallucinat ions, numbness, t ingling, weakness, or confusion.
Bi bl i ography
Wilson JF. In t he clinic. Migraine [errat um in Ann Int ern Med. 2008;148(5):408]. Ann Int ern Med. 2007;147(9):ITC11-1-ITC11-16. [PMID: 17975180]
Item 7 Answer: D
Educati onal Objecti ve: Diagnose tension-type headache.
This pat ient has t ension-t ype headache, t he most prevalent of all headache t ypes. Tension-t ype headache is a dull, bilat eral, or diffuse headache, oft en described as a pressure
or squeezing sensat ion of mild t o moderat e int ensit y. There are no accompanying migraine feat ures (nausea, emesis, phot ophobia, phonophobia), and t he pain neit her
worsens wit h movement nor prohibit s act ivit y. The key feat ure t hat est ablishes a diagnosis of t ension-t ype headache is t he lack of disabling pain.
Chronic daily headache is a nonspecific t erm t hat refers t o bot h primary (including migraine) and secondary headache disorders in which headache is present on more t han 15
days per mont h for at least 3 mont hs. Risk fact ors for chronic daily headache include obesit y, a hist ory of frequent headache (more t han 1 per week), caffeine consumpt ion,
and overuse (>10 days per mont h) of acut e headache medicat ions, including analgesics, ergot s, t ript ans, and opioids. In addit ion, more t han half of all pat ient s wit h chronic
daily headache have sleep dist urbance and mood disorders, such as depression and anxiet y. Chronic migraine and medicat ion overuse headache overwhelmingly represent t he
most common and challenging of t he chronic daily headache disorders in clinical pract ice.
Clust er headache is a painful, disabling headache t hat may be associat ed wit h aut onomic sympt oms such as t earing or rhinorrhea. Clust er headaches are t ypically unilat eral and
periorbit al/t emporal and are associat ed wit h at least one of t he following feat ures on t he same side as t he headache: conjunct ival irrit at ion/lacrimat ion, rhinorrhea/nasal
congest ion, eyelid edema, facial/forehead sweat ing, and miosis/pt osis. Clust er episodes usually last 6 t o 8 weeks and remission periods usually last 2 t o 6 mont hs.
Migraine headache is a recurrent headache disorder t hat manifest s in at t acks last ing 4 t o 72 hours. Typical charact erist ics of migraine are it s unilat eral locat ion, pulsat ing
qualit y, moderat e or severe int ensit y, aggravat ion by rout ine physical act ivit y, and associat ion wit h nausea and/or phot ophobia and phonophobia. This pat ient does not
describe disabilit y or any ot her feat ures of migraine headache. A neurologic aura occurs in only one t hird of pat ient s wit h migraine. The aura consist s of such visual sympt oms
as percept ions of flashes of light , arcs of flashing light t hat oft en form a zigzag pat t ern, and an area of loss of vision surrounded by a normal field of vision.
Key Poi nt
Tension-t ype headache is dist inguished from migraine by t he fact t hat pat ient s wit h t ension-t ype headache are not disabled and can carry out act ivit ies of daily living in a
normal, expedient manner.
Bi bl i ography
Sacco S. Diagnost ic issues in t ension-t ype headache. Curr Pain Headache Rep. 2008;12(6):437-441. [PMID: 18973737]
Item 8 Answer: C
Educati onal Objecti ve: Manage a thunderclap headache.
This pat ient should undergo noncont rast CT of t he head. She has experienced a t hunderclap headache, which is a severe and explosive headache t hat is maximal in int ensit y
at or wit hin 60 seconds of onset . Every t hunderclap headache must be immediat ely evaluat ed t o det ect pot ent ially cat ast rophic condit ions, especially subarachnoid
hemorrhage. A negat ive CT scan of t he head should be followed by a lumbar punct ure t o assess for blood in t he cerebrospinal fluid not det ect ed on t he CT scan.
If bot h t he CT scan of t he head and lumbar punct ure are negat ive, most of t he ot her causes of t hunderclap headache, such as an unrupt ured cerebral aneurysm, a carot id or
vert ebral art ery dissect ion, cerebral venous sinus t hrombosis, and reversible cerebral vasoconst rict ion syndrome, can be excluded by noninvasive angiography. CT angiography
of t he head and neck can det ect unrupt ured aneurysms as small as 3 mm in diamet er and t hus is adequat e t o exclude t his diagnosis. Magnet ic resonance angiography (MRA)
would also be appropriat e in t his set t ing. Bot h CT angiography and MRA can be performed wit h a venous phase t o exclude cerebral venous sinus t hrombosis. Given t hat most
causes of t hunderclap headache can be excluded by such noninvasive angiography, if prior cerebrospinal fluid analysis has shown no evidence of a subarachnoid hemorrhage,
convent ional cerebral angiography, in which a cat het er is insert ed int o a large art ery and advanced t hrough t he carot id art ery, is unnecessary.
Because t he pat ient may have int racerebral bleeding wit h mass effect , t he performance of a lumbar punct ure could result in brainst em herniat ion. This is why t he lumbar
punct ure is performed only aft er a CT scan is performed. If t he CT scan reveals int racerebral bleeding, a lumbar punct ure is unnecessary.
Treat ment wit h a vasoconst rict ive drug, such as sumat ript an, would not be appropriat e unt il t he ot her causes of t hunderclap headache have been excluded. Drugs wit h t he
pot ent ial t o const rict ext racranial and int racranial cerebral vessels can precipit at e or exacerbat e t he cerebral ischemia t hat may be associat ed wit h art erial dissect ion and
reversible cerebral vasoconst rict ion syndromes.
Key Poi nt
A t hunderclap headache is a pot ent ial neurologic emergency t hat must be immediat ely evaluat ed t o det ect pot ent ially cat ast rophic condit ions, especially subarachnoid
hemorrhage.
Bi bl i ography
Schwedt TJ, Mat haru MS, Dodick DW. Thunderclap headache. Lancet Neurol. 2006;5(7):621-631. [PMID: 16781992]
Item 9 Answer: B
Educati onal Objecti ve: Treat a patient prophylactically for migraine with propranolol.
The most appropriat e t reat ment for t his pat ient is propranolol. Prophylact ic t reat ment should be considered in pat ient s who experience 2 or more days of headache per
week. Nearly 40% of pat ient s wit h migraine need prevent ive t reat ment . There is evidence from at least t wo randomized, double-blind, placebo-cont rolled st udies t o support
t he use of eight drugs available in t he Unit ed St at es (t opiramat e, valproic acid, amit ript yline, met oprolol, propranolol, t imolol, and ext ract of t he plant But t erbur root
Petasites hybridus) and t wo nonpharmacologic approaches (relaxat ion t herapy and biofeedback).
Several randomized placebo-cont rolled t rials have found no consist ent , st at ist ically significant benefit s for bot ulinum t oxin inject ion in t he t reat ment of episodic migraine
headache. Similarly, t here is no evidence of efficacy for nort ript yline or sert raline in t he prevent ive t reat ment of migraine.
Key Poi nt
Prophylact ic medicat ion should be init iat ed in pat ient s wit h t wo or more migraine at t acks per week.
Bi bl i ography
Wilson JF. In t he clinic. Migraine [errat um in Ann Int ern Med. 2008;148(5):408]. Ann Int ern Med. 2007;147(9):ITC11-1-ITC11-16. [PMID: 17975180]
Item 10 Answer: B
Educati onal Objecti ve: Diagnose delirium superimposed on dementia.
This pat ient has delirium superimposed on dement ia. Delirium is an alt ered level of alert ness, oft en in connect ion wit h globally impaired cognit ion. It is t ypically
charact erized by abrupt onset and may be associat ed wit h rapid fluct uat ions of alert ness, at t ent ion, memory, and psychomot or act ivit y (for example, let hargy or agit at ion).
Dement ia is an acquired and persist ent impairment of int ellect ual abilit y t hat compromises at least t hree areas of ment al funct ioning: language, memory, visuospat ial skills,
emot ion or personalit y, or cognit ion. Dement ia t ypically has an insidious onset and is usually st able from day t o day. Over t he prot ract ed course of dement ia, many pat ient s
may experience an acut e delirium, wit h confused and slurred speech, somnolence, agit at ion, t remulousness, unst eadiness, falls, and worsened incont inence. Oft en, t he delirium
is from a superimposed illness (most commonly, a urinary t ract infect ion or pneumonia), a medicat ion error, an injury, or some ot her cause t hat must be sought and managed.
Psychosis encompasses delusions, hallucinat ions, disorganized speech, and disorganized or cat at onic behavior. Impaired cognit ion, including decrement s in short -t erm memory
and at t ent ion, is also charact erist ic. This pat ient 's sudden decline in t he set t ing of dement ia and absence of hallucinat ions and delusions is more likely t o represent an acut e
delirium rat her t han an acut e psychosis.
Key Poi nt
Over t he course of dement ia, many pat ient s may experience an acut e delirium, wit h confused and slurred speech, somnolence, agit at ion, t remulousness, unst eadiness, falls, and
worsened incont inence.
Bi bl i ography
Han JH, Wilson A, Ely EW. Delirium in t he older emergency depart ment pat ient : a quiet epidemic. Emerg Med Clin Nort h Am. 2010;28(3):611-31. [PMID: 20709246]
Item 11 Answer: A
Educati onal Objecti ve: Diagnose Alzheimer dementia.
The most likely diagnosis is Alzheimer dement ia. Dement ia is a clinical syndrome in which mult iple cognit ive domainsincluding memory, language, spat ial skills, judgment ,
and problem solvingare impaired t o a disabling degree. Some dement ing illnesses can also affect noncognit ive neurologic funct ions, such as gait . Diseases t hat cause
dement ia oft en produce charact erist ic pat t erns of cognit ive (and somet imes noncognit ive) impairment t hat can aid diagnosis. Alzheimer dement ia is charact erized by
prominent memory loss, anomia, const ruct ional apraxia, anosognosia (impaired recognit ion of illness), and variable degrees of personalit y change.
Creut zfeldt -Jakob disease (CJD) is t he most common of t he human prion diseases, wit h an annual incidence of less t han 1 in 1,000,000 persons. The main clinical feat ures of
CJD are dement ia t hat progresses over mont hs (rat her t han years, as in t his case) and st art le myoclonus, alt hough t he lat t er may not be present early in t he illness. Ot her
prominent feat ures include visual or cerebellar dist urbance, pyramidal/ext rapyramidal dysfunct ion, and akinet ic mut ism.
Dement ia wit h Lewy bodies is accompanied by parkinsonism, visual hallucinat ions, and fluct uat ing sympt oms, none of which t his pat ient has. The charact erist ic cognit ive
profile of dement ia in pat ient s wit h dement ia wit h Lewy bodies includes impaired learning and at t ent ion, psychomot or slowing, const ruct ional apraxia, and more profound
visuospat ial impairment but less memory impairment t han in similarly st aged pat ient s wit h Alzheimer dement ia.
Front ot emporal dement ia is a progressive neuropsychiat ric condit ion. Pat ient s init ially have behavioral and personalit y changes t hat range from apat hy t o social
disinhibit ion. They fail t o change t heir clot hes, brush t heir t eet h, pursue t heir former int erest s, or init iat e many of t heir previous act ivit ies t hat const it ut ed a normal day.
They may fixat e, in a seemingly idiosyncrat ic fashion, on a part icular act ivit y, such as going t o t he bat hroom, sort ing t hrough a wallet , hoarding magazines, or wat ching
t elevision. Some pat ient s have great er disinhibit ion and emot ional labilit y (crying or laughing inappropriat ely).
Key Poi nt
Alzheimer dement ia is charact erized by prominent memory loss, anomia, const ruct ional apraxia, anosognosia (impaired recognit ion of illness), and variable degrees of
personalit y change.
Bi bl i ography
Blass DM, Rabins PV. In t he clinic. Dement ia. Ann Int ern Med. 2008;148(7):ITC4-1-ITC4-16. [PMID: 18378944]
Item 12 Answer: A
Educati onal Objecti ve: Treat Alzheimer dementia with an acetylcholinesterase inhibitor (donepezil).
This pat ient should receive donepezil. The Folst ein Mini-Ment al St at e Examinat ion (MMSE) discriminat es well bet ween t he major st ages of dement ia used for prognosis and
management purposes. The MMSE score range of 21 t o 25 corresponds t o mild dement ia, 11 t o 20 t o moderat e dement ia, and 0 t o 10 t o severe dement ia. This pat ient has
Alzheimer dement ia and is at a mild st age of impairment . The most appropriat e medicat ion wit h which t o begin t reat ment is an acet ylcholinest erase inhibit or of which t here
are current ly t hree: donepezil, rivast igmine, and galant amine. In pat ient s wit h mild, moderat e, or severe Alzheimer dement ia t he use of acet ylcholinest erase inhibit ors are
associat ed wit h a small but st at ist ically significant improvement in performance of inst rument al and funct ional act ivit ies of daily living and caregiver st ress and may be
associat ed wit h improved cognit ive funct ion compared wit h pat ient s t reat ed wit h placebo. Treat ment effect s are small and not always apparent in pract ice. Cholinest erase
inhibit ors are generally safe but have significant ly more side effect s t han placebo, including diarrhea, nausea, vomit ing, and sympt omat ic bradycardia. The gast roint est inal side
effect s are usually t ransient and mild.
Ginkgo biloba, alt hough safe, has inconsist ent and unconvincing evidence of benefit in t he t reat ment of Alzheimer dement ia. Also, t here is no regulat ion regarding t he
cont ent s of herbal ext ract s, which allows for variabilit y in dose st rengt h and qualit y.
Quet iapine is an ant ipsychot ic drug, and sert raline is an ant idepressant agent . Alt hough bot h can be used in pat ient s wit h Alzheimer dement ia, t heir use is limit ed t o t reat ment
of behavioral sympt oms of psychosis and depression, respect ively, neit her of which t his pat ient has exhibit ed. However, if t hese medicat ions are t o be used in such pat ient s,
t he risks must first be carefully weighed against t he benefit s. Ant ipsychot ics have limit ed effect iveness in t reat ing behavioral problems and are associat ed wit h increased risk
of deat h in pat ient s wit h dement ia.
Key Poi nt
First -line pharmacot herapy for mild Alzheimer dement ia is an acet ylcholinest erase inhibit or.
Bi bl i ography
Mayeux R. Early Alzheimer's disease. N Engl J Med. 2010;362(23):2194-2201. [PMID: 20558370]
Item 13 Answer: A
Educati onal Objecti ve: Treat functional decline in a patient with advanced Alzheimer dementia with memantine.
The most appropriat e next st ep in t reat ment is t he addit ion of memant ine. This pat ient has Alzheimer dement ia t hat is moderat ely advanced and now has difficult ies wit h
basic act ivit ies of daily living. The N-met hyl-D-aspart at e recept or ant agonist memant ine is t he only drug approved by t he U.S. Food and Drug Administ rat ion as first -line
t reat ment of moderat e t o advanced Alzheimer dement ia. Memant ine has been shown t o improve cognit ion and global assessment of dement ia, but while t he changes have
been st at ist ically significant , t he clinical effect is not always evident . Memant ine may improve qualit y-of-life measures, but t hese findings are not robust . Alt hough evidence
is limit ed, t here is some suggest ion t hat t he st epped approach of adding memant ine t o a regimen t hat includes a cholinest erase inhibit or (such as donepezil) result s in a modest
addit ional benefit over subst it ut ing memant ine for t he cholinest erase inhibit or.
Quet iapine is an ant ipsychot ic medicat ion and sert raline is an ant idepressant agent . Alt hough bot h drugs can be used in pat ient s wit h Alzheimer dement ia, t heir use is limit ed
t o t he t reat ment of t he behavioral sympt oms of psychosis and depression, respect ively, neit her of which t his pat ient has at t his t ime. The effect iveness of ant ipsychot ic
medicat ions is on behavioral problems is limit ed and t heir use is associat ed wit h an increased risk of deat h in pat ient s wit h dement ia.
Discont inuing t he donepezil t aken by t his pat ient wit hout subst it ut ing anot her drug t o manage her funct ional decline would not help slow or ot herwise improve t he course of
her disease.
Key Poi nt
Memant ine is a first -line agent for t reat ment of moderat e t o advanced Alzheimer dement ia.
Bi bl i ography
Mayeux R. Early Alzheimer's disease. N Engl J Med. 2010;362(23):2194-201. [PMID: 20558370]
Item 14 Answer: A
Educati onal Objecti ve: Diagnose drug-induced dystonia.
The most likely diagnosis is drug-induced dyst onia. All medicat ions t hat block D
2
dopamine recept ors can cause acut e dyst onic react ions. Dyst onic movement s are due t o
sust ained cont ract ion of agonist and ant agonist muscles, which result s in t wist ing and repet it ive movement s or sust ained abnormal post ures. These movement s most
frequent ly affect t he ocular muscles (oculogyric crisis) and t he face, jaw, t ongue, neck, and t runk. The limbs are rarely affect ed. Neurolept ic, ant iemet ic, and serot oninergic
agent s have been implicat ed, and sympt oms usually occur wit hin 5 days of init iat ion of t he drug. Treat ment consist s of parent eral diphenhydramine, benzt ropine mesylat e, or
biperiden.
Cervical dyst onia, formerly known as t ort icollis, is a focal dyst onia t hat involves t he cervical musculat ure and causes abnormal post ures of t he head, neck, and shoulders.
Quick, nonrhyt hmic, repet it ive movement s can also occur and can be mist aken for t remor. Cervical dyst onia generally does not present so acut ely and does not explain t he
sust ained t ongue prot rusion.
Hunt ingt on disease is a heredit ary, progressive, neurodegenerat ive disorder charact erized by increasingly severe mot or impairment , cognit ive decline, and psychiat ric
sympt oms. The associat ed movement disorder is chorea. Chorea refers t o brief, irregular, nonst ereot ypical, nonrhyt hmic movement s and can involve t he ext remit ies, head,
t runk, and face. In addit ion t o chorea, ot her mot or sympt oms include at axia, dyst onia, slurred speech, swallowing impairment , and myoclonus. Sympt oms t ypically begin in
t he fourt h and fift h decade. Hunt ingt on disease does not present acut ely, as occurred in t his pat ient .
The neurolept ic malignant syndrome is a life-t hreat ening disorder caused by an idiosyncrat ic react ion t o neurolept ic t ranquilizers (dopamine D
2
-recept or ant agonist s) and
some ant ipsychot ic drugs, of which haloperidol is t he most common. Most pat ient s wit h t he syndrome develop muscle rigidit y, hypert hermia, cognit ive changes, aut onomic
inst abilit y, diaphoresis, sialorrhea, seizures, arrhyt hmias, and rhabdomyolysis wit hin 2 weeks of init iat ing t he drug. The lack of fever and generalized muscle rigidit y argue
st rongly against t his diagnosis.
Key Poi nt
Neurolept ic, ant iemet ic, and serot oninergic agent s have been implicat ed in acut e dyst onic react ions, which usually occur wit hin 5 days of init iat ing t he offending drug.
Bi bl i ography
Tarsy D, Simon DK. Dyst onia. N Engl J Med. 2006;355(8):818-29. [PMID: 16928997]
Item 15 Answer: D
Educati onal Objecti ve: Diagnose Parkinson disease.
The most likely diagnosis is Parkinson disease. Parkinson disease remains a clinical diagnosis t hat is based on a cardinal set of clinical feat ures, including rest ing t remor,
bradykinesia, rigidit y, and post ural inst abilit y; t he t remor, bradykinesia, and rigidit y are asymmet ric. Sust ained levodopa responsiveness is expect ed in Parkinson disease and
helps confirm t he clinical diagnosis. Signs suggest ing an alt ernat ive condit ion include symmet ric sympt oms or signs, early falls, rapid progression, poor or waning response t o
levodopa, dement ia, early aut onomic failure, and at axia.
The pat ient 's findings are not compat ible wit h cervical dyst onia, essent ial t remor, or Hunt ingt on disease. Cervical dyst onia, formerly known as t ort icollis, is a focal dyst onia
t hat involves t he cervical musculat ure and causes abnormal post ures of t he head, neck, and shoulders. Quick, nonrhyt hmic, repet it ive movement s can also occur and can be
mist aken for t remor.
Essent ial t remor is charact erized by an upper ext remit y high-frequency t remor, which is present wit h bot h limb movement and sust ained post ure of t he involved ext remit ies
and is absent at rest . The t remor is charact erist ically bilat eral, but t here can be mild t o moderat e asymmet ry. Essent ial t remors t ypically improve wit h alcohol and worsen
wit h st ress. Tremor amplit ude over t ime generally increases and can be so severe as t o int erfere wit h writ ing, drinking, and ot her act ivit ies requiring smoot h, coordinat ed
upper limb movement s.
Hunt ingt on disease is a heredit ary, progressive, neurodegenerat ive disorder charact erized by increasingly severe mot or impairment , cognit ive decline, and psychiat ric
sympt oms. In addit ion t o chorea, ot her mot or sympt oms include at axia, dyst onia, slurred speech, swallowing impairment , and myoclonus. Various psychiat ric sympt oms,
such as dysphoria, agit at ion, irrit abilit y, anxiet y, apat hy, disinhibit ion, delusions, and hallucinat ions, are commonly seen.
Key Poi nt
The diagnosis of Parkinson disease is based on a cardinal set of clinical feat ures, including rest ing t remor, bradykinesia, rigidit y, and post ural inst abilit y.
Bi bl i ography
Nut t JG, Woot en GF. Clinical pract ice. Diagnosis and init ial management of Parkinson's disease. N Engl J Med. 2005;353(10):1021-1027. [PMID: 16148287]
Item 16 Answer: C
Educati onal Objecti ve: Treat essential tremor with propranolol.
This pat ient should be t reat ed wit h propranolol. She has a hist ory and examinat ion findings consist ent wit h t he presence of essent ial t remor. Essent ial t remor primarily
occurs when a pat ient maint ains a post ure, such as when t he hands are out st ret ched. Essent ial t remor also may be present during movement , part icularly post ural adjust ment s.
Aut osomal dominant t ransmission occurs in approximat ely half of pat ient s wit h t his condit ion. Essent ial t remor most commonly affect s t he upper ext remit ies; however, t he
legs, head, t runk, face, and vocal cords may be involved. Up t o 15% of pat ient s wit h essent ial t remor have major disabilit y associat ed wit h t his condit ion. Progression of
essent ial t remor is t ypically slow, wit h int ermit t ent lengt hy periods of st able sympt oms. Feat ures t hat may be predict ive of a more severe essent ial t remor include a posit ive
family hist ory of t remor, longer t remor durat ion, voice t remor, and unilat eral t remor onset . Alcoholic beverage consumpt ion suppresses sympt oms in most pat ient s wit h t his
condit ion.
Treat ment opt ions for essent ial t remor are oft en limit ed and frequent ly only part ially effect ive. It has been est imat ed t hat 50% of pat ient s wit h essent ial t remor have no
response t o medical t reat ment . First -line medicat ions used t o t reat essent ial t remor include propranolol, primidone, gabapent in, and t opiramat e. Propranolol is t ypically t he
drug of choice in most pat ient s wit h essent ial t remor because of it s effect iveness, which has been est ablished in mult iple well-designed randomized clinical t rials.
Essent ial t remor is dist inguished from Parkinson disease by it s lack of parkinsonian feat ures, such as rigidit y, bradykinesia, post ural inst abilit y, and rest ing t remor. Carbidopa-
levodopa can be an appropriat e choice t o t reat Parkinson disease but is not useful in t he t reat ment of essent ial t remor. Parkinsonian t remor is t ypically post ural and kinet ic
(occurring wit h movement ). Ropinirole and pramipexole are dopamine agonist medicat ions used t o t reat Parkinson disease. Given t he absence of any ot her signs of Parkinson
disease, t hese medicat ions are not indicat ed in t his pat ient .
Key Poi nt
Propranolol is a first -line medicat ion for essent ial t remor.
Bi bl i ography
Lorenz D, Deuschl G. Updat e on pat hogenesis and t reat ment of essent ial t remor. Curr Opin Neurol. 2007;20(4):447-452. [PMID: 17620881]
Item 17 Answer: A
Educati onal Objecti ve: Diagnose Li steri a monocytogenes meningitis.
The most likely diagnosis is Listeria monocytogenes meningit is. Listeria monocytogenes is a gram-posit ive bacillus t hat can cause invasive disease in immunocompromised
st at es, including alcoholism, ext remes of age (neonat es and t hose >50 years of age), malignancy, immunosuppression, diabet es mellit us, pregnancy, hepat ic failure, chronic
kidney disease, iron overload, collagen vascular disorders, use of ant it umor necrosis fact or- agent s, and HIV infect ion. The gast roint est inal t ract is t he usual port al of ent ry
wit h sympt oms t ypically developing aft er consumpt ion of cont aminat ed cole slaw, raw veget ables, milk, cheese, processed meat s, smoked seafood, and hot dogs, pot ent ially
result ing in a febrile gast roent erit is syndrome including diarrhea. The organism can cont inue t o mult iply at refrigerat or-level t emperat ures.
Neisseria meningitidis meningit is occurs primarily in children and young adult s. This illness is charact erized by abrupt onset of flu-like illness including fever, headache, neck
st iffness, alt ered ment al st at us, int ense myalgias, and rash. The rash is oft en pet echial, purpuric, or maculopapular. The evolut ion of t his infect ion can be rapid and fulminant ,
pot ent ially result ing in sept ic shock and deat h. Invasive infect ions can be est ablished by t he growt h of t hese gram-negat ive diplococci from CSF and blood cult ures. Biopsy
and cult ure of skin lesions may also reveal t he organism.
Streptococcus pneumoniae is t he most common cause of bact erial meningit is in adult s. The clinical present at ion of pneumococcal meningit is is not specific, but CSF and
possibly blood cult ures will reveal growt h of gram-posit ive diplococci.
Pat ient s wit h viral meningit is can present wit h a syndrome similar t o bact erial meningit is. However, CSF findings t ypically reveal a lymphocyt ic pleocyt osis, a glucose level
great er t han 45 mg/dL (2.5 mmol/L), prot ein level less t han 200 mg/dL (2000 mg/L), and a negat ive Gram st ain. In t he evaluat ion of pat ient s wit h acut e bact erial or viral
meningit is, a CSF prot ein concent rat ion great er t han 220 mg/dL (2200 mg/L), CSF glucose less t han 34 mg/dL (1.9 mmol/L), CSF blood-glucose rat io less t han 0.2, CSF
leukocyt es great er t han 2000/L (2000 10
6
/L), or CSF neut rophils great er t han 1180/L (1180 10
6
/L) are individual predict ors of bact erial et iology wit h a 99% or great er
cert aint y.
Key Poi nt
Listeria monocytogenes is a gram-posit ive bacillus t hat can cause invasive disease in immunocompromised pat ient s, part icularly t hose wit h cell-mediat ed immunodeficiency.
Bi bl i ography
Nudelman Y, Tunkel AR. Bact erial meningit is: epidemiology, pat hogenesis and management updat e. Drugs. 2009;69(18):2577-96. [PMID: 19943708]
Item 18 Answer: A
Educati onal Objecti ve: Diagnose N. meni ngi ti di s serogroup B meningitis.
This pat ient 's illness, physical examinat ion, and CSF profile are consist ent wit h N. meningitidis meningit is. This infect ion most commonly occurs in children and young
adult s. The Cent ers for Disease Cont rol and Prevent ion (CDC) recommends rout ine immunizat ion wit h t he meningococcal vaccine, which prot ect s against serogroups A, C,
Y, and W-135, but not serogroup B, t he causat ive agent in as many as one t hird of U.S. cases and t he recent cause of ot her cases of meningit is on campus.
Rocky Mount ain spot t ed fever (RMSF) can manifest as headache, fever, myalgia, abdominal pain, and rash. The purpuric rash t ypically develops 3 t o 4 days aft er t he onset
of const it ut ional sympt oms and begins on t he wrist s and ankles before spreading cent ripet ally. Thrombocyt openia, a relat ive leukopenia, and elevat ed t ransaminases may
provide clues t o t he diagnosis, part icularly if t he pat ient resides or has t raveled t o areas where RMSF-associat ed American dog t icks are present . These t icks t ransmit
infect ion in spring and early summer but not in December, which is when t his pat ient became ill.
Streptococcus pneumoniae is t he most common cause of bact erial meningit is in adult s. The clinical present at ion of pneumococcal meningit is is not specific, but CSF and,
possibly, blood cult ures will reveal gram-posit ive (not gram-negat ive) diplococci.
Vibrio vulnificus is a gram-negat ive bacillus t hat can cause sept icemia, wound infect ion, and, rarely, gast roent erit is. Wound infect ion t ypically occurs by inoculat ion t hrough
t he skin, and sept icemia and gast roent erit is occurs aft er ingest ion of raw or undercooked shellfish. Invasive disease t ypically occurs in immunocompromised host s,
part icularly t hose wit h liver disease. These infect ions are more common in summer mont hs when warmer sea wat er t emperat ures support t he growt h of t his organism.
Meningit is is not charact erist ic of infect ion wit h t his organism.
Key Poi nt
The N. meningitidis vaccine does not provide prot ect ion against N. meningitidis serogroup B meningit is.
Bi bl i ography
Nudelman Y, Tunkel AR. Bact erial meningit is: epidemiology, pat hogenesis and management updat e. Drugs. 2009;69(18):2577-2596. [PMID: 19943708]
Item 19 Answer: B
Educati onal Objecti ve: Diagnose meningococcal meningitis.
This pat ient 's illness is most consist ent wit h Neisseria meningitidis (meningococcal) infect ion, which is charact erized by t he sudden onset of fever, myalgia, headache, and
rash in a previously healt hy pat ient . Early in it s course, meningococcal disease may be indist inguishable from ot her common viral illnesses; however, t he rapidit y wit h which
t he disease worsens (oft en over hours) and progresses t o sept ic shock different iat es it from t hese ot her illnesses. A pet echial rash is most common and may coalesce t o form
purpuric lesions. The diagnosis is est ablished on t he basis of clinical present at ion and confirmed wit h blood and cerebrospinal fluid (CSF) cult ures.
Meningit is caused by Listeria monocytogenes is associat ed wit h ext remes of age (neonat es and persons age >50 years), alcoholism, malignancy, immunosuppression, diabet es
mellit us, hepat ic failure, renal failure, iron overload, collagen vascular disorders, and HIV infect ion. The clinical present at ion of Listeria meningoencephalit is ranges from a
mild illness wit h fever and ment al st at us changes t o a fulminant course wit h coma. It is not associat ed wit h a rash.
The classic present at ion of Rocky Mount ain spot t ed fever is a severe headache, fever, myalgia, and art hralgia. Thrombocyt openia and acut e kidney injury can occur. A
maculopapular rash develops 3 t o 5 days lat er, beginning on t he wrist s and ankles and pot ent ially involving t he palms and soles. Rocky Mount ain spot t ed fever is t ransmit t ed
by t he American dog t ick in t he spring and early summer, which is inconsist ent wit h t he t iming of t his pat ient 's present at ion.
Viral meningit is can present wit h fever, headache, st iff neck, and phot ophobia and may be associat ed wit h a maculopapular erupt ion. However, acut e viral meningit is is rarely
associat ed wit h t hrombocyt openia, met abolic acidosis, and acut e kidney injury. Finally, CSF findings t ypically show a lymphocyt e-predominant leukocyt osis (leukocyt e count
<1000/L [1000 10
6
/L]), a glucose level great er t han 45 mg/dL (2.5 mmol/L), a prot ein level less t han 200 mg/dL (2000 mg/L), and a Gram st ain negat ive for organisms.
Key Poi nt
Meningococcal infect ion should be considered in t he different ial diagnosis of any previously healt hy pat ient who present s wit h acut e-onset fever, headache, rash, and myalgia.
Bi bl i ography
van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Communit y-acquired bact erial meningit is in adult s. N Engl J Med. 2006;354(1):44-53. [PMID: 16394301]
Item 20 Answer: C
Educati onal Objecti ve: Treat bacterial meningitis empirically with vancomycin, ampicillin, and ceftriaxone.
This pat ient most likely has bact erial meningit is and requires t herapy wit h vancomycin, ampicillin, and ceft riaxone. Bact erial meningit is in adult s is charact erized by fever,
headache, nuchal rigidit y, and signs of cerebral dysfunct ion. In elderly pat ient s, such as t his one, insidious onset wit h let hargy or obt undat ion and variable signs of meningeal
irrit at ion may be present , part icularly in t he set t ing of diabet es mellit us. This pat ient 's sympt oms and cerebrospinal fluid result s are consist ent wit h acut e bact erial meningit is.
The most likely et iologic agent s are Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis, and aerobic gram-negat ive bacilli. Pending cult ure result s and
result s of in vit ro suscept ibilit y t est ing, empiric t reat ment wit h ant imicrobial t herapy consist ing of vancomycin, ampicillin, and ceft riaxone for infect ion caused by penicillin-
resist ant pneumococci and L. monocytogenes is necessary. Administ rat ion of adjunct ive dexamet hasone should be st rongly considered in pat ient s wit h acut e bact erial
meningit is because clinical t rials have est ablished t he benefit of adjunct ive dexamet hasone on adverse out comes and deat h in adult s wit h suspect ed or proven S. pneumoniae
meningit is.
Int ravenous ceft riaxone or int ravenous penicillin G alone might not provide adequat e cerebrospinal fluid levels for t reat ment of penicillin-resist ant S. pneumoniae. Most
infect ious disease expert s would recommend vancomycin plus ceft riaxone for t he t reat ment of penicillin-resist ant S. pneumoniae; however, t his combinat ion would not
adequat ely t reat meningit is caused by L. monocytogenes, which requires t he addit ion of ampicillin. Trimet hoprim-sulfamet hoxazole does t reat Listeria meningit is, but t he
combinat ion of vancomycin plus t rimet hoprim-sulfamet hoxazole would be pot ent ially inadequat e t reat ment for S. pneumoniae meningit is.
Key Poi nt
Empiric t herapy of acut e bact erial meningit is in an older adult should include a t hird-generat ion cephalosporin, vancomycin, and ampicillin.
Bi bl i ography
Tunkel AR, Hart man BJ, Kaplan SL, et al. Pract ice guidelines for t he management of bact erial meningit is. Clin Infect Dis. 2004;39(9):1267-1284. [PMID: 15494903]
Item 21 Answer: D
Educati onal Objecti ve: Treat acute stroke with early mobilization.
The pat ient should begin physical and occupat ional t herapy. A t ot al of 40% of pat ient s who have a st roke ret ain moderat e funct ional impairment , and 15% t o 30% have
severe disabilit y. Current evidence point s t o t he benefit s of early mobilizat ion and graded exercise in promot ing more complet e recovery from st roke and in prevent ing
complicat ions such as decubit us ulcers, decondit ioning, and loss of funct ion. For t his reason, early mobilizat ion wit h physical and occupat ional t herapy and a variet y of
approaches is recommended. Confining t he pat ient t o bed for 48 hours or longer is associat ed wit h a great er incidence of prevent able complicat ions and less t han opt imal
funct ional recovery.
On admission t o a hospit al ward, a pat ient wit h st roke should be given not hing by mout h unt il a swallowing assessment is conduct ed. In a pat ient wit h significant language
dist urbance, t here is concern for t he possibilit y of aspirat ion and complicat ions from it ; t he pat ient should not be prescribed a diet unt il a swallowing assessment has been
conduct ed t o det ermine safet y in swallowing. The American Heart Associat ion/American St roke Associat ion recommends a wat er swallow t est performed at t he bedside by a
t rained observer as t he best bedside predict or of aspirat ion. A prospect ive st udy of t he wat er swallow t est demonst rat ed a significant ly decreased risk of aspirat ion pneumonia
of 2.4% versus 5.4% in pat ient s who were not screened.
Key Poi nt
Early mobilizat ion of st roke pat ient s is recommended as a st rat egy for reducing complicat ions.
Bi bl i ography
Smit h LN, James R, Barber M, Ramsay S, Gillespie D, Chung C; Guideline Development Group. Rehabilit at ion of pat ient s wit h st roke: summary of SIGN guidance. BMJ.
2010;340:c2845. [PMID: 20551122]
Item 22 Answer: D
Educati onal Objecti ve: Treat an acute hemispheric stroke with thrombolytic therapy (intravenous recombinant tissue plasminogen activator).
This pat ient should receive int ravenous recombinant t issue plasminogen act ivat or (rt PA). He has clinical sympt oms and signs and radiologic evidence of an acut e left
hemispheric st roke. The probable mechanism of st roke is ischemic infarct ion, given t he result s of t he head CT scan. He was brought t o t he emergency depart ment wit hin 1
hour of t he wit nessed onset of st roke sympt oms, and his evaluat ion is complet ed 1 hour lat er. He does not appear t o have any clinical, radiologic, or laborat ory
cont raindicat ion t o receiving t he preferred t reat ment of int ravenous rt PA, and he can receive it wit hin t he recommended window of 3 hours from st roke onset .
Aspirin is indicat ed for acut e ischemic st roke in pat ient s who are not eligible for rt PA. For pat ient s wit h acut e st roke who are eligible for t hrombolysis, aspirin should be
wit hheld in t he emergency depart ment and for 24 hours aft er rt PA administ rat ion.
Alt hough long-t erm ant icoagulat ion is an effect ive t reat ment for prevent ion of cardioembolic st roke in pat ient s wit h at rial fibrillat ion, acut e ant icoagulat ion wit h heparin has
not been shown t o be beneficial in pat ient s wit h acut e ischemic st roke.
Elevat ed blood pressure is common at t he t ime of init ial st roke present at ion, even among pat ient s wit hout chronic hypert ension. Rapid lowering of blood pressure may
furt her impair cerebral blood flow and worsen t he ischemic injury. Elevat ed blood pressure oft en will resolve spont aneously or improve gradually during t he first few days aft er
a st roke. The t hreshold for acut e blood pressure lowering in pat ient s wit h acut e st roke who are eligible for t hrombolysis is 185/110 mm Hg. In such a set t ing, preferred agent s
include int ravenous infusions of labet alol or nicardipine. Because t his pat ient 's blood pressure is already below t hat t hreshold, t here is no indicat ion for int ravenous use of
labet alol at t his t ime.
Key Poi nt
The preferred t reat ment of ischemic st roke is int ravenous recombinant t issue plasminogen act ivat or if it can be administ ered wit hin 3 hours from st roke onset .
Bi bl i ography
van der Worp HB, van Gijn J. Clinical pract ice. Acut e ischemic st roke. N Engl J Med. 2007;357(6):572-579. [PMID: 17687132]
Item 23 Answer: D
Educati onal Objecti ve: Manage hypertension in a patient with an acute ischemic stroke.
There is no urgent need t o t reat hypert ension in an uncomplicat ed ischemic st roke. For uncomplicat ed ischemic st rokes in pat ient s wit hout concurrent acut e coronary art ery
disease or heart failure, consensus exist s t hat ant ihypert ensive medicat ions, such as int ravenous labet alol or nicardipine, should be wit hheld if t he syst olic blood pressure is less
t han 220 mm Hg or t he diast olic blood pressure is less t han 120 mm Hg, unless t here are ot her manifest at ions of end-organ damage. This pat ient 's syst olic and diast olic blood
pressure levels are below t hese limit s and t here is no urgent need t o t reat hypert ension, such as aort ic dissect ion, myocardial infarct ion, or heart failure. Many such pat ient s
have spont aneous declines in blood pressure during t he first 24 hours aft er st roke onset .
Oral nifedipine is an inappropriat e t reat ment for t his pat ient not only because of it s ant ihypert ensive qualit ies, but also because of it s rout e of administ rat ion. Given t he
severit y of her st roke deficit s, in part icular t he dysart hria, she should receive not hing by mout h unt il a swallowing evaluat ion is carried out because of t he high risk of
aspirat ion.
Not ably, t he pat ient is not eligible for recombinant t issue plasminogen act ivat or t herapy because t he t ime int erval bet ween now and her previous sympt om-free st at e is more
t han 3 hours. Aspirin (160 t o 325 mg/d) administ ered wit hin 48 hours of st roke onset result s in a small but significant reduct ion in t he risk for recurrent st roke during t he first
2 weeks aft er t he st roke and improves out come at 6 mont hs. Therefore, aspirin is recommended as init ial t herapy for most pat ient s wit h acut e st roke. However, aspirin
should not be administ ered for at least 24 hours aft er administ rat ion of t hrombolyt ics.
Key Poi nt
For uncomplicat ed ischemic st rokes in pat ient s wit hout concurrent acut e coronary art ery disease, aort ic dissect ion, or heart failure, ant ihypert ensive medicat ions should be
wit hheld if t he syst olic blood pressure is less t han 220 mm Hg or t he diast olic blood pressure is less t han 120 mm Hg.
Bi bl i ography
Urrut ia VC, Wit yk RJ. Blood pressure management in acut e st roke. Neurol Clin. 2008;26(2):565-583, x-xi. [PMID: 18514827]
Item 24 Answer: A
Educati onal Objecti ve: Evaluate a subarachnoid hemorrhage with a lumbar puncture and cerebrospinal fluid analysis.
This pat ient should have a lumbar punct ure. A t hunderclap headache is a severe and explosive headache t hat is maximal in int ensit y at or wit hin 60 seconds of onset . CT
scanning is t he first t est t o be conduct ed in a pat ient wit h t hunderclap headache in whom a subarachnoid hemorrhage is suspect ed; a rupt ured int racranial aneurysm is t he most
serious cause of such headaches. The abilit y t o det ect subarachnoid hemorrhage is dependent on t he amount of subarachnoid blood, t he int erval aft er sympt om onset , t he
resolut ion of t he scanner, and t he skills of t he radiologist . On t he day of t he hemorrhage, ext ravasat ed blood will be present in more t han 95% of pat ient s, but in t he
following days, t his proport ion falls sharply. If an init ial CT scan of t he head reveals not hing, a lumbar punct ure should be performed next in pat ient s wit h t his present at ion.
The finding of xant hochromia or gross hemorrhage is diagnost ic for subarachnoid hemorrhage. Subsequent angiography (CT or MRI) can confirm t he presence of a rupt ured
aneurysm in pat ient s wit h a posit ive lumbar punct ure.
Early in t he diagnosis of subarachnoid hemorrhage, brain MRI is no more accurat e t han head CT. There is not hing t o be gained by performing brain MRI in t his pat ient wit h
negat ive findings on a head CT scan.
In pat ient s wit h an init ial subarachnoid hemorrhage, t here is subst ant ial risk of rebleeding (2% per day for t he first mont h). Rebleeding is associat ed wit h high mort alit y. The
t reat ment of subarachnoid hemorrhage involves localizing t he aneurysm wit h cerebral angiography and securing it t o prevent subsequent bleeding. Tradit ionally, surgical
clipping wit hin 72 hours of onset has been recommended. Aneurysms also may be t reat ed endovascularly by filling t hem wit h met allic coils and promot ing localized
t hrombosis wit hin t he aneurysm t o oblit erat e it from t he cerebral circulat ion. Hospit al observat ion as t he sole management opt ion for t his pat ient places her at increased risk
for rebleeding and deat h.
Treat ment wit h sumat ript an is indicat ed for migraine headache. All of t he t ript ans promot e vasoconst rict ion and block pain pat hways in t he brainst em. They are
cont raindicat ed in pat ient s wit h st roke and uncont rolled hypert ension. The use of sumat ript an in t his pat ient who has a high likelihood of subarachnoid hemorrhage is
cont raindicat ed.
Key Poi nt
A lumbar punct ure wit h subsequent cerebrospinal fluid analysis is necessary in any pat ient wit h t hunderclap headache and normal findings on a CT scan t o fully evaluat e a
possible subarachnoid hemorrhage.
Bi bl i ography
van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet . 2007;369(9558):306-318. [PMID: 17258671]
Item 25 Answer: C
Educati onal Objecti ve: Diagnose Bell palsy.
This pat ient 's physical examinat ion findings most st rongly suggest right facial nerve (Bell) palsy. The precise cause of Bell palsy is not known, and it is st ill considered an
idiopat hic disorder. Research st rongly suggest s it may be t he result of herpes simplex virus infect ion of t he facial nerve. Bell palsy is not considered cont agious. The sevent h
cranial nerve innervat es all muscles of facial expression (t he mimet ic muscles). Any cause of a complet e facial neuropat hy will t herefore impair t he ent ire hemiface, including
t he forehead corrugat ors t ypically spared by cerebral lesions. Bell phenomenon describes t he reflexive rolling upwards of t he globe during eye closure. When a normal pat ient
is asked t o close t he eyes, forced eyelid opening will reveal t his phenomenon, as will t he select ive paralysis of t he orbicularis oculi due t o a facial neuropat hy. Facial
neuropat hies will ot herwise spare t he ext raocular muscles t hat govern globe movement . Because Bell palsy is a diagnosis of exclusion, clinicians need t o make every effort t o
exclude ot her ident ifiable causes of facial paralysis, such as Lyme disease, HIV disease, acut e and chronic ot it is media, cholest eat oma, and mult iple sclerosis. Ot her common
causes of acut e peripheral facial paralysis will oft en have findings on hist ory or physical examinat ion t hat suggest t he correct diagnosis.
Graves opht halmopat hy can cause propt osis or ext raocular muscle edema wit h consequent eye movement abnormalit ies but is not associat ed wit h t he facial hemiparalysis
t ypical of facial nerve (Bell) palsy.
Cerebral infarct ion, brain hemorrhage, or any st ruct ural brain lesion can cause weakness of t he lower face but not of t he forehead because t he bilat eral cort ical represent at ion
of t he midline forehead spares t he forehead corrugat ors. Some limb or sensory abnormalit y is also oft en, but not universally, observed in t he set t ing of cerebral infarct ion; no
such abnormalit y was observed in t his pat ient . Therefore, despit e her cerebrovascular risk fact ors of oral cont racept ion and cigaret t e smoking, t his pat ient is unlikely t o have
had a cerebral infarct ion.
The t rigeminal nerve provides sensat ion, not movement , t o t he muscles of facial expression, so t rigeminal neuralgia is not a likely diagnosis in t his pat ient wit h normal
sensat ion.
Key Poi nt
Any cause of a complet e facial neuropat hy will impair t he ent ire hemiface, including t he forehead muscles.
Bi bl i ography
Tiemst ra JD, Khat khat e N. Bell's palsy: diagnosis and management . Am Fam Physician. 2007;76(7):997-1002. [PMID: 17956069]
Item 26 Answer: C
Educati onal Objecti ve: Diagnose Guillain-Barre syndrome.
This pat ient has a rapidly progressive disorder affect ing t he peripheral nervous syst em, most compat ible wit h a clinical diagnosis of Guillain-Barre syndrome. Pat ient s wit h
Guillain-Barre syndrome t ypically develop parest hesias dist ally in t he lower ext remit ies t hat are followed by limb weakness and gait unst eadiness. In addit ion t o sensory loss
and limb weakness, deep t endon reflexes are charact erist ically absent or markedly reduced. The diagnosis is confirmed by elect romyography, which usually shows a
demyelinat ing polyradiculoneuropat hy. Cerebrospinal fluid (CSF) analysis charact erist ically shows albuminocyt ologic dissociat ion, whereby t he spinal fluid cell count is
normal but t he spinal fluid prot ein level is elevat ed. CSF analysis may also yield normal result s early in t he course of t he disease. However, a normal CSF cell count is useful in
excluding ot her infect ious condit ions, such as polyradiculoneuropat hies associat ed wit h HIV and cyt omegalovirus infect ion, infect ion due t o West Nile virus, and
carcinomat ous or lymphomat ous nerve root infilt rat ion. By definit ion, sympt oms in pat ient s wit h Guillain-Barre syndrome peak wit hin 4 weeks of onset . Int ravenous
immune globulin and plasma exchange are equally efficacious in t he t reat ment of Guillain-Barre syndrome.
Amyot rophic lat eral sclerosis (ALS) is a degenerat ive disease of t he ant erior horn cells of t he spinal cord and present s wit h bot h upper and lower mot or neuron signs,
including hyperreflexia, spast icit y, and an ext ensor plant ar response (upper mot or neuron signs) and weakness, muscle at rophy, and fasciculat ions (lower mot or neuron signs).
The pat ient 's findings are not compat ible wit h ALS.
Diabet es mellit us most commonly causes a slowly progressive, dist al, symmet ric sensorimot or polyneuropat hy. Aut onomic dysfunct ion frequent ly is associat ed wit h diabet ic
neuropat hy and is charact erized by sympt oms of impot ence, ort host at ic hypot ension, and gast roparesis. The sympt oms of a dist al symmet ric sensorimot or neuropat hy may
be t he first clinical manifest at ion, but t he rapidly progressive course of t his pat ient 's neuropat hy rules out diabet ic neuropat hy.
A spinal cord lesion (myelopat hy) would be an unlikely cause of t he sympt oms not ed on clinical examinat ion. The absence of bowel or bladder impairment , t he lack of a
sensory level across t he t horax, and t he upper and lower limb areflexia argue against a cent ral nervous syst em disorder affect ing t he spinal cord.
Key Poi nt
Guillain-Barre syndrome is a disorder associat ed wit h rapidly progressive ext remit y weakness, parest hesias, and areflexia.
Bi bl i ography
Burns TM. Guillain-Barre syndrome. Semin Neurol. 2008;28(2):152-167. [PMID: 18351518]
Item 27 Answer: A
Educati onal Objecti ve: Diagnose carpal tunnel syndrome.
This pat ient most likely has carpal t unnel syndrome. Carpal t unnel syndrome refers t o median nerve compression at t he wrist in t he carpal t unnel. Sympt oms include aching
wrist pain wit h sparing of t he palm, numbness and t ingling in t he median nerve sensory dist ribut ion of t he fingers, and weakness of t he t henar muscles. The parest hesias are
oft en worse at night or when holding a book or st eering a car.
de Quervain t enosynovit is is an exercise-relat ed injury associat ed wit h knit t ing and sport s involving ext ensive wrist act ion. Tenderness may be elicit ed in t he anat omic
snuffbox (t he ext ensor pollicis brevis and abduct or pollicis longus t endons). Pain elicit ed by flexing t he t humb int o t he palm, closing t he fingers over t he t humb, and t hen
bending t he wrist in t he ulnar direct ion (Finkelst ein t est ) is confirmat ory.
Ganglion cyst s are synovia-filled cyst s arising from joint s or t endon sheat hs t hat t ypically appear on t he dorsal hand or vent ral wrist . They can cause pain and compress
ot her st ruct ures. The absence of cyst ic st ruct ures on t he dorsal and vent ral wrist and t he dist ribut ion of t he pat ient 's pain eliminat e t his diagnosis.
Ulnar nerve compression at t he wrist is also called Guyon t unnel syndrome, because t he ent rapment occurs where t he ulnar nerve t ransverses t he Guyon t unnel bet ween t he
pisiform and hamat e bones on t he ant erolat eral side of t he wrist , and cyclist 's palsy, because t he compression of t he ulnar nerve oft en occurs as t he hand rest s on t he
handlebars. However, t he ulnar nerve can be compressed by muscles, t umors (lipomas), scar t issue, synovial cyst s, or any ot her int ernal st ruct ure t hat passes close t o t he
t unnel. The present at ion is similar t o t hat of carpal t unnel syndrome, but wit h sympt oms and signs on t he ulnar dist ribut ion of t he hand.
Key Poi nt
Sympt oms of carpal t unnel syndrome include aching wrist pain wit h sparing of t he palm, numbness and t ingling in t he median nerve sensory dist ribut ion of t he fingers, and
weakness of t he t henar muscles.
Bi bl i ography
Keit h MW, Masear V, Chung K, et al. Diagnosis of carpal t unnel syndrome. J Am Acad Ort hop Surg. 2009;17(6):389-396. [PMID: 19474448]
Item 28 Answer: B
Educati onal Objecti ve: Diagnose diabetic polyneuropathy.
The fast ing blood glucose level will most likely provide a diagnosis for t he pat ient 's neurologic findings. Diabet ic neuropat hy involves injury t o sensory, mot or, and
aut onomic nerves. Loss of sensat ion in a "st ocking-glove" dist ribut ion t hat is associat ed wit h parest hesias or painful dysest hesias is t he most common present at ion of t his
condit ion. Loss of sensat ion in t he lower ext remit ies is t ypical and plays a major part in t he development of foot ulcerat ions, which can lead t o limb loss. No direct t reat ment
for diabet ic neuropat hy exist s, ot her t han t o improve glycemic cont rol. Pharmacologic t herapy, however, may help sympt oms. Part ial serot onin and norepinephrine
reupt ake inhibit ors (duloxet ine), t ricyclic ant idepressant s (amit ript yline), and various ant iseizure medicat ions (gabapent in, phenyt oin, carbamazepine) are frequent ly used t o
t reat t he pain associat ed wit h t his condit ion.
Obt aining a creat ine kinase level would be appropriat e in someone wit h suspect ed primary muscle disease, but t his diagnosis is not likely in t his pat ient , given t he presence of
neuropat hic pain and sensory loss wit hout muscle weakness. Lumbar punct ure and cerebrospinal fluid examinat ion should be considered in pat ient s wit h acut e, severe, or
rapidly progressive neuropat hy and in t hose wit h a demyelinat ing neuropat hy; in t hese sit uat ions, lumbar punct ure may help t o confirm t he presence of an inflammat ory
process in t he cerebrospinal fluid but would not result in a specific diagnosis. Mult iple sclerosis, t he most common example of a demyelinat ing disorder, is charact erized by
discret e subacut e episodes of neurologic dysfunct ion t hat progress over days t o weeks, plat eau, and t hen improve part ially or complet ely over subsequent days t o mont hs.
Sural nerve biopsy is most t ypically performed in pat ient s wit h suspect ed vasculit is or amyloidosis. Pat ient s wit h vasculit ic neuropat hy t ypically have a syst emic illness wit h
manifest at ions in ot her organs, including t he skin, lungs, and kidneys; vasculit ic neuropat hy as t he sole present ing feat ure of a syst emic illness would be very unusual. Like
vasculit is, amyloidosis is a syst emic disease wit h manifest at ions involving many organ syst ems and would not likely present wit h sympt oms confined t o t he peripheral
nervous syst em of t he lower ext remit ies.
Key Poi nt
Loss of sensat ion in a "st ocking-glove" dist ribut ion t hat is associat ed wit h parest hesias or painful dysest hesias is t he most common present at ion of diabet ic neuropat hy.
Bi bl i ography
Kanji JN, Anglin RE, Hunt DL, Panju A. Does t his pat ient wit h diabet es have large-fiber peripheral neuropat hy? JAMA. 2010;303(15):1526-1532. [PMID: 20407062]
Secti on 9. Oncol ogy
Questi ons
Item 1 [Advanced]
A 45-year-old woman is evaluat ed for a lump in t he right breast t hat has been present for 3 mont hs. The pat ient is gravida 1, para 1. She has menses every 28 days. She is
ot herwise healt hy. No family hist ory of breast cancer exist s. Her mot her died of endomet rial cancer at t he age of 63 years.
On physical examinat ion, vit al signs are normal. A firm and nont ender 2-cm mass in t he upper out er quadrant of t he right breast is palpat ed. No ot her masses or axillary
adenopat hy are not ed.
A mammogram is BI-RADS 2 (benign findings).
(A) Obt ain a fine needle aspirat e
(B) Obt ain an ult rasound of t he right breast
(C) Repeat mammogram in 1 year
(D) Test for BRCA-1 and BRCA-2 genes
Item 2 [Advanced]
A 55-year-old woman undergoes follow-up evaluat ion for a mildly prurit ic erupt ion on and surrounding her right nipple, which developed about 5 mont hs ago. Triamcinolone
acet onide cream was begun 1 mont h ago wit h no improvement in t he lesion. She has no personal or family hist ory of eczema or psoriasis, and she is ot herwise healt hy. Her
only medicat ion is t riamcinolone.
Breast findings are shown (Plat e 23).
(A) Chronic cut aneous lupus eryt hemat osus
(B) Lichen simplex chronicus
(C) Paget disease of t he breast
(D) Psoriasis
Item 3 [Basic]
A 49-year-old woman is evaluat ed aft er not icing a small lump in her right breast 3 weeks ago. It is painless and has not changed in size. She has no ot her pert inent medical
hist ory. Her last menst rual period was 2 weeks ago. Her mot her had breast cancer at age 55 years; t here is no ot her family hist ory of cancer.
On physical examinat ion, vit al signs are normal. There is a 1.0 1.5-cm firm, discret e, mobile mass in t he upper out er quadrant of t he right breast . There is no
lymphadenopat hy or ot her abnormalit ies on examinat ion.
A bilat eral mammogram does not reveal any suspicious lesion in eit her breast .
(A) Aspirat ion or biopsy
(B) Clinical reevaluat ion in 1 mont h
(C) MRI of bot h breast s
(D) Repeat mammography in 6 mont hs
Item 4 [Basic]
A 52-year-old woman undergoes evaluat ion aft er a recent diagnosis of invasive duct al adenocarcinoma of t he right breast . Her aunt died of breast cancer at age 85 years, but
t here is no ot her family hist ory of breast or ovarian cancer. The pat ient is ot herwise healt hy. Her physical examinat ion is normal.
The pat ient undergoes t umor resect ion and a sent inel lymph node biopsy of t he right axilla. On pat hologic examinat ion, a 1.2-cm invasive duct al adenocarcinoma wit h free
margins is confirmed, and t he lymph node reveals no met ast ases. Complet e blood count , met abolic profile, and liver chemist ry t est s are normal as are diagnost ic
mammography and chest radiography.
Whi ch of the fol l owi ng wi l l be most hel pful i n di recti ng the approach to management of thi s pati ent?
(A) Full right axillary lymph node dissect ion
(B) Genet ic t est ing for t he BRCA1/2 mut at ion
(C) Tumor est rogen and progest erone recept or assay
(D) Whole-body posit ron emission t omography
Item 5 [Basic]
A 48-year-old post menopausal woman is evaluat ed aft er a recent diagnosis of breast cancer. Her annual screening mammogram revealed a new 1.5-cm area of
microcalcificat ion in t he left breast wit hout any associat ed mass. St ereot act ic biopsy revealed grade 2, est rogen recept or-progest erone recept or-negat ive and HER2-negat ive
infilt rat ing duct al carcinoma. She is ot herwise healt hy.
Her physical examinat ion is normal except for ecchymosis at t he biopsy sit e.
(A) Left lumpect omy and t amoxifen
(B) Left lumpect omy followed by breast irradiat ion
(C) Left lumpect omy wit h sent inel lymph node biopsy and t amoxifen
(D) Left lumpect omy wit h sent inel lymph node biopsy followed by breast irradiat ion
Item 6 [Advanced]
A 51-year-old woman is evaluat ed during a rout ine healt h maint enance examinat ion. She is healt hy and t akes no medicat ions. She does not smoke or drink alcohol. She is up
t o dat e on all of her immunizat ions and cancer screening t est s. Her most recent screening colonoscopy was performed at age 50 years. The only new addit ion t o her hist ory is
a recent diagnosis of colorect al cancer in her 55-year-old brot her.
What i s the best col orectal cancer screeni ng strategy for thi s pati ent?
(A) APC gene mut at ions screening
(B) Colonoscopy at age 55 years and t hen every 3 t o 5 years
(C) Colonoscopy at age 60 years and t hen every 10 years
(D) Colonoscopy now and t hen every 2 years
Item 7 [Advanced]
A 59-year-old man is evaluat ed for a change in his bowel habit s over t he past 2 mont hs. Typically, he has a soft , formed bowel movement every ot her day, but he now passes
hard, pellet -like st ools alt ernat ing wit h loose st ools associat ed wit h a sense of bloat ing and abdominal fullness; t here is no blood. He has not lost weight . He has never
undergone colon cancer screening.
On physical examinat ion, vit al signs are normal. Abdominal examinat ion reveals normal bowel sounds and no evidence of t enderness or masses. Rect al examinat ion is
normal, and t he st ool is negat ive for occult blood. Rout ine screening chemist ry t est s are normal.
(A) Colonoscopy
(B) Cont rast -enhanced abdominal CT scan
(C) Flexible sigmoidoscopy
(D) Test ing t hree st ools for occult blood
Item 8 [Basic]
A 58-year-old woman undergoes a general physical examinat ion. She is asympt omat ic and t akes no medicat ions or over-t he-count er drugs. Family hist ory is unremarkable.
Her preferred met hod of colorect al cancer screening has been annual fecal occult blood t est ing (FOBT). Annual t est ing for t he past 8 years has been negat ive for fecal occult
blood.
Physical examinat ion is normal. Result s of rout ine laborat ory st udies are also normal, including a hemoglobin level of 14.8 g/dL (148 g/L). One of t hree st ool samples
submit t ed by t he pat ient for FOBT is posit ive.
Whi ch of the fol l owi ng i s the most appropri ate next step i n eval uati ng thi s pati ent?
(A) Colonoscopy
(B) Flexible sigmoidoscopy
(C) Repeat FOBT now
(D) Repeat FOBT in 1 year
Item 9 [Advanced]
A 27-year-old woman wit h an 8-year hist ory of ulcerat ive colit is is evaluat ed during a follow-up examinat ion. The init ial colonoscopy aft er diagnosis showed pancolit is. She
has been t reat ed wit h mesalamine since diagnosis and has had episodes of bloody diarrhea t wo or t hree t imes a year but has ot herwise been well. Her most recent colonoscopy
1 year ago when she had increased diarrhea and bleeding showed no progression of disease. Since t hen, she has been clinically st able. The pat ient 's medical hist ory is ot herwise
unremarkable, and her only medicat ions are low-dose mesalamine and a mult ivit amin. There is no family hist ory of colorect al cancer.
On physical examinat ion, vit al signs are normal. There is mild abdominal t enderness in t he right lower quadrant wit hout rebound or guarding. The rest of t he physical
Laborat ory st udies reveal a normal complet e blood count , including leukocyt e different ial, and a normal serum C-react ive prot ein level.
(A) Annual colonoscopy
(B) Annual fecal occult blood t est ing
(C) Annual flexible sigmoidoscopy
(D) Annual wireless capsule endoscopy
Item 10 [Basic]
A 66-year-old man is evaluat ed during a rout ine examinat ion. The pat ient has a 25-pack-year cigaret t e-smoking hist ory. He has t ried t o quit smoking wit h nicot ine gum and
varenicline wit h no success. He has mild airway obst ruct ion but good exercise t olerance and no cough, sput um product ion, or hemopt ysis. The import ance of smoking
cessat ion is reviewed wit h t he pat ient .
Whi ch of the fol l owi ng i s the recommended screeni ng strategy for l ung cancer i n thi s pati ent?
(A) 18F-fluorodeoxyglucose and posit ron emission t omography scan (FDG-PET)
(B) Chest radiography
(C) Spiral CT scan of t he chest
(D) Sput um cyt ology
(E) No screening
Item 11 [Advanced]
A 52-year-old woman is evaluat ed aft er an abdominal CT scan det ect ed a 3-mm nodule in t he right lower pulmonary lobe. The CT scan was obt ained t o evaluat e abdominal
pain, which has since complet ely resolved. The pat ient has never smoked. She works in t he home and has not been exposed t o pot ent ial carcinogens. She has not had a chest
radiograph or ot her imaging procedure, except mammography. Her medical hist ory is unremarkable, and she t akes no medicat ion. Her family hist ory is unremarkable.
The physical examinat ion is normal.
(A) Chest radiograph in 3 mont hs
(B) CT scan of t he chest in 3 mont hs
(C) CT scan of t he chest in 6 mont hs
(D) No follow-up
Item 12 [Basic]
A 78-year-old woman is evaluat ed for a 6-mont h hist ory of fat igue and an unint ent ional 9.0-kg (20-lb) weight loss.
On physical examinat ion, vit al signs are normal. There is a palpable 1.5-cm left supraclavicular lymph node. The skin is normal, t he lungs are clear, and t he abdomen is soft
and wit hout organomegaly.
Complet e blood count , liver enzymes, and serum calcium level are normal. Chest radiograph shows a 5-cm left lung mass wit h left hilar lymphadenopat hy. CT scan shows a 5-
cm left upper lobe mass wit h left hilar lymphadenopat hy and normal-sized mediast inal lymph nodes.
(A) Bronchoscopy wit h biopsy of t he mass
(B) CT-guided t ranst horacic needle biopsy of t he mass
(C) Posit ron emission t omography-CT (PET-CT)
(D) Supraclavicular lymph node biopsy
Item 13 [Advanced]
A 62-year-old man is evaluat ed for a recent diagnosis of biopsy-proven, limit ed-st age small cell lung cancer involving t he right upper lobe. The pat ient has excellent
performance st at us and has recent ly st opped smoking cigaret t es. He has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, vit al signs are normal; BMI is 24. Pulmonary examinat ion discloses decreased breat h sounds t hroughout all lung fields and a few early wheezes in t he
right upper chest . Neurologic examinat ion result s are normal.
(A) Chemot herapy and radiat ion t herapy
(B) Chemot herapy followed by aut ologous st em cell t ransplant at ion
(C) Radiat ion t herapy
(D) Right upper lobect omy
(E) Small cell lung cancer vaccinat ion
Item 14 [Basic]
A 60-year-old man is evaluat ed during a rout ine visit . He has no chronic medical problems or genit ourinary sympt oms. His physical examinat ion is normal, including a digit al
rect al examinat ion t hat reveals a slight ly enlarged, nont ender, smoot h prost at e gland.
He has previously decided t o undergo annual prost at e-specific ant igen (PSA) cancer screening. One year ago, his PSA was 2.5 ng/mL (2.5 g/L). A PSA measured yest erday
was 5.4 ng/mL (5.4 g/L).
(A) CT scan of t he pelvis
(B) Transrect al prost at e biopsy
(C) Radical prost at ect omy
(D) Repeat PSA measurement in 6 mont hs
Item 15 [Advanced]
A 57-year-old man is evaluat ed during a rout ine examinat ion. He asks if he should undergo prost at e-specific ant igen (PSA) t est ing. Medical hist ory is ot herwise unremarkable.
There is no family hist ory of cancer. Result s of t he physical examinat ion are unremarkable.
Whi ch of the fol l owi ng i s the best prostate cancer screeni ng opti on for thi s pati ent?
(A) Discuss t he risks and benefit s of screening for prost at e cancer
(B) Order PSA t est ing
(C) Order PSA t est ing and perform digit al rect al examinat ion (DRE)
(D) Perform DRE
Item 16 [Basic]
An 80-year-old man is evaluat ed aft er an elevat ed serum prost at e-specific ant igen (PSA) level of 5.7 ng/mL (5.7 g/L) was not ed during a communit y screening program. He
has no sympt oms relat ed t o t he genit ourinary syst em and denies bone pain, weight loss, or any change in his healt h st at us. The pat ient has hypert ension and
hypercholest erolemia. He also underwent four-vessel coronary art ery bypass graft surgery 5 years ago and has chronic st able angina. His current medicat ions are
hydrochlorot hiazide, at enolol, lisinopril, pravast at in, nit roglycerin, and low-dose aspirin.
On physical examinat ion, t he pat ient is afebrile, blood pressure is 140/80 mm Hg, and t he pulse rat e is 72/min and regular. The lungs are clear, and t he abdomen is soft and
nont ender. There is t race pedal edema in t he lower ext remit ies.
(A) Bone scan
(B) Repeat PSA
(C) Transrect al prost at e biopsy
(D) Observat ion
Item 17 [Advanced]
A 66-year-old man is evaluat ed because of an increasingly elevat ed serum prost at e-specific ant igen (PSA) level. The pat ient received a prost at e cancer diagnosis 4 years ago
and underwent definit ive radiat ion t herapy, following which his PSA level became undet ect able. He is current ly asympt omat ic.
A bone scan now shows mult iple met ast at ic lesions.
(A) Docet axel plus prednisone
(B) Hospice care
(C) Leuprolide
(D) Samarium-153
(E) Observat ion
Item 18 [Basic]
A 27-year-old woman wit h a hist ory of mult iple sex part ners is evaluat ed during a rout ine office visit . She feels well and has no sympt oms. She has never had an abnormal
Pap smear. She has been sexually act ive for 10 years and has not had any sexually t ransmit t ed diseases, alt hough she has not usually used condoms. Safe sex counseling is
provided.
Result s of a pelvic examinat ion are normal, and a Pap smear is obt ained. HIV t est ing is performed. Result s of t he Pap smear are posit ive for at ypical squamous cells of
undet ermined significance (ASCUS). Subsequent human papillomavirus t est ing is posit ive for subt ype 16.
Whi ch of the fol l owi ng i s the best next management step?
(A) Colposcopy
(B) Repeat human papillomavirus t est ing in 1 year
(C) Repeat Pap t est ing in 1 year
(D) Treat ment wit h int erferon
Item 19 [Basic]
A 19-year-old asympt omat ic woman is evaluat ed during a rout ine annual physical examinat ion. The pat ient st at es she is not sexually act ive and has not engaged in prior
sexual act ivit y. She has a boyfriend whom she has dat ed for t he past year. The pat ient complet ed her menst rual cycle 3 days ago. She has no pert inent family hist ory or
known drug allergies and t akes no medicat ions. She has not received a human papillomavirus vaccine.
Result s of t he physical examinat ion, including a breast and pelvic examinat ion, are normal.
(A) Human papillomavirus (HPV) vaccine at age 21 years
(B) HPV vaccine at onset of sexual act ivit y
(C) HPV vaccine at t ime of HPV seroconversion
(D) HPV vaccine now
Item 20 [Basic]
A 38-year-old woman comes t o t he office for a rout ine physical examinat ion and Pap smear. Her husband has been her only sexual part ner for t he past 14 years, and t hey are
bot h human immunodeficiency virus-negat ive. She has received annual Pap t est s since t he onset of sexual act ivit y at age 21 years and has never had an abnormal Pap smear.
If her current Pap smear i s normal , when does she need to have her next Pap test?
(A) Today
(B) In 6 mont hs
(C) In 3 years
(D) In 5 years
(E) Never, unless she has a new sexual part ner
Item 21 [Basic]
A 47-year-old woman undergoes her annual physical examinat ion. She has no medical problems and t akes no medicat ions. She had a complet e vaginal hyst erect omy for
abnormal ut erine bleeding caused by leiomyoma 2 years ago. She has had a monogamous sexual relat ionship wit h her husband since her marriage 24 years ago. She has had
cervical Pap t est s every 3 years since t he age of 30 years unt il 2 years ago, all of which have been normal.
Whi ch of the fol l owi ng i s the most appropri ate frequency of Pap tests for thi s pati ent?
(A) Annually, indefinit ely
(B) Every 3 years, indefinit ely
(C) Every 3 years unt il age 65 years
(D) Discont inue Pap smear
Item 22 [Advanced]
A 72-year-old man is evaluat ed for an asympt omat ic lesion on his forearm. It is firm t o palpat ion and has been gradually enlarging over t he past year. It does not it ch. No
ot her similar skin lesions are present .
Skin findings are shown (Plat e 24).
(A) Nummular eczema
(B) Psoriasis
(C) Squamous cell carcinoma in sit u
(D) Superficial basal cell carcinoma
(E) Superficial spreading melanoma
Item 23 [Basic]
A 62-year-old man is evaluat ed for a dark blue "berry-like" lesion t hat has been enlarging over t he past 6 mont hs. It is bot hersome, because it now t ends t o cat ch on his
clot hing.
(B) Kerat oacant homa
(C) Nodular melanoma
(D) Seborrheic kerat osis
(E) Spit z nevus
Item 24 [Advanced]
A 70-year-old man comes t o t he office t o ask about t he skin changes on his hands, as shown (Plat e 26).
The skin changes have been present for years, but he is concerned now about t he possibilit y of skin cancer.
(A) Act inic kerat oses
(B) Basal cell carcinoma
(C) Malignant melanoma
(D) Seborrheic kerat oses
Item 25 [Basic]
A 62-year-old man is evaluat ed for an asympt omat ic nodule on his shoulder t hat has been present for more t han 1 year.
(B) Pyogenic granuloma
(C) Seborrheic kerat osis
(D) Squamous cell carcinoma
Item 26 [Advanced]
A 62-year-old man is evaluat ed for a rapidly growing nodule on his face. The lesion has arisen wit hin t he past 4 t o 6 weeks and is painless. He does not recall a hist ory of
t rauma.
The lesion is shown (Plat e 28). It is not t ender, warm t o t he t ouch, or fluct uant . There is no associat ed lymphadenopat hy.
(A) Abscess
(B) Keloid
(C) Kerat oacant homa
(D) Nodular basal cell carcinoma
Item 27 [Basic]
A 69-year-old man is evaluat ed for low back discomfort . He has a hist ory of met ast at ic prost at e cancer t o t he spine wit hout evidence of spinal cord compression. He is
ambulat ory and funct ional in all act ivit ies of daily living. He recent ly received palliat ive radiat ion t herapy t o t reat met ast at ic disease in L1 and L3. The pat ient t akes at least
t wo naproxen 250-mg t ablet s daily. The pain medicat ion reduces, but does not eliminat e, his back discomfort .
On physical examinat ion, vit al signs are normal as are result s of neurologic and ment al st at us examinat ions. There is no point t enderness over t he lumbar vert ebrae.
Whi ch of the fol l owi ng i s the most appropri ate next therapeuti c step?
(A) Add a fent anyl pat ch
(B) Add an ext ended-release opioid
(C) Add a short -act ing opioid
(D) Discont inue naproxen and subst it ut e ibuprofen
Item 28 [Basic]
A 74-year-old man wit h met ast at ic lung cancer t o t he liver and pelvis is evaluat ed for low back pain. The pain is localized t o t he right ischial region and has progressively
worsened over t he past mont h despit e t he use of immediat e-release morphine (15 mg) every 6 hours. He st at es t he pain ret urns about 4 hours aft er t aking his medicat ion. He
has no sympt oms of spinal cord compression. He has declined radiat ion t herapy for his bony lesions.
On physical examinat ion, vit al signs are normal as are result s of neurologic and ment al st at us examinat ions.
Whi ch of the fol l owi ng i s the most appropri ate mai ntenance pai n management strategy?
(A) Add gabapent in t hree t imes daily
(B) Increase frequency of immediat e-release morphine t o every 4 hours
(C) Swit ch t o immediat e-release oxycodone every 4 hours
(D) Swit ch t o sust ained-release morphine t wice daily
Item 29 [Advanced]
A 67-year-old man wit h newly diagnosed, widely met ast at ic prost at e cancer is hospit alized for severe hip, chest wall, and shoulder pain. Adequat e dosages of acet aminophen,
ibuprofen, and hydrocodone have not relieved his pain. Several boluses of int ravenous morphine sulfat e are administ ered followed by a cont inuous infusion. Aft er 24 hours,
his pain is adequat ely cont rolled, and he is not experiencing any adverse effect s relat ed t o t he morphine administ rat ion.
Whi ch of the fol l owi ng i s the most appropri ate oral drug regi men after hospi tal di scharge?
(A) Hydrocodone as needed
(B) Long-act ing morphine sulfat e t wice daily and immediat e-release morphine sulfat e as needed
(C) Long-act ing morphine sulfat e t wice daily and oxycodone as needed
(D) Oxycodone as needed
Item 30 [Advanced]
A 79-year-old woman is evaluat ed at home by a visit ing hospice nurse for dyspnea t hat began 4 days ago and has worsened in t he past 24 hours. The pat ient has met ast at ic
breast cancer. She has execut ed a do-not -resuscit at e order and has discont inued cancer t reat ment . Over t he past 6 weeks, her oral int ake has worsened, and she cannot walk
wit hout assist ance because of weakness. Her pain is well cont rolled wit h ext ended-release morphine and immediat e-release morphine as needed for breakt hrough pain.
The hospice nurse report s t hat t he pat ient is alert and orient ed. Vit al signs are normal. Oxygen sat urat ion is 97% wit h t he pat ient breat hing ambient air. She has crackles and
early inspirat ory wheezing over bot h lung fields and a reduced cough effort . She has mild dullness t o percussion and reduced breat h sounds over t he right base. There is no S
3
,
jugular venous dist ent ion, or peripheral edema. Her last dose of ext ended-release morphine was 6 hours ago, and her last dose of immediat e-release morphine was yest erday.
Whi ch of the fol l owi ng i s the best management opti on for her dyspnea?
(A) A supplement al dose of immediat e-release morphine
(B) Emergency depart ment evaluat ion
(C) Furosemide
(D) Home oxygen t herapy
Item 1 Answer: B
Educati onal Objecti ve: Evaluate a breast mass.
The next management st ep for t his pat ient is t o obt ain an ult rasound of t he right breast . The Breast Imaging Report ing and Dat a Syst em (BI-RADS) is a st andardized
report ing syst em for mammography findings and a source of recommendat ions for furt her management . Cat egory assignment s are eit her incomplet e (cat egory 0) or final
assessment (cat egories 1 t hrough 6). Cat egory 2 findings correspond t o findings compat ible wit h benign nodules or cyst s or benign calcificat ions. But because t his pat ient 's
mass has persist ed t hrough several menst rual cycles, she needs furt her evaluat ion despit e t he normal mammogram. Because she is older t han 30 years and t he mammogram is
classified as BI-RADS 2, t he ult rasound is t he next appropriat e t est . This is t rue for mammograms rat ed BI-RADS 1-3. Ult rasound serves t o dist inguish cyst ic from solid
masses. A cyst ic mass should be aspirat ed and t he fluid sent for cyt ologic evaluat ion if bloody or recurrent . A solid mass requires biopsy by fine-needle aspirat ion, core needle,
or excision. If t he mammogram is classified as BI-RADS 4 or 5, malignancy is much more likely and a t issue diagnosis wit h fine needle aspirat e or biopsy is t he most
appropriat e management .
Inherit ed germline abnormalit ies in BRCA-1 and BRCA-2 genes confer very high risk for breast and ovarian cancer (absolut e risk of breast cancer great er t han 60% by age 50
years). Fewer t han 5% of all cases of breast cancer are at t ribut ed t o germline abnormalit ies in t hese genes, however, and t he prevalence of t hese abnormalit ies in t he general
populat ion is approximat ely 1/800. Test ing for BRCA-1 and BRCA-2 genes should be performed only in women who appear t o have a genet ic risk (mult iple relat ives wit h
breast or ovarian cancer, especially wit h early-onset of disease). These women and t heir families should be referred t o a genet ic counselor for discussion and considerat ion of
t hese complex issues. This pat ient does not have an increased genet ic risk for breast cancer and t est ing for BRCA-1 and BRCA-2 genes is not indicat ed.
Key Poi nt
Breast ult rasonography serves t o dist inguish cyst ic from solid masses.
Bi bl i ography
St ein L, Chellman-Jeffers M. The radiologic workup of a palpable breast mass. Cleve Clin J Med. 2009;76(3):175-80. [PMID: 19258464]
Item 2 Answer: C
Educati onal Objecti ve: Diagnose Paget disease of the breast.
This pat ient has Paget disease of t he breast , defined as a persist ent , scaling, eczemat ous, or ulcerat ed lesion involving t he nipple/areolar complex. Hist ologically, t he hallmark
of Paget disease of t he breast is t he presence of malignant , int raepit helial adenocarcinoma cells (Paget cells) wit hin t he epidermis of t he nipple associat ed wit h an underlying
invasive or int raduct al cancer. It is oft en misdiagnosed on t he first present at ion as eit her eczema or psoriasis, but when t here is a lack of response t o appropriat e t herapy, a
biopsy should be performed.
The most charact erist ic lesions of chronic cut aneous lupus eryt hemat osus are discoid lesions appearing as eryt hemat ous, infilt rat ed plaques t hat are covered wit h scale and are
associat ed wit h follicular plugging. These lesions are most oft en found on t he face, neck, and scalp. As t hey expand, t hey develop depressed cent ral scars. This pat ient 's
lesion, locat ion, and appearance are not clinically compat ible wit h chronic cut aneous lupus.
Lichen simplex chronicus is a localized disorder charact erized by int ense prurit us, which leads t o a localized area of lichenified skin (t hickened skin wit h increased and
exaggerat ed skin markings due t o scrat ching). This pat ient has no evidence of lichenificat ion.
The most common form of psoriasis is plaque psoriasis. The skin lesions of t his disorder are sharply demarcat ed, eryt hemat ous plaques covered by silvery-whit e scales t hat
affect t he scalp and ext ensor surfaces (elbows and knees) as well as t he nails. A single pat ch of psoriasis locat ed on t he nipple would be a very rare present at ion.
Key Poi nt
Paget disease of t he breast is a duct al carcinoma t hat present s as a persist ent , scaling, eczemat ous, or ulcerat ed lesion involving t he nipple/areolar complex and may be
mist aken for more benign condit ions such as eczema.
Bi bl i ography
Caliskan M, Gat t i G, Sosnovskikh I, et al. Paget 's disease of t he breast : t he experience of t he European Inst it ut e of Oncology and review of t he lit erat ure. Breast Cancer Res
Treat . 2008;112(3):513-521. [PMID: 18240020]
Item 3 Answer: A
Educati onal Objecti ve: Manage a breast mass with aspiration or biopsy.
The most appropriat e management opt ion is fine-needle aspirat ion or biopsy of t he breast mass. A pat ient wit h a breast mass requires t riple assessment : palpat ion,
mammography wit h or wit hout ult rasonography, and surgical evaluat ion for biopsy. Mammograms may be normal in 10% t o 15% of pat ient s wit h breast lumps, some of
which may be cancerous. Aft er performance of bilat eral diagnost ic mammography, t he init ial focus of t he workup of a dominant breast mass is t o dist inguish a simple cyst
from a solid mass by fine-needle aspirat ion (FNA) or ult rasonography. If t he fluid from FNA is bloody, t he fluid should undergo cyt ologic evaluat ion. Women wit h simple
cyst s should undergo a breast examinat ion 4 t o 6 weeks aft er cyst aspirat ion t o evaluat e for cyst recurrence or a residual lump. A solid mass requires a t issue diagnosis by fine-
needle aspirat ion biopsy (FNAB), core-needle biopsy, or excisional biopsy. Pat ient s wit h benign FNAB or core-needle biopsy result s and negat ive mammogram require close
clinical follow-up of t he breast abnormalit y.
It is inappropriat e t o observe t he pat ient wit hout furt her workup or t o just repeat mammography lat er, because she has a discret e mass t hat may represent breast cancer
despit e t he normal mammographic findings. Even if an ult rasound is negat ive, t he pat ient requires t issue sampling.
The role of breast MRI for screening high-risk pat ient s is current ly being evaluat ed. In pat ient s wit h an est ablished diagnosis of breast cancer, it may be of value in
det ermining t he ext ent of disease. In t his pat ient , a breast MRI would not obviat e t he need for fine-needle aspirat ion or biopsy and is much more expensive t han
ult rasonography.
Key Poi nt
A pat ient wit h a breast mass requires aspirat ion or biopsy regardless of mammography result s.
Bi bl i ography
Kerlikowske K, Smit h-Bindman R, Ljung BM, Grady D. Evaluat ion of abnormal mammography result s and palpable breast abnormalit ies. Ann Int ern Med 2003;139(4):274-
284. [PMID: 12965983]
Item 4 Answer: C
Educati onal Objecti ve: Evaluate a patient with early-stage breast cancer for tumor estrogen- and progesterone-receptor status.
The next st ep is a t umor est rogen-recept or (ER) and progest erone-recept or (PR) assay. This pat ient has early-st age breast cancer (st age I) based on t he t umor size (<2 cm);
absent lymph node involvement ; and no apparent met ast ases based on her sympt oms, physical examinat ion findings, and rout ine blood t est s. The st ep t hat would be most
helpful in direct ing t he approach t o management of t his pat ient is t o perform an assay for expression of ER and PR t o det ermine t he opt imal syst emic t reat ment , and t his
evaluat ive st ep should be performed in all cases of primary breast cancer. Endocrine t herapy (for example, t amoxifen, aromat ase inhibit ors, fulvest rant , and megest rol
acet at e) is beneficial only in pat ient s wit h ER-posit ive or PR-posit ive t umors. Pat ient s whose t umors are hormone recept or-negat ive are refract ory t o endocrine t reat ment
and should receive chemot herapy inst ead.
In pat ient s wit h early-st age breast cancer, t he rout ine evaluat ion is limit ed t o a t horough hist ory and physical examinat ion, diagnost ic mammography, chest radiography, and
rout ine blood t est s (including liver chemist ry t est s). The use of addit ional imaging st udies or blood t est s is not warrant ed in t he absence of specific sympt oms because t hey
may lead t o t he det ect ion of abnormalit ies of no significance (a false-posit ive t est result ).
In early-st age disease, t he posit ive predict ive value of abnormal findings of whole-body posit ron emission t omography is approximat ely 1%; t herefore, t his t ype of imaging
modalit y is not recommended. The absence of met ast ases in a sent inel axillary lymph node has a high negat ive predict ive value, obviat ing t he need for a complet e axillary
lymph node dissect ion wit h it s associat ed morbidit y.
About 5% of breast cancer cases are at t ribut able t o rare, high-penet rance mut at ions in a few specific genes; mut at ions in BRCA1 and BRCA2 account for up t o 50% of all
cases of heredit ary and familial breast cancer. This proport ion is higher in pat ient s wit h breast cancer at a younger age of onset and in families wit h mult iple breast or ovarian
cancer cases. Test ing for t he BRCA1 or BRCA2 gene in t his pat ient would not be indicat ed wit hout a more compelling family hist ory of disease.
Key Poi nt
Assay for expression of est rogen and progest erone recept ors is crucial in det ermining t he opt imal syst emic t reat ment for breast cancer and should be performed in all pat ient s
wit h primary breast cancer.
Bi bl i ography
Carlson RW, Allred DC, Anderson BO, Burst ein HJ, Cart er WB, Edge SB, Erban JK, Farrar WB, Goldst ein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung
BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smit h ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC; NCCN Breast
Cancer Clinical Pract ice Guidelines Panel. Breast cancer. Clinical pract ice guidelines in oncology. J Nat l Compr Canc Net w. 2009;7(2):122-92. [PMID: 19200416]
Item 5 Answer: D
Educati onal Objecti ve: Treat a patient with breast cancer and a small focal tumor with lumpectomy, sentinel node dissection, and radiation.
This pat ient should undergo breast lumpect omy plus sent inel lymph node biopsy followed by radiat ion t herapy. Breast lumpect omy plus radiat ion t herapy is known as
"breast -conserving t herapy." Breast -conserving t herapy consist s of excision of t he primary t umor followed by radiat ion t o t he remaining ipsilat eral breast t issue and is
generally indicat ed for pat ient s wit h focal disease and small t umors for which conservat ion will offer a good cosmet ic result . However, pat ient preferences must be considered
in t he surgical decision-making process. The survival rat e for women undergoing breast -conserving t herapy is equivalent t o t hat of t hose who undergo mast ect omy, wit h
breast -conserving t herapy result ing in improved cosmet ic out comes and less morbidit y t han mast ect omy. Most pat ient s t reat ed wit h lumpect omy wit hout radiat ion t herapy
have a high risk for local recurrence; t herefore, t his t reat ment modalit y cannot be recommended. In addit ion, sent inel lymph node biopsy is a safe and accurat e met hod for
screening t he axillary lymph nodes for met ast ases in women wit h small breast t umors. Sent inel lymph node biopsy has replaced full axillary lymph node dissect ion for t he
st aging of disease in many women wit h early-st age, clinically lymph node-negat ive breast cancer. The first draining (or sent inel) lymph node is ident ified by inject ing blue dye
and radioact ive colloid int o t he t umor sit e. If t he sent inel lymph node does not cont ain met ast ases, it is unlikely t hat more dist al axillary lymph nodes will cont ain
met ast ases; consequent ly, no furt her surgery is indicat ed in t his set t ing, and t he t oxicit y from a full axillary lymph node dissect ion is avoided. However, if t he sent inel lymph
node shows met ast at ic involvement , t hen axillary lymph node dissect ion is performed t o det ermine t he number of involved lymph nodes.
Select ive est rogen recept or modulat ors such as t amoxifen are not indicat ed in pat ient s wit h est rogen recept or-negat ive t umors.
Key Poi nt
Lumpect omy wit h sent inel lymph node biopsy followed by breast irradiat ion is t he appropriat e management of women wit h small, focal breast cancer.
Bi bl i ography
Buchholz TA. Radiat ion t herapy for early-st age breast cancer aft er breast -conserving surgery. N Engl J Med. 2009;360(1):63-70. [PMID: 19118305]
Item 6 Answer: B
Educati onal Objecti ve: Screen a patient at high risk for colorectal cancer.
The best colorect al cancer screening st rat egy for t his pat ient is colonoscopy at age 55 years and t hen every 3 t o 5 years. A family hist ory of colorect al cancer or
adenomat ous polyps significant ly increases a person's risk for colorect al cancer. The presence of colorect al cancer in a first -degree relat ive carries a t wofold t o t hreefold
increased lifet ime risk over t he general populat ion; t hat risk is doubled again if t he affect ed relat ive was diagnosed before age 45 years. If t wo first -degree relat ives have
colorect al cancer, t he colorect al cancer risk approaches 20%. For persons wit h a family hist ory of colorect al cancer in a first -degree relat ive, screening is init iat ed eit her at
age 40 years or beginning 10 years earlier t han t he diagnosis of t he youngest affect ed family member. If normal, colonoscopy is repeat ed every 3 t o 5 years. Because t his
pat ient had colonoscopy screening at t he age of 50 years, colonoscopy should be offered at some t ime bet ween ages 53 and 55 years.
Familial adenomat ous polyposis and at t enuat ed familial adenomat ous polyposis are most commonly diagnosed aft er polyposis is det ect ed on endoscopy. In t hese pat ient s,
t est ing for mut at ions in t he APC gene is reasonable. However, t his pat ient does not have a personal hist ory of polyposis.
Performing colonoscopy at age 50 years and t hen every 10 years is t he recommendat ion for pat ient s at average risk for colorect al cancer. Persons at average risk for
colorect al cancer include t hose wit h no personal or family hist ory of colon adenoma or cancer and who do not have a condit ion t hat predisposes t hem t o cancer.
Pat ient s wit h inflammat ory bowel disease have an increased risk for colorect al cancer. The most reliable est imat es suggest an annual colorect al cancer rat e in ext ensive colit is
of at least 0.5% per year aft er t he first decade of colit is. Screening recommendat ions include colonoscopy every 1 t o 2 years beginning 8 years aft er diagnosis. This screening
int erval is not appropriat e for t his pat ient who does not have inflammat ory bowel disease.
Key Poi nt
For persons wit h a family hist ory of colorect al cancer in a first -degree relat ive, screening is init iat ed eit her at age 40 years or beginning 10 years earlier t han t he diagnosis of
t he youngest affect ed family member.
Bi bl i ography
Geiger TM, Ricciardi R. Screening opt ions and recommendat ions for colorect al cancer. Clin Colon Rect al Surg. 2009;22(4):209-17. [PMID: 21037811]
Item 7 Answer: A
Educati onal Objecti ve: Evaluate a symptomatic patient for colon cancer with colonoscopy.
This pat ient requires a colonoscopy. Common signs and sympt oms of colorect al cancer are influenced by t he sit e of t he primary t umor and may include a change in bowel
habit s, diarrhea, const ipat ion, a feeling t hat t he bowel does not empt y complet ely, bright red blood in t he st ool or melanot ic st ools, and st ools t hat are narrower in caliber
t han usual. Ot her signs include general abdominal discomfort (frequent gas pains, bloat ing, fullness, or cramps), weight loss for no known reason, fat igue, and vomit ing.
Findings t hat should prompt invest igat ion for colon cancer include a rect al or abdominal mass, hepat omegaly, abdominal t enderness, or iron deficiency anemia. If one or
more such findings are present , a full colorect al examinat ion wit h colonoscopy should be done. However, t he examinat ion may be limit ed t o sigmoidoscopy for rect al
bleeding in most persons younger t han 40 years of age because colorect al cancer is uncommon in such pat ient s (except t hose wit h heredit ary colorect al cancer syndromes),
and in most young pat ient s wit h hemat ochezia, a rect osigmoid lesion, usually hemorrhoids, is t he cause of rect al bleeding. This pat ient is older t han 40 years, has concerning
sympt oms, and t herefore requires an immediat e colonoscopy.
A cont rast -enhanced CT scan of t he abdomen is not sensit ive for diagnosing colon cancer. Opt ions for colorect al cancer screening include colonoscopy, fecal occult blood
t est ing, flexible sigmoidoscopy, or barium enema used alone or in combinat ion for screening. However, t hese screening modalit ies are reserved for asympt omat ic pat ient s.
This pat ient is not asympt omat ic and screening modalit ies, such as fecal occult blood t est ing, are not adequat e owing t o lack of sensit ivit y in a pat ient wit h a higher t han
average probabilit y of disease. Even if t he t est result s were posit ive, addit ional diagnost ic st udies would be needed t o clarify t he diagnosis. Direct visualizat ion of t he colonic
mucosa wit h colonoscopy is needed for t his pat ient wit h sympt oms suggest ive of colon cancer.
Key Poi nt
Pat ient s wit h suspect ed colon cancer should be evaluat ed wit h colonoscopy.
Bi bl i ography
Kahi CJ, Rex DK, Imperiale TF. Screening, surveillance, and primary prevent ion for colorect al cancer: a review of t he recent lit erat ure. Gast roent erology. 2008;135(2):380-
99. Epub 2008 Jun 26. [PMID: 18582467]
Item 8 Answer: A
Educati onal Objecti ve: Evaluate a patient with a positive fecal occult blood test result with colonoscopy.
This pat ient has a posit ive result on a screening t est for colorect al neoplasia and should be evaluat ed next wit h colonoscopy. Fecal occult blood t est ing (FOBT) is associat ed
wit h a 15% t o 33% reduct ion in mort alit y rat es from colorect al cancer when annual or biennial t est ing is done. Six-window FOBT is performed by t aking t wo separat e
samples from each of t hree spont aneously passed st ools (six samples). Even t hough only one of t hree of t his pat ient 's samples submit t ed for fecal occult blood t est ing was
posit ive, she requires appropriat e follow-up wit h a diagnost ic t est such as colonoscopy.
Repeat ing t he FOBT is inappropriat e because one t est result was already posit ive. Since bleeding from colorect al neoplasia can occur int ermit t ent ly, a subsequent negat ive
FOBT would not rule out colon cancer or an adenomat ous polyp. Flexible sigmoidoscopy, because of it s limit ed abilit y t o examine t he ent ire colon, is inadequat e for
det ermining whet her t his pat ient has colorect al neoplasia. Wait ing a year t o repeat t he FOBT pot ent ially places t his pat ient at risk for missing a curable colon cancer and
cannot be recommended.
Key Poi nt
An asympt omat ic pat ient wit h a single posit ive fecal occult blood t est on rout ine screening requires follow-up wit h colonoscopy.
Bi bl i ography
Weinberg DS. In t he clinic. Colorect al cancer screening. Ann Int ern Med. 2008;148:ITC2-1-ITC2-16. [PMID: 18252680]
Item 9 Answer: A
Educati onal Objecti ve: Screen for colon cancer in a patient with inflammatory bowel disease.
The most appropriat e management for t his pat ient is annual colonoscopy beginning now. This pat ient has pancolit is of 8 years' durat ion. The inflammat ion involves t he
ileum and proximal colon. The colon cancer risk in pat ient s wit h ulcerat ive colit is or Crohn disease reaches a significant level (est imat e annual cancer risk of 1% t o 2% per
year) aft er 8 years of inflammat ion. The cancer risk is slight ly delayed for pat ient s wit h inflammat ion limit ed t o t he dist al colon. The recommendat ion is t o init iat e a
surveillance program wit h colonoscopy 8 years aft er onset of disease, wit h follow-up colonoscopy every 1 t o 2 years t hereaft er. Random biopsies are performed in four-
quadrant fashion t hroughout t he ent ire colon. Colect omy is recommended for pat ient s wit h dysplast ic findings on biopsy.
In wireless capsule endoscopy, a pat ient swallows a video capsule t hat by int est inal mot ilit y passes t hrough t he st omach and int o t he small int est ine. The video capsule
t ransmit s images t o a recording device worn by t he pat ient . The images are downloaded ont o a comput er where t hey can be reviewed. Wit h capsule endoscopy, t he small
bowel can be visualized in it s ent iret y. There is no recommendat ion for st andard screening for small-bowel carcinoma in t he set t ing of ulcerat ive colit is or Crohn disease, and
t herefore, capsule endoscopy is not indicat ed. Furt hermore, capsule endoscopy has no abilit y t o biopsy t he bowel wall and assess for dysplasia. Flexible sigmoidoscopy would
not reach t he at -risk colonic mucosa in t he proximal colon beyond t he reach of t he sigmoidoscope, and annual fecal occult blood t est ing is insensit ive t o t he diagnosis of
colonic dysplasia, t he earliest precursor of colon cancer.
Key Poi nt
Pat ient s wit h inflammat ory bowel disease should init iat e screening for colorect al cancer aft er 8 years' disease durat ion.
Bi bl i ography
Weinberg DS. In t he clinic. Colorect al cancer screening. Ann Int ern Med. 2008;148:ITC2-1-ITC2-16. [PMID: 18252680]
Item 10 Answer: E
Educati onal Objecti ve: Do not screen for lung cancer.
Screening for early-st age lung cancer is not now recommended wit h t he use of any met hodology, including spiral CT scan, chest radiography, sput um cyt ology, or 18F-
fluorodeoxyglucose (FDG)-PET scan. No met hod has been shown t o reduce deat h from lung cancer. Lung cancer screening wit h spiral CT scanning det ect s 60% or more of
incident St age I cancers. However, t he false-posit ive rat e (number of benign nodules det ect ed) wit h spiral CT lung cancer screening is high and may result in pat ient anxiet y
and unnecessary invasive t est ing. Recent large, single-arm observat ional st udies of spiral CT screening show t hat about 60% t o 85% of incident cancers (det ect ed aft er t he
baseline scan) are st age I and t hat t he survival rat e is bet t er t han t hat of hist orical unscreened cohort s. However, t his finding alone does not prove t hat lung cancer screening
is effect ive. Proof of efficacy for a lung cancer screening t est would be a reduct ion in t he mort alit y rat e among t hose screened compared wit h a comparable group at risk who
were not screened. Alt hough survival result s may be provocat ive in an observat ional st udy, t hey are subject t o bias. The survival rat e may be dramat ically improved wit hout
act ually result ing in a reduct ion in deat hs from lung cancer because of lead-t ime bias, lengt h-t ime bias, and overdiagnosis. A randomized, cont rolled t rial is generally accept ed
as t he definit ive means of est ablishing efficacy for a screening t est . Various screening st udies now under way are randomized t rials t hat might answer t he quest ion of t he
efficacy of screening for lung cancer.
Key Poi nt
Screening for early-st age lung cancer is not now recommended wit h t he use of any met hodology.
Bi bl i ography
Smit h RA, Cokkinides V, Brawley OW. Cancer screening in t he Unit ed St at es, 2008: a review of current American Cancer Societ y guidelines and cancer screening issues. CA
Cancer J Clin. 2008;58(3):161-179. [PMID: 18443206]
Item 11 Answer: D
Educati onal Objecti ve: Evaluate a patient at low-risk for lung cancer with a very small pulmonary nodule.
This pat ient requires no furt her follow up. St udies of chest CT screening have shown t hat 25% t o 50% of pat ient s have one or more pulmonary nodules det ect ed on t he
init ial CT scan. Even in pat ient s at relat ively high risk for lung cancer, t he likelihood t hat a small nodule is malignant is low. For example, t he risk of malignancy is about
0.2% for nodules smaller t han 3 mm in diamet er and 0.9% for nodules measuring 4 t o 7 mm in diamet er. The Fleischner Societ y recommendat ions include no follow-up for
low-risk pat ient s wit h nodules 4 mm or smaller and follow-up CT at 12 mont hs for pat ient s wit h such nodules who are at risk for lung cancer. This small nodule is not likely
t o be visible on chest radiograph, and, t herefore, such imaging would not be helpful.
Key Poi nt
In a pat ient at low risk for malignancy, no follow-up is required for an incident ally not ed pulmonary nodule of 4 mm or smaller in diamet er.
Bi bl i ography
MacMahon H, Aust in JH, Gamsu G, et al; Fleischner Societ y. Guidelines for management of small pulmonary nodules det ect ed on CT scans: a st at ement from t he Fleischner
Societ y. Radiology. 2005;237(2):395-400. [PMID: 16244247]
Item 12 Answer: D
Educati onal Objecti ve: Diagnose and stage advanced lung cancer with a peripheral lymph node biopsy.
The most appropriat e management for t his pat ient is supraclavicular lymph node biopsy. In t he evaluat ion of a pat ient wit h suspect ed lung cancer, obt aining a t issue
diagnosis is crit ical for t reat ment planning and det ermining prognosis. St aging t he cancer and det ermining whet her t he pat ient is a candidat e for resect ion are also import ant
part s of t he evaluat ion. In t his pat ient , det ermining whet her t he supraclavicular lymph node cont ains non-small cell cancer should be done, and t he next st ep in t he
evaluat ion would be t o sample t he lymph node; t his would likely est ablish bot h a diagnosis and t hat t he pat ient has advanced unresect able disease.
Because t he clinical st age is already suggest ing an advanced st age of disease, posit ron emission t omography (PET)-CT would not be needed for st aging if t he supraclavicular
lymph node is posit ive, and a posit ive PET-CT result of t he supraclavicular lymph nodes would not obviat e t he need for lymph node sampling. Biopsy of t he mass or hilar
lymph nodes by CT guidance or bronchoscopy would est ablish t he diagnosis but not t he st age and would not det ermine resect abilit y.
Key Poi nt
In t he evaluat ion of possible lung cancer, obt aining a t issue diagnosis and st aging for lung cancer should be done simult aneously whenever possible.
Bi bl i ography
Silvest ri GA, Gould MK, Margolis ML, et al; American College of Chest Physicians. Noninvasive st aging of non-small cell lung cancer: ACCP evidenced-based clinical
pract ice guidelines (2nd edit ion). Chest . 2007;132(3 Suppl):178S-201S. [PMID: 17873168]
Item 13 Answer: A
Educati onal Objecti ve: Manage a patient with limited-stage, small cell lung cancer.
This pat ient has limit ed-st age small-cell lung cancer (SCLC) and should receive chemot herapy and radiat ion t herapy. SCLC is considered a syst emic disease; pat ient s who
present wit h seemingly localized disease almost always have concurrent micromet ast ases and consequent ly t he more complicat ed st aging syst em of non-small cell lung cancer
does not apply. Pat ient s wit h visibly localized disease t hat can be encompassed wit hin a radiat ion t herapy port are designat ed as having limit ed-st age disease. Pat ient s wit h
t umor beyond t he confines of a radiat ion port are considered t o have ext ensive-st age disease. Chemot herapy plus radiat ion t herapy is considered first -line t reat ment for
pat ient s wit h limit ed-st age SCLC. Typical regimens consist of a combinat ion of a plat inum agent (carboplat in or cisplat in) and et oposide or irinot ecan. Combinat ion
chemot herapy and radiat ion t herapy is associat ed wit h a subst ant ially improved median survival compared wit h chemot herapy, surgery, or radiot herapy alone, alt hough cure
remains rare.
High-dose chemot herapy wit h aut ologous hemat opoiet ic st em cell t ransplant at ion is not recommended for pat ient s wit h SCLC because t he subst ant ial morbidit y associat ed
wit h t his t herapy negat es any benefit . Local t reat ment consist ing of surgery or radiat ion as single-modalit y t herapies does not have t he pot ent ial for cure. SCLC vaccinat ion
is not an effect ive t herapy for SCLC.
Key Poi nt
Chemot herapy and radiat ion t herapy is considered t he first -line t reat ment for pat ient s wit h limit ed-st age small cell lung cancer.
Bi bl i ography
Simon GR, Turrisi A; American College of Chest Physicians. Management of small cell lung cancer: ACCP evidence-based clinical pract ice guidelines (2nd edit ion). Chest .
2007;132(3 Suppl):324S-339S. [PMID: 17873178]
Item 14 Answer: B
Educati onal Objecti ve: Manage a rising PSA level with prostate biopsy.
Prost at e cancer is most oft en diagnosed following prost at e-specific ant igen (PSA) screening in asympt omat ic men. Pat ient s wit h an elevat ed or rising serum PSA level not ed
during rout ine screening should also undergo prost at e biopsy, even if t hey are asympt omat ic. Specifically, t hese pat ient s need ult rasound-guided biopsies of t heir prost at e
(t ypically in 6 random areas) t o assess for t he presence of prost at e cancer. Aft er prost at e cancer is diagnosed, addit ional st udies such as a bone scan or CT scan of t he
abdomen and pelvis should be considered in pat ient s wit h signs or sympt oms suggest ive of dist ant spread of t he malignancy.
Pat hologic proof of prost at e cancer is needed before embarking on definit ive t herapy such as radical prost at ect omy. A PSA great er t han 4.0 ng/mL (4.0 g/L) is only 25%
sensit ive for prost at e cancer. In t he absence of a hist ologic diagnosis for prost at e cancer, surgical int ervent ion is not appropriat e.
Pat ient s wit h "borderline" PSA measurement s might be appropriat ely managed by repeat ing t he measurement in 6 mont hs; however, t his pat ient has had a rapid rise in t he
PSA level. Any rise great er t han 0.75 ng/mL/year (0.75 g/L/year) is considered abnormal and should be evaluat ed.
Key Poi nt
Pat ient s wit h a prost at e-specific ant igen (PSA) level great er t han 4.0 ng/dL (4.0 g/L) should have furt her evaluat ion for prost at e cancer.
Bi bl i ography
Lin K, Lipsit z R, Miller T, Janakiraman S; U.S. Prevent ive Services Task Force. Benefit s and harms of prost at e-specific ant igen screening for prost at e cancer: an evidence
updat e for t he U.S. Prevent ive Services Task Force. Ann Int ern Med. 2008;149(3):192-9. [PMID: 18678846]
Item 15 Answer: A
Educati onal Objecti ve: Manage prostate cancer screening by discussing risks and benefits.
This 57-year-old asympt omat ic man should part icipat e in a discussion wit h his doct or about t he risks and benefit s of prost at e cancer screening. The U.S. Prevent ive Services
Task Force (USPSTF) concluded t hat t he evidence was insufficient t o recommend for or against prost at e cancer screening using prost at e-specific ant igen (PSA) t est ing or
digit al rect al examinat ion (DRE) and recommended t hat physicians discuss pot ent ial, but uncert ain, benefit s and possible harms (complicat ions of fut ure diagnost ic t est ing and
t herapies, including incont inence; erect ile dysfunct ion; and bowel dysfunct ion) before ordering PSA t est ing. The USPSTF also recommended against prost at e cancer screening
in men aged 75 years or older. They not ed t hat if screening were t o be performed, men ages 50 t o 70 years would benefit most . The USPSTF st at ed t hat men should be
informed of t he gaps and conflict ing result s in t he evidence and should be assist ed in considering t heir personal preferences before deciding whet her t o be t est ed. The
American Cancer Societ y recommends t hat PSA t est ing be offered t o men at age 50 years (age 45 years for men at high risk owing t o a posit ive family hist ory of prost at e
cancer or who are black) and t hat informat ion about limit at ions and benefit s be provided.
Two large randomized screening t rials st udied t he effect of screening on rat e of deat h from prost at e cancer. There was no difference in t he rat e of deat h from prost at e cancer
bet ween screened and cont rol groups in one st udy. In t he second st udy, t he prost at e cancer deat h rat e per 1000 person-years was 0.35 in t he screened group versus 0.41 in t he
cont rol group (P = 0.04). The number needed t o screen was 1410 and t he number needed t o t reat t o prevent one prost at e cancer-relat ed deat h over a 10-year period was 48.
About 50% t o 75% of t hose 48 men would be expect ed t o have some complicat ion of t reat ment . In evaluat ing t he limit ed benefit demonst rat ed in t his t rial, one must
consider t he increased number of false diagnoses (false-posit ive rat e of 75.9% of t hose undergoing biopsy) and unnecessary t reat ment s.
Key Poi nt
Physicians should discuss pot ent ial, but uncert ain, benefit s and possible harms before ordering prost at e-specific ant igen t est ing.
Bi bl i ography
U.S. Prevent ive Services Task Force. Screening for prost at e cancer: U.S. Prevent ive Services Task Force recommendat ion st at ement . Ann Int ern Med. 2008;149(3):185-91.
[PMID: 18678845]
Item 16 Answer: D
Educati onal Objecti ve: Manage an elderly patient with prostate cancer and medical comorbidities.
The most appropriat e next st ep in t he management of t his pat ient is observat ion. Alt hough screening by prost at e-specific ant igen (PSA) measurement does result in
det ect ion of some cases of cancer, no definit ive benefit s result ing from such det ect ion have been report ed. In t his older pat ient , observat ion or wat chful wait ing is t he most
appropriat e management .
According t o t he U.S. Prevent ive Services Task Force (USPSTF), t here is inadequat e evidence t o suggest t hat t reat ment of pat ient s younger t han 75 years wit h screening-
det ect ed prost at e cancer result s in improved out comes compared wit h t reat ment of pat ient s wit h clinically det ect ed (sympt omat ic) prost at e cancer. Adequat e evidence
indicat es t hat t he increment al benefit s of t reat ment of pat ient s 75 years of age or older wit h screening-det ect ed prost at e cancer are small t o none. Moderat e t o subst ant ial
harms, including erect ile dysfunct ion, urinary incont inence, bowel dysfunct ion, and deat h, in addit ion t o small harms, including prost at e biopsy-induced pain and discomfort
and psychological effect s of false-posit ive t est result s, are associat ed wit h prost at e cancer screening. Because prost at e cancer sympt oms may not develop in many older
pat ient s who receive t reat ment for screening-det ect ed prost at e cancer during t heir lifet ime, considerat ion of t hese harms is import ant .
In view of t he recommendat ions from t he USPSTF and t he evidence support ing t hose recommendat ions, repeat ing t he PSA, bone scan, and t ransrect al prost at e biopsy are all
inappropriat e choices for t his 80-year-old man wit h significant comorbidit ies.
Key Poi nt
In men age 75 years or older t here is lit t le t o no benefit associat ed wit h prost at e cancer screening.
Bi bl i ography
U.S. Prevent ive Services Task Force. Screening for prost at e cancer: U.S. Prevent ive Services Task Force recommendat ion st at ement . Ann Int ern Med. 2008;149(3):I85-I91.
[PMID: 18678845]
Item 17 Answer: C
Educati onal Objecti ve: Treat asymptomatic metastatic prostate cancer with androgen deprivation therapy.
The most appropriat e management of t his pat ient is androgen deprivat ion t herapy wit h leuprolide. This pat ient has met ast at ic prost at e cancer involving t he bones. Prost at e
cancer is a hormone-responsive t umor, and his disease will most likely respond t o hormone deprivat ion t herapy wit h surgical cast rat ion or gonadot ropin hormone-releasing
hormone (GnRH) agonist s such as leuprolide. GnRH t herapy causes impot ence, hot flushes, gynecomast ia, and loss of libido, as does orchiect omy. Pat ient s may experience
t umor-flare react ions wit h t he use of GnRH agonist s, which init ially cause an increase in lut einizing and follicle-st imulat ing hormones. These hormones lead t o a t ransient
increase in t est ost erone, which can exacerbat e prost at e cancer sympt oms. This react ion can be prevent ed by a brief course of concomit ant ant iandrogen t herapy wit h agent s
such as bicalut amide, nilut amide, or flut amide.
Alt hough docet axel-based chemot herapy has been shown t o improve survival, t his agent is generally indicat ed only for pat ient s wit h hormone-refract ory cancer. Several
st udies have demonst rat ed an improvement in overall survival wit h docet axel-based chemot herapy in t his set t ing.
Hospice care is premat ure because mult iple sequent ial medical int ervent ions are likely t o improve t his pat ient 's overall and progression-free survival. Observat ion is
inappropriat e because his disease is likely t o progress wit hout any int ervent ion.
Samarium-153 is a radionuclide t hat is t aken up by bone. It may be useful in t reat ing prost at e cancer wit h painful bone met ast ases but may cause bone marrow suppression and
should be used only in pat ient s whose cancer is no longer responsive t o ot her t herapies.
Key Poi nt
Androgen deprivat ion t herapy wit h surgical cast rat ion or gonadot ropin hormone-releasing hormone agonist s is first -line t herapy for asympt omat ic pat ient s wit h met ast at ic
prost at e cancer.
Bi bl i ography
Ramirez ML, Keane TE, Evans CP. Managing prost at e cancer: t he role of hormone t herapy. Can J Urol. 2007;14 Suppl 1:10-8. [PMID: 18163939]
Item 18 Answer: A
Educati onal Objecti ve: Manage an adult patient with an abnormal Pap smear and high-risk human papillomavirus serology with colposcopy.
The most appropriat e next management st ep is colposcopy. The most common abnormal finding following cervical cancer screening is at ypical squamous cells (ASC), which
is report ed in approximat ely 5% of t est result s. Most ASC abnormalit ies resolve spont aneously, but approximat ely 15% of pat ient s harbor a precancerous lesion discovered
on biopsy. Adult women wit h ASC should be t est ed for human papillomavirus infect ion. If t he pat ient wit h ASC t est s posit ive for high-risk human papillomavirus subt ypes
(for example, 16 or 18), colposcopy wit h biopsy is performed. Colposcopy provides an illuminat ed, magnified view of t he cervix, vagina, and vulva and enhances t he abilit y
of t he operat or t o det ect premalignant and malignant lesions t hat can biopsied.
In a pat ient wit h ASC and high-risk human papillomavirus infect ion, delaying invest igat ion for t he presence of possible premalignant or malignant lesions for 1 year is
excessively long and inappropriat e. There is no effect ive t reat ment for cervical human papillomavirus infect ion, including int erferon.
Key Poi nt
Colposcopy wit h biopsy is indicat ed for pat ient s wit h at ypical squamous cells on cervical cyt ologic screening and who t est posit ive for high-risk human papillomavirus
subt ypes.
Bi bl i ography
Apgar BS, Kit t endorf AL, Bet t cher CM, Wong J, Kaufman AJ. Updat e on ASCCP consensus guidelines for abnormal cervical screening t est s and cervical hist ology. Am Fam
Physician. 2009;80(2):147-55. [PMID: 19621855]
Item 19 Answer: D
Educati onal Objecti ve: Prevent human papillomavirus infection with human papillomavirus immunization.
The Advisory Commit t ee on Immunizat ion Pract ices of t he Cent ers for Disease Cont rol and Prevent ion recommends t he quadrivalent human papillomavirus (HPV) vaccine
for cervical cancer prevent ion for all girls and women bet ween t he ages of 9 and 26 years regardless of sexual act ivit y. The vaccine has a high success rat e in prevent ing
infect ions wit h HPV st rains 6, 11, 16, and 18, which cause most cases of genit al wart s and cervical cancer.
HPV infect ion is predominant ly spread by sexual cont act . This pat ient st at es she is not sexually act ive; however, t he vaccine should be recommended now because it is of low
risk, and vaccine efficacy last s for at least several years. The vaccine does not prot ect against all t ypes of HPV, and roughly 30% of cervical cancers will not be prevent ed by
t he vaccine; t herefore, women should cont inue t o receive regular Pap smears even aft er complet ing t he vaccinat ion series.
The HPV quadrivalent vaccine is not effect ive in prevent ing HPV-relat ed diseases in women who have an est ablished infect ion at t he t ime of vaccinat ion; t herefore, wait ing
for HPV seroconversion prior t o vaccinat ion is inappropriat e.
Alt hough t he HPV vaccine is well t olerat ed in men, and high rat es of seroconversion against pat hologic HPV have been demonst rat ed, efficacy of male vaccinat ion in
prevent ing clinical disease in men and women remains uncert ain, and cost -effect iveness is unproved. The Cent ers for Disease Cont rol and Prevent ion does not recommend
rout ine HPV immunizat ion for boys.
Key Poi nt
A human papillomavirus quadrivalent vaccinat ion series should be offered t o all girls and women ages 9 t hrough 26 years, and women should cont inue t o get regular Pap
smears even aft er complet ing t he vaccinat ion series.
Bi bl i ography
Barr E, Sings HL. Prophylact ic HPV vaccines: new int ervent ions for cancer cont rol. Vaccine. 2008;26:6244-57. Epub 2008 Aug 9. [PMID: 18694795]
Item 20 Answer: C
Educati onal Objecti ve: Screen for cervical cancer every 3 years in low-risk women.
This pat ient is at low risk for cervical cancer. She is in a long-t erm, monogamous relat ionship and has had many normal Pap smears, so it is appropriat e t o lengt hen t he
screening int erval for Pap t est s t o every 3 years. The Unit ed St at es Prevent ive Services Task Force recommends cervical cancer screening for women who are sexually act ive
and have a cervix. Screening should begin wit hin 3 years of onset of sexual act ivit y but no lat er t han age 21 years. Aft er age 65 years, t he effect iveness of screening is low in
women who have had recent negat ive Pap smears. Women at normal risk can be screened every 3 years, alt hough t he American Cancer Societ y recommends wait ing unt il age
30 years before lengt hening t he screening int erval from an annual basis. Annual Pap t est s do not ident ify more invasive cancer t han t est s performed every 2 or 3 years in
low-risk women who have had several normal t est s.
Women who have human immunodeficiency virus infect ion should be screened for cervical cancer more frequent ly, because human papillomavirus can grow fast er and lesions
can progress more quickly in significant ly immunosuppressed pat ient s. Women who have mult iple sex part ners, have a hist ory of abnormal Pap smears, or have recent ly been
diagnosed wit h a sexually t ransmit t ed disease are at higher risk for cervical cancer, and current guidelines suggest screening such women annually.
Key Poi nt
In women older t han 30 years wit h t hree previous normal annual Pap smears, t he screening int erval can be lengt hened t o every 3 years.
Bi bl i ography
Safaeian M, Solomon D, Cast le PE. Cervical cancer prevent ioncervical screening: science in evolut ion. Obst et Gynecol Clin Nort h Am. 2007;34:739-60, ix. [PMID:
18061867]
Item 21 Answer: D
Educati onal Objecti ve: Discontinue screening for cervical cancer in patients who have had a hysterectomy for benign disease.
In asympt omat ic women who have had a vaginal hyst erect omy for benign disease, t here is no proven benefit t o rout ine Pap t est ing t o det ect cancer. The Unit ed St at es
Prevent ive Service Task Force recommends cervical cancer screening only for women who are sexually act ive and have a cervix. Vaginal hyst erect omy for benign disease is
not associat ed wit h an increased incidence of vaginal malignancy. Est imat es of t he posit ive predict ive value of an abnormal vaginal smear in t his set t ing approach zero.
Key Poi nt
In asympt omat ic women who have had a vaginal hyst erect omy for benign disease, t here is no proven benefit t o rout ine Pap t est ing t o det ect cancer.
Bi bl i ography
St okes-Lampard H, Wilson S, Waddell C, Ryan A, Holder R, Kehoe S. Vaginal vault smears aft er hyst erect omy for reasons ot her t han malignancy: a syst emat ic review of t he
lit erat ure. BJOG. 2006;113:1354-65. [PMID: 17081187]
Item 22 Answer: C
Educati onal Objecti ve: Diagnose squamous cell carcinoma in situ (Bowen disease).
This lesion is most consist ent wit h squamous cell carcinoma in sit u (Bowen disease). It is a form of int raepidermal carcinoma, a malignant t umor of kerat inocyt es. It present s
as a single lesion in t wo t hirds of cases. The head, neck, and ext remit ies are t he most commonly affect ed sit es in men. The cheeks and lower ext remit ies are t he most
commonly affect ed sit es in women. Lesions vary from a few millimet ers t o several cent imet ers in diamet er. Lesions can arise de novo or from a preexist ing act inic kerat osis.
Et iology is most likely mult ifact orial and includes chronic ult raviolet radiat ion, arsenic exposure, human papillomavirus, immunosuppression, genet ic fact ors, t rauma, x-ray
radiat ion, and chemical carcinogens.
Nummular eczema present s as circular, eryt hemat ous, well-demarcat ed, int ensely prurit ic, pat ches 2 t o 10 cm in diamet er, usually found on t he t runk and lower ext remit ies.
Onset is usually spont aneous wit h no incit ing event .
Psoriasis is a chronic skin condit ion t hat usually present s in young adult s. Lesions are charact erized as 1 t o 10 cm in diamet er eryt hemat ous papules and plaques wit h silver
scales, having sharply defined margins raised above t he normal surrounding skin. These plaques are symmet rically dist ribut ed and usually involve t he scalp, ext ensor elbows,
knees, and back.
Superficial basal cell carcinoma is recognized as a solit ary, well-defined, pink, pearly t ranslucent , dome-shaped papule wit h t elangiect asias. Wit h t ime, t he cent er may
umbilicat e and ulcerat e t o produce t he charact erist ic rolled borders. Eight y percent of t hese occur on t he head and neck.
Superficial spreading melanoma present s as a variably pigment ed plaque wit h an irregular border, ranging from a few t o several cent imet ers. It is not scaly. It can occur
anywhere, but is commonly seen on t he back in men and t he legs in women.
Key Poi nt
Bowen disease is recognized as a gradually enlarging, well-demarcat ed, eryt hemat ous scaly plaque t hat can resemble superficial basal cell carcinoma, psoriasis, or eczema.
Bi bl i ography
Madan V, Lear JT, Szeimies RM. Non-melanoma skin cancer. Lancet . 2010;375(9715):673-85. [PMID: 20171403]
Item 23 Answer: C
Educati onal Objecti ve: Diagnose nodular melanoma.
The most likely diagnosis is nodular melanoma. Nodular melanoma oft en present s as uniformly dark blue or black "berry-like" lesions t hat most commonly originat e from
normal skin. It is most oft en found in people aged 60 years or older. Nodular melanomas oft en do not fulfill t he ABCDE (asymmet ry, irregular borders, color variegat ion,
expanding diamet er, evolut ion over t ime) crit eria for melanoma and t end t o expand vert ically rat her t han horizont ally. Nodular melanomas are most ly symmet ric, elevat ed,
and one color.
Basal cell carcinoma present s classically as a solit ary, well-defined, pink, pearly t ranslucent , dome-shaped papule wit h t elangiect asias. Wit h t ime, t he cent er may umbilicat e
and ulcerat e t o produce t he charact erist ic rolled borders. Eight y percent of t hese occur on t he head and neck.
Kerat ocant homa is a rapidly growing skin cancer t hought t o be a form of squamous cell cancer. Early lesions present as solit ary, round nodules t hat grow rapidly. As t he
lesions mat ure, a cent ral kerat ot ic plug becomes visible and t he lesion becomes crat er-like. It rarely progresses t o invasive or met ast at ic cancer and oft en involut es wit hin
mont hs.
Seborrheic kerat osis is a benign common epidermal t umor, usually t an, brown, or black in color wit h discret e borders most commonly found on t he t runk, face, and upper
ext remit ies. It is elevat ed from t he surface of t he skin and has a "st uck-on" wart y or waxy appearance. It is most commonly found in persons older t han 50 years. The
number of lesions can vary from one t o hundreds in a person.
Spit z nevus is a clinically benign mole usually found in children or young adult s t hat present s as a dome-shaped uniformly pink, red, or pigment ed nodule. It s surface can be
smoot h or verrucous and is most commonly found on t he face and lower ext remit ies. It can have hist opat hologic feat ures t hat overlap wit h t hose of melanoma.
Key Poi nt
Nodular melanomas oft en present as uniformly dark blue or black "berry-like" lesions t hat are most ly symmet ric, elevat ed, and one color.
Bi bl i ography
Chamberlain AJ, Frit schi L, Kelly JW. Nodular melanoma: pat ient s' percept ions of present ing feat ures and implicat ions for earlier det ect ion. J Am Acad Dermat ol.
2003:48(5):694-701. [PMID: 12734497]
Item 24 Answer: A
Educati onal Objecti ve: Diagnose actinic keratoses.
This pat ient has act inic kerat oses, common lesions t hat occur on sun-exposed skin of older whit e-skinned persons. Act inic kerat oses are believed t o be t he earliest clinically
recognized st ep in a biologic cont inuum t hat may result in invasive squamous cell carcinoma. Act inic kerat oses are 1- t o 3-mm, elevat ed, flesh-colored or red papules,
surrounded by a whit ish scale. They are oft en easier t o feel as "rough spot s" on t he skin t han t hey are t o see. Most pat ient s will have, on average, 6 t o 8 lesions. Most remain
st able and some regress, but ot hers enlarge t o become invasive squamous cell carcinomas. The appearance of t he pat ient 's lesion is not consist ent wit h basal cell carcinoma,
melanoma, or seborrheic kerat osis.
A basal cell carcinoma classically present s as a pink, pearly or t ranslucent , dome-shaped papule wit h t elangiect asias. The papule may have cent ral umbilicat ion.
A melanoma is classically a pigment ed macule or plaque t hat is asymmet ric and has irregular, scalloped, not ched, or indist inct borders. It is black or dark brown or has
variegat ed (mult iple) colorat ion, including shades of black, red, and blue. Melanomas may also have depigment ed or whit e areas, which represent regression of t he lesion.
Rarely, melanomas are not pigment ed and can resemble basal cell carcinomas.
Seborrheic kerat oses can be brown or black but have discret e borders, are elevat ed above t he surface of t he skin, and have a "st uck-on" wart y or waxy appearance.
Key Poi nt
Act inic kerat oses are precancerous lesions t hat can develop int o invasive squamous cell carcinoma and t hat t ypically appear as eryt hemat ous lesions wit h overlying
hyperkerat osis.
Bi bl i ography
Schwart z RA, Bridges TM, But ani AK, Ehrlich A. Act inic kerat osis: an occupat ional and environment al disorder. J Eur Acad Dermat ol Venereol. 2008;22(5):606-615.
[PMID: 18410618]
Item 25 Answer: A
Educati onal Objecti ve: Diagnose basal cell carcinoma.
The most likely diagnosis is basal cell carcinoma. Basal cell carcinoma (BCC) t ypically present s as a pearly, pink papule or nodule wit h t elangiect at ic vessels. As BCC grows,
t he cent ral area oft en ulcerat es, result ing in it s charact erist ic rolled edge. Flecks of melanin pigment are commonly present . A biopsy is necessary, as amelanot ic melanoma
may have a similar appearance. Common biopsy t echniques include shave or punch. Most nodular BCCs are t reat ed wit h excision, whereas ill-defined lesions, high-risk
hist ologic t ypes, and t umors on t he face and hands are t reat ed wit h Mohs micrographic surgery. Select ed superficial lesions can be t reat ed wit h curet t age, imiquimod,
cryot herapy, or excision.
Pyogenic granulomas are t ypically bright red and friable, are commonly crust ed, and develop over a few days t o weeks. Removal is necessary only if t he lesion is cosmet ically
unaccept able, painful, causes unwant ed bleeding, or is ot herwise bot hersome.
Seborrheic kerat osis is a painless, nonmalignant growt h appearing as a waxy brownish pat ch or plaque. Seborrheic kerat oses lack a pearly appearance and t ypically exhibit
horn cyst s (epidermal cyst s filled wit h kerat in) on t he surface t hat can best be visualized wit h a magnifying lens. Treat ment is necessary only if lesions are sympt omat ic or
int erfere wit h funct ion.
Squamous cell carcinomas are rapidly growing, hyperkerat ot ic, flesh-colored, pink or red ulcerat ed macules, papules, or nodules t hat commonly appear on t he scalp, neck, and
pinnae. A shave or punch biopsy is used t o confirm t he diagnosis of suspicious lesions.
Key Poi nt
Basal cell carcinomas present as pink, pearly nodules wit h t elangiect ases and, commonly, flecks of melanin pigment .
Bi bl i ography
Mogensen M, Jemec GB. Diagnosis of nonmelanoma skin cancer/kerat inocyt e carcinoma: a review of diagnost ic accuracy of nonmelanoma skin cancer diagnost ic t est s and
t echnologies. Dermat ol Surg. 2007;33(10):1158-1174. [PMID: 17903149]
Item 26 Answer: C
Educati onal Objecti ve: Diagnose keratoacanthoma.
The most likely diagnosis is kerat oacant homa. Kerat oacant homa is an epit helial neoplasm t hat is charact erized by rapid growt h over 2 t o 6 weeks and by a crat er-like
configurat ion. Early lesions are frequent ly misdiagnosed as skin infect ions. The t ypical early lesion is a hard, eryt hemat ous nodule wit h a kerat ot ic (horny) cent er.
Kerat oacant homas t ypically occur on heavily sun-damaged skin, usually in older persons, wit h a peak age of 60 years. As t he lesion enlarges, t he cent er of t he crat er becomes
more prominent . Unlike t ypical squamous cell carcinomas, kerat oacant homas are capable of spont aneous resolut ion by t erminal different iat ion, in which t he t umor
"kerat inizes it self t o deat h." The clinical present at ion and charact erist ic hist ologic feat ures est ablish t he diagnosis.
Because kerat oacant homas may cause significant local t issue dest ruct ion, simple observat ion is generally not recommended despit e t he t endency for spont aneous involut ion.
Prompt surgical excision is recommended for solit ary lesions on t he t runk or ext remit ies. Int ralesional 5-fluorouracil or met hot rexat e, t opical imiquimod, and radiat ion
t herapy have also been used t o t reat large lesions or t hose in areas where surgical excision would be anat omically difficult .
An abscess is warm, red, and t ender and may be fluct uant if palpat ed. This is not consist ent wit h t he pat ient 's findings.
Keloids present as slow-growing, hard nodules, oft en wit h a dumbbell shape. They occur at sit es of prior t rauma.
Nodular basal cell carcinoma is oft en found on t he face and is charact erized by slow growt h and t he presence of a skin-t oned t o pink, pearly, t ranslucent papule wit h
t elangiect asia, rolled borders, and cent ral depression, oft en wit h ulcerat ion. The rapid growt h and appearance of t he pat ient 's lesion is not consist ent wit h nodular basal cell
carcinoma.
Key Poi nt
Kerat oacant homas are rapidly growing, nont ender, firm nodules wit h depressed kerat ot ic cent ers.
Bi bl i ography
Sarabi K, Selim A, Khachemoune A. Sporadic and syndromic kerat oacant homas: diagnosis and management . Dermat ol Nurs. 2007;19(2):166-170. [PMID: 17526304]
Item 27 Answer: C
Educati onal Objecti ve: Use short-acting opioid medications for mild to moderate cancer-related pain.
The most appropriat e next t herapeut ic st ep is t o add a short -act ing opioid. The pain in pat ient s wit h advanced malignancy oft en out paces t he abilit y of non-narcot ic
analgesics t o cont rol t he pain. In pat ient s wit h cancer who have mild t o moderat e pain such as t his one, an effect ive st rat egy is moving t o st ep 2 on t he World Healt h
Organizat ion t hree-st ep pain relief ladder by prescribing an int ermit t ent low-dose narcot ic in addit ion t o adjuvant , non-narcot ic pain medicine. Appropriat e choices include
immediat e-release formulat ions of oxycodone, morphine, or oxymorphone.
Init iat ing a long-act ing narcot ic such as a fent anyl t ransdermal pat ch or ext ended-release oxycodone would not be indicat ed unt il t he pat ient 's pain is adequat ely cont rolled
wit h short -act ing narcot ics, which can be rapidly t it rat ed t o achieve adequat e pain cont rol. Once pain cont rol is est ablished, t he cumulat ive dose of t he short -act ing opioid
can be used t o calculat e an effect ive dose of a long-act ing opioid, wit h t he dose reduced by 30% t o 50% and access t o a short -act ing opioid maint ained for break-t hrough pain.
If t he short -act ing opioid is needed more t han t hree t imes daily, t he amount of long-act ing opioid is increased.
Changing t o a different NSAID is much less likely t o cont rol t his pat ient 's pain t han is adding a short -act ing opioid analgesic.
Key Poi nt
For mild t o moderat e cancer-associat ed pain, a short -act ing opioid is indicat ed when non-opioid drugs fail t o adequat ely cont rol pain.
Bi bl i ography
Bruera E, Kim HN. Cancer Pain. JAMA. 2003;290(18):2476-2479. [PMID: 14612485]
Item 28 Answer: D
Educati onal Objecti ve: Use sustained-release morphine to treat moderate to severe cancer-related pain.
The most appropriat e pain management st rat egy for t his pat ient is swit ching t o sust ained-release morphine. Pain cont rol is a common management issue in t erminally ill
pat ient s. The use of as-needed doses of opioid analgesics combined wit h non-opioid adjunct ive t herapy is an effect ive management st rat egy for mild t o moderat e cancer pain.
When t his st rat egy no longer suffices, however, addit ional pain relief must be given. This pat ient has discomfort from pain t hat ret urns before he is scheduled t o t ake his next
dose of analgesic t herapy, and he is t aking t he medicat ion on a cont inual basis. This pat ient would benefit most from t he addit ion of a longer-act ing narcot ic t o t reat his pain.
An appropriat e solut ion would be t o give him sust ained-release morphine t wice daily. A breakt hrough pain st rat egy should be cont inued so t he pat ient has opt ions if t he
longer-act ing pain medicat ion does not provide complet e relief. When adding a long-act ing opioid, a st rat egy t o avoid overmedicat ion is t o give a st art ing dose of 30% t o
50% of t he pat ient 's average 24-hour dosage of narcot ic. The dose of t he opioid for breakt hrough pain is calculat ed as 10% of t he t ot al daily opioid dose given as an
immediat e-release opioid.
Gabapent in can be useful in t reat ing neuropat hic pain but would likely not be useful for reducing pain from bony met ast ases. Increasing t he frequency of t he immediat e-release
medicat ion is not t he best answer because of t he pat ient 's need t o re-dose frequent ly owing t o mult iple recurrent bout s of pain. The goal of palliat ive t herapy for pain is t o
relieve t he pat ient of significant pain for most of t he day, which will result in t he infrequent need for addit ional doses of immediat e-release pain medicat ion. Swit ching t he
medicat ion from one immediat e-release formulat ion t o anot her is also unlikely t o make t he pat ient more comfort able.
Key Poi nt
Long-act ing narcot ics are useful in pain cont rol for pat ient s wit h recurrent pain while on short -act ing, as-needed narcot ic t herapy.
Bi bl i ography
Bruera E, Kim HN. Cancer Pain. JAMA. 2003;290(18):2476-2479. [PMID: 14612485]
Item 29 Answer: B
Educati onal Objecti ve: Treat cancer pain with long-acting and immediate-release morphine sulfate.
Because of t he severit y of t his pat ient 's pain, long-act ing morphine sulfat e (or ot her st rong opioids such as hydromorphone or fent anyl) and immediat e-act ing morphine
sulfat e for breakt hrough pain is t he t herapy of choice. The t ransit ion from parent eral t o oral morphine is st raight forward: 10 mg of int ravenous morphine is equivalent t o 30
mg of oral morphine. In t his case, t he pat ient 's t ot al daily dose of morphine sulfat e should be calculat ed (including t ot al doses of bolus and cont inuous infusion) and is
mult iplied by 3 t o obt ain t he equivalent oral dose. Because long-act ing morphine is dosed every 12 hours, half of t he calculat ed oral dose is given t wice daily. Ten percent of
t he t ot al oral dose is made available as immediat e-act ing morphine t o use as needed for breakt hrough pain (t he "rescue dose"). If t he immediat e-act ing opioid is needed more
t han t hree t imes per day, t he dose of long-act ing opioid can be increased.
Hydrocodone is a weak opiat e and is not indicat ed in t he t reat ment of severe pain. Furt hermore, hydrocodone has proven ineffect ive for t his pat ient in t he past . Alt hough
long-act ing morphine sulfat e and oxycodone as needed may provide adequat e pain relief, it is appropriat e t o use t he same drug whenever possible for bot h breakt hrough and
basal dosing in order t o simplify fut ure dose t it rat ions as well as minimize drug-relat ed side effect s. In addit ion, in t reat ing severe pain, analgesics provided on an as-needed
basis are less effect ive t han regularly dosed, long-act ing opioids supplement ed wit h immediat e-act ing agent s for breakt hrough pain.
Key Poi nt
Moderat e t o severe pain requires t reat ment wit h a st rong opioid analgesic, usually in bot h long-act ing and immediat e-act ing formulat ions.
Bi bl i ography
Jost L, Roila F; ESMO Guidelines Working Group. Management of cancer pain: ESMO clinical recommendat ions. Ann Oncol. 2009;20 Suppl 4:170-3. [PMID: 19454446]
Item 30 Answer: A
Educati onal Objecti ve: Treat dyspnea in a palliative care setting with an opioid.
The home hospice nurse of t his pat ient should be advised t o administ er t he immediat e-release morphine t o t reat t he dyspnea. In t erminally ill pat ient s wit h malignancy or
cardiopulmonary disease, narcot ics can be an effect ive t reat ment for dyspnea. In a randomized t rial t hat evaluat ed narcot ics for dyspnea in pat ient s already on t hese
medicat ions for pain, t he int ensit y of dyspnea and t he respirat ion rat e improved wit h administ rat ion of a supplement al dose of opioid. In a st udy of pat ient s wit h cancer who
were not oxygen dependent , caut ious t it rat ion of parent eral opioids was not associat ed wit h respirat ory depression. Similar st udies have not been performed wit h oral agent s.
An emergency depart ment visit would be unlikely t o provide long-t erm improvement s in comfort or prognosis and would be generally inappropriat e for a hospice pat ient .
The result s of t he pat ient 's physical examinat ion are consist ent wit h a right pleural effusion, which could be a sign of heart failure. However, t he pat ient has no ot her signs
suggest ive of heart failure, and a diuret ic such as furosemide is t herefore not indicat ed.
Alt hough supplement al oxygen is oft en used in t he palliat ive care set t ing t o relieve dyspnea in nonhypoxemic pat ient s wit h malignancy, t his approach is not effect ive. A
met a-analysis demonst rat ed no improvement in pat ient s' percept ion of dyspnea at act ivit y or at rest aft er receiving 4 t o 10 L/min of oxygen.
Key Poi nt
Morphine is effect ive in t reat ing cancer-relat ed dyspnea as well as dyspnea relat ed t o end-st age cardiopulmonary disorders.
Bi bl i ography
Est fan B, Mahmoud F, Shaheen P, et al. Respirat ory funct ion during parent eral opioid t it rat ion for cancer pain. Palliat Med. 2007;21(2):81-86. [PMID: 17344255]
Secti on 10. Pul monary Medi ci ne
Questi ons
Item 1 [Basic]
A 60-year-old man is evaluat ed for progressive exert ional dyspnea. For t he past year, he has been unable t o walk t hree blocks wit hout st opping t wice because of short ness of
breat h. He has a daily cough product ive of a small amount of whit e sput um. He has smoked 1 pack per day since t he age of 20 years.
On physical examinat ion, he is comfort able at rest . Vit al signs are normal. Oxygen sat urat ion by pulse oximet ry is 90% on ambient air. Est imat ed cent ral venous pressure is
normal and no murmurs or ext ra cardiac sounds are heard. His lung examinat ion reveals decreased air movement wit hout wheezes or crackles. The remainder of t he
Chest x-ray shows increased radiolucency and low-lying diaphragms.
Pulmonary funct ion st udies following administ rat ion of a bronchodilat or:
FEV
1
65% of predict ed
FVC 75% of predict ed
FEV
1
/FVC rat io 0.60
Tot al lung capacit y (TLC) 105% of predict ed
Diffusing capacit y of lung for carbon dioxide (DLCO) 44% of predict ed
(A) Ast hma
(B) Chronic obst ruct ive pulmonary disease
(C) Heart failure
(D) Int erst it ial lung disease
Item 2 [Basic]
A 25-year-old woman is evaluat ed for a 3-mont h hist ory of progressive breat hlessness and decreased exercise capacit y. She report s no recent illness, fever, cough, or previous
hist ory of breat hing problems. She has a 1-year hist ory of pain and st iffness in t he joint s of her hands and wrist s.
On physical examinat ion, her vit al signs are normal. She has a normal cardiopulmonary examinat ion. She has act ive synovit is involving her wrist s and second and t hird
met acarpophalangeal joint s bilat erally.
The chest x-ray is normal.
Pulmonary funct ion st udies following administ rat ion of a bronchodilat or:
FEV
1
60% of predict ed
FEV
1
/FVC rat io 0.85
Tot al lung capacit y(TLC) 65% of predict ed
Diffusing capacit y of lung for carbon dioxide (DLCO) 45% of predict ed
Whi ch of the fol l owi ng i s the most l i kel y di agnosi s i n thi s pati ent?
(A) Chronic obst ruct ive lung disease
(B) Ast hma
(D) Int erst it ial lung disease
Item 3 [Basic]
A 56-year-old woman is evaluat ed for a 2-year hist ory of episodic cough and chest t ight ness. Her sympt oms began aft er a severe respirat ory t ract infect ion. Since t hen, she
has had cough and chest discomfort aft er similar infect ions, t ypically last ing several weeks before resolving. She feels well bet ween episodes. She is ot herwise healt hy and
t akes no medicat ions. Physical examinat ion reveals no abnormalit ies. Chest radiograph and spiromet ry are normal.
(A) Bronchoscopy
(B) CT scan of t he sinuses
(C) Exercise echocardiography
(D) Met hacholine challenge t est
Item 4 [Advanced]
A 60-year-old man is hospit alized because of progressive dyspnea during t he past mont h. He has a 45-pack-year smoking hist ory, but he has no ot her medical problems.
On physical examinat ion, he is cyanot ic and has paradoxical respirat ory movement s of his rib cage and abdomen. Blood pressure is 140/78 mm Hg, pulse rat e is 105/min, and
respirat ion rat e is 28/min. Jugular venous dist ent ion is present . The lungs are clear. The remainder of t he examinat ion is normal.
Pulmonary funct ion st udies:
Tot al lung capacit y 85% of predict ed
Residual volume 72% of predict ed
FEV
1
63% of predict ed
FEV
1
/FVC rat io 105%
Residual volume/t ot al lung capacit y 163%
Maximum inspirat ory pressure 36% of predict ed
Maximum expirat ory pressure 45% of predict ed
DLCO 82% of predict ed
Art erial blood gases st udies show a pH of 7.3, a PO
2
of 42 mm Hg (5.6 kPa), a PCO
2
of 55 mm Hg (7.3 kPa), and a bicarbonat e level of 27 meq/L (27 mmol/L).
Whi ch of the fol l owi ng i s the most l i kel y cause of hi s respi ratory fai l ure?
(A) Chronic obst ruct ive pulmonary disease
(B) Idiopat hic pulmonary fibrosis
(C) Neuromuscular weakness
(D) Pulmonary art erial hypert ension
Item 5 [Advanced]
A 63-year-old man is evaluat ed for a 1-year hist ory of dyspnea t hat has gradually worsened during t he past 6 mont hs. He has dyspnea at rest , but has no ort hopnea. The
pat ient report s his breat hing is bet t er when lying flat and is worse when sit t ing upright . He previously abused alcohol and int ravenous drugs. Medical hist ory is significant for
cirrhosis and port al hypert ension.
On physical examinat ion, t he pat ient is afebrile. Blood pressure is 110/68 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 24/min. Oxygen sat urat ion by pulse oximet ry is
85% on ambient air. The cardiac examinat ion is normal. Lungs are clear. Ascit es is present as are clubbing, peripheral cyanosis, and spider nevi. Lower ext remit ies show 1+
pit t ing edema.
The chest x-ray is normal.
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's dyspnea?
(A) Bronchogenic carcinoma
(B) Const rict ive pericardit is
(C) Emphysema
(D) Hepat opulmonary syndrome
Item 6 [Basic]
A 60-year-old woman is evaluat ed for an 18-mont h hist ory of progressive dyspnea on exert ion and a 3-mont h hist ory of ort hopnea. She is ot herwise well and t akes no
medicat ions.
On examinat ion, she is afebrile, blood pressure is 110/85 mm Hg, pulse rat e is 100/min, and respirat ion rat e is 24/min. The carot id upst roke is diminished and delayed
compared wit h t he apical pulsat ion. Cardiac examinat ion shows a sust ained cardiac apex impulse, grade 3/6 lat e-peaking syst olic eject ion murmur at t he right upper st ernal
border radiat ing t o t he carot id art eries, and an S
4
. Lungs are clear t o auscult at ion. The remainder of t he examinat ion is normal.
(C) Pulmonary art erial hypert ension
(D) Pulmonary valvular st enosis
Item 7 [Basic]
A previously healt hy 30-year-old man who is a lifelong nonsmoker is evaluat ed in t he emergency depart ment for sudden onset of right -sided chest pain and short ness of
breat h.
On physical examinat ion, vit al signs are normal. There are decreased breat h sounds over t he post erior right t horax. The cardiac examinat ion is normal.
A chest radiograph is obt ained and is shown.
(A) Heart failure
(B) Hydropneumot horax
(C) Pneumonia
Item 8 [Advanced]
A 20-year-old woman is evaluat ed in t he emergency depart ment for an acut e episode of wheezing and dyspnea wit hout cough or sput um product ion. She has had frequent
evaluat ions in emergency depart ment s for similar episodes. In bet ween t hese episodes, findings on physical examinat ion and pulmonary funct ion t est ing, including
met hacholine challenge, have been normal. She is ot herwise healt hy and t akes no medicat ions.
On physical examinat ion, t he pat ient has inspirat ory and expirat ory wheezing and is in moderat e discomfort . The t emperat ure is 37.1C (98.8F), pulse rat e is 100/min, and
respirat ion rat e is 24/min; oxygen sat urat ion on ambient air is 96%. Aft er receiving albut erol and int ravenous cort icost eroids, she cont inues t o wheeze and is in moderat e
respirat ory dist ress. Oxygen sat urat ion on ambient air remains at 96%. Chest radiograph shows decreased lung volumes.
(A) Chest CT scan
(B) Int ravenous aminophylline
(C) Int ravenous azit hromycin
(D) Laryngoscopy
Item 9 [Advanced]
A 60-year-old woman is evaluat ed for a 4-mont h hist ory of progressive fat igue and dyspnea on exert ion. She does not smoke cigaret t es and denies chest pain, palpit at ions,
dizziness, or syncope. She has a 12-year hist ory of limit ed cut aneous syst emic sclerosis. A screening cardiopulmonary evaluat ion 3 years ago was normal. She also has
gast roesophageal reflux disease and Raynaud phenomenon. She int ermit t ent ly develops ulcers on t he fingert ips. Current medicat ions are amlodipine, omeprazole, and
nit roglycerin oint ment .
On physical examinat ion, t emperat ure is 37.0F (98.6F), blood pressure is 120/80 mm Hg, pulse rat e is 84/min, and respirat ion rat e is 16/min. Cardiac examinat ion reveals a
loud pulmonic component of S
2
wit h fixed split t ing and a 2/6 early syst olic murmur at t he lower left st ernal border t hat increases wit h inspirat ion. The lungs are clear t o
auscult at ion. The abdominal examinat ion is unremarkable. Sclerodact yly is present , and pit t ing scars are visible over several fingert ips. There is no peripheral edema.
Complet e blood count and eryt hrocyt e sediment at ion rat e are normal. Elect rocardiogram shows evidence of right vent ricular hypert rophy. Chest radiograph shows no
infilt rat es.
Pulmonary funct ion st udies:
FEV
1
/FVC 80%
(A) Chronic obst ruct ive pulmonary disease
(B) Int erst it ial lung disease
(C) Left vent ricular failure
(D) Pulmonary art erial hypert ension
Item 10 [Advanced]
A 55-year-old man is found t o have a pleural effusion aft er a 2-week hist ory of cough, sput um product ion, dyspnea, chills, and pleurit ic chest pain. Upright and lat eral
decubit us chest x-rays confirm t hat t he effusion is free flowing (wit hout evidence of loculat ion). He has ot herwise been in good healt h and t akes no medicat ions.
A t horacent esis is performed and 1.2 L of fluid is removed. Analysis of t he pleural fluid is performed.
Leukocyt es 3000/L (3 10
9
/L) wit h 82% neut rophils
pH 6.95
Gram st ain and cult ure are pending. Blood cult ures are obt ained. Empiric broad-spect rum ant ibiot ics are begun.
(A) Chest CT
(B) Chest t ube drainage of t he effusion
(C) Video-assist ed t horascopic surgery (VATS)
(D) No addit ional t reat ment
Item 11 [Basic]
A 24-year-old man is evaluat ed in t he emergency depart ment for a 10-day hist ory of increasing short ness of breat h and dry cough. Before t his t ime, t he pat ient was healt hy
and t ook no medicat ions.
On physical examinat ion, t emperat ure is 37.9C (100.3F), blood pressure is 105/70 mm Hg, pulse is 106/min, and respirat ions are 32/min. A lung examinat ion reveals
dullness t o percussion, decreased t act ile fremit us, and decreased breat h sounds at t he right base. The remainder of his physical examinat ion is unremarkable.
(A) Heart failure
(B) Lobar consolidat ion
(C) Pleural effusion
(D) Pneumot horax
Item 12 [Advanced]
A 30-year-old medical resident is evaluat ed for cough, right -sided chest pain, and fever of 3 weeks' durat ion. He has no significant medical hist ory, and he t akes no
medicat ions.
Hemoglobin is 14 g/dL (140 g/L), and t he leukocyt e count is 8000/L (8.0 10
9
/L). Chest radiograph shows a right pleural effusion occupying approximat ely 50% of t he
hemit horax wit hout ot her abnormalit ies. Thoracent esis yields t urbid, yellow fluid, and analysis shows t he following:
Eryt hrocyt e count 500/L (500 10
6
/L)
Nucleat ed cell count 3500/L (3.5 10
9
/L) wit h 20% neut rophils, 60% lymphocyt es, 10% macrophages, 4% mesot helial cells, and 6% eosinophils
pH 7.35
Serum t ot al prot ein is 7.0 g/dL (70 g/L) and serum lact at e dehydrogenase is 100 U/L. Gram st ain shows no organisms and cult ure is pending.
(A) Azit hromycin for 5 days
(B) Chest CT scan
(C) Flexible bronchoscopy
(D) Pleural biopsy
Item 13 [Advanced]
A 40-year-old man is evaluat ed for short ness of breat h and left -sided chest discomfort wit hout cough, fever, or hemopt ysis. The pat ient has a hist ory of lymphoma t hat is
now in remission.
Examinat ion of t he chest shows dullness t o percussion and decreased breat h sounds on t he left side. Chest radiograph shows a moderat e-sized, left -sided pleural effusion
wit hout a pneumot horax. Serum prot ein is 5.8 g/dL (58 g/L), cholest erol is 200 mg/dL (5.2 mmol/L), and t riglycerides are 100 mg/dL (1.1 mmol/L). Thoracent esis yields 500
mL of milky-appearing pleural fluid, and analysis shows t he following:
Cell count
Eryt hrocyt es 300/L (300 106/L); leukocyt es 890/L (890 10
9
/L) wit h 65% lymphocyt es, 22% neut rophils, 8% mesot helial cells, and 4%
eosinophils
Lact at e
dehydrogenase
250 U/L
pH 7.50
Amylase 25 U/L
Cholest erol 38 mg/dL (1.0 mmol/L)
Cyt ology, Gram st ain, acid-fast bacilli st ain, and bact erial cult ure are negat ive.
(A) Chylot horax
(B) Heart failure
(C) Parapneumonic effusion
(D) Tuberculous pleural effusion
Item 14 [Advanced]
A 33-year-old woman is evaluat ed in t he emergency depart ment for a 6-hour hist ory of worsening ast hma sympt oms. Her medicat ions include albut erol and an inhaled
cort icost eroid. She is t reat ed wit h int ravenous cort icost eroids and albut erol. Aft er 4 hours of t reat ment , she remains sympt omat ic and can speak only one t o t wo words
bet ween breat hs.
On physical examinat ion, she appears uncomfort able and t ired. Temperat ure is 36.8C (98.2F), blood pressure is 150/90 mm Hg, heart rat e is 124/min, and respirat ion rat e
is 32/min. Oxygen sat urat ion by pulse oximet ry is 92% wit h oxygen 2 L/min by nasal cannula. Lung examinat ion reveals poor air movement and diffuse expirat ory wheezes.
Result s of art erial blood gas st udies: pH, 7.2; PCO
2
, 45 mm Hg (6.0 kPa); PO
2
, 70 mm Hg (9.3 kPa). Peak flow is 30% of best performance.
Whi ch of the fol l owi ng the most appropri ate management for thi s pati ent?
(A) Admission t o t he hospit al ward
(B) Int ubat ion and mechanical vent ilat ion
(C) Cont inued t herapy in t he emergency depart ment
(D) Discharge home
Item 15 [Basic]
A 40-year-old woman is evaluat ed for worsening ast hma sympt oms aft er resolut ion of an acut e respirat ory t ract infect ion t hat was t reat ed wit h support ive measures. The
pat ient has a 15-year hist ory of ast hma t hat has been well cont rolled on moderat e-dose inhaled cort icost eroids plus as-needed inhaled albut erol. Since her respirat ory t ract
infect ion 10 days ago, her ast hma sympt oms have worsened; she has had frequent night t ime episodes of wheezing and has used her albut erol inhaler six t o eight t imes a day.
On physical examinat ion, t he pat ient is afebrile and has no chest pain or significant sput um product ion. Her peak flow is more t han 40% below her baseline value.
(A) 7-Day course of a fluoroquinolone
(B) Leukot riene-modifying agent
(C) Long-act ing -agonist
(D) Nebulized albut erol at home
(E) Short course of an oral cort icost eroid
Item 16 [Basic]
A 24-year-old woman wit h persist ent ast hma, which is well cont rolled on low-dose flut icasone and albut erol as needed, became pregnant 2 mont hs ago and asks for advice
about ast hma t herapy during her pregnancy. Before she st art ed flut icasone t herapy, she had frequent ast hma sympt oms and occasional exacerbat ions requiring emergency
depart ment t reat ment . Since she became pregnant , her ast hma has remained under good cont rol. The physical examinat ion is unremarkable, and spiromet ry is normal.
(A) Cont inue t he current regimen
(B) St op flut icasone; add inhaled cromolyn
(C) St op flut icasone; add salmet erol
(D) St op flut icasone; add t heophylline
Item 17 [Basic]
A 75-year-old woman wit h long-st anding ast hma is evaluat ed for a 1-mont h hist ory of noct urnal ast hma sympt oms at least weekly and t he need t o use an albut erol inhaler
daily. Her ast hma t herapy is a moderat e-dose inhaled cort icost eroid. The pat ient is ot herwise healt hy.
On physical examinat ion, she has occasional wheezing, but t he rest of t he examinat ion is unremarkable. On office spiromet ry, t he FEV
1
is 70% of predict ed and FVC is 85%
of predict ed.
(A) Adding a leukot riene-modifying agent
(B) Adding a long-act ing ant icholinergic agent
(C) Adding a long-act ing -agonist
(D) Adding t heophylline
(E) Doubling t he cort icost eroid dose
Item 18 [Advanced]
A 37-year-old man wit h ast hma is evaluat ed for frequent episodes of wheezing and dyspnea unrelieved by short -act ing -agonist t herapy. He uses his cont roller medicat ions
regularly, including an inhaled long-act ing -agonist and inhaled high-dose cort icost eroids. He has sympt oms daily and frequent noct urnal sympt oms.
On physical examinat ion, t he pat ient is in mild respirat ory dist ress. The t emperat ure is 37.0C (98.6F), blood pressure is 140/85 mm Hg, pulse rat e is 90/min, and
respirat ion rat e is 18/min. He has bilat eral wheezing. Spiromet ry shows an FEV
1
of 65% of predict ed. Aft er t he supervised use of a bronchodilat or in t he office, t here was
relief of sympt oms, and repeat spiromet ry 10 minut es aft er t he administ rat ion of t he bronchodilat or showed t hat t he FEV
1
increased t o 85% of predict ed.
(A) Add a leukot riene-modifying drug
(B) Have t he pat ient demonst rat e his inhaler t echnique
(C) Have t he pat ient keep a sympt om and t reat ment log
(D) St art oral prednisone t herapy
Item 19 [Advanced]
A 65-year-old man wit h chronic obst ruct ive pulmonary disease is evaluat ed in t he emergency depart ment for a 4-day hist ory of worsening dyspnea, cough, and increased
product ion of purulent sput um. His albut erol inhaler has been ineffect ive in relieving his sympt oms.
On physical examinat ion, t he pat ient is in respirat ory dist ress using pursed-lip breat hing. Temperat ure is 36.7C (98.0F), blood pressure is 145/84 mm Hg, pulse rat e is
102/min, and respirat ion rat e is 20/min. He has audible polyphonic wheezes but no crackles. Heart sounds are dist ant but ot herwise normal. The remainder of his physical
Art erial blood gases performed on 2 L/min nasal cannula: pH, 7.31; PCO
2
, 50 mm Hg (6.7 kPa); PO
2,
65 mm Hg (8.6 kPa). Chest radiograph displays hyperinflat ion but no
infilt rat es.
Int ravenous cort icost eroids and inhaled albut erol are begun.
Whi ch of the fol l owi ng treatments shoul d al so be i ni ti ated?
(A) Amoxicillin
(B) Inhaled cort icost eroids
(C) Levofloxacin
(D) Theophylline
Item 20 [Basic]
A 58-year-old man wit h chronic obst ruct ive pulmonary disease (COPD) is evaluat ed for slowly progressive dyspnea beginning 6 mont hs ago. He now has dyspnea wit h
minimal exert ion, such as walking t wo blocks, and he can no longer climb a flight of st airs. He has a 42-pack-year smoking hist ory, quit t ing 2 years ago. His medicat ions are
albut erol and t iot ropium inhalers.
On physical examinat ion, t emperat ure is 36.6C (97.8F), blood pressure is 140/86 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 16/min. Oxygen sat urat ion by pulse
oximet ry is 87% on ambient air. Breat h sounds are decreased, but no audible wheezes are present .
Art erial blood gas analysis, on ambient air, reveals: pH, 7.38; PO
2
2
, 45 mm Hg (6.0 kPa). Chest radiograph shows hyperinflat ion. Spiromet ry
shows an FEV
1
1
/FVC rat io of 50%.
Whi ch of the fol l owi ng i nterventi ons i s most l i kel y to i mprove thi s pati ent's survi val ?
(A) Cont inuous oxygen t herapy
(B) Inhaled cort icost eroid
(C) Inhaled salmet erol
(D) Theophylline
Item 21 [Basic]
A 55-year-old man wit h a 7-year hist ory of severe chronic obst ruct ive pulmonary disease is evaluat ed aft er being discharged from t he hospit al following an acut e
exacerbat ion; he has had t hree exacerbat ions over t he previous 18 mont hs. He is a long-t erm smoker who st opped smoking 1 year ago. His medicat ions are albut erol as
needed and inhaled t iot ropium and salmet erol.
On physical examinat ion, vit al signs are normal. Breat h sounds are decreased bilat erally; t here is no edema or cyanosis. Oxygen sat urat ion aft er exert ion is 92% on ambient
air. Spiromet ry shows an FEV
1
1
/FVC rat io of 40%. Chest radiograph done in t he hospit al 3 weeks ago showed no act ive disease.
Whi ch of the fol l owi ng medi cati ons shoul d now be i ni ti ated?
(A) An inhaled cort icost eroid
(B) Iprat ropium
(C) N-acet ylcyst eine
(D) Oral prednisone
Item 22 [Advanced]
A 64-year-old man wit h a hist ory of chronic obst ruct ive pulmonary disease is evaluat ed in t he emergency depart ment for increased dyspnea over t he past 48 hours. There is
no change in his baseline product ion of whit e sput um, but he has increased nasal congest ion and sore t hroat . His medicat ions are inhaled t iot ropium, flut icasone, salmet erol,
and albut erol. Therapy wit h met hylprednisolone, inhaled albut erol, and iprat ropium bromide is st art ed.
The pat ient is alert but in mild respirat ory dist ress. The t emperat ure is 38.6C (101.5F), t he blood pressure is 150/90 mm Hg, t he pulse rat e is 108/min, and t he respirat ion
rat e is 30/min. Breat h sounds are diffusely decreased wit h bilat eral expirat ory wheezes; he is using accessory muscles t o breat he. Wit h t he pat ient breat hing oxygen, 2 L/min
by nasal cannula, art erial blood gases are pH 7.27, PCO
2
60 mm Hg (8.0 kPa), and PO
2
62 mm Hg (8.2 kPa); oxygen sat urat ion is 91%.
Whi ch of the fol l owi ng i s the most appropri ate next step?
(A) Increase oxygen t o 5 L/min
(B) Int ubat ion and mechanical vent ilat ion
(C) St art aminophylline infusion
(D) St art noninvasive posit ive-pressure vent ilat ion
Item 23 [Advanced]
A 72-year-old woman is evaluat ed for fat igue and decreased exercise capacit y. She has severe chronic obst ruct ive pulmonary disease, which was first diagnosed 10 years ago.
She was hospit alized 1 mont h ago for her second exacerbat ion t his year. She st opped smoking 5 years ago. She has no ot her significant medical problems. Her medicat ions are
albut erol as needed, an inhaled cort icost eroid, a long-act ing bronchodilat or, and oxygen, 2 L/min by nasal cannula.
On physical examinat ion, vit al signs are normal. Breat h sounds are decreased. Spiromet ry done 1 mont h ago showed an FEV
1
of 28% of predict ed, and blood gases measured
at t hat t ime (on supplement al oxygen) showed a pH of 7.41, PCO
2
of 43 mm Hg (5.7 kPa), and PO
2
of 64 mm Hg (8.4 kPa); DLCO is 30% of predict ed. There is no
noct urnal oxygen desat urat ion. Chest radiograph at t his t ime shows hyperinflat ion. CT scan of t he chest shows homogeneous dist ribut ion of emphysema.
(A) Lung t ransplant at ion
(B) Lung volume reduct ion surgery
(C) Noct urnal assist ed vent ilat ion
(D) Pulmonary rehabilit at ion
Item 24 [Basic]
A 40-year-old man who is a new pat ient is evaluat ed for a 6-mont h hist ory of mild short ness of breat h, which occurs primarily wit h exert ion, and also occasional wheezing.
He has smoked a half pack of cigaret t es daily since t he age of 18 years. He is ot herwise healt hy and t akes no medicat ions. He works in an aut omobile repair shop. His fat her,
a cigaret t e smoker, died of emphysema at t he age of 55 years.
On physical examinat ion, vit al signs are normal. Breat h sounds are diminished bilat erally, and t here is occasional wheezing post eriorly. Spiromet ry shows an FEV
1
of 58% of
predict ed and an FEV
1
/FVC rat io of 65%. Chest radiograph shows bilat eral basilar lucency (lung bullae).
(A) Measure plasma
1
-ant it rypsin
(B) Measure sweat chloride
(C) Obt ain a flow-volume loop
(D) Obt ain high-resolut ion CT scan of t he chest
Item 25 [Basic]
A 45-year-old man is evaluat ed at t he insist ence of his wife because of his loud snoring. On quest ioning, t he pat ient admit s t o morning headaches, nasal congest ion, and falling
asleep once while driving. He does not smoke cigaret t es. He has no ot her medical problems and t akes no medicat ions.
On physical examinat ion, t emperat ure is 36.6C (97.8F), blood pressure is 148/90 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 12/min. BMI is 34. Oxygen sat urat ion
by pulse oximet ry is 90% on ambient air. The cardiopulmonary examinat ion is normal. No peripheral edema is present .
Whi ch of the fol l owi ng shoul d be done next to eval uate thi s pati ent's symptoms?
(A) Brain nat riuret ic pept ide (BNP) measurement
(B) Coronary art ery calcium (CAC) score
(C) CT pulmonary angiography
(D) Polysomnography and art erial blood gas measurement
Item 26 [Advanced]
A 55-year-old man is evaluat ed for fat igue t hat has been present for more t han 1 year. He feels t ired on awakening and requires at least one nap daily t o accomplish his work
t asks. He report s no ot her changes in his sleep pat t ern or sympt oms of depression. He does not smoke cigaret t es, drink alcohol, or t ake illicit drugs. His only ot her medical
problem is a 2-year hist ory of difficult -t o-cont rol hypert ension. Medicat ions are lisinopril, hydrochlorot hiazide, and amlodipine.
On physical examinat ion, t emperat ure is normal, blood pressure is 140/92 mm Hg, pulse rat e is 78/min, and respirat ion rat e is 14/min. BMI is 36. The cardiopulmonary
examinat ion is normal. The vascular examinat ion is normal wit hout evidence of carot id, abdominal, or femoral bruit s. The remainder of t he physical examinat ion is
unremarkable.
Rout ine laborat ory t est ing, including fast ing blood glucose, serum elect rolyt es, and kidney funct ion t est s are normal.
(A) 24-Hour urine free cort isol measurement
(B) Percut aneous renal art ery angiography
(C) Plasma aldost erone-renin act ivit y rat io
(D) Polysomnography
Item 27 [Advanced]
A 64-year-old woman is evaluat ed for a 6-week hist ory of dyspnea, dry cough, fever, chills, night sweat s, and fat igue, which have not responded t o t reat ment wit h
azit hromycin and levofloxacin; she has lost 2.2 kg (5 lb) during t hat t ime. The pat ient had an examinat ion 6 mont hs ago while she was asympt omat ic t hat included rout ine
laborat ory st udies, age- and sex-appropriat e cancer screening, and a chest radiograph; all result s were normal. The pat ient has never smoked, has had no known
environment al exposures, and has not t raveled recent ly or been exposed t o anyone wit h a similar illness. Her only medicat ions are aspirin and a mult ivit amin.
On physical examinat ion, t emperat ure is 37.8C (100.0F); ot her vit al signs are normal. Cardiac examinat ion is normal. There are scat t ered crackles in t he mid-lung zones
wit h associat ed rare expirat ory wheezes. There is no digit al clubbing. Musculoskelet al and skin examinat ions are normal. Chest radiograph is shown.
(A) Asbest osis
(B) Communit y-acquired pneumonia
(C) Crypt ogenic organizing pneumonia
(D) Idiopat hic pulmonary fibrosis
Item 28 [Advanced]
A 74-year-old man is evaluat ed for a 5-year hist ory of gradually progressive dyspnea and dry cough wit hout wheezing or hemopt ysis. He has not had fever or lost weight . He
smoked one pack of cigaret t es per day bet ween t he ages of 18 and 60 years. He worked as an insulat or for 40 years.
Physical examinat ion shows no digit al clubbing or cyanosis. Auscult at ion of t he lungs reveals bilat eral end-inspirat ory crackles. Pulmonary funct ion t est ing shows t he
following:
Tot al lung capacit y 67% of predict ed
Residual volume 72% of predict ed
FEV
1
75% of predict ed
FEV
1
/FVC rat io 89%
His chest radiograph is shown.
(A) Asbest osis
(B) Idiopat hic pulmonary fibrosis
(C) Pulmonary sarcoidosis
(D) Rheumat oid int erst it ial lung disease
Item 29 [Basic]
A 55-year-old man has a 1-year hist ory of fat igue, chronic morning headache, dayt ime hypersomnolence, and frequent night t ime awakenings. The pat ient has hypert ension
and a 48-pack-year smoking hist ory. His only medicat ion is lisinopril. His family hist ory is noncont ribut ory.
On physical examinat ion, t emperat ure is normal, blood pressure is 135/85 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 28/min. BMI is 35. The examinat ion is
ot herwise unremarkable.
Hemat ocrit 53% (normal 5 years ago)
9
/L)
9
/L)
Eryt hropoiet in Elevat ed
Art erial oxygen sat urat ion (on ambient air) 98%
Cyt ogenet ic st udies are negat ive for t he JAK2 gene mut at ion.
Whi ch of the fol l owi ng i s the most l i kel y cause of the pati ent's el evated hematocri t?
(A) High-oxygen-affinit y hemoglobin
(B) Polycyt hemia vera
(C) Sleep apnea
(D) Volume cont ract ion
Item 30 [Advanced]
A 38-year-old woman wit h a 4-year hist ory of syst emic sclerosis is evaluat ed for a 6-mont h hist ory of dry cough and short ness of breat h. She has no fever, sput um
product ion, or ort hopnea. The clinical manifest at ions of her syst emic sclerosis include art hralgia, gast roesophageal reflux disease, and Raynaud phenomenon.
oximet ry is 90% on ambient air. Fine bibasilar lat e inspirat ory crackles are heard. Cardiac examinat ion is normal wit hout murmurs or ext ra sounds.
Complet e blood count , serum elect rolyt es, and met abolic panel are normal. Chest x-ray is normal. Result s of pulmonary funct ion t est ing: FEV
1
, 75% of predict ed; FVC, 71%
of predict ed; FEV
1
/FVC rat io, 100% of predict ed; and diffusing capacit y of lung for carbon monoxide (DLCO), 64% of predict ed. Ant it opoisomerase I ant ibody t est ing is
posit ive.
(A) Bronchoalveolar lavage
(B) High resolut ion chest CT
(C) Lung biopsy
(D) Pulmonary art ery angiogram
Item 31 [Advanced]
A 60-year-old woman is evaluat ed for a 2-mont h hist ory of progressive exert ional dyspnea, low-grade fever, and cough. She has never smoked and has worked all her life as a
homemaker. Medical hist ory includes 10-year hist ory of hypert ension and a 3-mont h hist ory of at rial fibrillat ion. Her medicat ions are hydrochlorot hiazide, at enolol,
amiodarone, and warfarin.
On physical examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 138/78 mm Hg, pulse rat e is 92/min, respirat ion rat e is 24/min. Oxygen sat urat ion on pulse
oximet ry is 94% on ambient air. No evidence of jugular venous dist ent ion is seen. Heart sounds are normal wit hout ext ra cardiac sounds or murmur. Bilat eral crackles at t he
lung bases are not ed. No clubbing is not ed.
Hemoglobin is 11 mg/dL (110 g/L), leukocyt e count is 12,800/L (12.8 10
9
/L) wit h 9% eosinophils. Chest x-ray shows diffuse int erst it ial infilt rat es wit h basilar
predominance.
(A) Acut e eosinophilic pneumonit is
(B) Asbest osis
(C) Drug-induced lung t oxicit y
(D) Heart failure
Item 32 [Basic]
A 75-year-old woman is admit t ed t o t he hospit al from her home for t reat ment of communit y-acquired pneumonia because of ext reme weakness and nausea. She has a hist ory
of hypert ension and compensat ed heart failure. Medicat ions are met oprolol, lisinopril, and hydrochlorot hiazide.
oximet ry is 92% on ambient air. Crackles are heard at t he left lower lung base. Cardiopulmonary examinat ion is ot herwise normal.
9
/L)
9
/L)
Whi ch of the fol l owi ng venous thrombosi s prophyl acti c i nterventi ons i s most appropri ate for thi s pati ent?
(A) Aspirin
(B) Knee-high compression st ockings
(C) Lepirudin
(D) Unfract ionat ed heparin
(E) Prophylaxis not indicat ed
Item 33 [Advanced]
A 54-year-old man is evaluat ed in t he emergency depart ment for a 1-hour hist ory of chest pain and dyspnea. The pat ient had been hospit alized 1 week ago for a colect omy
for colon cancer. His medical hist ory also includes hypert ension and nephrot ic syndrome secondary t o membranous glomerulonephrit is. His medicat ions are furosemide,
ramipril, and pravast at in.
On physical examinat ion, t he t emperat ure is 37.5C (99.5F), t he blood pressure is 110/60 mm Hg, t he pulse rat e is 120/min, t he respirat ion rat e is 24/min, and t he BMI is
30. Oxygen sat urat ion is 89% wit h t he pat ient breat hing ambient air and 97% on oxygen, 4 L/min. Cardiac examinat ion shows t achycardia and an S
4
. Breat h sounds are
normal. Serum creat inine concent rat ion is 2.1 mg/dL (185.6 mol/L). Chest radiograph is normal. Empiric unfract ionat ed heparin t herapy is begun.
Whi ch of the fol l owi ng tests shoul d be done next?
(A) Assay for plasma D-dimer
(B) CT pulmonary angiography
(C) Lower ext remit y ult rasonography
(D) Measurement of ant it hrombin III
(E) Vent ilat ion/perfusion scan
Item 34 [Advanced]
A 50-year-old woman is evaluat ed in t he emergency depart ment for a 4-day hist ory of pain, swelling, and eryt hema of t he left leg. There is no hist ory of recent
immobilizat ion, cancer, surgery, or deep venous t hrombosis.
On physical examinat ion, t emperat ure is 37.7C (100.0F), blood pressure is 132/82 mm Hg, pulse rat e is 65/min, and respirat ion rat e is 16/min. Examinat ion of t he left leg
discloses warmt h and circumscribed eryt hema and t enderness limit ed t o t he post erior t ibial port ion of t he leg. The circumference of t he left leg is 1 cm great er t han t he right
when measured 10 cm below t he t ibial t uberosit y. Localized t enderness along t he dist ribut ion of t he deep venous syst em and pit t ing edema are absent , as are venous
varicosit ies.
Whi ch of the fol l owi ng i s the most appropri ate next step i n di agnosi s?
(A) CT of t he leg
(B) D-dimer assay
(C) MRI of t he leg
(D) Venography
Item 35 [Advanced]
A 57-year-old woman is evaluat ed in t he emergency depart ment for a 1-week hist ory of swelling and pain in t he left leg. She has had t wo normal pregnancies and no
miscarriages. There is no family or personal hist ory of t hromboembolic disease. The pat ient is ot herwise healt hy.
A proximal deep venous t hrombosis is confirmed on ult rasound. Unfract ionat ed heparin is given as an init ial bolus followed by a cont inuous infusion at a dose t o prolong t he
act ivat ed part ial t hromboplast in t ime t o t wo t imes t he cont rol value. Warfarin, 5 mg/d, is also init iat ed.
Whi ch of the fol l owi ng i s the most appropri ate durati on of hepari n therapy for thi s pati ent?
(A) Minimum of 3 days
(B) Minimum of 3 days, wit h one INR measurement of >2
(C) Minimum of 5 days
(D) Minimum of 5 days, wit h t wo INR measurement s of >2, 24 h apart
Item 1 Answer: B
Educati onal Objecti ve: Diagnose chronic obstructive pulmonary disease.
The most likely diagnosis is chronic obst ruct ive pulmonary disease (COPD). A clinical diagnosis of COPD should be considered in any pat ient who has dyspnea, chronic cough
or sput um product ion, or a hist ory of risk fact ors for t he disease. The diagnosis of COPD is confirmed and st aged by spiromet ry. Spiromet ry should be performed aft er t he
administ rat ion of an adequat e dose of an inhaled bronchodilat or (for example, salbut amol 400 g) t o minimize variabilit y. Alt hough measurement s of post bronchodilat or
FEV
1
/FVC rat io and FEV
1
are recommended for t he diagnosis and assessment of severit y of COPD, respect ively, det ermining t he degree of reversibilit y of airflow limit at ion
(change in FEV
1
aft er administ rat ion of bronchodilat ors or cort icost eroids) is no longer recommended for diagnosis, for dist inguishing COPD from ast hma, or for predict ing
t he response t o long-t erm t reat ment wit h bronchodilat ors or cort icost eroids. A post bronchodilat or FEV
1
less t han 80% of predict ed and FEV
1
/FVC rat io less t han 0.70
confirm t he presence of airflow limit at ion t hat is not fully reversible, est ablishes t he diagnosis of COPD, and excludes t he diagnosis of ast hma. Finally, t his pat ient has a low
DLCO, which is not compat ible wit h ast hma. DLCO measures t he abilit y of t he lungs t o t ransfer gas from alveoli t o t he red blood cells in pulmonary capillaries. It is low in
condit ions charact erized by barriers t o diffusion (int erst it ial edema, int erst it ial infilt rat es, t issue fibrosis) or loss of lung t issue (for example, emphysema).
Heart failure is usually associat ed wit h increased cent ral venous pressure, an S
3
on cardiac examinat ion, and crackles on lung auscult at ion. Pat ient s wit h heart failure t ypically
have normal pulmonary funct ion t est ing, except for t he possibilit y of decreased DLCO due t o int erst it ial edema. In int erst it ial lung disease, t he pat ient may have dry crackles
on examinat ion. Addit ionally, pulmonary funct ion t est ing t ypically shows a proport ionat e decrease in FEV1 and FVC result ing in a normal FEV1/FVC rat io, a decreased TLC,
and decreased DLCO.
Key Poi nt
A post bronchodilat or FEV
1
less t han 80% of predict ed and FEV
1
/FVC rat io less t han 0.70 confirm t he presence of airflow limit at ion t hat is not fully reversible and est ablishes
t he diagnosis of chronic obst ruct ive pulmonary disease.
Bi bl i ography
Sweit zer BJ, Smet ana GW. Ident ificat ion and evaluat ion of t he pat ient wit h lung disease. Med Clin Nort h Am. 2009;93(5):1017-30. [PMID: 19665617]
Item 2 Answer: D
Educati onal Objecti ve: Diagnose interstitial lung disease.
The most likely diagnosis is rheumat oid art hrit is-int erst it ial lung disease. The diagnosis of rheumat oid art hrit is is suggest ed by t he symmet rical synovit is of t he wrist s and
met acarpophalangeal joint s. The chest x-ray is oft en normal in pat ient s wit h rheumat oid art hrit is-int erst it ial lung disease, part icularly in t he early course of t he disease.
However, t he pulmonary funct ion t est s show proport ionat e reduct ion in FEV
1
and FVC result ing in a normal FEV
1
/FVC rat io. This finding is consist ent wit h a rest rict ive
pat t ern, which is support ed by t he finding of reduced TLC. Addit ionally, t he decreased DLCO is compat ible wit h int erst it ial lung disease. DLCO measures t he abilit y of t he
lungs t o t ransfer gas from alveoli t o t he red blood cells in pulmonary capillaries. It is low in condit ions charact erized by loss of lung t issue or barriers t o gas diffusion (for
example, int erst it ial edema, int erst it ial infilt rat es, t issue fibrosis) or loss of lung t issue (emphysema).
Chronic obst ruct ive lung disease and ast hma would have shown an obst ruct ive pat t ern, wit h reduced FEV
1
/FVC rat io; t he TLC may be normal or increased. In COPD, t he
DLCO is oft en low but it is normal in pat ient s wit h ast hma. A pulmonary embolism would not affect t he spiromet ry or lung volumes, but may show a decrease in DLCO.
Key Poi nt
Int erst it ial lung disease is charact erized by pulmonary funct ion t est s showing proport ionat e reduct ion in FEV
1
and FVC, result ing in a normal FEV
1
/FVC rat io, reduced TLC
and decreased DLCO.
Bi bl i ography
Dempsey OJ, Kerr KM, Remmen H, Denison AR. How t o invest igat e a pat ient wit h suspect ed int erst it ial lung disease. BMJ. 2010;340:c2843. [PMID: 20534676]
Item 3 Answer: D
Educati onal Objecti ve: Diagnose asthma with a methacholine challenge test.
The most appropriat e next diagnost ic t est is a met hacholine challenge. This pat ient 's hist ory is consist ent wit h, but not t ypical of, ast hma. This present at ion is somet imes
referred t o as cough-variant ast hma. Ast hma is oft en an episodic disease, wit h normal examinat ion findings and spiromet ry bet ween episodes. In such cases, a bronchial
challenge t est , such as wit h met hacholine, can induce bronchoconst rict ion even when t he pat ient is asympt omat ic and spiromet ry is normal. Met hacholine challenge t est ing
is done by giving t he pat ient increasing concent rat ions of met hacholine by nebulizat ion and performing spiromet ry aft er each dose unt il t here is a great er t han 20% decrease
in FEV
1
from baseline. The met hacholine dose t hat leads t o a 20% decrease in t he FEV
1
is known as t he provocat ive concent rat ion 20 (PC
20
) and is calculat ed from a dose-
response curve. In general, a PC
20
of less t han 4 mg/mL is consist ent wit h ast hma. A PC
20
bet ween 4 and 16 mg/mL suggest s some bronchial hyperreact ivit y and is less
specific for ast hma. A PC
20
above 16 mg/mL is considered normal. The sensit ivit y of a posit ive met hacholine challenge t est in ast hma is in t he range of 85% t o 95%. False-
posit ive result s can occur in pat ient s wit h allergic rhinit is, chronic obst ruct ive pulmonary disease, heart failure, cyst ic fibrosis, or bronchit is.
Bronchoscopy t o evaluat e t he t rachea could be helpful if an anat omic lesion is suspect ed. However, t he sympt oms in pat ient s wit h such lesions are persist ent or progressive
rat her t han int ermit t ent . Since t his pat ient has int ermit t ent sympt oms, bronchoscopy is not indicat ed. Exercise echocardiography could help det ermine t he presence of
cardiac ischemia or myocardial dysfunct ion, t he t ypical sympt oms of which are dyspnea on exert ion, chest t ight ness, or pain. Cough and wheezing can occur in coronary
art ery disease, part icularly when associat ed wit h acut e decompensat ion of t he left vent ricle, but t his pat ient 's int ermit t ent episodes of cough and wheezing are provoked by an
upper respirat ory t ract infect ion, making t he diagnosis of coronary art ery disease unlikely. Pat ient s wit h rhinosinusit is have sympt oms consist ing of nasal congest ion,
purulent nasal secret ions, sinus t enderness, and facial pain. Radiography, including sinus CT scan, is not indicat ed in t he init ial evaluat ion of acut e sinusit is.
Key Poi nt
Met hacholine challenge t est ing is most useful in evaluat ing pat ient s wit h suspect ed ast hma who have episodic sympt oms and normal baseline spiromet ry.
Bi bl i ography
Panet t ieri RA Jr. In t he clinic. Ast hma. Ann Int ern Med. 2007;146(11):ITC6-1-ITC6-16. [PMID: 17548407]
Item 4 Answer: C
Educati onal Objecti ve: Diagnose respiratory failure caused by neuromuscular weakness.
This pat ient most likely has severe muscle weakness due t o a subacut e or chronic neuromuscular disorder such as amyot rophic lat eral sclerosis or myast henia gravis. Eit her
condit ion can present wit h respirat ory failure. An increased residual volume/t ot al lung capacit y (RV/TLC) rat io is commonly seen in obst ruct ive disorders, but it may also be
caused by a neuromuscular rest rict ive disorder. In such cases, t he normal FEV
1
/FVC rat io and t he low maximum respirat ory pressures indicat e neuromuscular weakness rat her
t han an obst ruct ive lung disease.
Int erst it ial lung diseases, such as idiopat hic pulmonary fibrosis (IPF), cause rest rict ion but would not explain t he increased RV/TLC rat io, normal DLCO, and reduced
maximum respirat ory pressures. When respirat ory failure develops wit h IPF, it is usually charact erized by hypoxemia. Hypercapnic respirat ory failure is rare in IPF.
Similarly, pulmonary hypert ension present s wit h hypoxia and hypocapnia; hypercapnia would be unusual. In some pat ient s, pulmonary art erial hypert ension may be
associat ed wit h a mild decrease FEV
1
or FVC but t he RV/TLC and maximal inspirat ory pressure are normal. Finally, t he DLCO is usually decreased in pulmonary art erial
hypert ension, and t his is not compat ible wit h t his pat ient 's findings.
Key Poi nt
In pat ient s wit h neuromuscular respirat ory failure, an increased residual volume/t ot al lung capacit y rat io, normal FEV
1
/FVC rat io, low maximum respirat ory pressures, and
normal DLCO are t ypical.
Bi bl i ography
Vazquez-Sandoval A, Huang EJ, Jones SF. Hypovent ilat ion in neuromuscular disease. Semin Respir Crit Care Med. 2009;30(3):348-358. [PMID: 19452395]
Item 5 Answer: D
Educati onal Objecti ve: Diagnose hepatopulmonary syndrome.
This pat ient most likely has hepat opulmonary syndrome, which manifest s as dyspnea at rest or on exert ion, plat ypnea, and hypoxemia in t he set t ing of chronic liver disease.
In t he cont ext of chronic liver disease, clubbing, cyanosis, and hypoxemia are charact erist ic of hepat opulmonary syndrome. The hypoxemia result s from pulmonary vascular
dilat at ion wit h int rapulmonary shunt and vent ilat ion-perfusion mismat ch, which may worsen when t he individual is in an upright posit ion. These can cause ort hodeoxia (fall
in part ial pressure of oxygen wit h upright post ure) and plat ypnea (dyspnea worse when sit t ing upright ). The chest x-ray in pat ient s wit h hepat opulmonary syndrome is
t ypically normal; occasionally, subt le bibasilar infilt rat es may be seen.
Bronchogenic carcinoma may be associat ed wit h clubbing, but t he pat ient has no cough, hemopt ysis, or focal pulmonary findings on physical examinat ion t o suggest t his
diagnosis, and t he chest x-ray is normal.
Emphysema can cause dyspnea, hypoxemia, and diminished breat h sounds. However, no feat ures, such as cough, or physical examinat ion findings, such as hyperresonance t o
percussion, wheezes, or prolonged expirat ion, are present . Finally, emphysema would not explain t he plat ypnea.
Const rict ive pericardit is may present wit h t wo t ypes of sympt om complexes: fluid overload causing ascit es, jugular venous dist ent ion, hepat ic congest ion, and lower
ext remit y edema; and diminished cardiac out put causing fat igue and dyspnea on exert ion. The pat ient has no suggest ive findings of const rict ive pericardit is such as elevat ed
jugular venous pressure, pulsus paradoxus, or pericardial knock.
Key Poi nt
The main feat ures of hepat opulmonary syndrome include signs of port al hypert ension, dyspnea, plat ypnea, hypoxemia wit h ort hodeoxia, cyanosis, and clubbing.
Bi bl i ography
Rodriguez-Roisin R, Krowka MJ. Hepat opulmonary syndromea liver-induced lung vascular disorder. N Engl J Med. 2008;358(22):2378-87. [PMID: 18509123]
Item 6 Answer: A
Educati onal Objecti ve: Diagnose severe aortic stenosis.
Heart failure due t o aort ic st enosis is t he most likely cause of t his pat ient 's dyspnea on exert ion and ort hopnea. Classic manifest at ions of severe aort ic st enosis are angina,
syncope, and heart failure. In early st ages, aort ic st enosis may present subt ly, wit h dyspnea or a decrease in exercise t olerance. About one half of pat ient s wit h aort ic st enosis
are diagnosed when heart failure develops. This pat ient has charact erist ic findings of severe aort ic st enosis, including narrow pulse pressure; delayed, diminished carot id
upst roke; sust ained apical impulse; lat e-peaking syst olic eject ion murmur radiat ing t o t he carot ids; and S
4
.
Adult s wit h unrepaired at rial sept al defect s may be asympt omat ic or may present wit h sympt oms relat ed t o excess pulmonary blood flow, including fat igue, dyspnea,
palpit at ions, or right -sided heart failure. At rial arrhyt hmias, including at rial fibrillat ion or flut t er and sick sinus syndrome, are common. The charact erist ic physical
examinat ion findings in at rial sept al defect are fixed split t ing of t he S
2
and a right vent ricular heave. A pulmonary midsyst olic flow murmur and a t ricuspid diast olic flow
rumble caused by increased flow t hrough t he right -sided valves from a large left -t o-right shunt may be heard. The pat ient is quit e old t o be diagnosed wit h congenit al heart
disease and she has no findings t o support t his diagnosis.
The sympt oms of pulmonary art erial hypert ension t end t o be nonspecific, including progressively worsening dyspnea and dizziness, alt hough t hese sympt oms usually occur in
t he absence of (or out of proport ion t o) pulmonary disease or left -sided heart disease. Physical examinat ion may disclose signs of elevat ed pulmonary art ery pressure and
right vent ricular st rain (loud P
2
, fixed split S
2
, t ricuspid regurgit at ion, elevat ed jugular venous dist ent ion), which are not present in t his pat ient .
Valvular pulmonary st enosis is usually an isolat ed congenit al abnormalit y and causes obst ruct ion t o t he right vent ricular out flow. Severe valvular obst ruct ion may be t olerat ed
for many years before development of sympt oms. In severe pulmonary st enosis, t he jugular venous pressure demonst rat es a prominent a wave. A right vent ricular lift is
common. An eject ion click is common, and a syst olic murmur is present , wit h t he pulmonic component of t he S
2
delayed.
Key Poi nt
Classic manifest at ions of severe aort ic st enosis are angina, syncope, and heart failure.
Bi bl i ography
Cheit lin MD. Pat hophysiology of valvular aort ic st enosis in t he elderly. Am J Geriat r Cardiol. 2003;12(3):173-7. [PMID: 12732812]
Item 7 Answer: B
Educati onal Objecti ve: Diagnose hydropneumothorax on a chest radiograph.
This pat ient has a hydropneumot horax. Spont aneous pneumot horax is a relat ively common event in healt hy young persons. The radiographic abnormalit y is charact erized
by t he loss of normal lung markings in t he periphery of t he hemit horax and t he presence of a well-defined, visceral pleural line at some point bet ween t he chest wall and t he
hilum. Spont aneous pneumot horax occurs when a subpleural bleb rupt ures int o t he pleural space, an event t hat commonly occurs during exert ion. The presence of air wit hin
t he pleural space allows t he lung t o collapse t oward t he hilum. Frequent ly, a small amount of bleeding accompanies rupt ure of t he bleb and produces t he charact erist ic
appearance of a flat -line junct ion bet ween t he air and t he fluid t hat collect s at t he base of t he hemit horax; t his is known as a hydropneumot horax. Large pneumot horaces
require insert ion of a chest t ube t o drain t he pleural space and reexpand t he lung. An init ial chest radiograph showing shift of t he mediast inum away from t he side of t he
pneumot horax indicat es t he development of a t ension pneumot horax and requires immediat e chest t ube insert ion.
Typical radiographic findings of heart failure include cardiomegaly, pulmonary vascular congest ion, Kerley B-lines, and pleural effusions; pulmonary edema may be recognized
as perihilar int erst it ial infilt rat es. Pneumonia may have various radiographic present at ions, including lobar consolidat ion, int erst it ial infilt rat es, and cavit at ion. Radiographic
abnormalit ies are commonly associat ed wit h pulmonary embolism but are not specific. Findings such as at elect asis, infilt rat es, and pleural effusions are found as frequent ly in
pat ient s wit h pulmonary embolism as in pat ient s wit hout pulmonary embolism. Slight ly over 10% of pat ient s wit h pulmonary embolism will have a normal chest radiograph.
Key Poi nt
The radiographic abnormalit y t hat defines pneumot horax is t he loss of normal lung markings in t he periphery of t he hemit horax and t he presence of a well-defined, visceral
pleural line at some point bet ween t he chest wall and t he hilum.
Bi bl i ography
Currie GP, Alluri R, Christ ie GL, Legge JS. Pneumot horax: an updat e. Post grad Med J. 2007;83:461-465. Errat um in: Post grad Med J. 2007;83:722. [PMID: 17621614]
Item 8 Answer: D
Educati onal Objecti ve: Diagnose vocal cord dysfunction with laryngoscopy.
The most appropriat e management for t his pat ient is laryngoscopy. She likely has vocal cord dysfunct ion (VCD). Pat ient s wit h VCD can have t hroat or neck discomfort ,
wheezing, st ridor, and anxiet y. The disorder can be difficult t o different iat e from ast hma; however, affect ed pat ient s do not respond t o t he usual ast hma t herapy. Diagnosing
VCD is made more difficult by t he fact t hat many of t hese pat ient s also have ast hma. The chest radiograph in t his pat ient showed decreased lung volumes, which is in
cont rast t o hyperinflat ion t hat would be expect ed in acut e ast hma. Oxygen sat urat ion is t ypically normal in pat ient s wit h VCD.
Laryngoscopy, especially when done while t he pat ient is sympt omat ic, can reveal charact erist ic adduct ion of t he vocal cords during inspirat ion. Anot her t est t hat helps make
t he diagnosis is flow volume loops, in which t he inspirat ory and expirat ory flow rat es are recorded while a pat ient is asked t o t ake a deep breat h and t hen t o exhale. In
pat ient s wit h VCD, t he inspirat ory limb of t he flow volume loop is "flat t ened" owing t o narrowing of t he ext rat horacic airway (at t he level of t he vocal cords) during
inspirat ion. Recognit ion of VCD is essent ial t o prevent lengt hy courses of cort icost eroids and t o init iat e t herapies t arget ed at VCD, which include speech t herapy, relaxat ion
t echniques, and t reat ing underlying causes such as anxiet y.
The chest CT scan can be used t o exclude parenchymal lung disease or evaluat e t he possibilit y of a pulmonary embolism; however, t hese disorders are unlikely in t his pat ient
wit h previous normal pulmonary examinat ions and radiographs and excellent oxygenat ion.
Int ravenous aminophylline is not recommended for t reat ing eit her acut e ast hma or VCD.
Azit hromycin is a reasonable choice for acut e bronchit is in pat ient s wit h underlying lung disease, but t here is lit t le evidence t hat t his pat ient has acut e bronchit is, which would
manifest wit h cough, sput um product ion, and fever.
Key Poi nt
Laryngoscopy during an exacerbat ion of vocal cord dysfunct ion shows adduct ion of t he vocal cords during inspirat ion.
Bi bl i ography
King CS, Moores LK. Clinical ast hma syndromes and import ant ast hma mimics. Respir Care. 2008;53(5):568-580. [PMID: 18426611]
Item 9 Answer: D
Educati onal Objecti ve: Diagnose pulmonary arterial hypertension associated with systemic sclerosis.
This pat ient most likely has pulmonary art erial hypert ension (PAH) associat ed wit h collagen vascular disease relat ed t o syst emic sclerosis. Pulmonary disease is t he primary
cause of morbidit y in pat ient s wit h syst emic sclerosis; PAH is among t he most common manifest at ions of lung involvement in t hese pat ient s, part icularly in t hose wit h
limit ed cut aneous disease. This pat ient 's worsening fat igue and dyspnea on exert ion in t he presence of clear lung fields are consist ent wit h PAH.
Physical signs of elevat ed pulmonary art ery pressure include a loud P
2
, fixed split S
2
, pulmonic flow murmur, and t ricuspid regurgit at ion. Chest radiographs are usually normal
in early disease but may show enlargement of t he pulmonary art eries, t he right at rium, and t he right vent ricle. Elect rocardiograms in t hese pat ient s may show right
vent ricular st rain or hypert rophy.
Pulmonary funct ion st udies in pat ient s wit h PAH usually reveal an isolat ed decreased DLCO in t he set t ing of normal airflow and lung volumes (excluding rest rict ive lung
disease). Echocardiography is an early diagnost ic t est for pat ient s wit h signs and sympt oms of PAH. This st udy is used t o exclude congenit al heart disease, such as at rial sept al
defect , and valvular heart disease, such as mit ral st enosis, t hat may manifest as pulmonary hypert ension. Echocardiography may be used t o est imat e peak right vent ricular
syst olic pressure if t ricuspid regurgit at ion is not ed on examinat ion.
A clinical diagnosis of chronic obst ruct ive pulmonary disease (COPD) should be considered in any pat ient who has dyspnea, chronic cough or sput um product ion, and/or a
hist ory of risk fact ors for t he disease. The diagnosis of COPD is confirmed and st aged by spiromet ry. This pat ient has no risk fact ors, sympt oms, or physical examinat ion
findings (barrel chest , decreased breat h sounds, wheezing) t o support t he diagnosis of COPD. Pat ient s wit h COPD have FEV
1
/FVC <70%.
Int erst it ial lung disease (ILD) is a common pulmonary manifest at ion in pat ient s wit h syst emic sclerosis who also have dyspnea and fat igue, and pat ient s wit h ILD also usually
have dry cough. The absence of lat e inspirat ory crackles on pulmonary examinat ion and t he presence of normal lung volumes on pulmonary funct ion t est ing furt her argue
against t his condit ion. In pat ient s wit h ILD, t he lung volumes are less t han 80% of predict ed.
Left vent ricular failure may manifest as dyspnea and fat igue and may be associat ed wit h cardiac murmurs. However, t his condit ion is unlikely in t he absence of addit ional
abnormal cardiopulmonary examinat ion findings, such as an S
3
or S
4
gallop and pulmonary crackles. In addit ion, chest radiographs in pat ient s wit h left vent ricular heart
failure usually demonst rat e pulmonary vascular congest ion.
Key Poi nt
Physical signs of elevat ed pulmonary art ery pressure include a loud P
2
, fixed split S
2
, pulmonic flow murmur, and t ricuspid regurgit at ion.
Bi bl i ography
Highland KB, Garin MC, Brown KK. The spect rum of scleroderma lung disease. Semin Respir Crit Care Med. 2007;28(4):418-429. [PMID: 17764059]
Item 10 Answer: B
Educati onal Objecti ve: Treat a complicated pleural effusion with chest tube drainage.
The next st ep in t he management of t his pat ient is chest t ube drainage of t he pleural effusion. In pleural effusions associat ed wit h pneumonia, t he presence of loculat ed
pleural fluid, pleural fluid wit h a pH less t han 7.20, pleural fluid wit h a glucose level less t han 60 mg/dL (3.3 mmol/L), lact at e dehydrogenase level great er t han 1000 U/L,
posit ive pleural fluid Gram st ain or cult ure, or t he presence of gross pus in t he pleural space predict s a poor response t o ant ibiot ics alone; such effusions are t reat ed wit h
drainage of t he fluid t hrough a cat het er or chest t ube.
This pat ient 's hist ory is compat ible wit h communit y-acquired pneumonia (cough, sput um, fever, chills), and t he radiographic findings are consist ent wit h a free-flowing
pleural effusion. Because t his pat ient 's pleural fluid findings predict a poor response t o ant ibiot ics alone, his effusion is called a complicated parapneumonic effusion. A CT
scan may be helpful t o det ect very small effusions, t o det ermine t hickness of t he pleural lining, t o dist inguish empyema (pus in t he pleural space) from a lung abscess, or t o
det ect an underlying malignancy obscured by t he pleural fluid; however, none of t hese indicat ions apply t o t his pat ient and a CT scan is not needed.
Most pleural effusions resolve wit h t reat ment of t he underlying disease. The only effusions t hat usually require invasive t reat ment are complicat ed parapneumonic effusions
(such as t his one), empyema, and malignancy. In pat ient s wit h pneumonia, t horacic empyema develops when ant ibiot ics are not given (or delayed) and t he pleural space is
not drained in a t imely manner. In t his case, video-assist ed t horascopic surgery (VATS) is indicat ed t o break down loculat ions and drain pus from t he pleural cavit y.
Therefore, not int ervening wit h chest t ube placement is inappropriat e for t his pat ient , and VATS surgery is overly aggressive t herapy at t his point in t ime.
Key Poi nt
In parapneumonic effusion, t he presence of loculat ed pleural fluid, pleural fluid wit h a pH less t han 7.20, pleural fluid wit h a glucose level less t han 60 mg/dL (3.3 mmol/L),
lact at e dehydrogenase great er t han 1000 U//L, posit ive pleural fluid Gram st ain or cult ure, or t he presence of gross pus in t he pleural space predict s t he need for chest t ube
drainage.
Bi bl i ography
Sahn SA. Diagnosis and management of parapneumonic effusions and empyema. Clin Infect Dis. 2007;45(11):1480-6. [PMID: 17990232]
Item 11 Answer: C
Educati onal Objecti ve: Diagnose pleural effusion.
The most likely diagnosis is parapneumonic pleural effusion. Large fluid accumulat ion in t he pleural space blocks t ransmission of sound bet ween t he lung and t he chest wall;
percussion over an effusion is dull, and t act ile (vocal) fremit us is diminished or absent . On auscult at ion, t he most common findings are decreased t o absent breat h sounds over
t he effusion. Fever and pleural effusion suggest s an underlying infect ion, malignancy, or associat ed collagen vascular disease. The pat ient 's hist ory of recent onset of fever and
cough makes a pneumonia-relat ed parapneumonic effusion most likely.
Heart failure can be associat ed wit h a pleural effusion, but ot her sympt oms and signs of heart failure such as ort hopnea, elevat ed cent ral venous pressure, S
3
, and peripheral
edema are likely t o be present . Furt hermore, heart failure in a 24-year-old person who was previously well is very unusual.
Pat ient s wit h lobar pneumonia t ypically have t achypnea, fever, crackles, bronchial breat h sounds, and dullness t o percussion wit h reduced breat h sounds. Because consolidat ed
lung t issue is an excellent t ransmit t er of sound and vibrat ion, t act ile fremit us is increased, not decreased as in pleural effusion
Pneumot horax should be considered in any pat ient wit h sudden onset of pleurit ic chest pain and dyspnea. The physical examinat ion may show decreased breat h sounds and
hyperresonance t o percussion on t he affect ed side rat her t han dullness t o percussion.
Key Poi nt
Large pleural effusion is associat ed wit h dullness t o percussion and absent or decreased t act ile (vocal) fremit us and breat h sounds over t he affect ed area.
Bi bl i ography
Wong CL, Holroyd-Leduc J, St raus SE. Does t his pat ient have a pleural effusion? JAMA. 2009;301(3):309-17. [PMID: 19155458]
Item 12 Answer: D
Educati onal Objecti ve: Evaluate a tuberculous pleural effusion with a pleural biopsy.
The most appropriat e next st ep is a pleural biopsy. He likely has a t uberculous pleural effusion based on t he subacut e (3-week) durat ion of sympt oms and t he charact erist ics
of t he pleural effusion. Because of t he pat ient 's age and t he present at ion wit h an isolat ed pleural effusion, primary t uberculosis is most likely. A t uberculous effusion is
t ypically exudat ive by bot h prot ein (pleural fluid t o serum prot ein rat io great er t han 0.5) and lact at e dehydrogenase (LDH) crit eria (pleural fluid t o serum LDH rat io great er
t han 0.6 and pleural fluid t o serum upper limit s of normal LDH rat io great er t han 0.6). The cellular response in t he pleural fluid is classically lymphocyt ic (great er t han 80%
mat ure lymphocyt es). However, it can be neut rophilic wit hin t he first 2 weeks, aft er which it t ypically evolves int o t he classic lymphocyt e-predominant exudat e. Whereas
pleural fluid cult ures for Mycobacterium are posit ive in less t han one t hird of cases, t he combinat ion of pleural biopsy for hist ologic evaluat ion and cult ure is t ypically
posit ive in more t han t wo t hirds of cases.
The 3-week hist ory of sympt oms is t oo long for a t ypical bact erial pneumonia, no definit e infilt rat e was present on t he chest radiograph, and t he cellular response in t he
pleural fluid was primarily lymphocyt ic rat her t han neut rophilic. Therefore, a bact erial pneumonia wit h a parapneumonic effusion is unlikely, and an empiric course of
azit hromycin would not be appropriat e.
Chest CT scan might be helpful t o assess whet her t here is an underlying parenchymal infilt rat e t hat was not visible on plain chest radiograph, but it would not help in
det ermining t he underlying cause of t he pleural effusion.
Flexible bronchoscopy, wit h collect ion of samples for hist ology and cult ure, is useful for diagnosing pulmonary t uberculosis in t he set t ing of pulmonary parenchymal disease.
However, t he yield from cult ure of bronchopulmonary secret ions (obt ained eit her as sput um or bronchoscopic samples) is low, especially in t he absence of pulmonary
parenchymal abnormalit ies on chest radiograph.
Key Poi nt
A pat ient wit h t uberculous pleural effusion t ypically present s wit h a lymphocyt e-predominant exudat ive effusion.
Bi bl i ography
Escalant e P. In t he clinic. Tuberculosis [errat um in Ann Int ern Med. 2009;151(4):292.]. Ann Int ern Med. 2009;150(11):ITC61-614; quiz ITV616. [PMID: 19487708]
Item 13 Answer: A
Educati onal Objecti ve: Diagnose chylothorax.
The most likely diagnosis is chylot horax. Chylot horax is drainage of lymphat ic fluid int o t he pleural space secondary t o disrupt ion or blockage of t he t horacic duct or one of
it s lymphat ic t ribut aries. Malignancy is t he most common cause of chylot horax, but t rauma is t he second most common cause. Chylot horax can also occur in associat ion
wit h pulmonary t uberculosis and chronic mediast inal infect ions, sarcoidosis, lymphangioleiomyomat osis, and radiat ion fibrosis. The pleural fluid in chylot horax is usually
milky but may also be serous or serosanguineous in malnourished pat ient s wit h lit t le fat int ake. The pleural fluid t riglyceride concent rat ion in a chylot horax is t ypically
great er t han 110 mg/dL (1.24 mmol/L) and occurs in associat ion wit h a low pleural fluid cholest erol concent rat ion. If t he pleural fluid t riglyceride level is less t han 50 mg/dL
(0.6 mmol/L), chylot horax is unlikely.
Heart failure is associat ed wit h a t ransudat ive pleural effusion. The pleural fluid prot ein t o serum prot ein rat io is >0.5 and milky appearance of t he effusion excludes heart
failure as a possible diagnosis. Parapneumonic effusion is usually associat ed wit h a neut rophilic pleocyt osis. Tuberculosis is t he most common cause of lymphocyt e-
predominant exudat e worldwide, t ypically as high as 90% t o 95% lymphocyt es. Pat ient s wit h t uberculous pleural effusion usually present wit h a nonproduct ive cough, chest
pain, and fever, and t he effusion is usually pale yellow in color. This pat ient 's present at ion and hist ory of lymphoma do not support t uberculosis as t he cause of t he effusion.
Key Poi nt
The most common causes of chylot horax are cancer and t rauma; ot her causes are pulmonary t uberculosis, chronic mediast inal infect ions, sarcoidosis,
lymphangioleiomyomat osis, and radiat ion fibrosis.
Bi bl i ography
Agrawal V, Doelken P, Sahn SA. Pleural fluid analysis in chylot horax. Chest . 2008;133(6):1436-1441. [PMID: 18339791]
Item 14 Answer: B
Educati onal Objecti ve: Treat respiratory failure with mechanical ventilation.
The most appropriat e management for t his pat ient is int ubat ion and mechanical vent ilat ion and admission t o t he int ensive care unit . The cause of acut e vent ilat ory failure in
pat ient s wit h exacerbat ions of ast hma is increased airway resist ance and also dynamic hyperinflat ion t hat reduces chest -wall compliance. Bot h cont ribut e t o excessive work of
breat hing. Bronchospasm, airway edema, and secret ions, as well as excessive expirat ory airway collapse, can severely reduce airway diamet er, result ing in markedly prolonged
expirat ion. Increased respirat ory drive and high met abolic demands increase minut e vent ilat ion, and expirat ion bet ween breat hs is incomplet e. Progressive st acking of breat hs
leads t o an equilibrat ion at a higher lung volume wit h higher posit ive end-expirat ory alveolar pressure (aut o-PEEP or int rinsic PEEP), associat ed wit h dynamic air t rapping
and hyperinflat ion. The associat ed flat t ening of t he diaphragm decreases it s funct ion and forces great er reliance on accessory muscles, furt her increasing carbon dioxide
product ion and oxygen consumpt ion as a result of t he inefficiency of t hese muscles compared wit h a properly funct ioning diaphragm. Severe air t rapping can also cause
alveolar rupt ure and marked reduct ions in venous ret urn t o t he right heart , result ing in pneumot horax and hypot ension, respect ively. Typically, pat ient s wit h an ast hma
exacerbat ion init ially present wit h respirat ory alkalosis. Slight ly elevat ed or even normal PaCO
2
levels oft en indicat e impending respirat ory failure rat her t han recovery, and
clinical correlat ion is crit ical for int erpret ing art erial blood gas findings in t his set t ing. Addit ional feat ures t hat suggest respirat ory failure in t his pat ient include pulse
oximet ry less t han 95%, PO
2
less t han 75 mm Hg (10.0 kPa), respirat ion rat e great er t han 30/min, and heart rat e great er t han 120/min.
Key Poi nt
Respirat ory acidosis, hypoxemia, and fat igue are indicat ions for int ubat ion and mechanical vent ilat ion in pat ient s wit h an acut e exacerbat ion of ast hma.
Bi bl i ography
Lazarus SC. Clinical pract ice. Emergency t reat ment of ast hma. N Engl J Med. 2010;363(8):755-64. [PMID: 20818877]
Item 15 Answer: E
Educati onal Objecti ve: Begin step-up therapy for asthma with systemic corticosteroids.
The most appropriat e management for t his pat ient is a short course of oral cort icost eroids. This pat ient wit h previously well-cont rolled ast hma has had "loss of cont rol"
aft er a respirat ory t ract infect ion. A short course of an oral cort icost eroid (for example, prednisone, 0.5 mg/kg daily, for 5 t o 7 days) can resolve t he ast hma sympt oms and
enable t he pat ient t o regain cont rol of her disease. It is unclear whet her doubling (or even quadrupling) t he dose of inhaled cort icost eroids is an effect ive st rat egy in place of
oral cort icost eroids.
Ant ibiot ics are generally not recommended for acut e respirat ory infect ions in ast hma because most of t hese infect ions are viral and t he rout ine use of ant ibiot ics in pat ient s
wit h an ast hma exacerbat ion is not recommended.
Nebulized t herapy at home should be reserved for pat ient s who cannot use a met ered-dose inhaler appropriat ely. Alt hough nebulized bronchodilat or t herapy can be more
effect ive in reversing bronchoconst rict ion t han met ered-dose inhaled bronchodilat ors, nebulized t herapy should not be used as a subst it ut e for oral cort icost eroid t herapy in
pat ient s wit h ast hma exacerbat ions. Adding a leukot riene-modifying agent can be considered in pat ient s who cannot or will not t ake oral cort icost eroids; however, leukot riene
recept or ant agonist s are less pot ent ant i-inflammat ory agent s t han cort icost eroids and are not effect ive in pat ient s wit h significant exacerbat ions. Adding a long-act ing -
agonist would be reasonable in t his pat ient if her sympt oms persist aft er t he oral cort icost eroid t herapy, but t he persist ence and severit y of t he pat ient 's current sympt oms
suggest t hat t here is ongoing airway inflammat ion and t hat a syst emic cort icost eroid is warrant ed.
Key Poi nt
A short course of oral cort icost eroids may help rest ore ast hma cont rol in previously well-cont rolled pat ient s who have developed unst able disease as a result of a respirat ory
t ract infect ion.
Bi bl i ography
Item 16 Answer: A
Educati onal Objecti ve: Manage persistent asthma during pregnancy with inhaled corticosteroids.
The best management for t his pat ient is t o cont inue her current ast hma regimen. Ast hma during pregnancy follows t he rule of t hirds: t he condit ion improves in one t hird of
pat ient s, worsens in one t hird, and remains unchanged in one t hird. Uncont rolled ast hma has a significant ly worse impact on pregnancy out come t han t he pot ent ial risk of
medicat ions during pregnancy. Short -act ing -agonist s are regarded as safe during pregnancy. Budesonide has been st udied in pregnancy and has been shown t o be safe. There
are fewer dat a on ot her inhaled cort icost eroids, such as flut icasone, which is a U.S. Food and Drug Administ rat ion pregnancy risk cat egory C drug (st udies of safet y in
pregnancy are lacking but t he pot ent ial benefit of t he drug may just ify t he pot ent ial risk). The inhaled cort icost eroids are, however, believed from clinical experience t o be
safe during pregnancy; t herefore, it is generally recommended t o keep t he pat ient on t he regimen t hat has been effect ive for cont rol of ast hma.
Theophylline and aminophylline are pregnancy risk cat egory C drugs also, but ext ensive clinical experience suggest s t hat t hey are safe during pregnancy. However, t he
met abolism of t hese agent s may be alt ered in pregnancy, requiring increased drug level monit oring. Also, inhaled cort icost eroids are as effect ive as t heophylline wit h fewer
side effect s in pregnant pat ient s.
The Nat ional Ast hma Educat ion and Prevent ion Program expert panel guidelines in 2007 affirmed t he recommendat ion of adding long-act ing -agonist s t o pat ient s whose
ast hma is not cont rolled wit h an inhaled cort icost eroid but advised against using long-act ing -agonist s as a single cont roller t herapy. There is no need t o add a long-act ing -
agonist t o t his pat ient 's ast hma regimen because her sympt oms are well cont rolled, and subst it ut ing t he long-act ing -agonist for inhaled flut icasone may result in loss of
sympt om cont rol and possible increased risk of ast hma-relat ed deat h. Cromolyn is also considered safe in pregnancy but no safer t han inhaled cort icost eroids and less
effect ive in persist ent ast hma.
Key Poi nt
Clinical experience has shown t hat inhaled cort icost eroids are safe and effect ive in pregnant pat ient s wit h ast hma.
Bi bl i ography
Schat z M, Dombrowski MP. Clinical pract ice. Ast hma in pregnancy. N Engl J Med. 2009;360(18):1862-1869. [PMID: 19403904]
Item 17 Answer: C
Educati onal Objecti ve: Treat inadequately controlled persistent asthma by adding a long-acting -agonist.
The most appropriat e management for t his pat ient is t he addit ion of a long-act ing -agonist . She has persist ent ast hma, which is defined as ast hma sympt oms occurring 2 or
more days per week or 2 or more night s per mont h. Pat ient s wit h persist ent ast hma should be t reat ed wit h daily inhaled cort icost eroid t herapy. When ast hma is not
adequat ely cont rolled on low- or moderat e-dose inhaled cort icost eroid t herapy, adding a long-act ing -agonist (salmet erol or formot erol) has been shown t o be superior t o
doubling t he dose of t he cort icost eroid for improving ast hma cont rol and qualit y of life. The concerns about increased ast hma-relat ed deat hs in pat ient s using a long-act ing -
agonist led t he U.S. Food and Drug Administ rat ion t o include a black box warning in t he package insert for t hese drugs. The Nat ional Ast hma Educat ion and Prevent ion
Program expert panel guidelines in 2007 affirmed t he recommendat ion of adding a long-act ing -agonist in pat ient s whose disease is not cont rolled wit h an inhaled
cort icost eroid but advised against using a long-act ing -agonist as a single cont roller t herapy.
Theophylline and leukot riene-modifying drugs are t hird-line agent s t hat should be considered in pat ient s who remain sympt omat ic despit e t he addit ion of a long-act ing -
agonist t o t he cort icost eroid t herapy. Long-act ing ant icholinergic drugs are beneficial in pat ient s wit h chronic obst ruct ive pulmonary disease; however, t heir role in
management of ast hma is not defined.
Key Poi nt
In pat ient s wit h persist ent ast hma not adequat ely cont rolled wit h daily low- or moderat e-dose inhaled cort icost eroids, adding a long-act ing -agonist improves ast hma cont rol
and qualit y of life.
Bi bl i ography
Item 18 Answer: B
Educati onal Objecti ve: Recognize poor inhaler technique as a possible cause of medication failure in asthma.
The best init ial management approach for t his pat ient is t o have him demonst rat e his inhaler t echnique. Pat ient educat ion is a key component in ast hma care. St udies have
shown t hat pat ient educat ion by t he physician decreases t he number of visit s t o t he emergency depart ment and improves ast hma cont rol. Improper t echnique in t he use of
inhalers is a major reason t hat pat ient s do not respond well t o medicat ions. A clue suggest ing poor inhaler t echnique is t he pat ient 's rapid improvement in FEV
1
aft er t he
supervised use of a bronchodilat or. Alt hough t here used t o be one t ype of inhalat ion device (t he met ered-dose inhaler) wit h one t echnique t hat could be t aught t o t he pat ient ,
t here are now several new and different devices wit h significant differences in t he t echnique needed for t heir use. Physicians should learn t he proper t echnique for use of t hese
inhalers before prescribing t hem t o pat ient s in order t o ensure proper t echnique t o opt imize drug delivery and effect iveness and t o reduce side effect s.
Adding a leukot riene-modifying agent would be appropriat e if t he pat ient is effect ively using t he current medicat ions. Oral prednisone would be appropriat e for an
exacerbat ion of poorly cont rolled severe persist ent ast hma. It would improve ast hma cont rol, but wit hout proper educat ion in t he use of t he inhaler, sympt oms would most
likely ret urn when t he cort icost eroid dosage is t apered. Furt hermore, oral cort icost eroids have increased adverse effect s. Simply having t he pat ient ret urn wit h a sympt om and
t reat ment log would not be expect ed t o ident ify poor inhaler t echnique, alt hough it would be helpful t o assess compliance and sympt om pat t ern.
Key Poi nt
Poor inhaler t echnique is a major reason why pat ient s wit h ast hma do not respond well t o specific ast hma t herapy.
Bi bl i ography
Item 19 Answer: C
Educati onal Objecti ve: Treat an exacerbation of chronic obstructive pulmonary disease (COPD) with antibiotics.
Levofloxacin should be init iat ed at t his t ime. Oral or int ravenous cort icost eroids, short -act ing bronchodilat ors (such as albut erol or iprat ropium), and supplement al oxygen
are t he principle t reat ment s for acut e exacerbat ions of COPD; however, many pat ient s will also benefit from t he addit ion ant ibiot ics. In select populat ions, ant ibiot ics have
improved several clinical out comes, including resolut ion of sympt oms, short er hospit al st ay, and mort alit y. Ant ibiot ics are recommended for pat ient s wit h severe COPD
exacerbat ions and t hose on mechanical vent ilat ion. Pat ient s wit h moderat e t o severe exacerbat ions charact erized by increased dyspnea, increased sput um volume, increased
sput um purulence, or need for hospit alizat ion also benefit from ant ibiot ics.
The opt imal ant ibiot ic regimen for t he t reat ment of exacerbat ions is based on t he most commonly isolat ed bact erial pat hogens, including Haemophilus influenzae,
Streptococcus pneumoniae, and Moraxella catarrhalis. Generally, ant ibiot ic regimens for communit y-acquired infect ion include coverage wit h a t hird-generat ion
cephalosporin in combinat ion wit h a macrolide or monot herapy wit h a fluoroquinolone. Because of t he high incidence of H. influenzae and M. catarrhalis resist ance,
amoxicillin is no longer considered a first -line agent for pat ient s wit h moderat e t o severe COPD exacerbat ions.
The addit ion of inhaled cort icost eroids would not likely add any benefit t o a pat ient already receiving int ravenous (or oral) cort icost eroids. Theophylline is not recommended
for t he t reat ment of acut e exacerbat ions of COPD because it provides no addit ional benefit beyond t hat of inhaled bronchodilat ors and oral or inhaled cort icost eroids but is
associat ed wit h significant side effect s, including nausea, vomit ing, palpit at ions, and arrhyt hmias.
Key Poi nt
Recommended ant ibiot ics for moderat e t o severe exacerbat ions of COPD include a t hird-generat ion cephalosporin combined wit h a macrolide or monot herapy wit h a
fluoroquinolone.
Bi bl i ography
Lit t ner MR. Chronic obst ruct ive pulmonary disease. Ann Int ern Med. 2011;154(7):ITC41. [PMID: 21464346]
Item 20 Answer: A
Educati onal Objecti ve: Treat hypoxic COPD with oxygen.
The use of long-t erm oxygen t herapy in pat ient s wit h chronic respirat ory failure improves survival and has a beneficial effect on hemodynamics, exercise capacit y, and
ment al st at us. Oxygen is usually prescribed for pat ient s who have art erial PO
2
less t han 55 mm Hg (7.3 kPa) or oxygen sat urat ion less t han 88% wit h or wit hout hypercapnia
or who exhibit art erial PO
2
of 56 t o 59 mm Hg (7.4 t o 7.8 kPa) or oxygen sat urat ion less t han 89% wit h one or more of t he following: pulmonary hypert ension, evidence of
cor pulmonale or edema as a result of right heart failure, or hemat ocrit great er t han 56%. The durat ion of t reat ment should be at least 15 hours a day. Oxygen as needed or
oxygen wit h act ivit y has no proven mort alit y benefit .
Inhaled cort icost eroids and a long-act ing -agonist , such as salmet erol, may be indicat ed in t his pat ient and likely would reduce t he frequency of exacerbat ions, reduce
hospit alizat ions, and improve lung funct ion, but t hese medicat ions do not increase survival. Met hylxant hines, such as t heophylline, are usually used only aft er ot her long-
act ing bronchodilat ors have been t ried. They have a narrow t herapeut ic window, and most pat ient s are effect ively t reat ed wit h plasma levels of 5 t o 12 g/mL (27.8 t o 66.6
mol/L). Toxicit y is dose-relat ed, and common side effect s include headache, insomnia, nausea, and heart burn, as well as a pot ent ial for development of arrhyt hmias and
t remor. Met hylxant hines are met abolized by cyt ochrome P450, and drug int eract ions are common. Met hylxant hines decrease dyspnea and improve lung funct ion, but do not
impact survival.
Key Poi nt
Cont inuous oxygen improves mort alit y in pat ient s wit h hypoxic COPD.
Bi bl i ography
Lit t ner MR. Chronic obst ruct ive pulmonary disease. Ann Int ern Med. 2011;154(7):ITC41. [PMID: 21464346]
Item 21 Answer: A
Educati onal Objecti ve: Treat severe chronic obstructive pulmonary disease by adding an inhaled corticosteroid.
This pat ient should be st art ed on an inhaled cort icost eroid. Regular use of inhaled cort icost eroids in pat ient s wit h chronic obst ruct ive pulmonary disease (COPD) is associat ed
wit h a reduct ion in t he rat e of exacerbat ions, and pat ient s who have frequent exacerbat ions benefit most . The Global Init iat ive for Chronic Obst ruct ive Lung Disease
guidelines recommend considerat ion of inhaled cort icost eroids in pat ient s whose lung funct ion is less t han 50% and t hose who have exacerbat ions. When inhaled
cort icost eroids are combined wit h a long-act ing
2
-agonist , t he rat e of decline in qualit y of life and healt h st at us is significant ly reduced; lung funct ion is also improved and
dyspnea is alleviat ed. The effect s of combinat ion t herapy on mort alit y are uncert ain.
Ant icholinergic agent s in COPD are especially useful when combined wit h short -act ing or long-act ing
2
-agonist s. Tiot ropium is effect ive in pat ient s wit h st able COPD for up
t o 24 hours and should not be combined wit h short -act ing ant icholinergic agent s, such as iprat ropium. Mucolyt ic agent s have lit t le effect on lung funct ion. The ant ioxidant
N-acet ylcyst eine, a drug wit h bot h mucolyt ic and ant ioxidant act ion, did not reduce t he number of exacerbat ions of COPD in a large prospect ive 3-year t rial. Oral
cort icost eroids are not recommended for regular use in a long-t erm maint enance program because t heir use is not associat ed wit h superior out comes compared wit h st andard
t herapy and is associat ed wit h increased side effect s.
Key Poi nt
Inhaled cort icost eroids may offer significant benefit in pat ient s wit h severe chronic obst ruct ive pulmonary disease.
Bi bl i ography
Lit t ner MR. In t he clinic. Chronic obst ruct ive pulmonary disease. Ann Int ern Med. 2008;148(5):ITC3-1-ITC3-16. [PMID: 18316750]
Item 22 Answer: D
Educati onal Objecti ve: Manage chronic obstructive pulmonary disease exacerbation with noninvasive positive-pressure ventilation.
The pat ient is having a moderat e t o severe exacerbat ion of chronic obst ruct ive pulmonary disease (COPD) and should be placed on noninvasive posit ive-pressure vent ilat ion
(NPPV). A landmark st udy found t hat NPPV reduced t he need for int ubat ion, t he lengt h of hospit al st ay, and t he mort alit y rat e in such pat ient s. Suit able candidat es for
NPPV include pat ient s wit h moderat e t o severe dyspnea, use of accessory respirat ory muscles, respirat ion rat e great er t han 25/min, and pH less t han 7.35 wit h PCO
2
great er
t han 45 mm Hg (6.0 kPa). Cont raindicat ions t o NPPV include impending respirat ory arrest , cardiovascular inst abilit y, alt ered ment al st at us, high aspirat ion risk, product ion
of copious secret ions, and ext reme obesit y, as well as surgery, t rauma, or deformit y of t he face or upper airway.
Int ubat ion is inappropriat e because t he pat ient is not in respirat ory arrest and is a suit able candidat e for NPPV. However, if t he pat ient 's condit ion det eriorat es or does not
improve aft er 1 t o 2 hours of NPPV, int ubat ion should be considered. Most pat ient s wit h exacerbat ions of COPD are usually easily oxygenat ed on low levels of inspired
oxygen, as was t he pat ient in t his case. Excessive oxygen supplement at ion can worsen carbon dioxide ret ent ion during a COPD exacerbat ion. Therefore, oxygen should be
t it rat ed t o maint ain a sat urat ion of approximat ely 90%; increasing t he nasal oxygen t o 5 L/min is not indicat ed at t his t ime.
Met hylxant hines are generally not recommended for t he t reat ment of acut e exacerbat ions of COPD because t hey are not more effect ive t han inhaled bronchodilat ors and
cort icost eroid t herapy but can cause nausea and vomit ing.
Key Poi nt
Noninvasive posit ive-pressure vent ilat ion should be init iat ed early in t he course of moderat e or severe exacerbat ions of chronic obst ruct ive pulmonary disease.
Bi bl i ography
Lit t ner MR. In t he clinic. Chronic obst ruct ive pulmonary disease. Ann Int ern Med. 2008;148(5):ITC3-1-ITC3-16. [PMID: 18316750]
Item 23 Answer: D
Educati onal Objecti ve: Prescribe pulmonary rehabilitation for a patient with severe chronic obstructive pulmonary disease.
This pat ient , who is on maximum medical t reat ment for chronic obst ruct ive pulmonary disease (COPD) and is st ill sympt omat ic, would benefit from pulmonary
rehabilit at ion. Comprehensive pulmonary rehabilit at ion includes pat ient educat ion, exercise t raining, psychosocial support , and nut rit ional int ervent ion as well as t he
evaluat ion for oxygen supplement at ion. Referral should be considered for any pat ient wit h chronic respirat ory disease who remains sympt omat ic or has decreased funct ional
st at us despit e ot herwise opt imal medical t herapy. Pulmonary rehabilit at ion increases exercise capacit y, reduces dyspnea, improves qualit y of life, and decreases healt h care
ut ilizat ion.
Lung t ransplant at ion should be considered in pat ient s who are hospit alized wit h COPD exacerbat ion complicat ed by hypercapnia (PCO
2
great er t han 50 mm Hg [6.7 kPa])
and pat ient s wit h FEV
1
not exceeding 20% of predict ed and eit her homogeneous disease on high-resolut ion CT scan or DLCO less t han 20% of predict ed who are at high risk
of deat h aft er lung volume reduct ion surgery. Lung t ransplant at ion is, t herefore, not an opt ion for t his pat ient .
The effect of lung volume reduct ion surgery is larger in pat ient s wit h predominant ly upper-lobe disease and limit ed exercise performance aft er rehabilit at ion. The ideal
candidat e should have an FEV
1
bet ween 20% and 35% of predict ed, a DLCO no lower t han 20% of predict ed, hyperinflat ion, and limit ed comorbidit ies.
There is no indicat ion for noct urnal assist ed vent ilat ion in t his pat ient because she does not have dayt ime hypercapnia and worsening oxygen desat urat ion during sleep.
Key Poi nt
Pulmonary rehabilit at ion in pat ient s wit h advanced lung disease can increase exercise capacit y, decrease dyspnea, improve qualit y of life, and decrease healt h care ut ilizat ion.
Bi bl i ography
ZuWallack R, Hedges H. Primary care of t he pat ient wit h chronic obst ruct ive pulmonary disease - part 3: pulmonary rehabilit at ion and comprehensive care for t he pat ient
wit h chronic obst ruct ive pulmonary disease. Am J Med. 2008;121 (suppl 7):S25-S32. [PMID: 18558104]
Item 24 Answer: A
Educati onal Objecti ve: Diagnose
1
-antitrypsin deficiency.
This pat ient may have
1
-ant it rypsin (AAT) deficiency, a clinically underdiagnosed disorder t hat primarily affect s t he lungs but also t he liver and, rarely, t he skin. AAT
prot ect s against prot eolyt ic degradat ion of elast in, a prot ein t hat promot es elast icit y of connect ive t issue. The normal plasma concent rat ion of AAT is 150 t o 350 mg/dL
(1.5 t o 3.5 g/L). Pat ient s wit h plasma levels lower t han 50 t o 80 mg/dL (0.5 t o 0.8 g/L) have severe deficiency. In t he lungs, severe deficiency of AAT predisposes t o early-
onset chronic obst ruct ive pulmonary disease, especially panacinar emphysema, which involves t he lung bases. This pat ient is younger t han 45 years and has bilat eral basilar
emphysema, and, t herefore, AAT deficiency must be ruled out .
The sweat chloride t est is a screening t est for cyst ic fibrosis. Nearly 10% of pat ient s diagnosed wit h cyst ic fibrosis are older t han 18 years. Of t hese pat ient s, gast roint est inal
sympt oms and infert ilit y are t he most common present ing problems. In cyst ic fibrosis lung disease, chest radiography t ypically shows hyperinflat ion and accent uat ed
bronchovascular markings, appearing first in t he upper lobes, followed by bronchiect asis and cyst format ion. This pat ient 's age, present ing sympt oms, and chest radiograph
findings make cyst ic fibrosis unlikely.
A flow-volume loop, which includes forced inspirat ory and expirat ory maneuvers, is indicat ed for pat ient s wit h unexplained dyspnea and can det ect upper airway obst ruct ion
t hat cannot be diagnosed wit h spiromet ry. However, t his pat ient has no physical findings suggest ive of upper airway obst ruct ion (for example, st ridor), and even if such
findings were present , t hey would not explain t he pat ient 's findings on chest radiography.
High-resolut ion CT scan is not helpful in t he diagnosis of AAT deficiency, alt hough it may be useful in evaluat ing t he ext ent of t he disease.
Key Poi nt
Pat ient s wit h severe
1
-ant it ryspin deficiency are predisposed t o early-onset chronic obst ruct ive pulmonary disease, especially panacinar emphysema, which involves t he lung
bases.
Bi bl i ography
American Thoracic Societ y; European Respirat ory Societ y. American Thoracic Societ y/European Respirat ory Societ y St andards for t he diagnosis and management of
individuals wit h alpha 1 ant it ryspin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900. [PMID: 14522813]
Item 25 Answer: D
Educati onal Objecti ve: Evaluate a patient with probable obstructive sleep apnea with polysomnography and arterial blood gases.
Polysomnography and art erial blood gas measurement should be performed next t o evaluat e t his pat ient . Alt hough snoring, morning headaches, and dayt ime sleepiness are
common sympt oms of obst ruct ive sleep apnea (OSA), clinical and physical examinat ion feat ures are neit her sensit ive nor specific enough for t he diagnosis.
Polysomnography is required t o det ermine t he presence and severit y of OSA. However, t his pat ient also has low oxygen sat urat ion while awake as measured by pulse
oximet ry, suggest ing t he presence of obesit y-hypovent ilat ion syndrome. The sympt oms of obesit y-hypovent ilat ion syndrome are t he same as obst ruct ive sleep apnea, and
most pat ient s wit h obesit y-hypovent ilat ion syndrome also have obst ruct ive sleep apnea. The diagnosis is est ablished by document ing alveolar hypovent ilat ion (PCO
2
>45
mm Hg [6.0 kPa]) in t he absence of ot her known causes. Addit ional st udies t o evaluat e ot her causes of alveolar hypovent ilat ion include chest x-ray and pulmonary funct ion
t est ing.
B-t ype nat riuret ic pept ide (BNP) may be helpful for different iat ing heart failure from noncardiac causes of short ness of breat h in t he acut e set t ing. Pat ient s present ing t o t he
emergency depart ment wit h acut e dyspnea wit h a serum BNP concent rat ion less t han 100 pg/mL are unlikely t o have acut e heart failure. However, t his pat ient does not have
acut e dyspnea or any signs of heart failure, and BNP t est ing is not indicat ed. Addit ionally, fact ors ot her t han vent ricular wall st ress t hat influence BNP levels include renal
failure, older age, and female sex, all of which increase BNP, and obesit y, which reduces BNP. Int erpret at ion of BNP result s should t ake t hese fact ors int o account .
The CAC score correlat es wit h cardiovascular risk but is not a direct measure of t he severit y of luminal coronary disease, and CAC scores are not indicat ed for rout ine
screening. CAC measurement may be considered in asympt omat ic pat ient s wit h an int ermediat e risk of coronary art ery disease (10%-20% 10-year risk), because a high CAC
score is an indicat ion for more int ensive prevent ive medical t reat ment . This pat ient may have an increased risk of coronary art ery disease, and a lipid profile and use of t he
Framingham risk calculat or will est imat e t he pat ient 's 10-year risk for a major cardiovascular event . However, an abnormal CAC cannot explain t he pat ient 's sympt oms or
waking hypoxemia and is, t herefore, not t he most appropriat e next diagnost ic t est .
A CT pulmonary angiogram is a reasonable diagnost ic t est if pulmonary embolism is a considerat ion. However, t he pat ient has no sympt oms referable t o possible pulmonary
embolism such as dyspnea and chest pain. Pulmonary embolism should be considered in all pat ient s wit h obst ruct ive sleep apnea and compat ible sympt oms, because it is a
frequent cause of deat h in t his group of pat ient s.
Key Poi nt
The sympt oms of obesit y-hypovent ilat ion syndrome are t he same as obst ruct ive sleep apnea, and most pat ient s wit h obesit y-hypovent ilat ion syndrome also have obst ruct ive
sleep apnea.
Bi bl i ography
Piper AJ, Grunst ein RR. Obesit y hypovent ilat ion syndrome: mechanisms and management . Am J Respir Crit Care Med. 2011;183(3):292-98. [PMID: 21037018]
Item 26 Answer: D
Educati onal Objecti ve: Diagnose obstructive sleep apnea as a secondary cause of hypertension.
The next diagnost ic t est should be polysomnography. Risk fact ors for obst ruct ive sleep apnea (OSA) include excessive body weight , abnormalit ies of craniofacial anat omy,
male sex, underlying medical or neurologic disorders (myxedema, acromegaly, and st roke), alcohol use, cert ain medicat ions (muscle relaxant s, sedat ives, opioids, and
anest het ics), and aging. Pat ient s wit h unt reat ed OSA have a great er likelihood of developing syst emic and pulmonary art erial hypert ension, coronary art ery disease, acut e
myocardial infarct ion during sleep, heart failure, recurrent at rial fibrillat ion, st roke, insulin resist ance, mood disorders, and parasomnias. OSA may also negat ively affect
qualit y of life and academic and occupat ional performance, may increase t he risk of vehicular and work-relat ed accident s, and may increase t he overall mort alit y rat e.
Polysomnography is required t o det ermine t he presence and severit y of OSA. Therapy is recommended for all pat ient s wit h OSA and excessive dayt ime sleepiness, insomnia,
impaired cognit ion, mood disorder, hypert ension, ischemic heart disease, or st roke. Treat ment of OSA modest ly reduces blood pressure in many, but not all, pat ient s wit h
hypert ension.
A 24-hour urine free cort isol measurement is a screening t est for Cushing syndrome. Alt hough pat ient s wit h hypercort isolism may develop obesit y and hypert ension, t his
pat ient has few ot her findings compat ible wit h t his disorder such as muscle weakness, ecchymosis, hypokalemia, unexplained ost eoporosis, and diabet es mellit us. Percut aneous
renal art ery angiography is used t o diagnose renal art ery st enosis. At herosclerot ic renovascular disease is usually associat ed wit h widespread at herosclerosis, peripheral vascular
disease, cardiovascular disease, and ischemic t arget organ damage, which is not evident in t his pat ient . The rat io of plasma aldost erone t o plasma renin act ivit y is t he
preferred screening t est for hyperaldost eronism. Hyperaldost eronism causes hypert ension, hypokalemia, and met abolic alkalosis. Because t hese findings are not present in
t his pat ient , a plasma aldost erone-renin act ivit y rat io is not indicat ed.
Key Poi nt
Pat ient s wit h unt reat ed obst ruct ive sleep apnea have a great er likelihood of developing syst emic hypert ension.
Bi bl i ography
Bagai K. Obst ruct ive sleep apnea, st roke, and cardiovascular diseases. Neurologist . 2010;16(6):329-39. [PMID: 21150380]
Item 27 Answer: C
Educati onal Objecti ve: Diagnose cryptogenic organizing pneumonia.
The most likely diagnosis is crypt ogenic organizing pneumonia (COP). This nonsmoker wit hout any exposure hist ory has acut e t o subacut e development of nonspecific
syst emic and respirat ory sympt oms wit h a dominant alveolar (opacificat ion) process on chest radiograph. The t empo of t he disease process is t he key t o different iat ing COP
from ot her int erst it ial lung diseases. COP is oft en acut e or subacut e, wit h sympt om onset occurring wit hin 2 mont hs of present at ion in t he majorit y of pat ient s. The
present at ion is so suggest ive of an acut e or subacut e lower respirat ory t ract infect ion t hat pat ient s have almost always been t reat ed wit h and failed t o respond t o one or more
courses of ant ibiot ics before diagnosis.
The diagnosis of asbest osis is based on a convincing hist ory of asbest os exposure and definit e evidence of int erst it ial fibrosis. The most specific finding on chest radiograph is
bilat eral part ially calcified pleural plaques. This pat ient lacks an exposure hist ory, an int erst it ial infilt rat e and evidence of pleural disease, making asbest osis an unlikely
diagnosis.
Communit y-acquired pneumonia is an acut e infect ious process t hat progresses over days, not weeks, and would have responded t o levofloxacin.
Idiopat hic pulmonary fibrosis (IPF) t ypically follows a prolonged course wit h evidence of respirat ory sympt oms and radiographic findings t hat progress slowly over mont hs
or years. Radiographic findings in COP are also dist inct from t hose in IPF. A dominant alveolar opacificat ion process is t ypically present in pat ient s wit h COP. The opacit ies
are almost always bilat eral wit h varied dist ribut ion. One of t he key radiographic feat ures of COP is t he t endency for COP opacit ies t o "migrat e" or involve different areas of
t he lung on serial examinat ions. Alt hough t he radiographic findings of IPF are varied, it has a dominant int erst it ial (ret icular) pat t ern wit h or wit hout opacit ies.
Key Poi nt
Crypt ogenic organizing pneumonia most oft en present s wit h subacut e disease progression and bilat eral alveolar-filling opacit ies on chest radiograph.
Bi bl i ography
Ryu JH, Daniels CE, Hart man TE, et al. Diagnosis of int erst it ial lung diseases. Mayo Clin Proc. 2007;82(8):976-986. [PMID: 17673067]
Item 28 Answer: A
Educati onal Objecti ve: Diagnose asbestosis.
The diagnosis of asbest osis is based on a convincing hist ory of asbest os exposure wit h an appropriat ely long lat ent period (10 t o 15 years) and definit e evidence of int erst it ial
fibrosis wit hout ot her likely causes. This pat ient worked as an insulat or when asbest os exposure was st ill widespread and is at risk for asbest os-relat ed lung disease. The most
specific finding on chest radiograph is bilat eral part ially calcified pleural plaques. Pleural plaques are focal, oft en part ially calcified, fibrous t issue collect ions on t he pariet al
pleura and are considered a marker of asbest os exposure.
Idiopat hic pulmonary fibrosis present s wit h slowly progressive dyspnea and a chronic, nonproduct ive cough. The chest radiograph is almost always abnormal at t he t ime of
present at ion, wit h decreased lung volumes and basal ret icular opacit ies. Almost all pat ient s have a physiologic rest rict ive process (decreased FVC, t ot al lung capacit y,
funct ional residual capacit y) as well as impaired gas exchange wit h a decreased DLCO. However, asbest osis is a much more likely diagnosis in a pat ient wit h a posit ive
exposure hist ory and radiographic evidence of pleural plaques.
Sarcoidosis occurs most commonly in young and middle-aged adult s, wit h a peak incidence in t he t hird decade. More t han 90% of pat ient s wit h sarcoidosis have lung
involvement . The chest radiograph may show hilar lymphadenopat hy alone, hilar lymphadenopat hy and ret icular opacit ies predominant ly in t he upper lung zone, or ret icular
opacit ies wit hout hilar lymphadenopat hy. Pulmonary funct ion t est s may reveal a rest rict ive pat t ern and reduct ion in DLCO or may be normal. The pat ient 's age,
predominant ly lower lobe involvement , occupat ional hist ory, and pleural plaques argue against pulmonary sarcoidosis.
Rheumat oid lung disease has many manifest at ions, including an int erst it ial lung disease, which is most common in pat ient s wit h severe rheumat oid art hrit is. This pat ient does
not have evidence of rheumat oid art hrit is.
Key Poi nt
Pleural plaques are focal, oft en part ially calcified, fibrous t issue collect ions on t he pariet al pleura and are a marker of asbest os exposure.
Bi bl i ography
Aberle DR, Balmes JR. Comput ed t omography of asbest os-relat ed pulmonary parenchymal and pleural disease. Clin Chest Med. 1991;12(1):115-131. [PMID: 2009740]
Item 29 Answer: C
Educati onal Objecti ve: Diagnose secondary polycythemia due to sleep apnea.
This obese man most likely has sleep apnea wit h secondary polycyt hemia. Excessive dayt ime sleepiness is t he hallmark of sleep apnea. Ot her clinical manifest at ions t hat
should alert t he clinician t o t he presence of sleep apnea include morning headaches, noct uria, and alt erat ions in mood. Hypoxia is t he main inducer of eryt hropoiet in
product ion by t he proximal nephrons, and an elevat ed eryt hropoiet in level st rongly support s a diagnosis of secondary polycyt hemia. Some pat ient s wit h cardiopulmonary
disease or sleep apnea will not show reduced oxygen sat urat ion at rest or during t he dayt ime. In t hese cases, pulse oximet ry should be obt ained aft er exert ion, and, depending
on t he clinical hist ory, sleep st udies may be indicat ed t o confirm t he diagnosis of sleep apnea and t o det ect noct urnal oxygen desat urat ion. In pat ient s wit h sleep apnea, t he
secondary polycyt hemia will most likely resolve once t he sleep apnea is correct ed.
Congenit al polycyt hemia due t o a high-oxygen-affinit y hemoglobin is suspect ed when polycyt hemia is discovered during childhood or when it is associat ed wit h a posit ive
family hist ory of polycyt hemia. In t hese cases, t he serum eryt hropoiet in level is normal. This pat ient lacks an appropriat e childhood or family hist ory, and his normal
hemat ocrit 5 years ago and elevat ed eryt hropoiet in level argue against a high-oxygen-affinit y hemoglobin.
Polycyt hemia vera is charact erized by a low serum eryt hropoiet in level and an increased eryt hrocyt e mass and may be accompanied by mild elevat ion in leukocyt e and
plat elet count s. Hemat ocrit values great er t han 60% for men and 56% for women in t he absence of secondary causes of eryt hrocyt osis and t he presence of splenomegaly
est ablish t he diagnosis of polycyt hemia vera. A JAK2 mut at ion is det ect ed in 95% of pat ient s wit h polycyt hemia vera, and a polymerase chain react ion assay for t his
mut at ion can aid in est ablishing t he different ial from secondary causes of eryt hrocyt osis. This pat ient 's hist ory, which is st rongly suggest ive of sleep apnea, argues st rongly
against t he diagnosis of polycyt hemia vera.
Relat ive polycyt hemia oft en accompanies plasma volume cont ract ion as a result of excessive sweat ing, diarrhea, vomit ing, capillary leak syndrome, and, occasionally,
diuret ic use. The hemat ocrit or hemoglobin appears increased because of a reduct ion in plasma volume. There is not hing in t he hist ory t o suggest t he presence of relat ive
polycyt hemia, and relat ive polycyt hemia is not associat ed wit h an increase in t he eryt hropoiet in level as seen in t his case.
Key Poi nt
Sleep apnea wit h noct urnal hypoxemia may be associat ed wit h secondary polycyt hemia.
Bi bl i ography
Lengfelder E, Merx K, Hehlmann R. Diagnosis and t herapy of polycyt hemia vera. Semin Thromb Hemost . 2006;32(3):267-275. [PMID: 16673281]
Item 30 Answer: B
Educati onal Objecti ve: Diagnose scleroderma-related diffuse parenchymal lung disease.
The most appropriat e next diagnost ic t est is high resolut ion chest CT. Connect ive t issue diseases, along wit h drugs and environment al causes, are t he most common known
causes of diffuse parenchymal lung disease (DPLD). DPLD is most likely in pat ient s wit h syst emic sclerosis who develop ant it opoisomerase I (ant i-Scl-70) ant ibody
posit ivit y. DPLD associat ed wit h syst emic sclerosis usually manifest s as dyspnea, dry cough, and decreased exercise t olerance. Fine bibasilar crackles t hat ext end int o lat e
inspirat ion are heard on physical examinat ion. On pulmonary funct ion t est ing, t hese pat ient s have a rest rict ive pat t ern wit h a decreased FVC and DLCO (and normal
FEV
1
/FVC rat io). High-resolut ion CT (HRCT) is more sensit ive t han chest x-ray for DPLD and reveals ground-glass and ret icular linear opacit ies, subpleural cyst s, and
honeycombing in pat ient s wit h advanced disease. Toget her, t he clinical findings and HRCT can est ablish t he diagnosis in t his pat ient .
If t he clinical cont ext , t emporal pat t ern of disease, and HRCT findings do not yield a diagnosis, it may be reasonable t o obt ain a bronchoscopic or surgical lung biopsy. The
diagnost ic yield of surgical lung biopsy is approximat ely 90%. However, a limit ed number of hist opat hologic pat t erns are recognized for a large number of DPLDs, and t he
specificit y of lung biopsy depends on t he pat t ern. Bronchoalveolar lavage can provide addit ional diagnost ic informat ion, including cult ure, cyt ology, and cell different ial.
Bronchoalveolar lavage is safe and simple t o perform and may be helpful t o diagnose infect ions and carcinoma, as well as eosinophilic pneumonia. Neit her t est is
recommended before an HRCT.
In pat ient s wit h syst emic sclerosis, pulmonary vascular disease may manifest as isolat ed pulmonary art erial hypert ension (PAH) or as a complicat ion of vascular oblit erat ion
in pat ient s wit h DPLD. Pat ient s wit h PAH may present wit h fat igue, decreased exercise t olerance, dyspnea, or syncope. Physical examinat ion findings include an increased P
2
and a persist ent ly split S
2
. Chest radiographs are usually normal. A decrease in DLCO in t he set t ing of normal lung volumes is consist ent wit h PAH. This pat ient has a
rest rict ive physiology on pulmonary funct ion t est ing and no physical examinat ion findings t o support PAH.
Key Poi nt
Connect ive t issue diseases, along wit h drugs and environment al causes, are t he most common known causes of diffuse parenchymal lung disease
Bi bl i ography
Eickelberg O, Selman M. Updat e in diffuse parenchymal lung disease 2009. Am J Respir Crit Care Med. 2010;181(9):883-8. [PMID: 20430925]
Item 31 Answer: C
Educati onal Objecti ve: Diagnose drug-induced lung toxicity.
The most likely diagnosis is drug-induced lung t oxicit y. A high index of suspicion for drug-induced lung disease is essent ial, because early ident ificat ion and drug wit hdrawal can
prevent morbidit y and mort alit y. Est ablishment of a definit ive diagnosis of drug-induced lung disease requires exclusion of ot her known causes and sympt om improvement
wit h drug wit hdrawal. Most offending drugs cause a hypersensit ivit y-t ype react ion, wit h present ing sympt oms of fat igue, low-grade fever, and cough. Peripheral blood
eosinophilia may be present . Amiodarone is a well-known cause of drug-induced lung t oxicit y, and t his diagnosis is support ed by t he t emporal relat ionship bet ween st art ing
amiodarone for at rial fibrillat ion and onset of sympt oms.
The diagnosis of heart failure is unlikely in t he absence of ort hopnea, jugular venous dist ent ion, or an S
3
. Addit ionally, heart failure cannot account for t he pat ient 's low-grade
fever and eosinophilia.
Acut e eosinophilic pneumonit is is a rapidly progressive illness occurring over days t o 3 weeks associat ed wit h fever, sput um product ion, eosinophilia, and a peripherally
dist ribut ed infilt rat e. The pat ient 's subacut e illness t hat began 2 mont hs ago is not consist ent wit h t his diagnosis nor is t he pat t ern of infilt rat es on her chest x-ray.
The t erm asbest osis refers t o bilat eral int erst it ial fibrosis of t he lung parenchyma caused by inhalat ion of asbest os fibers. An exposure hist ory of appropriat e durat ion, lat ency
(t ypically 20-30 years), and int ensit y and radiographic evidence of int erst it ial fibrosis on chest radiograph or chest CT scan are usually sufficient for diagnosis. Sympt oms
include breat hlessness, bibasilar inspirat ory crackles, and digit al clubbing and pulmonary funct ion t est ing showing a rest rict ive pat t ern. This pat ient has a subacut e process and
no hist ory of asbest os exposure, making asbest osis an unlikely diagnosis.
Key Poi nt
Drug-induced lung t oxicit y t ypically present s as a hypersensit ivit y-t ype react ion, wit h sympt oms of fat igue, low-grade fever, cough, and peripheral eosinophilia.
Bi bl i ography
Dempsey OJ, Kerr KM, Remmen H, Denison AR. How t o invest igat e a pat ient wit h suspect ed int erst it ial lung disease. BMJ. 2010;340:c2843. [PMID: 20534676]
Item 32 Answer: D
Educati onal Objecti ve: Prevent deep venous thrombosis with prophylactic unfractionated heparin.
The most appropriat e venous t hrombosis prophylact ic int ervent ion for t his pat ient is unfract ionat ed heparin. Prevent ing venous t hromboembolism (VTE) was t he highest
ranked int ervent ion for pat ient safet y in a recent Agency for Healt hcare Research and Qualit y report . Appropriat e prophylaxis can reduce t he rat e of VTE by approximat ely
t wo t hirds; however, various st udies have shown subopt imal use of prophylaxis in medical and surgical pat ient s. The American College of Chest Physicians (ACCP) guidelines
recommends t he use of unfract ionat ed heparin, low-molecular-weight heparin (LMWH), and fondaparinux for prevent ion of venous t hromboembolism in hospit alized,
medically ill pat ient s. In pat ient s wit h renal impairment (glomerular filt rat ion rat e <30 mL/min/1.73 m
2
), dosing of LMWH must be adjust ed and fondaparinux is
cont raindicat ed.
ACCP guidelines st at e t hat aspirin should not be used as t he sole prophylaxis in any high-risk group because it is not as effect ive as equally safe alt ernat ives. The evidence for
graduat ed compression st ockings in t he prevent ion of venous t hromboembolism is weak, and compression st ockings are not recommended as primary prophylaxis in
hospit alized pat ient s.
Three direct t hrombin inhibit ors are in clinical use: lepirudin, t he recombinant form of t he leech enzyme hirudin; bivalirudin, an engineered form of hirudin t hat alt ers it s
t hrombin-binding capacit y and half-life; and argat roban, a small molecule t hat binds irreversibly t o t he act ive sit e of t hrombin. Each of t hese is a parent erally administ ered
drug wit h limit ed Food and Drug Administ rat ion-approved indicat ions, and all require t herapeut ic monit oring. Lepirudin should be considered when a pat ient has heparin-
induced t hrombocyt openia, which is not present in t his pat ient . Addit ionally, lepirudin is very expensive. Lepirudin is not indicat ed for rout ine prevent ion of venous
t hromboembolism in t he hospit alized, medically-ill pat ient .
Key Poi nt
Unfract ionat ed heparin, low-molecular-weight heparin (LMWH), and fondaparinux can be used for prevent ion of venous t hromboembolism in hospit alized, medically ill
pat ient s.
Bi bl i ography
Goodacre S. In t he clinic. Deep venous t hrombosis. Ann Int ern Med. 2008;149(5):ITC3-1. [PMID: 18765697]
Item 33 Answer: E
Educati onal Objecti ve: Diagnose acute pulmonary embolism with a ventilation/perfusion scan.
A vent ilat ion/perfusion lung scan should be done next . This pat ient is at high risk for pulmonary embolism (PE) because of his recent hospit alizat ion, cancer, and nephrot ic
syndrome. A posit ive vent ilat ion/perfusion scan would confirm t he diagnosis of PE in t his pat ient wit h a high pret est probabilit y for t he condit ion, especially in t he absence
of parenchymal lung defect s on chest radiograph.
The probabilit y of PE is very high based on t his pat ient 's present at ion t hat included chest pain, dyspnea, recent hospit alizat ion and surgery, act ive cancer, and prot ein-losing
nephropat hy. A negat ive D-dimer t est would not be sufficient evidence t o rule out a PE under t hese circumst ances, and a high D-dimer level would add lit t le t o t he diagnost ic
evaluat ion.
CT angiography is an accept able modalit y t o diagnose acut e PE but requires a significant amount of cont rast infusion, which would be cont raindicat ed in a pat ient wit h an
elevat ed serum creat inine level.
Lower ext remit y ult rasonography can disclose asympt omat ic deep venous t hrombosis in a small percent age of pat ient s present ing wit h sympt oms of PE. However, t he yield
is relat ively low and vent ilat ion/perfusion scanning would have a much higher degree of accuracy.
Decreased ant it hrombin III levels may result from nephrot ic syndrome, and levels are lowered during acut e t hrombosis, especially during t reat ment wit h heparin. Therefore,
measuring ant it hrombin III would add lit t le t o t he accuracy of t he diagnosis of PE or have any implicat ion for immediat e management decisions.
Key Poi nt
Vent ilat ion/perfusion scanning is an appropriat e noninvasive t est t o diagnose acut e pulmonary embolism, especially in t he presence of chronic kidney disease.
Bi bl i ography
Agnelli G, Becat t ini C. Acut e pulmonary embolism. N Engl J Med. 2010;363(3):266-74. [PMID: 20592294]
Item 34 Answer: B
Educati onal Objecti ve: Evaluate low-probability venous thrombosis with a D-dimer test.
The most appropriat e next diagnost ic t est is a D-dimer assay. Several imaging procedures can exclude deep venous t hrombosis (DVT), but t he diagnost ic goal is t o use t he
most efficient , least invasive, and least expensive met hod wit h t he fewest side effect s. A D-dimer assay is a simple, relat ively noninvasive t est t hat has been shown t o have a
high negat ive predict ive value, especially if t he suspicion for DVT is low. The Wells crit eria have been est ablished t o help t he clinician assess t he likelihood of DVT, and
st udies have shown t hat wit h a low clinical suspicion (as in t his pat ient ) and a negat ive D-dimer assay, t he presence of DVT can be reliably excluded wit hout t he need for more
invasive or complex imaging.
In t he Wells crit eria, t he following clinical variables each earn 1 point : act ive cancer; paralysis or recent plast er cast ; recent immobilizat ion or major surgery; t enderness
along t he deep veins; swelling of t he ent ire leg; great er t han a 3-cm difference in calf circumference compared wit h t he ot her leg; pit t ing edema; and collat eral superficial
veins. The clinical suspicion t hat an alt ernat ive diagnosis is likely earns -2 point s. Based on t his syst em, t he pret est probabilit y of DVT is considered high in pat ient s wit h
scores of great er t han or equal t o 3, moderat e in pat ient s wit h scores of 1 t o 2, and low in pat ient s wit h scores less t han or equal t o 0. This pat ient 's Wells score is -2, and t he
likelihood for DVT is t herefore low. This pat ient 's fever, circumscribed area of warmt h, and t enderness localized t o t he post erior calf could represent cellulit is, a reasonable
alt ernat ive t o t he diagnosis of venous t hrombosis.
Venography, t he t radit ional gold st andard for diagnosis of DVT, is rarely performed t oday because of it s invasiveness, discomfort , cost s, and complexit y. Neit her an MRI nor
CT of t he leg has been subst ant ially validat ed as a reliable diagnost ic t est for DVT.
Key Poi nt
Negat ive D-dimer assay result s and a low Wells crit eria probabilit y score reliably exclude a diagnosis of deep venous t hrombosis.
Bi bl i ography
Harget t CW, Tapson VF. Clinical probabilit y and D-dimer t est ing: how should we use t hem in clinical pract ice? Semin Respir Crit Care Med. 2008;29(1):15-24. [PMID:
18302083]
Item 35 Answer: D
Educati onal Objecti ve: Treat a patient with an idiopathic deep venous thrombosis with heparin.
The appropriat e t reat ment for a pat ient wit h deep venous t hrombosis t hat is eit her idiopat hic or associat ed wit h a t ransient risk fact or is an init ial short course of an
immediat e-act ing ant icoagulant such as unfract ionat ed heparin, low-molecular-weight heparin, or fondaparinux for at least 5 days. Warfarin should be st art ed at
approximat ely t he same t ime t hat heparin is administ ered, and t he t wo drugs should be overlapped unt il t he INR reaches a t herapeut ic range (>2) measured on t wo occasions
approximat ely 24 hours apart . This t iming allows for furt her reduct ion of prot hrombin, t he vit amin K-dependent fact or wit h t he longest half-life (approximat ely 60 h),
which is responsible for much of t he ant it hrombot ic effect of warfarin. Usually 5 t o 7 days of t herapy are required t o achieve t his t herapeut ic level. The init ial recommended
daily warfarin dose is 5 mg, but occasionally 7.5 t o 10 mg may be used. Lower doses (2.5 mg) are recommended in t he elderly, especially in t he set t ing of malnourishment ,
liver disease, or recent major surgery.
Key Poi nt
Treat ment of deep venous t hrombosis consist s of an immediat e-act ing ant icoagulant such as unfract ionat ed heparin, low-molecular-weight heparin, or fondaparinux for at
least 5 days.
Bi bl i ography
Gage BF, Fihn SD, Whit e RH. Management and dosing of warfarin t herapy. Am J Med. 2000;109(6):481-488. [PMID: 11042238]
Secti on 11. Rheumatol ogy
Questi ons
Item 1 [Basic]
A 60-year-old woman has not ed recurrent , right elbow pain. The pain occurs mainly wit h t he use of t he arm and hand, not wit h bending t he elbow. She has not ed no pain or
t enderness in ot her joint s.
Examinat ion of t he right arm shows marked t enderness over t he lat eral epicondyle. The elbow range of mot ion is normal, and t here is no redness or swelling. Resist ed wrist
ext ension exacerbat es t he elbow pain.
Whi ch one of the fol l owi ng i s the most l i kel y di agnosi s?
(A) Cubit al t unnel syndrome
(B) Lat eral epicondylit is
(C) Olecranon bursit is
(D) Sept ic art hrit is
Item 2 [Advanced]
A 45-year-old woman is evaluat ed in t he office for a 3-mont h hist ory of pain, st iffness, and swelling of t he small joint s of t he hands and feet . She also has increasing fat igue
t hat has caused her t o miss work at least 1 day per week. She has no ot her medical problems.
On physical examinat ion, t he vit al signs and general physical examinat ion, including skin examinat ion, are normal. A phot ograph of one of her hands is shown (Plat e 29).
Complet e blood count , serum chemist ries, and urinalysis are all normal. Eryt hrocyt e sediment at ion rat e is 44 mm/h.
(A) Ost eoart hrit is
(B) Psoriat ic art hrit is
(C) Rheumat oid art hrit is
Item 3 [Basic]
A 78-year-old obese woman is evaluat ed because right hip pain t hat worsens when she goes up and down st airs. She says t hat she cannot sleep on her right side because of pain
over t he hip and can localize t he pain by point ing t he lat eral aspect of her hip. She has been act ive and in good healt h.
On physical examinat ion, moving t he hip t hrough rot at ion, flexion, and ext ension does not elicit pain, but abduct ion reproduces t he pain minimally. There is full,
unrest rict ed range of mot ion. There is t enderness t o pressure over t he lat eral aspect of t he right hip.
(A) Avascular necrosis of t he femoral head
(B) Ost eoart hrit is
(D) Trochant eric bursit is
Item 4 [Basic]
A 35-year-old woman is evaluat ed for a 5-day hist ory of acut e right knee pain t hat began when she hopped down from t he bed of a t ruck, t wist ing her knee. She experienced a
popping sensat ion and a gradual onset of knee joint swelling over t he next several hours. Since t hen, she has cont inued t o have moderat e pain, part icularly when walking up
or down st airs. She report s no locking or giving way of t he knee or any previous knee injury.
On physical examinat ion, t he right knee has a minimal effusion wit h full range of mot ion. The medial aspect of t he joint line is t ender t o palpat ion. Maximally flexing t he
hip and knee and applying abduct ion (valgus) force t o t he knee while ext ernally rot at ing t he foot and passively ext ending t he knee (McMurray t est ) result in a palpable snap
but no crepit us.
(A) Anserine bursit is
(B) Ant erior cruciat e ligament t ear
(C) Meniscal t ear
(D) Pat ellofemoral pain syndrome
Item 5 [Advanced]
A 66-year-old woman is evaluat ed because of right knee pain of 4 weeks' durat ion. Alt hough t he knee is st iff for 20 t o 30 minut es in t he morning, she does not have much
pain at work. Walking up t he st airs in her house, however, causes a good deal of pain, which is not relieved by ibuprofen or acet aminophen. Kneeling also causes pain. Knee
radiographs done 6 weeks ago show mild medial compart ment ost eoart hrit is bilat erally.
On physical examinat ion, she is overweight . There is coarse crepit us wit h flexion and ext ension of t he right knee. Bot h knees are in slight varus angulat ion ("bow-legged").
On palpat ion, t here is t enderness along t he joint margins of bot h knees and exquisit e t enderness t o digit al pressure at t he medial upper t ibia on t he right t hat reproduces her
pain. In addit ion, wit h t he pat ient 's right knee semiflexed, palpat ion along t he medial semimembranous t endinous (hamst ring) edge of t he t high elicit s pain when t he
examining fingers meet t he t ibia.
Whi ch of the fol l owi ng i s most l i kel y responsi bl e for the exacerbati on of the ri ght knee pai n?
(A) Anserine bursit is
(B) Gout
(C) Ost eoart hrit is
(D) Rheumat oid art hrit is
Item 6 [Basic]
A 47-year-old man is evaluat ed for right lat eral shoulder pain. He has been pit ching during bat t ing pract ice for his son's baseball t eam for t he past 2 mont hs. He has shoulder
pain when lift ing his right arm overhead and also when lying on t he shoulder while sleeping. Acet aminophen does not relieve t he pain.
On physical examinat ion, he has no shoulder deformit ies or swelling. Range of mot ion is normal. He has subacromial t enderness t o palpat ion, wit h shoulder pain elicit ed at 60
degrees of passive abduct ion. He also has pain wit h resist ed mid-arc abduct ion but no pain wit h resist ed elbow flexion or forearm supinat ion. He is able t o lower his right arm
smoot hly from a fully abduct ed posit ion, and his arm st rengt h for abduct ion and ext ernal rot at ion against resist ance is normal.
(A) Adhesive capsulit is
(B) Bicipit al t endinit is
(C) Glenohumeral art hrit is
(D) Rot at or cuff t ear (complet e)
(E) Rot at or cuff t endinit is
Item 7 [Advanced]
A 59-year-old woman is evaluat ed for a 3-week hist ory of pain in t he right upper scapula and t rapezius areas. There are no parest hesias.
On physical examinat ion, t he shoulder has full range of mot ion wit hout elicit ing worse pain or alt ering t he charact er of t he pain. There is no sign of rot at or cuff pain or
weakness wit h t est ing against resist ance. There are no signs of impingement . The shoulder apprehension t est is negat ive. St rengt h, deep t endon reflexes, and sensat ion are
normal bilat erally.
What i s the most appropri ate next step i n thi s pati ent's management?
(B) Int ra-art icular cort icost eroid inject ion
(C) Physical t herapy
(D) Radiograph of t he shoulder
(E) Skelet al muscle relaxant
Item 8 [Advanced]
An 82-year-old woman is evaluat ed for a flare of polymyalgia rheumat ica manifest ed by aching in t he shoulders and hips t hat began 2 weeks ago. She also has fat igue and
malaise. She was diagnosed wit h polymyalgia rheumat ica 8 mont hs ago. At t hat t ime, she was prescribed prednisone, 20 mg/d; her sympt oms prompt ly resolved; and her
prednisone dosage was gradually t apered. Four mont hs ago, her prednisone dosage was decreased from 7.5 mg/d t o 5 mg/d, and her sympt oms ret urned. Her prednisone dosage
was t hen increased t o 10 mg/d followed by a slow t aper of t his agent . Her prednisone dosage was most recent ly decreased from 7 mg/d t o 6 mg/d, which is her current dosage.
She also t akes calcium and vit amin D supplement s and a bisphosphonat e.
On physical examinat ion, vit al signs are normal. Range of mot ion of t he shoulders, neck, and hips elicit s mild pain. There is no t emporal art ery t enderness.
(A) Increase prednisone t o 20 mg/d
(B) Increase prednisone t o 7.5 mg/d; add met hot rexat e
(C) Increase prednisone t o 20 mg/d; add met hot rexat e
(D) Increase prednisone t o 7.5 mg/d; add infliximab
Item 9 [Advanced]
A 62-year-old woman is evaluat ed for a 3-day hist ory of fever and left knee pain and swelling. She has a 30-year hist ory of rheumat oid art hrit is t reat ed wit h met hot rexat e
and nonst eroidal ant i-inflammat ory drugs. She has no ot her medical problems.
On physical examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 140/78 mm Hg, pulse rat e is 86/min, and respirat ion rat e is 14/min. The left knee is swollen, red,
warm, and t ender t o palpat ion. Range of mot ion is limit ed because of pain.
Art hrocent esis is performed, and t he following result s are report ed: synovial fluid leukocyt e count 75,000/L (75 10
9
/L) wit h 69% neut rophils. Gram st ain is posit ive for
gram-posit ive cocci.
Whi ch woul d be the most appropri ate i ni ti al anti bi oti c therapy pendi ng cul ture resul ts?
(A) Cefazolin
(B) Ceft riaxone
(C) Nafcillin
(D) Vancomycin
Item 10 [Basic]
A 32-year-old woman is evaluat ed in t he emergency depart ment for a 4-day hist ory of pain and swelling of t he right wrist and low-grade fever. She has a 7-year hist ory of
severe rheumat oid art hrit is. She does not recall any specific t rauma involving t he wrist but has recent ly been very physically act ive. Medicat ions are met hot rexat e, a folic
acid supplement , et anercept , prednisone, and ibuprofen.
On physical examinat ion, t emperat ure is 37.8C (100.0F), blood pressure is 118/68 mm Hg, pulse rat e is 90/min, and respirat ion rat e is 18/min. BMI is 22. Cardiopulmonary
examinat ion is normal. There is no rash. The right wrist is swollen and t ender and has a decreased range of mot ion. There are a subcut aneous nodule and small flexion
deformit y on t he left elbow but no act ive synovit is. Mild synovit is is present on t he second met acarpophalangeal joint s bilat erally. The hips, knees, and feet are not t ender or
swollen and have full range of mot ion.
Whi ch of the fol l owi ng di agnosti c studi es of the wri st wi l l be most hel pful i n establ i shi ng thi s pati ent's di agnosi s?
(A) Art hrocent esis
(B) Art hroscopy
(C) Bone scan
(D) MRI
(E) Radiography
Item 11 [Advanced]
A 67-year-old man is evaluat ed in t he emergency depart ment for a 2-week hist ory of pain involving t he left hip. He has had no fever. Four years ago, he underwent t ot al
art hroplast y of t he left hip joint t o t reat ost eoart hrit is. One mont h ago, he underwent t oot h ext ract ion for an abscessed t oot h.
On physical examinat ion, t emperat ure is 36.6C (98.0F), blood pressure is normal, and pulse rat e is 90/min. Cardiopulmonary examinat ion is normal. A well-healed surgical
scar is present over t he left hip, and t here is no warmt h or t enderness. Ext ernal rot at ion of t he left hip joint is markedly painful.
Laborat ory st udies reveal an eryt hrocyt e sediment at ion rat e of 88 mm/h.
Radiograph of t he left hip shows a normally seat ed left hip prost hesis. Fluoroscopic-guided art hrocent esis is performed. The synovial fluid leukocyt e count is 38,000/L (38
10
9
/L) (90% neut rophils). Polarized light microscopy of t he fluid shows no cryst als, and Gram st ain is negat ive. Cult ure result s are pending.
(A) Asept ic loosening
(B) Gout
(C) Pigment ed villonodular synovit is
(D) Prost het ic joint infect ion
Item 12 [Basic]
A 36-year-old man is evaluat ed for t he acut e onset of a warm swollen right ankle of 3 days' durat ion. He had a similar episode 2 years ago involving his left great t oe t hat
resolved in 5 days. He is ot herwise healt hy and t akes no medicat ions.
On physical examinat ion, t emperat ure is 36.7C (98.0F), blood pressure is 140/90 mm Hg, pulse rat e is 80/min, and respirat ion rat e is 12/min. Abnormal findings are limit ed
t o a warm swollen right ankle wit h painful range of mot ion.
An art hrocent esis is performed. Synovial fluid cell count is 30,000/L (30 10
9
/L) wit h 95% polymorphonuclear cells and 5% lymphocyt es. Gram st ain is negat ive for
bact eria.
Polarized microscopy demonst rat es int racellular monosodium urat e cryst als.
(A) Allopurinol
(B) Colchicine
(C) Febuxost at
(D) Indomet hacin
Item 13 [Basic]
A 68-year-old man is evaluat ed for hyperuricemia. He has had mult iple at t acks of acut e gout t ypically affect ing t he great t oe, but 2 weeks ago he had an at t ack involving his
right great t oe and bot h ankles. Art hrocent esis confirmed t he presence of monosodium urat e cryst als. He was successfully t reat ed wit h ibuprofen.
Physical examinat ion is normal except for a t ophaceous deposit on t he right forefoot .
Laborat ory st udies are normal except for a serum uric acid level of 11.2 mg/dL (0.7 mmol/L).
Whi ch of the fol l owi ng i s the most appropri ate therapy for thi s pati ent?
(A) Allopurinol
(B) Low-dose colchicine
(C) Low-dose colchicine and allopurinol
(D) Low-dose indomet hacin
Item 14 [Basic]
An 82-year-old woman wit h a 2-year hist ory of ost eoart hrit is of t he knees is evaluat ed for persist ent swelling and pain in t he right knee of 3 mont hs' durat ion. She now uses a
cane for ambulat ion and is unable t o go grocery shopping. Medicat ions are naproxen and hydrocodone-acet aminophen as needed.
On physical examinat ion, vit al signs are normal. The right knee has a large effusion and a valgus deformit y. There is decreased flexion of t he right knee secondary t o pain
and st iffness, and she is unable t o fully ext end t his joint . Range of mot ion of bot h knees elicit s coarse crepit us.
Laborat ory st udies reveal a serum creat inine level of 1.1 mg/dL (97.2 mol/L) and a serum uric acid level of 8.2 mg/dL (0.5 mmol/L).
Radiograph of t he right knee reveals a large effusion and changes consist ent wit h end-st age ost eoart hrit is. Aspirat ion of t he right knee is performed. Synovial fluid leukocyt e
count is 3200/L (3.2 10
9
/L). Polarized light microscopy of t he fluid demonst rat es rhomboid-shaped weakly posit ively birefringent cryst als. Result s of Gram st ain and
cult ures are pending.
(A) Calcium pyrophosphat e dihydrat e deposit ion disease
(B) Chronic apat it e deposit ion disease
(C) Gout
(D) Sept ic art hrit is
Item 15 [Advanced]
A 70-year-old male dairy farmer is evaluat ed for a 1-year hist ory of pain in t he left knee t hat worsens wit h act ivit y and is relieved wit h rest . On physical examinat ion, vit al
signs are normal. A small effusion is present on t he left knee, but t here is no eryt hema or warmt h. Range of mot ion of t he left knee elicit s pain and is slight ly limit ed.
Ext ension of t his joint is limit ed t o approximat ely 10 degrees, but flexion is nearly full. The remainder of t he musculoskelet al examinat ion is normal.
The eryt hrocyt e sediment at ion rat e is 15 mm/h. A st anding radiograph of t he left knee is shown.
(A) Avascular necrosis
(D) Torn medial meniscus
Item 16 [Basic]
A 72-year-old woman is evaluat ed for a 1-year hist ory of progressive pain in t he right knee. The pain is most acut e along t he medial aspect of t he joint , worsens wit h
act ivit y, and is relieved wit h rest . She has no st iffness in t he morning and has had no swelling. She also has not experienced locking or giving away of t his joint .
On physical examinat ion, vit al signs are normal. There is bony enlargement of t he proximal and dist al int erphalangeal joint s. There is no evidence of a right knee effusion.
Passive flexion and ext ension of t he right knee are painful.
Laborat ory st udies, including complet e blood count , eryt hrocyt e sediment at ion rat e, and C-react ive prot ein, are normal. Radiograph of t he right knee also is normal.
In addi ti on to acetami nophen as needed, whi ch of the fol l owi ng i s the most appropri ate next step i n thi s pati ent's management?
(A) Art hroscopy
(B) Aspirat ion of t he knee
(C) MRI of t he knee
(D) Physical t herapy
Item 17 [Basic]
A 60-year-old woman is evaluat ed for wrist pain of 6 mont hs' durat ion. The pain is locat ed at t he base of t he right t humb at t he wrist . She is a wat ercolor art ist and a graphic
designer and is right handed. The pain is described as a persist ent ache for which she t akes acet aminophen, which provides moderat e relief. She has 20 minut es of morning
st iffness in t he right t humb t hat improves wit h a hot shower.
On physical examinat ion, vit al signs are normal. Examinat ion of her hands shows no soft t issue swelling, warmt h, or redness of any hand or wrist joint s. Bilat eral boney
hypert rophy of t he proximal int erphalangeal joint s is present bilat erally. Range of mot ion of t he right t humb is limit ed by pain. Point t enderness is elicit ed at t he base of t he
right t humb at t he first carpomet acarpal joint . Circular movement of her right t humb exacerbat es t he pain. Tapping t he flexor ret inaculum does not reproduce or aggravat e
t he pain nor does passively st ret ching t he t endons over t he radial st yloid.
(A) Carpal t unnel syndrome
(B) Cryst al-induced art hrit is
(C) de Quervain t enosynovit is
(D) Ost eoart hrit is
(E) Rheumat oid art hrit is
Item 18 [Basic]
A 67-year-old man is evaluat ed in t he office for acut e right knee pain t hat developed 6 days ago aft er working on his car. The pain is worse when he walks or climbs st airs and
improves when he rest s. He has no fever and denies knee st iffness. He has minimal pain relief wit h maximal dosage of acet aminophen and t he applicat ion of ice. He has no
ot her medical illness and t akes no medicat ions.
On examinat ion, his t emperat ure is 36.8C (98.2F), blood pressure is 132/75 mm Hg, heart rat e is 92/min and respirat ory rat e is 14/min. BMI is 27. Moderat e valgus
deformit y of bot h knees is present . The right knee has a moderat e effusion wit hout warmt h or eryt hema. Pain is elicit ed wit h passive and act ive range of mot ion. The
remainder of his examinat ion is normal.
Plain radiographs of his left knee show severe medial joint space narrowing wit h subchondral sclerosis and ost eophyt e format ion. Analysis of t he synovial fluid reveals 1100
leukocyt es/L (1.1 10
9
/L) (79% lymphocyt es, 10 % macrophages).
Whi ch of the fol l owi ng i s the best management for thi s pati ent's knee pai n?
(A) Begin a nonst eroidal ant i-inflammat ory drug
(B) Begin empiric ant ibiot ics
(C) Inject int ra-art icular cort icost eroids
(D) Obt ain right knee magnet ic resonance imaging (MRI)
(E) Refer for t ot al knee art hroplast y
Item 19 [Advanced]
A 60-year-old woman is evaluat ed for bilat eral joint pain and swelling in her hands. She has 2 hours of morning st iffness t hat improves slight ly wit h act ivit y. Acet aminophen
and nonst eroidal ant i-inflammat ory drugs provide only minimal sympt om relief. She has no ot her medical problems and t akes no addit ional medicat ions.
On physical exam, vit al signs are normal. She has symmet ric joint swelling and t enderness t he second and t hird met acarpophalangeal joint s and t enderness over t he left fift h
met at arsophalangeal joint .
Whi ch of the fol l owi ng test resul ts woul d most l i kel y support a di agnosi s of rheumatoi d arthri ti s i n thi s pati ent?
(A) Elevat ed eryt hrocyt e sediment at ion rat e
(B) Normocyt ic, normochromic anemia
(C) Posit ive rheumat oid fact or
(D) Radiographs showing marginal joint erosions
Item 20 [Advanced]
A 19-year-old woman wit h a 4-year hist ory of rheumat oid art hrit is is evaluat ed because of a 3-mont h hist ory of worsening sympt oms. She had previously good disease
cont rol wit h met hot rexat e. She is ot herwise well and denies fevers, night sweat s and weight loss.
On physical examinat ion, vit al signs are normal. There is act ive synovit is involving t he left first and second met acarpophalangeal joint s and right wrist . The remainder of
t he physical examinat ion is normal.
Hand x-rays reveal a new erosion on t he right ulnar st yloid and t he left second MCP joint .
Init iat ion of t he t umor necrosis fact or (TNF)- inhibit or, adalimumab, is recommended.
Whi ch of the fol l owi ng tests shoul d be performed pri or to i ni ti ati ng adal i mumab therapy?
(A) Brain MRI
(B) Chest CT
(C) Thyroid st imulat ing hormone measurement
(D) Tuberculin skin t est
Item 21 [Basic]
A 26-year-old woman is evaluat ed for a 2-mont h hist ory of pain and swelling in t he hands and daily morning st iffness t hat last s for 3 t o 4 hours. She is 4 mont hs post part um,
and her pregnancy was wit hout complicat ions. She has no hist ory of rash and is ot herwise well. Her only medicat ion is ibuprofen, which has not sufficient ly relieved her
sympt oms.
On physical examinat ion, t emperat ure is normal, blood pressure is 110/68 mm Hg, pulse rat e is 82/min, and respirat ion rat e is 16/min. The second and t hird proximal
int erphalangeal and met acarpophalangeal joint s and t he wrist s are t ender and swollen bilat erally.
Laborat ory st udies show an eryt hrocyt e sediment at ion rat e of 67 mm/h, and t it ers of IgM ant ibodies against parvovirus B19 are negat ive.
(A) Gout
(C) Parvovirus B19 infect ion
(D) Rheumat oid art hrit is
Item 22 [Basic]
A 55-year-old woman is evaluat ed for a 3-mont h hist ory of fat igue, morning st iffness last ing for 1 hour, and decreased grip st rengt h. She drinks t wo glasses of wine daily and
is unwilling t o st op. Her only medicat ion is over-t he-count er ibuprofen, 400 mg t hree t imes daily, which has helped t o relieve her joint st iffness.
On physical examinat ion, vit al signs are normal. Musculoskelet al examinat ion reveals swelling of t he met acarpophalangeal and proximal int erphalangeal joint s of t he hands
and decreased grip st rengt h. There are effusions on bot h knees. The remainder of t he physical examinat ion is normal.
Eryt hrocyt e sediment at ion rat e 35 mm/h
C-react ive prot ein Normal
Rheumat oid fact or Posit ive
Ant inuclear ant ibodies Posit ive
Ant i-cyclic cit rullinat ed pept ide ant ibodies Posit ive
Radiographs of t he hands show soft -t issue swelling but no erosions or joint -space narrowing. Radiographs of t he feet are normal.
(A) Add hydroxychloroquine
(B) Add met hot rexat e
(C) Add subcut aneous et anercept
(D) Increase ibuprofen dosage
Item 23 [Advanced]
A 23-year-old man is evaluat ed for art hrit is of 6 weeks' durat ion involving his hands and right knee. He also report s a hist ory of psoriasis t hat began abrupt ly 3 mont hs ago
and has spread rapidly. He has no hist ory of t rauma or preceding illness, including diarrhea, uret hrit is, or conjunct ivit is. He has no ot her medical problems and t akes no
medicat ions.
On physical examinat ion, t emperat ure is 37.2C (99.0F), blood pressure is 120/76 mm Hg, pulse rat e is 78/min, and respirat ion rat e is 12/min. A right knee effusion is
present . The right knee is eryt hemat ous, warm, and t ender t o palpat ion wit h limit ed range of mot ion because of pain. The t hird right t oe is swollen and red. Evidence of
synovit is is present involving t he dist al int erphalangeal joint s of bot h hands. Typical psoriat ic lesions are not ed involving t he elbows, knees, periumbilical area, sacrum, soles,
and palms.
A right knee art hrocent esis is performed and result s are compat ible wit h an inflammat ory art hrit is. Synovial fluid Gram st ain is negat ive and fluid is sent for cult ure.
Whi ch of the fol l owi ng addi ti onal tests shoul d be performed?
(A) Ant inuclear ant ibody
(B) HIV t est ing
(C) HLA-B27 ant igen
(D) Rheumat oid fact or
Item 24 [Advanced]
A 28-year-old woman is evaluat ed for a 3-week hist ory of pain and swelling of t he right knee and ankle. For t he past 6 weeks, she has had diffuse, crampy abdominal pain.
For t he past week, t he pain has been accompanied by four t o six daily episodes of bloody diarrhea and fecal urgency. She has lost approximat ely 1.5 kg (3.3 lb) since t he
onset of her sympt oms. She has not not iced a rash or ot her joint or soft -t issue involvement . She has not t raveled out side of her homet own and has a monogamous sexual
relat ionship wit h her husband. She has no ot her medical problems and does not t ake any medicat ions.
On physical examinat ion, t emperat ure is 37.7C (99.9F), blood pressure is 128/72 mm Hg, pulse rat e is 98/min, and respirat ion rat e is 18/min. The abdomen is soft and
diffusely t ender t o palpat ion. Bowel sounds are normal, and t here is no organomegaly. Rect al examinat ion reveals t enderness of t he rect al canal and st ool associat ed wit h
bright red blood. The right ankle and knee are swollen and slight ly warm t o t he t ouch, and range of mot ion of t hese joint s elicit s pain. The remainder of t he physical
Plain radiographs of t he ankle and knee are normal. Art hrocent esis is performed. Synovial fluid analysis reveals a leukocyt e count of 14,000/L (14 10
9
/L) (92%
polymorphonuclear cells, 8% macrophages).
Whi ch of the fol l owi ng i s the most l i kel y cause of thi s pati ent's joi nt symptoms?
(A) Cryst al-induced art hrit is
(B) Ent eropat hic art hrit is
(C) Gonococcal art hrit is
(D) Whipple disease
Item 25 [Basic]
A 23-year-old man is evaluat ed in t he emergency depart ment for a 5-day hist ory of headache, blurred vision, and right eye pain. His eye pain increases when he at t empt s t o
read or when exposed t o light . He also has a 3-year hist ory of back st iffness t hat is worse in t he morning and t ends t o improve as he becomes more act ive. He does not have
art hralgia, art hrit is, or rash. He t akes no medicat ions and is monogamous.
On physical examinat ion, t emperat ure is 36.8C (98.2F), blood pressure is 130/76 mm Hg, pulse rat e is 85/min, and respirat ion rat e is 14/min. There are no skin lesions.
The appearance of t he right eye is shown (Plat e 30).
Phot ophobia is present during t he penlight examinat ion of t he pupil. Bot h pupils react t o light . An emergency referral is made t o an opht halmologist .
Fol l owi ng resol uti on of the eye probl em, thi s pati ent shoul d be eval uated for whi ch of the fol l owi ng systemi c di seases?
(A) Ankylosing spondylit is
(B) Sarcoidosis
(C) Sjogren syndrome
Item 26 [Advanced]
A 26-year-old female elect rical engineer is evaluat ed for a 2-year hist ory of persist ent pain and st iffness involving t he low back. These sympt oms are worse in t he morning
and are alleviat ed wit h exercise and hot showers. There are no radicular sympt oms. Her only medicat ion is ibuprofen, which has helped t o relieve her sympt oms. She has no
ot her medical problems and t akes no addit ional medicat ions.
On physical examinat ion, vit al signs are normal. Cut aneous examinat ion is normal. Palpat ion of t he pelvis and low back elicit s pain. There is loss of normal lumbar lordosis,
and forward flexion of t he lumbar spine is decreased. Reflexes and st rengt h are int act .
Radiographs of t he lumbar spine and pelvis are normal.
Whi ch of the fol l owi ng studi es i s most l i kel y to establ i sh the di agnosi s i n thi s pati ent?
(A) Ant i-cyclic cit rullinat ed pept ide ant ibodies
(B) Eryt hrocyt e sediment at ion rat e
(C) HLA-B27
(D) MRI of t he sacroiliac joint s
Item 27 [Basic]
A 36-year-old woman is evaluat ed for a 5-mont h hist ory of fever, joint swelling, and pleurit ic chest pain. Her sympt oms have not responded t o daily naproxen.
On physical examinat ion, t emperat ure is 36.6C (97.8F), blood pressure is 140/85 mm Hg, pulse rat e is 102/min, and respirat ion rat e is 14/min. She has a shallow, nont ender
hard palat e ulcer and cent ral facial redness sparing t he nasolabial folds. She has bilat eral synovit is of her wrist and met acarpophalangeal joint s.
Hemoglobin 10.7 mg/dL (107 g/L)
Leukocyt e count 3000/L (3 10
9
/L)
Ant inuclear ant ibody (ANA) Posit ive, 1:640
Urine prot ein 1.5 g/24 hours
Whi ch of the fol l owi ng serol ogi c tests i s most l i kel y to confi rm the di agnosi s?
(A) Ant i-double-st randed DNA ant ibody
(B) Ant iribonucleoprot ein ant ibody
(C) Ant i-SS-A (Ro) and ant i-SS-B (La) ant ibodies
(D) Ant i-t opoisomerase I (ant i-Scl-70) ant ibody
(E) Rheumat oid fact or
Item 28 [Advanced]
A 55-year-old woman is evaluat ed for progressive polyart hralgia, phot osensit ive rash, and lower-ext remit y purpura of 7 weeks' durat ion. She also has daily low-grade fever
and int ermit t ent pleurit ic chest pain. She has an 11-year hist ory of rheumat oid art hrit is t reat ed wit h oral met hot rexat e and int ravenous infliximab. Her disease has been
most ly st able except for occasional flares t reat ed wit h prednisone.
On physical examinat ion, vit al signs are normal except for a t emperat ure of 38.0C (100.4F). Malar rash is present . Cardiopulmonary examinat ion reveals normal breat h
sounds, and no rubs are heard. She is unable t o t ake a deep breat h because of pain. Several small 1-cm maculopapular erupt ions are visible on t he lower ext remit ies bilat erally.
Musculoskelet al examinat ion reveals synovit is of t he met acarpophalangeal and proximal int erphalangeal joint s and t he wrist s bilat erally. The left elbow has a nodule. Range
of mot ion of t he right wrist is decreased.
Rheumat oid fact or Posit ive
Ant inuclear ant ibodies Tit er of 1:640
Ant i-double-st randed DNA ant ibodies Posit ive
Chest radiograph reveals small bilat eral pleural effusions.
Whi ch of the fol l owi ng i s the most appropri ate next step i n thi s pati ent's treatment?
(A) Add sulfasalazine
(B) Discont inue infliximab; begin prednisone
(C) Discont inue met hot rexat e; begin hydroxychloroquine
(D) Discont inue met hot rexat e; begin sulfasalazine
Item 29 [Advanced]
A 25-year-old woman is evaluat ed during a rout ine follow-up visit . Four mont hs ago, she was diagnosed wit h syst emic lupus eryt hemat osus t hat manifest ed as fat igue, malar
rash, oral ulcers, pleurit is, and art hralgia. At t hat t ime, she began t reat ment wit h hydroxychloroquine and a 1-mont h course of low-dose prednisone.
On physical examinat ion t oday, she st at es t hat her sympt oms have resolved somewhat but t hat she st ill has slight fat igue and mild art hralgia in her hands, feet , and knees.
Temperat ure is 36.4C (97.6F), blood pressure is 130/92 mm Hg, pulse rat e is 84/min, and respirat ion rat e is 18/min. She has a mild malar flush, a painless ulcer on t he hard
palat e, and t race bilat eral ankle edema. The remainder of t he examinat ion is normal.
9
/L)
9
/L)
Serum complement (C3 and C4) Decreased
Urinalysis 2+ prot ein; 3+ blood; 5-10 leukocyt es, 15-20 eryt hrocyt es, and 1 eryt hrocyt e cast /hpf
Whi ch of the fol l owi ng i s the next best step i n thi s pati ent's treatment?
(A) Amlodipine
(B) High-dose prednisone
(C) Ibuprofen
(D) Low-dose prednisone
Item 30 [Basic]
A 22-year-old woman is evaluat ed because of a 3-week hist ory of pain in her joint s and a rash. Bot h t he skin rash and art hralgia began aft er a 2-week sailing vacat ion in July
on Lake Michigan. The joint pain involves primarily t he wrist s and hands bilat erally, and t ends t o be worse in t he morning and improve as t he day progresses. She originally
t hought t hat t he rash was t he result of sunburn, but it has not gone away, and is shown (Plat e 31). It is not painful and does not it ch.
Whi ch of the fol l owi ng condi ti ons i s most l i kel y responsi bl e for thi s pati ent's rash?
(B) Rosacea
Item 31 [Advanced]
A 63-year-old woman wit h dermat omyosit is is evaluat ed for cough and dyspnea. She was diagnosed wit h polymyosit is 6 mont hs ago and has been t reat ed wit h prednisone and
met hot rexat e. She was doing very well unt il 6 weeks ago when she developed a dry cough and progressive dyspnea. She has no hist ory of pulmonary disease and does not
smoke.
On physical examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 110/60 mm Hg, pulse rat e is 88/min, and respirat ion rat e is 20/min. The cardiac examinat ion is
normal. No jugular venous dist ent ion or peripheral edema is evident . On pulmonary auscult at ion, bibasilar crackles are heard. Muscle st rengt h is normal, and no skin rash is
evident .
Laborat ory evaluat ion shows a normal complet e blood count , comprehensive chemist ry panel, and serum creat ine kinase level. Chest x-ray shows increased int erst it ial
markings in bot h lung bases.
(A) Communit y-acquired pneumonia
(B) Heart failure
(C) Int erst it ial lung disease
(D) Pneumocyst is pneumonia
Item 32 [Advanced]
A 41-year-old woman is evaluat ed for int ermit t ent pain and cyanosis of t he fingers t hat is usually associat ed wit h exposure t o cold t emperat ures or st ress. She does not
smoke, and her effort s t o keep room t emperat ures warm and t o wear gloves and layers of clot hing t o maint ain her core t emperat ure have not been successful in managing her
sympt oms.
She was diagnosed wit h limit ed cut aneous syst emic sclerosis 1 year ago. She also has gast roesophageal reflux disease. Her only medicat ion is omeprazole.
On physical examinat ion, t emperat ure is 37.0C (98.6F), blood pressure is 128/72 mm Hg, and pulse rat e is 88/min. Cut aneous examinat ion of t he hands shows
sclerodact yly. Radial and ulnar pulses are 2+ and equal bilat erally.
Whi ch of the fol l owi ng i s the most appropri ate addi ti onal treatment for thi s pati ent?
(A) Amlodipine
(B) Isosorbide dinit rat e
(C) Prednisone
(D) Propranolol
Item 33 [Basic]
A 25-year-old woman is evaluat ed during a follow-up visit for a 6-mont h hist ory of diffuse muscle and joint pain above and below t he waist , fat igue, and difficult y sleeping.
She has a 2-year hist ory of hypot hyroidism t reat ed wit h levot hyroxine. Her only ot her medicat ion is hydrocodone-acet aminophen, which has not relieved her pain.
examinat ion is normal. Musculoskelet al examinat ion reveals diffuse periart icular t enderness, including bilat eral t enderness in t he biceps brachii, t highs, and calves. Muscle
st rengt h t est ing cannot be complet ed because of pain. The joint s are not swollen, and she does not have lower-ext remit y edema.
Complet e blood count Normal
Complet e met abolic panel Normal
Creat ine kinase 100 U/L
Ant inuclear ant ibodies Tit er of 1:640
Urinalysis Normal
Whi ch of fol l owi ng i s the most l i kel y di agnosi s?
(A) Fibromyalgia
(B) Polymyosit is
Item 34 [Basic]
A 68-year-old woman is evaluat ed because of recent soft t issue swelling post erior t o t he mandible, and dryness of bot h eyes, dry mout h. Her medical hist ory is ot herwise
unremarkable.
Physical examinat ion reveals normal vit al signs, bilat eral parot id gland swelling, diffuse lymphadenopat hy, and t race joint effusion in bot h knees. Schirmer's t est shows 8 mm,
right eye; 5 mm, left eye (normal, great er t han 15 mm/5 min), consist ent wit h decreased t ear product ion.
(A) Hodgkin disease
(B) Sarcoidosis
Item 35 [Advanced]
A 69-year-old woman is evaluat ed for a progressive 6-mont h hist ory of fat igue and weakness. She has had painful parest hesias on t he dorsum of t he right foot for t he past 10
days and weakness in t he right wrist for t he past 2 days. She also has had fever and night sweat s accompanied by art hralgia and myalgia. She has had a 4.1-kg (9-lb) weight loss
during t his t ime and over t he past mont h has developed anorexia and nausea. Colonoscopy, mammography, and Pap smear performed 2 mont hs ago were normal. Her
medical hist ory is ot herwise unremarkable, and she t akes no medicat ions.
On physical examinat ion, t emperat ure is normal, blood pressure is 155/115 mm Hg, pulse rat e is 102/min, and respirat ion rat e is 18/min. BMI is 28. There is jugular venous
dist ent ion. Cardiac examinat ion reveals a summat ion gallop. Left and right renal bruit s are heard during syst ole and diast ole. The lungs are clear t o auscult at ion. She is unable
t o dorsiflex t he right foot , and ext ension of t he right wrist is weak. There is 2+ ankle edema bilat erally. There are no skin lesions and no evidence of synovit is.
Ant inuclear ant ibodies Negat ive
Rheumat oid fact or Negat ive
c-ANCA Negat ive
p-ANCA Negat ive
C3 and C4 Normal
Urinalysis 2+ prot ein; no cast s
Serum and urine elect rophoreses are negat ive. Blood cult ures are pending. Echocardiography is negat ive for valvular disease, valvular veget at ion, or t umor. On kidney
ult rasound, t he kidneys are 11 cm bilat erally. There is no hydronephrosis.
Whi ch of the fol l owi ng studi es i s most l i kel y to yi el d a defi ni ti ve di agnosi s?
(A) Abdominal fat pad aspirat ion
(B) Angiography of t he renal art eries
(C) Kidney biopsy
(D) Skin biopsy
Item 36 [Advanced]
A 57-year-old man is evaluat ed in t he emergency depart ment for t he acut e onset of rapidly worsening dyspnea. For t he past 10 weeks, he has had pain and swelling in t he
small joint s of t he hands and in t he knees; he was diagnosed wit h seronegat ive symmet ric inflammat ory polyart hrit is 2 weeks ago and was st art ed on low-dose met hot rexat e, a
folic acid supplement , low-dose prednisone, and naproxen at t hat t ime. He also has a hist ory of refract ory ot it is media and underwent bilat eral t ympanost omy t ube placement
6 mont hs ago.
He is in respirat ory failure and is int ubat ed, mechanically vent ilat ed, and admit t ed t o t he hospit al. Blood is not ed when he is int ubat ed. On physical examinat ion on admission,
t emperat ure is 38.5C (101.3F), blood pressure is 135/95 mm Hg, pulse rat e is 125/min, and respirat ion rat e is 24/min. There is no bleeding from t he gums. Pulmonary
examinat ion reveals diffuse crackles t hroughout all lung fields. The met acarpophalangeal and proximal int erphalangeal joint s are swollen, and bot h knees have medium-sized
effusions. Palpable purpura is present on t he calves.
9
/L) (80% neut rophils)
Rheumat oid fact or Negat ive
Ant inuclear ant ibodies Negat ive
c-ANCA Posit ive
Ant i-cyclic cit rullinat ed pept ide ant ibodies Negat ive
Ant iprot einase-3 ant ibodies Posit ive
Serologic t est for HIV ant ibodies Negat ive
Urinalysis 2+ prot ein; 1+ blood; 15 eryt hrocyt es/hpf
A chest radiograph shows normal heart size and diffuse alveolar infilt rat es in bot h lung fields.
Ceft riaxone, azit hromycin, and hydrocort isone are st art ed. His previous medicat ions are discont inued.
(A) Int erst it ial pneumonit is
(B) Met hot rexat e-induced pneumonit is
(C) Pneumocystis pneumonia
(D) Wegener granulomat osis
Item 37 [Basic]
A 75-year-old woman is evaluat ed for a sudden loss of vision in t he left eye t hat began 30 minut es ago. She has a 2-week hist ory of fat igue; malaise; and pain in t he shoulders,
neck, hips, and lower back. She also has a 5-day hist ory of mild bit emporal headache.
On physical examinat ion, t emperat ure is 37.3C (99.1F), blood pressure is 140/85 mm Hg, pulse rat e is 72/min, and respirat ion rat e is 16/min. BMI is 31. The left t emporal
art ery is t ender. Funduscopic examinat ion reveals a pale, swollen opt ic disc. Range of mot ion of t he shoulders and hips elicit s moderat e pain.
9
/L)
9
/L)
(A) Brain MRI
(B) High-dose int ravenous met hylprednisolone
(C) Low-dose oral prednisone
(D) Temporal art ery biopsy
Item 1 Answer: B
Educati onal Objecti ve: Diagnose lateral epicondylitis of the elbow ("tennis elbow").
This woman has lat eral epicondylit is of t he elbow, commonly referred t o as "t ennis elbow." Epicondylit is is caused by microt earing of t he t endons result ing from repet it ive
mot ions. Lat eral epicondylit is is t he most common cause of elbow pain. Sympt oms are t enderness of t he lat eral epicondyle and pain on resist ed wrist ext ension and hand
gripping. Medial epicondylit is, or golfer's elbow, is less common. There is t enderness in t he medial epicondyle and pain wit h wrist flexion. Only a minorit y of cases of lat eral
epicondylit is can be at t ribut ed t o playing t ennis. Treat ment of t he disorder consist s of applicat ion of ice, nonst eroidal ant i-inflammat ory drugs, local st eroid inject ion, and a
forearm brace or isomet ric exercises t o st rengt hen t he forearm.
Cubit al t unnel syndrome, or ulnar nerve ent rapment , is a common cause for pain and sensory and mot or loss in t he ulnar region and for parest hesias in t he ulnar aspect of t he
arm and hand. Syst emic diseases such as end-st age renal disease may be involved; ext rinsic causes such as ganglion cyst s or ext ernal pressure are common as well.
Olecranon bursit is, or carpet -layers elbow, occurs when t he olecranon bursa develops an effusion, eit her from t rauma, an inflammat ory process, or infect ion. On examinat ion,
an inflamed bursa does not cause rest rict ion or pain wit h range of mot ion of t he elbow, providing evidence t hat t he joint is not involved. However, t he bursa can be ext remely
t ender t o palpat ion.
A hist ory of joint pain, joint swelling, and fever are t he only findings associat ed wit h sept ic art hrit is t hat occur in more t han 50% of affect ed pat ient s. Approximat ely 85%
t o 90% of pat ient s have involvement of only one joint . Common sit es of infect ion include t he knee, wrist s, ankles, and hips. The hallmark of a sept ic joint is pain on
passive range of mot ion in t he absence of t rauma, and an infect ed joint t ypically appears swollen and warm wit h overlying eryt hema.
Key Poi nt
Lat eral epicondylit is is a clinical diagnosis based upon t he presence of localized pain made worse by wrist ext ension, point t enderness, and an absence of signs of limit at ion of
mot ion or inflammat ion of t he elbow joint .
Bi bl i ography
Calfee RP, Pat el A, DaSilva MF, Akelman E. Management of lat eral epicondylit is: current concept s. J Am Acad Ort hop Surg. 2008;16(1):19-29. [PMID: 18180389]
Item 2 Answer: C
Educati onal Objecti ve: Diagnose rheumatoid arthritis.
This pat ient has sympt oms and signs consist ent wit h rheumat oid art hrit is. Different joint s are variably affect ed by different disorders. Rheumat oid art hrit is and ost eoart hrit is
can bot h involve t he proximal int erphalangeal joint s of t he hands, but met acarpophalangeal joint involvement occurs in rheumat oid art hrit is but not t ypically in
ost eoart hrit is. Dist al int erphalangeal joint involvement is charact erist ic of ost eoart hrit is but not rheumat oid art hrit is. Unless a secondary condit ion, such as t rauma,
met abolic disorder, or inflammat ory art hrit is, has already affect ed t he joint , ost eoart hrit is does not occur in t he met acarpophalangeal, wrist , elbow, shoulder, and ankle joint s.
This pat ient has eryt hema and swelling of t he met acarpophalangeal joint s and loss of funct ion leading t o absent eeism from work; t hese findings are most consist ent wit h
rheumat oid art hrit is.
Psoriasis is associat ed wit h an underlying inflammat ory art hrit is in up t o 30% of pat ient s wit h skin disease; nail pit t ing suggest s psoriat ic art hrit is, even in t he absence of
psoriat ic skin lesions. These changes are not present in t his pat ient .
More t han 90% of pat ient s wit h SLE develop joint involvement t hat can manifest as art hralgia or t rue art hrit is. Joint pain is oft en migrat ory and can be oligoart icular or
polyart icular and asymmet ric or symmet ric. Pain t ypically involves t he large and small joint s; t he wrist s and met acarpophalangeal and proximal int erphalangeal joint s in
part icular are most commonly affect ed. The absence of ot her manifest at ions of SLE (serosit is, cyt openias, kidney disease, rash, phot osensit ivit y) make t his diagnosis
unlikely.
Key Poi nt
Rheumat oid art hrit is and ost eoart hrit is can bot h involve t he proximal int erphalangeal joint s of t he hands, but met acarpophalangeal joint involvement occurs in rheumat oid
art hrit is and not ost eoart hrit is.
Bi bl i ography
Majit hia V, Geraci SA. Rheumat oid art hrit is: diagnosis and management . Am J Med. 2007;120:936-9. [PMID: 17976416]
Item 3 Answer: D
Educati onal Objecti ve: Diagnose trochanteric bursitis.
Many pat ient s wit h pain over t he great er t rochant er describe it as hip pain. Oft en pat ient s can point wit h one finger t o t he source of t he pain on t he lat eral hip. Act ively
resist ed abduct ion of t he hip worsens t he pain. The t reat ment of choice is a cort icost eroid inject ion. Formal inst ruct ion in exercises t o st ret ch t he iliot ibial band and
st rengt hen t he glut eus medius and minimus muscles may be helpful, as will nonst eroidal ant i-inflammat ory drugs or hot packs.
Pat ient s wit h hip joint pat hology t ypically have pain t hat is localized t o t he groin and have painful, oft en rest rict ed range of hip mot ion. The pat ient 's abilit y t o precisely
localize t he pain t o t he lat eral aspect of t he hip is not consist ent wit h hip joint pat hology. Finally, findings on physical examinat ion indicat e t hat t he source of pain is not
t he hip joint it self; t herefore, ost eoart hrit is, rheumat oid art hrit is, and avascular necrosis of t he femoral head are unlikely causes of t he pain.
Key Poi nt
Pat ient s wit h t rochant eric bursit is can point wit h one finger t o t he source of t he pain on t he lat eral hip and act ively resist ed abduct ion of t he hip worsens t he pain.
Bi bl i ography
Shbeeb MI, Mat t eson EL. Trochant eric bursit is (great er t rochant er pain syndrome). Mayo Clin Proc. 1996;71:565-9. [PMID: 8642885]
Item 4 Answer: C
Educati onal Objecti ve: Diagnose meniscal tear.
The pat ient 's hist ory is suspicious for a meniscal t ear. Pat ient s t ypically describe a t wist ing injury wit h t he foot in a weight -bearing posit ion, in which a popping or t earing
sensat ion is oft en felt , followed by severe pain. Swelling occurs over several hours, in cont rast t o ligament ous injuries, in which swelling is immediat e. Pat ient s wit h meniscal
t ears may report a clicking or locking of t he knee secondary t o loose cart ilage in t he knee but oft en have pain only on walking, part icularly going up or down st airs. Pain
along t he joint line is 76% sensit ive for a meniscal t ear, and an audible pop or snap on t he McMurray t est is 97% specific for a meniscal t ear.
Anserine bursit is is charact erized by pain and t enderness over t he ant eromedial aspect of t he lower leg below t he joint line of t he knee. The locat ion of t he pat ient 's pain and
her abnormal physical examinat ion findings do not support t he diagnosis of anserine bursit is.
Ligament ous damage usually occurs as a result of forceful st ress or direct blows t o t he knee while t he ext remit y is bearing weight . Excessive medial rot at ion wit h a plant ed
foot st resses t he ant erior cruciat e ligament . A popping or t earing sensat ion is frequent ly report ed in pat ient s wit h ligament ous damage. This pat ient 's physical examinat ion
findings, part icularly t he result of t he McMurray t est , support a diagnosis of meniscal, rat her t han ligament ous, injury.
Pat ellofemoral pain syndrome is t he most common cause of chronic knee pain in act ive adult s, part icularly women, younger t han 45 years. The exacerbat ion of t he pain by
going down st eps and t he development of knee st iffness and pain at rest when t he knee is flexed for an ext ended period of t ime are clues t o t he diagnosis. Reproducing t he
pain by firmly moving t he pat ella along t he femur confirms t he diagnosis. This pat ient 's hist ory and physical examinat ion findings are consist ent wit h acut e injury t o t he
meniscus rat her t han t he pat ellofemoral pain syndrome.
Key Poi nt
Pain along t he joint line is 76% sensit ive for a meniscal t ear, and a pop or snap on t he McMurray t est is 97% specific.
Bi bl i ography
Jackson JL, O'Malley PG, Kroenke K. Evaluat ion of acut e knee pain in primary care. Ann Int ern Med. 2003;139(7):575-588. [PMID: 14530229]
Item 5 Answer: A
Educati onal Objecti ve: Diagnose anserine bursitis.
The pat ient has anserine bursit is; t he maneuver wit h t he knee semiflexed helps t o confirm t he diagnosis. In anserine bursit is, t he diagnosis rest s on t he finding of focal
t enderness on t he upper, inner t ibia, about 5 cm dist al t o t he medial art icular line of t he knee. Pat ient s are usually middle-aged or older and oft en have knee ost eoart hrit is, but
t he problem can occur in act ive young people also. Usually, t here is no redness, swelling, or increased warmt h at t he painful sit e. It may be t hat t he underlying problem is
st rain of t he pes anserinus t endon rat her t han t rue bursit is. Cort icost eroid inject ion at t he bursal sit e almost always provides relief of pain. Oft en, knee pain at t ribut ed t o even
severe ost eoart hrit is of t he knee disappears aft er t reat ment of t he anserine bursit is. Because t he cort icost eroid is inject ed int o soft t issue, t he risk of t endon rupt ure is
minimal. In addit ion, pat ient s should adhere t o a regimen of isomet ric quadriceps exercises and, if applicable, weight reduct ion.
Ost eoart hrit is and gout would produce findings limit ed t o t he knee joint , and are not associat ed wit h focal t enderness of t he upper, inner t ibia. Rheumat oid art hrit is of t he
knee is uncommon, part icularly if it is asymmet rical, and would not produce focal t enderness along t he upper t ibia.
Key Poi nt
In anserine bursit is, t he diagnosis rest s on t he finding of focal t enderness on t he upper, inner t ibia, about 5 cm dist al t o t he medial art icular line of t he knee.
Bi bl i ography
Larsson LG, Baum J. The syndrome of anserine bursit is: An overlooked diagnosis. Art hrit is Rheum. 1985;28:1062-5. [PMID: 4038358]
Item 6 Answer: E
Educati onal Objecti ve: Diagnose rotator cuff tendinitis.
Rot at or cuff t endinit is, an inflammat ion of t he supraspinat us and/or infraspinat us t endon t hat can also involve t he subacromial bursa, is a common overuse injury. This injury
is charact erized by subacromial t enderness and impingement painful compression of t he rot at or cuff t endons and subacromial bursa bet ween t he humeral head and t he
acromion wit h arm elevat ion. Pain in pat ient s wit h rot at or cuff t endinit is oft en occurs wit h reaching overhead and when lying on t he shoulder. The passive painful-arc
maneuver assesses t he degree of impingement . The examiner places one hand on t he acromion and t he ot her on t he forearm and abduct s t he arm while prevent ing t he pat ient
from shrugging. Subacromial pain at 60 t o 70 degrees of abduct ion suggest s moderat e impingement , while pain at 45 degrees or less suggest s severe impingement . Pain wit h
resist ed mid-arc abduct ion is a specific finding for rot at or cuff t endinit is. Appropriat e t reat ment s for acut e t endinit is include NSAIDs, ice, and exercises; overhead reaching
and lift ing should be limit ed.
Adhesive capsulit is (frozen shoulder) is charact erized by a decreased range of shoulder mot ion predominant ly result ing from st iffness rat her t han from pain or weakness.
Bicipit al t endinit is is also an overuse injury in which t he bicipit al groove may be t ender, and ant erior shoulder pain is elicit ed wit h resist ed forearm supinat ion or elbow
flexion.
Glenohumeral art hrit is is oft en relat ed t o t rauma and t he gradual onset of pain and st iffness over mont hs t o years.
A t orn rot at or cuff usually result s in arm weakness, part icularly wit h abduct ion and/or ext ernal rot at ion. A posit ive drop-arm t est (inabilit y t o smoot hly lower t he affect ed
arm from full abduct ion) is a very specific but relat ively insensit ive met hod for diagnosing rot at or cuff t ear.
Key Poi nt
Rot at or cuff t endinit is is charact erized by subacromial t enderness and impingement ; pain oft en occurs wit h reaching overhead and when lying on t he shoulder.
Bi bl i ography
Koest er MC, George MS, Kuhn JE. Shoulder impingement syndrome. Am J Med. 2005;118(5):452-455. [PMID: 15866244]
Item 7 Answer: A
Educati onal Objecti ve: Diagnose referred shoulder pain.
The most appropriat e next st ep in t his pat ient 's management is a chest radiograph t o evaluat e for a cause of referred pain t o t he shoulder. Referred shoulder pain, in cont rast
t o int rinsic shoulder problems, is always associat ed wit h a normal shoulder examinat ion t hat does not alt er t he severit y or t he charact er of t he pain. This pat ient 's
examinat ion is not specific for a process involving t he shoulder apparat us. There are no physical examinat ion signs t hat localize t he pain t o any shoulder st ruct ure. Radicular
sympt oms due t o nerve ent rapment at t he level of t he cervical spine might be poorly localized t o t he t rapezius or arm; however, t hese sympt oms are usually accompanied by
parest hesias, muscle weakness, and abnormal reflexes, which are absent in t his pat ient . Referred shoulder pain is oft en t he result of an underlying int rat horacic process. A
chest radiograph may help t o ident ify an underlying int rat horacic process, such as an apical lung t umor, effusion, or pneumot horax.
Physical t herapy would be a reasonable opt ion if t he shoulder pain were found t o be musculoskelet al in nat ure; however, given her full range of mot ion and no localizing signs
on examinat ion, physical t herapy is unlikely t o be helpful and furt her evaluat ion for t he cause of t he shoulder pain is warrant ed. Likewise, wit hout evidence of eit her a
musculoskelet al or an int ra-art icular et iology, neit her a skelet al muscle relaxant nor int ra-art icular cort icost eroid inject ion would be appropriat e.
Plain radiography has limit ed ut ilit y in t he init ial evaluat ion of shoulder pain in t he absence of t rauma or shoulder deformit y. Imaging may be necessary in pat ient s wit h
severe or persist ent pain and/or funct ional loss. In t his pat ient , a radiograph would be unlikely t o demonst rat e changes, given t hat she has had no t rauma and her physical
examinat ion shows no findings of shoulder pat hology.
Key Poi nt
Referred shoulder pain, in cont rast t o int rinsic shoulder problems, is always associat ed wit h a normal shoulder examinat ion t hat does not alt er t he severit y or t he charact er of
t he pain.
Bi bl i ography
Mit chell C, Adebajo A, Hay E, Carr A. Shoulder pain: diagnosis and management in primary care. BMJ. 2005;331(7525):1124-8. [PMID: 16282408]
Item 8 Answer: B
Educati onal Objecti ve: Treat polymyalgia rheumatica.
The most appropriat e management in t his pat ient is t o increase t he prednisone dosage t o 7.5 mg/d and add met hot rexat e, 10 mg weekly. Typically, pat ient s wit h
polymyalgia achieve resolut ion of t heir sympt oms wit h low-dose prednisone (10 t o 20 mg/d); once t hese sympt oms are cont rolled, t he prednisone dosage can t hen be
t apered. However, polymyalgia rheumat ica commonly recurs when t he prednisone dosage is being t apered. During flares, t he prednisone dosage should be increased t o t he
minimum amount needed t o provide sympt omat ic relief; once sympt oms subside, slower t apering of t he dosage is warrant ed.
Because t wo previous at t empt s t o t aper t his pat ient 's prednisone dosage below 7.5 mg/d have been unsuccessful, t he addit ion of a st eroid-sparing agent as well as an increase in
her prednisone dosage is warrant ed. Met hot rexat e in part icular has been shown t o be an effect ive st eroid-sparing agent in pat ient s wit h polymyalgia rheumat ica.
This pat ient 's prednisone dosage should be increased t o t he minimum dosage needed t o cont rol her sympt oms, which in t his individual has been shown t o be bet ween 7 and 7.5
mg/d. Increasing t his pat ient 's prednisone dosage t o 20 mg/d would unnecessarily place her at great er risk for cort icost eroid t oxicit y. Infliximab has not been shown t o be an
effect ive st eroid-sparing agent in pat ient s wit h polymyalgia rheumat ica and t herefore would not be indicat ed for t his pat ient .
Key Poi nt
Met hot rexat e is an effect ive st eroid-sparing agent in t he t reat ment of polymyalgia rheumat ica.
Bi bl i ography
Caporali R, Cimmino MA, Feraccioli G, et al; Syst emic Vasculit is St udy Group of t he It alian Societ y for Rheumat ology. Prednisone plus met hot rexat e for polymyalgia
rheumat ica: a randomized, double-blind, placebo-cont rolled t rial. Ann Int ern Med. 2004;141 (7):493-500. [PMID: 15466766]
Item 9 Answer: D
Educati onal Objecti ve: Treat presumed methicillin-resistant Staphyl ococcus aureus septic arthritis with vancomycin.
The most appropriat e init ial ant ibiot ic select ion for t his pat ient is vancomycin. Sept ic art hrit is is a medical emergency. Hemat ogenous spread is t he most common
mechanism of joint infect ion, because t he synovium has no basement membrane and is, t herefore, part icularly vulnerable t o infect ion. Staphylococcus is t he most common
gram-posit ive organism affect ing nat ive and prost het ic joint s, and infect ion wit h t he met hicillin-resist ant st rain is becoming increasingly common. Joint s t hat have been
previously damaged are more likely t o become infect ed t han st ruct urally normal joint s. In part icular, pat ient s wit h rheumat oid art hrit is have usually used int ra-art icular
cort icost eroids or immunosuppressive agent s at some point in t heir disease course and are, t herefore, part icularly suscept ible t o infect ion. Sept ic art hrit is also is more likely
t o have a polyart icular present at ion in pat ient s wit h pre-exist ing rheumat oid art hrit is t han in ot her pat ient s. In general, vancomycin is t he empiric t herapy of choice for
communit y-acquired sept ic art hrit is and synovial fluid posit ive for gram-posit ive cocci or in pat ient s at low risk for gram-negat ive infect ion and wit h a negat ive synovial fluid
Gram st ain. Because t his pat ient 's synovial fluid is posit ive for gram-posit ive cocci and because of increasing concern about met hicillin-resist ant Staphylococcus aureus
(MRSA) infect ion in t he communit y, vancomycin is t he init ial t reat ment of choice pending cult ure result s. Modificat ions of t he init ial ant ibiot ic regimen can be made t o
narrow coverage wit h cefazolin or nafcillin when cult ure result s are available but are not generally recommended as init ial empiric t herapy because of t he prevalence of MRSA
in t he communit y.
Ceft riaxone is t he init ial ant ibiot ic of choice in pat ient s at risk for gonococcal infect ion. Gonococcal art hrit is is t he most common form of bact erial art hrit is in young,
sexually act ive persons and should be considered in pat ient s who present wit h migrat ory t enosynovit is and art hralgia.
Key Poi nt
In general, vancomycin is t he empiric t herapy of choice for communit y-acquired sept ic art hrit is wit h synovial fluid posit ive for gram-posit ive cocci and in pat ient s at low
risk for gram-negat ive infect ions and wit h a negat ive Gram st ain result .
Bi bl i ography
Mat hews CJ, West on VC, Jones A, Field M, Coakley G. Bact erial sept ic art hrit is in adult s. Lancet . 2010;375(9717):846-55. [PMID: 20206778]
Item 10 Answer: A
Educati onal Objecti ve: Diagnose septic arthritis in a patient with rheumatoid arthritis.
This pat ient most likely has sept ic art hrit is, which usually manifest s as acut e monoart hrit is and is charact erized by pain on passive range of mot ion in t he absence of known
t rauma. Art hrocent esis of t he wrist will most likely help t o est ablish a diagnosis in t his pat ient .
Sept ic art hrit is should part icularly be suspect ed in pat ient s wit h underlying rheumat ologic disorders such as rheumat oid art hrit is who present wit h a sudden single joint flare
t hat is not accompanied by ot her feat ures of t he pre-exist ing disorder. However, all pat ient s who present wit h acut e monoart hrit is should be presumed t o have sept ic art hrit is
unt il synovial fluid analysis via art hrocent esis excludes t his condit ion. Synovial fluid analysis is t he only definit ive way t o diagnose sept ic art hrit is and is crit ical t o guide
ant ibiot ic t reat ment . Pat ient s wit h suspicion for t his condit ion should begin empiric syst emic ant ibiot ic t herapy unt il cult ure result s are available.
Surgical drainage or debridement via art hroscopy may be warrant ed in pat ient s wit h sept ic art hrit is who do not respond t o repeat ed percut aneous drainage and appropriat e
ant ibiot ic t herapy but would not be an appropriat e init ial int ervent ion.
Joint and bone damage due t o infect ion are relat ively lat e radiographic findings. In acut e sept ic art hrit is, nonspecific soft -t issue fullness and joint effusions are oft en t he only
init ial radiographic findings and do not est ablish t he diagnosis of infect ion. Bone scans are more sensit ive in det ect ing inflammat ory lesions in bones and joint s but also are
not specific for infect ion.
MRI of t he affect ed joint is especially useful in det ect ing avascular necrosis, soft -t issue masses, and collect ions of fluid not visualized by ot her imaging modalit ies but would
not est ablish t he diagnosis of infect ion.
Key Poi nt
All pat ient s who present wit h acut e monoart hrit is should be presumed t o have sept ic art hrit is unt il synovial fluid analysis via art hrocent esis excludes t his condit ion.
Bi bl i ography
Kherani RB, Shojania K. Sept ic art hrit is in pat ient s wit h pre-exist ing inflammat ory art hrit is. CMAJ. 2007;176(11):1605-1608. [PMID: 17515588]
Item 11 Answer: D
Educati onal Objecti ve: Diagnose prosthetic joint infection.
This pat ient most likely has prost het ic joint infect ion, which may occur at any t ime in t he post operat ive period. Prost het ic joint infect ions t hat occur aft er t he first
post operat ive year are most frequent ly caused by hemat ogenous spread of organisms t o t he prost het ic joint . The source of infect ion in t his set t ing is oft en obvious and
includes skin or genit ourinary t ract infect ion or, as in t his pat ient , an abscessed t oot h. Pain is t he predominant or only sympt om in pat ient s wit h prost het ic joint infect ion,
and fever and leukocyt osis are frequent ly absent . Pat ient s wit h prost het ic joint infect ion usually have an elevat ed eryt hrocyt e sediment at ion rat e. Radiography may reveal
prost het ic loosening, but hardware loosening may occur in pat ient s wit hout infect ion, as well.
The gold st andard for diagnosing prost het ic joint infect ion is art hrocent esis or int raoperat ive t issue sampling wit h cult ure before ant ibiot ic t herapy is init iat ed. The synovial
fluid leukocyt e count in pat ient s wit h prost het ic joint infect ion is usually lower compared wit h t hat in pat ient s wit h ot her forms of sept ic art hrit is.
Asept ic loosening refers t o loss of fixat ion of t he art hroplast y component s, which is a major long-t erm complicat ion of hip art hroplast y. The most st riking manifest at ion of
t his condit ion is pain in t he proximal and medial aspect of t he t high t hat is worse wit h weight bearing. Ost eolysis is t ypically seen on radiographs of affect ed pat ient s, which
t his pat ient does not have. Asept ic loosening also would not explain t his pat ient 's inflammat ory synovial fluid.
This pat ient 's elevat ed synovial fluid leukocyt e count wit h a predominance of neut rophils is suggest ive of gout , but t his condit ion does not have a subacut e onset and does not
commonly affect t he hips. An acut e at t ack of gout also would be associat ed wit h cryst als visible on polarized light microscopy of t he synovial fluid.
Pigment ed villonodular synovit is is a rare proliferat ive synovit is t hat most commonly involves t he hip or knee. Radiographs in pat ient s wit h t his condit ion may reveal bone
erosions or may be normal. Pigment ed villonodular synovit is t ypically develops in young pat ient s and is not associat ed wit h prost het ic joint placement .
Key Poi nt
In pat ient s wit h prost het ic joint infect ion, pain is t he predominant or only sympt om, and fever and leukocyt osis are frequent ly absent .
Bi bl i ography
Trampuz A, Zimmerli W. Diagnosis and t reat ment of implant -associat ed sept ic art hrit is and ost eomyelit is. Curr Infect Dis Rep. 2008;10(5):394-403. [PMID: 18687204]
Item 12 Answer: D
Educati onal Objecti ve: Treat acute gout with a nonsteroidal anti-inflammatory drug (NSAID).
The most appropriat e t reat ment for t his pat ient is administ rat ion of an NSAID such as indomet hacin. Definit ive diagnosis of gout requires t he ident ificat ion of monosodium
urat e cryst als on art hrocent esis or aspirat ion of a t ophus. During an at t ack of gout , needle-shaped monosodium urat e cryst als t hat t ypically appear engulfed by t he
neut rophils are visible on compensat ed polarized light microscopy. NSAIDs, cort icost eroids, and colchicine are opt ions in t he t reat ment of an acut e at t ack of gout . NSAIDs
are highly effect ive when administ ered during an acut e at t ack, but t hey should be used wit h caut ion in pat ient s at risk for renal impairment , bleeding, or ulcer disorders,
especially in t he elderly. Oral, int ra-art icular, or int ravenous cort icost eroid t herapy is also effect ive in acut e gout y at t acks. However, oral and int ravenous t herapy may be
problemat ic in pat ient s wit h diabet es mellit us. Colchicine is most effect ive in pat ient s wit h monoart icular involvement and, when used wit hin t he first 24 hours of sympt oms,
can abort a severe at t ack. At t he first sign of an at t ack in pat ient s wit h normal renal funct ion, t his agent is usually administ ered t wo or t hree t imes daily unt il t he pat ient
experiences sympt omat ic relief, develops gast roint est inal t oxicit y, or reaches a maximum dose of 6 mg per at t ack.
Allopurinol and febuxost at are xant hine oxidase inhibit ors useful in reducing uric acid levels in pat ient s wit h recurrent at t acks of acut e gout and pat ient s wit h uric acid t ophi or
renal st ones. Rapid cont rol of serum uric acid levels generally is not necessary during an acut e at t ack, and acut e increases and decreases in t he uric acid level alt er t he st eady
st at e and may prolong t he current at t ack or precipit at e new at t acks. Prophylact ic colchicine, low-dose cort icost eroids, or NSAIDs init iat ed at least 1 week before beginning
or adjust ing t he dose of uric acid-lowering t herapy help t o prevent disease flares associat ed wit h changes in uric acid levels and may need t o be cont inued unt il t herapeut ic
serum uric acid levels have been achieved (<6 mg/dL [0.4 mmol/L]). Prolonged use of t hese agent s may be indicat ed in pat ient s wit h chronic t ophaceous gout unt il t he disease
is cont rolled.
Key Poi nt
NSAIDs, cort icost eroids, and colchicine are opt ions in t he t reat ment of an acut e at t ack of gout .
Bi bl i ography
Wilson JF. In t he clinic. Gout . Ann Int ern Med. 2010;152(3):ITC2-1-ITC2-16. [PMID: 20124228]
Item 13 Answer: C
Educati onal Objecti ve: Treat hyperuricemia with uric acid-lowering therapy.
The most appropriat e t herapy for t his pat ient is low-dose colchicine and allopurinol. Crit eria for init iat ing t reat ment of hyperuricemia in pat ient s wit h sympt omat ic gout
include t he presence of t ophi or renal st ones, mult iple at t acks of acut e gout , or a hist ory of a decreasing period bet ween at t acks. Uric acid-lowering t herapy t ypically is not
init iat ed unt il a pat ient experiences t wo document ed acut e at t acks. Diet ary purine rest rict ion, weight loss, and discont inuat ion of alcohol may help t o decrease uric acid levels
in pat ient s wit h mild hyperuricemia and sympt omat ic gout . Medicat ions t hat raise serum uric acid levels, such as t hiazide diuret ics and low-dose salicylat es, should be
discont inued if alt ernat ive t herapy is available. However, most pat ient s wit h recurrent gout y at t acks, part icularly t hose wit h t ophaceous deposit s, require pharmacologic
t herapy t o lower serum levels of uric acid. The goal in uric acid-lowering t herapy is t o achieve a serum uric acid level less t han 6.0 mg/dL (0.4 mmol/L), not just levels wit hin
t he normal range. When t he uric acid levels are below 6.0 mg/dL (0.4 mmol/L), monosodium urat e cryst als from wit hin t he joint and from soft -t issue t ophaceous deposit s are
reabsorbed. Prophylact ic colchicine, low-dose cort icost eroids (10 mg/d or less), or nonst eroidal ant i-inflammat ory drugs (NSAIDs) init iat ed at least 1 week before beginning
or adjust ing t he dose of uric acid-lowering t herapy help t o prevent disease flares associat ed wit h changes in uric acid levels and may need t o be cont inued unt il t herapeut ic
serum uric acid levels have been achieved.
Low-dose NSAIDs, such as indomet hacin, or low-dose colchicine may prevent at t acks of gout but do not lower uric acid levels and, t herefore, cannot prevent t he cont inued
accumulat ion of uric acid in soft t issues (t ophi), uric acid kidney st ones, or dest ruct ive art hrit is.
Key Poi nt
Prophylact ic colchicine, low-dose cort icost eroids, or NSAIDs are init iat ed at least 1 week before beginning or adjust ing t he dose of uric acid-lowering t herapy t o prevent
disease flares associat ed wit h changes in uric acid levels.
Bi bl i ography
Wilson JF. In t he clinic. Gout . Ann Int ern Med. 2010;152(3):ITC2-1-ITC2-16. [PMID: 20124228]
Item 14 Answer: A
Educati onal Objecti ve: Diagnose calcium pyrophosphate dihydrate deposition disease.
This pat ient has calcium pyrophosphat e dihydrat e (CPPD) deposit ion disease present ing as pseudogout . Pseudogout manifest s as acut e or subacut e at t acks of warmt h and
swelling in one t o t wo joint s t hat resemble acut e gout y art hropat hy. Pseudogout is associat ed wit h inflammat ory synovial fluid and t he presence of CPPD cryst als t hat are
weakly posit ively birefringent and rhomboid in shape seen on polarized light microscopy. Treat ment of an acut e pseudogout at t ack primarily involves NSAIDs, but a
cort icost eroid or colchicine would be appropriat e alt ernat ive choices.
This pat ient 's radiographic and physical examinat ion findings also are suggest ive of ost eoart hrit is. Ost eoart hrit is t hat manifest s in pat ient s wit h CPPD deposit ion or t he
presence of chondrocalcinosis on radiography is known as pseudo-ost eoart hrit is. This degenerat ive condit ion mimics ost eoart hrit is except t hat it may affect joint s not
t ypically involved in ost eoart hrit is, such as t he wrist s, met acarpophalangeal joint s, shoulders, and ankles. The synovial fluid in pat ient s wit h pseudo-ost eoart hrit is is
noninflammat ory. Bot h pseudo-ost eoart hrit is and pseudogout may be present in t he same pat ient . The t reat ment of pseudo-ost eoart hrit is is no different t han t he t reat ment
of ost eoart hrit is and includes adequat e analgesia, physical and occupat ional t herapy, and art hroplast y for sympt omat ic disease unresponsive t o more conservat ive t herapy.
Charact erist ic feat ures of chronic apat it e deposit ion disease include large, minimally inflammat ory effusions t hat usually develop in t he shoulder or knee, dest ruct ion of
associat ed t endon st ruct ures, and chronic pain. Calcium apat it e cryst als may only appear as amorphous nonbirefringent cryst alline clumps on synovial fluid analysis and
t herefore are not ident ified on rout ine examinat ion. Ident ificat ion of t hese cryst als requires special st aining or cryst al analysis t hat is not rout inely available. The absence of
t hese cryst als in t his pat ient excludes t his condit ion.
Gout is caused by t he deposit ion of monosodium urat e cryst als in t he t issues of and around t he joint s. Early at t acks of gout are monoart icular and most commonly involve t he
first met at arsophalangeal joint , whereas chronic gout may manifest as symmet ric involvement of t he small joint s of t he hands and feet accompanied by t ophi and subcort ical
erosions on radiography. Definit ive diagnosis of gout is est ablished by t he presence of st rongly negat ively birefringent needle-shaped cryst als on polarized light microscopy of
synovial fluid or fluid from a t ophus, which is not consist ent wit h t his pat ient 's findings.
The diagnosis of sept ic art hrit is should be considered in all pat ient s wit h acut e monoart hrit is and a sudden increase in pain in a chronically damaged joint . This pat ient 's joint
fluid is inflammat ory, but t he leukocyt e count is not sufficient ly elevat ed t o suggest sept ic art hrit is.
Key Poi nt
Pseudogout is associat ed wit h acut e or subacut e at t acks of warmt h and swelling in one t o t wo joint s t hat resemble acut e gout y art hropat hy and weakly posit ive birefringent
cryst als t hat are rhomboid in shape seen on polarized light microscopy of synovial fluid.
Bi bl i ography
Rosent hal AK. Updat e in calcium deposit ion diseases. Curr Opin Rheumat ol. 2007;19(2):158-162. [PMID: 17278931]
Item 15 Answer: B
Educati onal Objecti ve: Diagnose osteoarthritis of the knee.
This pat ient most likely has ost eoart hrit is of t he knee. He has t wo risk fact ors for t his condit ion, advanced age and an occupat ion involving repet it ive bending and physical
labor. Ost eoart hrit is commonly affect s weight -bearing joint s such as t he knees and is charact erized by pain on act ivit y t hat is relieved wit h rest . Swelling in pat ient s wit h t his
condit ion is usually minimal, and range of mot ion may be limit ed. According t o t he American College of Rheumat ology, ost eoart hrit is of t he knee can be diagnosed if knee
pain is accompanied by at least t hree of t he following feat ures: age great er t han 50 years, morning st iffness last ing less t han 30 minut es, crepit us, bony t enderness, bony
enlargement , and an absence of palpable warmt h. This pat ient 's radiographic findings of ost eophyt es, joint -space narrowing, sclerosis, and cyst format ion are t ypical of t his
condit ion. Art hrocent esis is not necessary t o est ablish a diagnosis of ost eoart hrit is.
Pat ient s wit h avascular necrosis of t he knee t ypically experience pain on weight bearing and may have a painful, limit ed range of mot ion. However, t his condit ion also is
associat ed wit h pain on rest and most commonly occurs in pat ient s who use cort icost eroids, have syst emic lupus eryt hemat osus, or consume excessive amount s of alcoholic
beverages. Radiographs in pat ient s wit h avascular necrosis usually reveal densit y changes; subchondral radiolucency; cyst s; sclerosis; and, event ually, joint -space narrowing.
Rheumat oid art hrit is may be associat ed wit h a limit ed range of mot ion and joint -space narrowing visible on radiography. Pat ient s wit h rheumat oid art hrit is usually have
symmet ric art hrit is t hat affect s at least t hree joint s as well as an elevat ed eryt hrocyt e sediment at ion rat e and is associat ed wit h morning st iffness t hat persist s for more t han
30 minut es. In addit ion, rheumat oid art hrit is also would not explain t he presence of subchondral sclerosis and ost eophyt es on radiography.
A t orn medial meniscus would cause pain in t he knee and can occur in t he elderly in associat ion wit h ost eoart hrit is. Pat ient s wit h acut e meniscal damage oft en describe a
t wist ing injury wit h t he foot in a weight -bearing posit ion in which a popping or t earing sensat ion is felt , followed by severe pain; in addit ion, t his condit ion is charact erized by
t he sensat ion t hat t he knee "locks" or "gives out ."
Key Poi nt
Physical examinat ion findings consist ent wit h ost eoart hrit is of t he knee include crepit us, bony t enderness, bony enlargement , and an absence of palpable warmt h.
Bi bl i ography
Felson DT. Clinical pract ice. Ost eoart hrit is of t he knee [errat um in N Engl J Med. 2006;354(23):2520]. N Engl J Med. 2006;354(8):841-848. [PMID: 16495396]
Item 16 Answer: D
Educati onal Objecti ve: Manage osteoarthritis of the knee.
This pat ient has ost eoart hrit is of t he knee. The most appropriat e next st ep in her management is referral for physical t herapy, which is an appropriat e first -line
management opt ion for pat ient s wit h t his condit ion. Quadriceps muscle t raining in part icular has been shown t o reduce pain in t his populat ion group. Use of over-t he-count er
acet aminophen or an NSAID on an as-needed basis also may benefit t his pat ient .
Art hroscopy and MRI of t he knee would most likely reveal abnormalit ies of t he art icular cart ilage not visible on plain radiography but are not needed t o est ablish t he
diagnosis of ost eoart hrit is. Similarly, aspirat ion of t he knee joint would be warrant ed in pat ient s wit h an effusion t o obt ain a synovial fluid leukocyt e count but is not needed
t o est ablish a diagnosis; furt hermore, t his pat ient does not have an effusion.
Key Poi nt
Physical t herapy is an appropriat e first -line management opt ion for pat ient s wit h ost eoart hrit is of t he knee, and quadriceps muscle t raining in part icular has been shown t o
reduce pain in t his set t ing.
Bi bl i ography
Bennell KL, Hinman RS, Met calf BR, et al. Efficacy of physiot herapy management of knee joint ost eoart hrit is: a randomised, double blind, placebo cont rolled t rial. Ann
Rheum Dis. 2005;64(6):906-912. [PMID: 15897310]
Item 17 Answer: D
Educati onal Objecti ve: Diagnose osteoarthritis of the first carpometacarpal joint.
This pat ient most likely has ost eoart hrit is of t he first carpomet acarpal joint . Ost eoart hrit is in t his locat ion oft en present s wit h well localized t enderness t o palpat ion.
Movement of t he t humb in a circular mot ion ("grind t est ") will oft en elicit t he pain. Predisposing fact ors include repet it ive use of t he wrist or t humb. Pat ient s may present
wit h pain, swelling, or enlargement of t he carpomet acarpal joint recognized as squaring or boxing at t he base of t he t humb. Associat ed findings of ost eoart hrit is are common
and may include boney enlargement of t he dist al int erphalangeal joint s (Heberden nodes) or t he proximal int erphalangeal joint s (Bouchard nodes).
Rheumat oid art hrit is is an inflammat ory art hrit is most oft en affect ing t he small joint s of t he hands (wrist , met acarpophalangeal and proximal int erphalangeal joint s) and feet
(met at arsophalangeal joint s) in a symmet ric pat t ern. St iffness in rheumat oid art hrit is usually last s more t han 1 hour, and synovial swelling, t enderness, and warmt h are
apparent on examinat ion.
de Quervain t enosynovit is is an inflammat ion of t he abduct or pollicis longus and ext ensor pollicis brevis t endons. Pain is present on palpat ion of t he dist al aspect of t he
radial st yloid. This point is more proximal t han t he first carpomet acarpal joint . Pain elicit ed by flexing t he t humb int o t he palm, closing t he fingers over t he t humb, and t hen
bending t he wrist in t he ulnar direct ion (Finkelst ein t est ) is confirmat ory.
Carpal t unnel syndrome will oft en present wit h pain, numbness, and t ingling in t he t humb and first t wo fingers of t he hand. Tapping t he flexor ret inaculum (Tinel sign) or
flexing t he wrist s against each ot her (Phalen sign) may exacerbat e sympt oms. Sympt oms are oft en worse at night or wit h repet it ive movement s or cont inuous pressure on
t he wrist such as t yping on a keyboard.
Cryst al-induced art hrit is in t he hands is usually associat ed wit h evidence of joint inflammat ion such as redness and warmt h. Addit ionally, t he chronicit y of t his pat ient 's
sympt oms argues against cryst al-induced art hropat hy. Secondary ost eoart hrit is, however, can develop in t he set t ing of chronic inflammat ion from cryst al-induced art hrit is.
Key Poi nt
Chronic pain at t he base of t he t humb is suggest ive of ost eoart hrit is.
Bi bl i ography
Hunt er DJ. In t he clinic. Ost eoart hrit is. Ann Int ern Med. 2007;147(3):ITC8-1-ITC8-16. [PMID: 17679702]
Item 18 Answer: A
Educati onal Objecti ve: Manage acute osteoarthritis of the knee with nonsteroidal anti-inflammatory drugs.
The best management for t his pat ient is t o begin a nonst eroidal ant i-inflammat ory drug (NSAID). This pat ient most likely has acut e ost eoart hrit is of t he knee. Classic
findings of ost eoart hrit is include pain wit h act ivit y t hat is relieved wit h rest . The pat ient 's radiographic findings of joint space narrowing, subchondral sclerosis and
ost eophyt e format ion are consist ent wit h ost eoart hrit is, and his valgus deformit y predisposes him t o medial compart ment ost eoart hrit is due t o uneven loading forces when
ambulat ing. He has failed t reat ment wit h acet aminophen and t herefore an oral NSAID such as ibuprofen is t he appropriat e next management st ep. Physical t herapy,
t emporary use of a cane and bracing or t aping are also reasonable init ial int ervent ions. NSAIDs are associat ed wit h an increased risk of gast roint est inal bleeding and
cardiovascular disease. The American College of Rheumat ology guidelines recommend t hat physicians and pat ient s weigh t he pot ent ial risks and benefit s of t reat ment wit h
NSAIDs, but no evidence-based guidelines yet exist t o indicat e which pat ient s can safely use t hese agent s.
Int ra-art icular cort icost eroid or hyaluronan inject ions may be considered in pat ient s wit h mono- or pauciart icular ost eoart hrit is in whom NSAIDs are eit her cont raindicat ed
or do not provide adequat e pain relief. Referral t o an ort hopedic surgeon for considerat ion of t ot al joint art hroplast y (replacement ) of t he knee is warrant ed only when no
furt her medical t herapy is available and t he pat ient decides t hat t he impairment caused by his or her condit ion warrant s t his int ervent ion. This pat ient has not had a sufficient
t rial of more conservat ive measures t o warrant eit her of t hese t herapies.
Magnet ic resonance imaging would be indicat ed if t here were feat ures on hist ory or physical exam t hat suggest ed anot her et iology for t he pain. Meniscal t ears are seen almost
universally in pat ient s wit h ost eoart hrit is of t he knee and are not necessarily a cause of increased sympt oms. Removal of menisci should be avoided unless sympt oms of knee
locking or t he inabilit y t o ext end t he knee are present .
Ant ibiot ic t reat ment is not indicat ed because art hrocent esis does not suggest sept ic art hrit is. In noninflammat ory art hrit is, t he synovial fluid leukocyt e count is usually less
t han 2000/L (2.0 10
9
/L). Sept ic art hrit is usually has leukocyt e count s great er t han 50,000/L (50 10
9
/L) and a predominance of polymorphonuclear cells.
Key Poi nt
In pat ient s wit h ost eoart hrit is not adequat ely cont rolled wit h acet aminophen, t he next pharmacological int ervent ion is usually a nonst eroidal ant i-inflammat ory drug.
Bi bl i ography
Hunt er DJ. In t he clinic. Ost eoart hrit is. Ann Int ern Med. 2007;147:ITC8-1-ITC8-16. [PMID: 17679702]
Item 19 Answer: D
Educati onal Objecti ve: Diagnose rheumatoid arthritis with characteristic radiographic findings.
A radiograph showing marginal joint erosions would most likely support a diagnosis of rheumat oid art hrit is (RA). Plain radiographs of t he hands and feet should be performed
at t he t ime of diagnosis in pat ient s wit h rheumat oid art hrit is t o det ect erosions and joint -space narrowing. Erosions of cart ilage and bone are cardinal feat ures of RA. Erosions
and joint -space narrowing may develop as early as 2 t o 3 mont hs, and are oft en present 6 mont hs aft er t he onset of rheumat oid art hrit is. Progression is more rapid early in
t he disease. In a pat ient wit h symmet rical synovit is of t he small joint s of t he hand and prolonged morning st iffness, x-rays showing joint erosions is most support ive of
rheumat oid art hrit is.
The result s of init ial laborat ory st udies in pat ient s wit h rheumat oid art hrit is may be normal but can reveal t hrombocyt osis, leukocyt osis, mild anemia (normochromic,
normocyt ic, or microcyt ic), an elevat ed eryt hrocyt e sediment at ion rat e, or an elevat ed C-react ive prot ein level. Normochromic, normocyt ic anemia is a nonspecific
response t o chronic inflammat ion and is not specific for RA. An elevat ed eryt hrocyt e sediment at ion rat e does not always indicat e inflammat ion, just as a normal result does
not exclude it . Serologic markers for rheumat oid art hrit is, including rheumat oid fact or and ant i-cyclic cit rullinat ed pept ide (CCP) ant ibodies, have been found in t he serum of
pat ient s years before t he onset of clinically apparent disease. Approximat ely 75% of pat ient s wit h rheumat oid art hrit is are rheumat oid fact or posit ive, but t he prevalence
rat e may be as low as 50% in early disease. Rheumat oid fact or posit ivit y is not specific for rheumat oid art hrit is and frequent ly occurs in ot her aut oimmune disorders and
chronic infect ions, most not ably chronic act ive hepat it is C virus infect ion.
Key Poi nt
Erosions of cart ilage and bone are cardinal x-ray feat ures of rheumat oid art hrit is.
Bi bl i ography
Huizinga TW, Pincus T. In t he clinic. Rheumat oid art hrit is. Ann Int ern Med. 2010;153(1):ITC1-1-ITC1-15. [PMID: 20621898]
Item 20 Answer: D
Educati onal Objecti ve: Screen for latent tuberculosis prior to initiating tumor necrosis factor- inhibitor therapy.
A t uberculin skin t est should be performed prior t o init iat ing t herapy wit h adalimumab. When adequat e disease cont rol is not achieved wit h oral disease modifying
ant irheumat ic drugs (DMARDs) such as met hot rexat e, biologic t herapy should be init iat ed. The init ial biologic t herapy should be a TNF- inhibit or. This agent generally
should be added t o t he baseline met hot rexat e t herapy, because t he rat e of radiographic progression has been shown t o decrease wit h combinat ion t herapy. Rarely, serious
infect ions have occurred in pat ient s t reat ed wit h t hese agent s; among t hese infect ious complicat ions, react ivat ion t uberculosis is t he most common. Tuberculin skin t est ing is
indicat ed before beginning t reat ment wit h t hese agent s, and posit ive result s on t his t est warrant t reat ment for lat ent t uberculosis. Furt hermore, periodic t uberculin skin t est ing
for t uberculosis is now recommended during t reat ment wit h a TNF- inhibit or. A chest CT scan is not necessary prior t o init iat ing t herapy wit h a TNF- inhibit or. If t he
pat ient has a posit ive t uberculin skin t est (>5 mm indurat ion), a chest x-ray will be required t o exclude act ive pulmonary t uberculosis but neit her t his t est nor a chest CT scan
is indicat ed in an asympt omat ic person wit h a negat ive t uberculin skin t est .
Rare cases of mult iple sclerosis or demyelinat ing condit ions such as opt ic neurit is have been report ed as a pot ent ial complicat ion of TNF- inhibit or t herapy but usually remit
upon discont inuat ion of t herapy. There is no value in screening asympt omat ic pat ient s for mult iple sclerosis wit h a brain MRI. Numerous ot her condit ions, such as migraine,
cerebrovascular disease, hypert ension, smoking, diabet es mellit us, hyperlipidemia, and head t rauma, are also associat ed wit h whit e mat t er abnormalit ies on brain MRI.
Misint erpret at ion of whit e mat t er abnormalit ies discovered incident ally in a pat ient wit h nonspecific sympt oms is a leading cause of mult iple sclerosis misdiagnosis
Many drugs can int erfere wit h t hyroid hormone product ion, release, t ransport and act ivit y; however drugs t o t reat rheumat oid art hrit is do not usually fall int o t his cat egory.
Cort icost eroids, for example, can int erfere wit h TSH release and decrease t hyroid binding globulin, but TNF- inhibit ors do not int erfere wit h t hyroid funct ion and t here is no
need t o obt ain a TSH measurement in t his pat ient prior t o init iat ing t herapy.
Key Poi nt
The most common infect ious complicat ion of TNF- inhibit ors is react ivat ion t uberculosis.
Bi bl i ography
Huizinga TW, Pincus T. In t he clinic. Rheumat oid art hrit is. Ann Int ern Med. 2010;153(1):ITC1-1-ITC1-15; quiz ITC1-16. [PMID: 20621898]
Item 21 Answer: D
Educati onal Objecti ve: Diagnose rheumatoid arthritis.
This pat ient most likely has rheumat oid art hrit is, which is t he most common cause of chronic, inflammat ory polyart hrit is in premenopausal women. Rheumat oid art hrit is
commonly affect s t he met acarpophalangeal, proximal int erphalangeal, and wrist joint s. This pat ient 's swelling, prolonged morning st iffness, and elevat ed eryt hrocyt e
sediment at ion rat e are consist ent wit h t his diagnosis. Furt hermore, women are t hree t imes more likely t o develop rheumat oid art hrit is t han men and have a slight ly increased
risk of developing t his condit ion during t he first 3 mont hs post part um.
Gout may involve t he hand and wrist and is associat ed wit h inflammat ory feat ures. However, gout usually has an asymmet ric present at ion and is unlikely t o develop in a
premenopausal woman.
Ost eoart hrit is may manifest as chronic art hrit is involving t he proximal int erphalangeal joint s but would not affect t he met acarpophalangeal joint s or t he wrist s. Secondary
ost eoart hrit is relat ed t o t rauma or a met abolic condit ion such as hemochromat osis may explain t his pat ient 's pat t ern of joint involvement , but t his condit ion would be
unlikely in a 26-year-old woman. Ost eoart hrit is also would not have an inflammat ory present at ion.
Viral art hrit is usually is self-limit ed except when associat ed wit h hepat it is B and C virus infect ion. Parvovirus B19 infect ion in adult s may induce an acut e rheumat oid fact or-
posit ive oligo- or polyart hrit is. Most adult pat ient s wit h parvovirus B19 infect ion also develop rash, but only rarely in adult s does rash manifest as t he classic rash seen in
childhood eryt hema infect iosum, t he "slapped cheek" rash. Diagnosis of acut e parvovirus B19 infect ion may be est ablished by det ect ing circulat ing IgM ant ibodies against
parvovirus B19.
Viral art hrit is usually resolves wit hin 3 weeks, alt hough a minorit y of pat ient s may develop persist ent art hrit is. The art hrit is associat ed wit h acut e parvovirus B19 infect ion
does not cause joint dest ruct ion, and support ive analgesic t herapy wit h NSAIDs is appropriat e as t olerat ed. Parvovirus B19 infect ion is unlikely in t his pat ient considering t he
durat ion of her sympt oms, absence of rash, and negat ive t it ers of IgM ant ibodies against parvovirus B19.
Key Poi nt
Rheumat oid art hrit is is t he most common cause of chronic, inflammat ory polyart hrit is in premenopausal women.
Bi bl i ography
Item 22 Answer: A
Educati onal Objecti ve: Treat early rheumatoid arthritis.
This pat ient has rheumat oid art hrit is, and t he most appropriat e t reat ment pat ient is t he addit ion of hydroxychloroquine, 400 mg/d. Prominent morning st iffness t hat usually
last s for more t han 1 hour and fat igue are consist ent wit h early present at ions of rheumat oid art hrit is. This condit ion most oft en involves t he small joint s of t he hands and
feet in a symmet ric pat t ern, but involvement of t he large joint s also may occur. The presence of bot h rheumat oid fact or and ant i-cyclic cit rullinat ed pept ide ant ibodies is
highly specific for rheumat oid art hrit is, and radiographic manifest at ions of affect ed pat ient s include periart icular ost eopenia and, event ually, art icular erosions.
In pat ient s wit h rheumat oid art hrit is, early, aggressive disease cont rol is crit ical and should be inst it ut ed as soon as t he diagnosis is est ablished. Expert s recommend t hat
affect ed pat ient s begin disease-modifying ant irheumat ic drug (DMARD) t herapy wit hin 3 mont hs of t he onset of t his condit ion. Hydroxychloroquine is warrant ed in a pat ient
wit h early, mild, and nonerosive rheumat oid art hrit is and is well t olerat ed.
Met hot rexat e is oft en used as an init ial DMARD in t he t reat ment of rheumat oid art hrit is. However, t his agent is associat ed wit h hepat ot oxicit y, and risk for t his condit ion is
increased in pat ient s who regularly consume alcoholic beverages; t herefore, met hot rexat e is not indicat ed for t hese pat ient s. The amount of alcohol t hat can safely be
consumed in pat ient s who use met hot rexat e has not yet been det ermined, but daily consumpt ion of alcoholic beverages while using t his agent is not recommended and most
expert s advise against t he use of met hot rexat e for pat ient s who regularly consume alcohol.
The biologic DMARD et anercept would be an appropriat e adjunct medicat ion in a pat ient wit h rheumat oid art hrit is in whom oral DMARD t herapy has not provided adequat e
disease cont rol. Et anercept and ot her t umor necrosis fact or inhibit ors have great er efficacy when used in combinat ion wit h met hot rexat e. However, t here is current ly
insufficient evidence showing t hat single-agent use of a biologic DMARD is an appropriat e init ial t reat ment for t his condit ion.
Combinat ion t herapy wit h an NSAID and a DMARD has been shown t o reduce joint pain and swelling in pat ient s wit h rheumat oid art hrit is. However, increasing t his pat ient 's
ibuprofen dosage in t he absence of DMARD t herapy would not help t o cont rol her disease progression or prevent radiographic damage.
Key Poi nt
In pat ient s wit h rheumat oid art hrit is, disease-modifying ant irheumat ic drug t herapy should be init iat ed as soon as t he diagnosis is est ablished.
Bi bl i ography
Item 23 Answer: B
Educati onal Objecti ve: Diagnose HIV-related psoriatic arthritis.
The most appropriat e diagnost ic approach is t est ing for t he presence of HIV infect ion. HIV-infect ed pat ient s wit h a CD4 cell count less t han 200/L who are not t aking
ant iret roviral t herapy commonly have psoriasis or ot her skin condit ions, including phot odermat it is, prurigo nodularis, molluscum cont agiosum, and drug react ions. Psoriasis
in pat ient s wit h a low CD4 cell count can be severe, affect more t han 50% of t he body surface area, and present in an at ypical fashion (more severe, explosive onset ). In
pat ient s wit h psoriasis, 20% t o 40% develop art hrit is. A diagnosis of HIV-relat ed psoriat ic art hrit is should be suspect ed in pat ient s wit h explosive onset , widespread psoriasis
and t he occurrence of dact ylit is; marked dist al int erphalangeal (DIP) joint involvement ; asymmet ric joint involvement ; sympt oms of ent hesit is; or joint ankylosis.
No confirmat ory laborat ory t est s for psoriat ic art hrit is are available. In pat ient s wit h psoriat ic art hrit is, low t it er ant inuclear ant ibody t est s and rheumat oid fact or are found
in less 50% and 10% of pat ient s, respect ively. HLA-B27 ant igen t est ing is neit her sensit ive nor specific for psoriat ic art hrit is and is not helpful in est ablishing t he diagnosis.
Key Poi nt
Unt reat ed HIV infect ion is associat ed wit h t he occurrence of explosive-onset , widely dist ribut ed psoriasis and 20% t o 40% of pat ient s wit h psoriasis may go on t o develop
psoriat ic art hrit is.
Bi bl i ography
Cant ini F, Niccoli L, Nannini C, Kaloudi O, Bert oni M, Cassara E. Psoriat ic art hrit is: a syst emat ic review. Int J Rheum Dis. 2010;13(4):300-17. [PMID:21199465]
Item 24 Answer: B
Educati onal Objecti ve: Diagnose enteropathic arthritis.
This pat ient 's joint sympt oms are most likely caused by ent eropat hic art hrit is. She has a 6-week hist ory of crampy abdominal pain and t he recent onset of bloody diarrhea
and rect al urgency. She also has had weight loss. This clinical present at ion raises suspicion for inflammat ory bowel disease.
For t he past 3 weeks, t his pat ient also has had acut e art hrit is of t he right knee and ankle accompanied by inflammat ory feat ures such as t enderness and swelling; her synovial
fluid findings confirm t he presence of an inflammat ory process. The presence of acut e oligoart icular art hrit is involving t he lower ext remit ies in a pat ient wit h an
inflammat ory diarrheal illness is suggest ive of ent eropat hic art hrit is; ent eropat hic art hrit is also may manifest as axial art hrit is, such as a spondyloart hropat hy.
Cryst al-induced art hrit is t ypically manifest s as acut e monoart icular art hrit is and would be unlikely in a premenopausal woman.
Gonococcal art hrit is may be associat ed wit h oligoart icular art hrit is, and joint manifest at ions in t his condit ion may be migrat ory. However, pat ient s wit h gonococcal art hrit is
commonly have t enosynovit is and cut aneous involvement , which are not present in t his pat ient . Furt hermore, neit her gonococcal nor cryst al-induced art hrit is would explain
t his pat ient 's diarrhea and abdominal pain.
Whipple disease is an ext remely rare infect ious syndrome caused by Tropheryma whippelii. The most common present ing sympt om in affect ed pat ient s is art hrit is; ot her
sympt oms include diarrhea, malabsorpt ion, and cent ral nervous syst em and const it ut ional sympt oms. Joint involvement is usually migrat ory and follows a chronic course.
Key Poi nt
The presence of acut e oligoart icular art hrit is involving t he lower ext remit ies in a pat ient wit h inflammat ory bowel disease is suggest ive of ent eropat hic art hrit is.
Bi bl i ography
Holden W, Orchard T, Wordswort h P. Ent eropat hic art hrit is. Rheum Dis Clin Nort h Am. 2003;29(3):513-530, viii. [PMID: 12951865]
Item 25 Answer: A
Educati onal Objecti ve: Diagnose ankylosing spondylitis in a patient with anterior uveitis.
The pat ient has ant erior uveit is wit h a hypopyon, and t he associat ed syst emic disease is most likely ankylosing spondylit is. The classic t riad for acut e ant erior uveit is is pain,
sensit ivit y t o light , and blurred vision; headache, t enderness, and t earing may also occur. Phot ophobia during penlight examinat ion has a posit ive predict ive value of 60% for
severe eye disease and a negat ive predict ive value of 90%.
Prospect ive st udies have document ed syst emic illness in 53% of pat ient s wit h ant erior uveit is. Pat ient s wit h uveit is associat ed wit h syst emic disease usually have a hist ory or
physical examinat ion findings t hat suggest an underlying disorder. The most commonly diagnosed syst emic illnesses in t his set t ing are react ive art hrit is, ankylosing
spondylit is, and sarcoidosis.
Acut e ant erior uveit is, part icularly unilat eral present at ions t hat fluct uat e bet ween bot h eyes over t ime, is st rongly associat ed wit h t he HLA-B27-relat ed art hropat hies,
including ankylosing spondylit is. In addit ion, t his pat ient 's chronic back st iffness is highly suggest ive of ankylosing spondylit is. Furt hermore, in up t o 65% of pat ient s wit h
uveit is, spondyloart hropat hy remains undiagnosed unt il t hese pat ient s present wit h uveit is.
Post erior uveit is may be relat ed t o sarcoidosis or vasculit is but is not t ypically associat ed wit h pain or redness of t he eye. Pat ient s wit h post erior uveit is also oft en have
decreased visual acuit y and float ers, which is not consist ent wit h t his pat ient 's present at ion. Furt hermore, sarcoidosis is an unlikely cause of t his pat ient 's chronic low back
pain.
Sicca syndrome manifest s as dryness of t he mout h, eyes, and vagina and variable enlargement of t he parot id glands in associat ion wit h concomit ant redness and grit t y
irrit at ion of t he eyes. This condit ion is suggest ive of primary or secondary Sjogren syndrome. However, Sjogren syndrome would not cause ant erior uveit is and also would not
explain t he presence of chronic low back pain in a young man.
Ant erior uveit is is associat ed wit h psoriasis and, in rare cases, Whipple disease, syst emic lupus eryt hemat osus, and t he syst emic vasculit ides. However, t he pat ient 's long
hist ory of back pain in t he absence of cut aneous and ot her manifest at ions of syst emic lupus eryt hemat osus makes t his diagnosis unlikely.
Key Poi nt
The most commonly diagnosed syst emic illnesses in pat ient s wit h ant erior uveit is are react ive art hrit is, ankylosing spondylit is, and sarcoidosis.
Bi bl i ography
Sampaio-Barros PD, Conde RA, Bonfiglioli R, Bert olo MB, Samara AM. Charact erizat ion and out come of uveit is in 350 pat ient s wit h spondyloart hropat hies. Rheumat ol Int .
2006;26(12):1143-1146. [PMID: 16957887]
Item 26 Answer: D
Educati onal Objecti ve: Diagnose ankylosing spondylitis with an MRI of the sacroiliac joints.
This pat ient most likely has ankylosing spondylit is, and MRI of t he sacroiliac joint s is most likely t o est ablish a diagnosis. Radiographic evidence of sacroiliit is is required for
definit ive diagnosis and is t he most consist ent finding associat ed wit h t his condit ion. Onset of ankylosing spondylit is usually occurs in t he t eenage years or 20s and manifest s
as persist ent pain and morning st iffness involving t he low back t hat are alleviat ed wit h act ivit y. This condit ion also may be associat ed wit h t enderness of t he pelvis.
Typically, t he earliest radiographic changes in affect ed pat ient s involve t he sacroiliac joint s, but t hese changes may not be visible for several years; t herefore, t his pat ient 's
normal radiographs of t he pelvis do not exclude sacroiliit is. MRI, especially wit h gadolinium enhancement , is considered a sensit ive met hod for det ect ing early erosive
inflammat ory changes in t he sacroiliac joint s and spine and can assess sit es of act ive disease and response t o effect ive t herapy.
Ant i-cyclic cit rullinat ed pept ide ant ibodies are highly specific for rheumat oid art hrit is. However, rheumat oid art hrit is does not involve t he sacroiliac joint s or lumbar spine,
and t est ing for t his condit ion in t his pat ient is t herefore not indicat ed.
An elevat ed eryt hrocyt e sediment at ion rat e would raise suspicion for an inflammat ory process but would not help t o est ablish a specific diagnosis. In addit ion, t he eryt hrocyt e
sediment at ion rat e does not correlat e wit h disease act ivit y in pat ient s wit h ankylosing spondylit is, and measurement of t his value is t herefore not useful in diagnosing or
monit oring pat ient s wit h t his condit ion.
HLA-B27 posit ivit y is a st rong risk fact or for ankylosing spondylit is. However, less t han 5% of pat ient s who have t his allele develop t his condit ion. In addit ion, not all
pat ient s who have ankylosing spondylit is have t his allele. Therefore, it is neit her 100% sensit ive nor 100% specific for t he diagnosis of ankylosing spondylit is.
Key Poi nt
MRI, especially wit h gadolinium enhancement , is a sensit ive met hod for det ect ing early erosive inflammat ory changes in t he sacroiliac joint s and spine.
Bi bl i ography
Maksymowych WP. MRI in ankylosing spondylit is. Curr Opin Rheumat ol. 2009;21(4):313-7. [PMID: 19496307]
Item 27 Answer: A
Educati onal Objecti ve: Diagnose systemic lupus erythematosus with anti-double-stranded DNA antibody.
The next , most helpful serologic t est for t his pat ient is t he ant i-double-st randed DNA ant ibody. This pat ient wit h pleurit ic chest pain, symmet ric synovit is of t he hand and
wrist joint s, leukopenia, prot einuria, and a posit ive ANA likely has syst emic lupus eryt hemat osus (SLE). Pat ient s wit h a high pret est probabilit y of SLE and ANAs (t it er
1:160) should undergo confirmat ory t est ing, such as measurement of compliment levels C3, C4, and t ot al hemolyt ic compliment (CH50) and more specific aut oant ibody
t est ing, such as ant i-double-st randed DNA ant ibody t est ing (specificit y, 75%-100%).
The ant iribonucleoprot ein ant ibody is st rongly associat ed wit h mixed connect ive t issue disease but also can be seen in pat ient s wit h SLE and myosit is, but is neit her very
sensit ive nor specific for SLE. Ant i-SS-A and ant i-SS-B ant ibodies (somet imes referred t o as ant i-Ro and ant i-La, respect ively) are neit her sensit ive nor specific for SLE; t hey
are seen in Sjogren syndrome. In pat ient s wit h SLE, a posit ive ant i-SS-A ant ibody is oft en associat ed wit h subacut e cut aneous lupus eryt hemat osus. Two ant ibodies are
associat ed wit h syst emic sclerosis: ant i-t opoisomerase I (ant i-Scl-70) and ant icent romere. The ant i-Scl-70 ant ibody is seen in approximat ely half of t he pat ient s wit h diffuse
syst emic sclerosis and is associat ed wit h t he development of int erst it ial lung disease. The ant icent romere ant ibody is associat ed wit h limit ed cut aneous syst emic sclerosis.
Approximat ely 75% of pat ient s wit h rheumat oid art hrit is are rheumat oid fact or posit ive, but t he prevalence rat e of rheumat oid art hrit is may be as low as 50% in early
disease. Rheumat oid fact or posit ivit y is not specific for rheumat oid art hrit is and frequent ly occurs in ot her aut oimmune disorders, including SLE, and chronic infect ions, most
not ably chronic act ive hepat it is C virus infect ion.
Key Poi nt
The ant i-double-st randed DNA ant ibody is very specific for syst emic lupus eryt hemat osus.
Bi bl i ography
Cabral AR, Alarcon-Segovia D. Aut oant ibodies in syst emic lupus eryt hemat osus. Curr Opin Rheumat ol. 1997;9(5):387-92. [PMID: 9309193]
Item 28 Answer: B
Educati onal Objecti ve: Treat drug-induced lupus.
This pat ient most likely has drug-induced lupus caused by t he t umor necrosis fact or inhibit or infliximab. The most appropriat e next st ep in t his pat ient 's management is t o
discont inue infliximab and begin prednisone.
Many pat ient s who use t umor necrosis fact or inhibit ors develop aut oant ibodies, including ant inuclear, ant i-double-st randed DNA, and ant i-Smit h ant ibodies; rarely, t hese
pat ient s develop drug-induced lupus. Pat ient s wit h t his condit ion may present wit h t ypical manifest at ions of syst emic lupus eryt hemat osus but are part icularly likely t o have
cut aneous and pleuropericardial involvement . Renal and neurologic manifest at ions are ext remely rare.
The most appropriat e management of a pat ient wit h drug-induced lupus caused by a t umor necrosis fact or inhibit or is discont inuat ion of t he offending agent , which usually
resolves t his condit ion. Prednisone also should be added t o t his pat ient 's medicat ion regimen t o cont rol pleurit is and synovit is associat ed wit h drug-induced lupus.
Alt hough t his pat ient 's worsening joint sympt oms may be relat ed t o her underlying rheumat oid art hrit is, her rheumat oid art hrit is had been well cont rolled on her current
medicat ion regimen. If her flare were relat ed t o act ive rheumat oid art hrit is, her sympt oms would most likely be alleviat ed by init iat ion of sulfasalazine or an increase in her
infliximab dosage. However, her musculoskelet al feat ures, fever, malar rash, phot osensit ivit y, purpura, sympt oms of pleurit is, ant inuclear and ant i-double-st randed DNA
ant ibody posit ivit y, and findings on chest radiography also raise st rong suspicion for drug-induced lupus. Therefore, progressive rheumat oid art hrit is is a less likely
explanat ion for t his pat ient 's current sympt oms t han is drug-induced lupus, and init iat ion of sulfasalazine or an increase in her infliximab dosage would not be indicat ed.
Hydroxychloroquine may be useful for t he t reat ment of syst emic lupus eryt hemat osus and drug-induced lupus and could be added t o t his pat ient 's exist ing medicat ion regimen,
but discont inuing met hot rexat e would not be appropriat e.
Key Poi nt
The most appropriat e management of a pat ient wit h drug-induced lupus caused by a t umor necrosis fact or inhibit or is discont inuat ion of t he offending agent .
Bi bl i ography
Ramos-Casals M, Brit o-Zeron P, Munoz S, et al. Aut oimmune diseases induced by TNF-t arget ed t herapies: analysis of 233 cases. Medicine (Balt imore). 2007;86(4):242-251.
[PMID: 17632266]
Item 29 Answer: B
Educati onal Objecti ve: Treat suspected lupus glomerulonephritis.
This pat ient 's hypert ension, ankle edema, hemat uria, prot einuria, hypoalbuminemia, and eryt hrocyt e cast s on urinalysis are highly suggest ive of lupus nephrit is despit e t he
absence of renal insufficiency. To prevent irreversible renal damage, early t reat ment wit h a high-dose cort icost eroid such as prednisone is indicat ed for pat ient s whose
condit ion raises st rong suspicion for lupus nephrit is. Whet her renal biopsy is necessary in t his clinical sit uat ion in order t o est ablish a diagnosis remains uncert ain, and
t reat ment wit h high-dose cort icost eroids would not significant ly alt er subsequent biopsy result s.
Init iat ion of ant ihypert ensive t herapy would benefit t his pat ient but is not t he most appropriat e next st ep in t he management of her condit ion; t reat ment of her nephrit is
t akes precedence and may it self help t o cont rol her hypert ension. Inst ead of a calcium channel blocker such as amlodipine, angiot ensin-convert ing enzyme inhibit ors are t he
ant ihypert ensive drugs of choice in pat ient s wit h lupus nephrit is because t hese agent s help t o cont rol prot einuria.
Ibuprofen may help t o cont rol t his pat ient 's art hralgia. However, NSAIDs can significant ly worsen renal funct ion in pat ient s wit h lupus nephrit is and are t herefore
cont raindicat ed in t his pat ient populat ion.
Low-dose prednisone may help t o alleviat e t his pat ient 's art hralgia and rash but would not t reat her lupus nephrit is.
Key Poi nt
Early t reat ment wit h high-dose cort icost eroids is indicat ed in pat ient s whose condit ion raises st rong suspicion for lupus nephrit is.
Bi bl i ography
Buhaescu I, Covic A, Deray G. Treat ment of proliferat ive lupus nephrit isa crit ical approach. Semin Art hrit is Rheum. 2007;36(4):224-237. [PMID: 17067659]
Item 30 Answer: D
Educati onal Objecti ve: Diagnose the malar skin rash of systemic lupus erythematosus.
This woman most likely has syst emic lupus eryt hemat osus (SLE). Pat ient s wit h SLE have sun sensit ivit y, and t heir disease is t riggered or exacerbat ed by light in t he
ult raviolet A and ult raviolet B spect rums. The facial rash, seen in t he figure, is a classic present at ion, involving t he bridge of t he nose, malar areas, and forehead (not seen),
wit h eryt hemat osus plaques and a fine scale. The nasolabial folds are relat ively prot ect ed from t he sun, and t he absence of t he rash in t his area helps t o dist inguish it from
ot her common rashes of t he face, including rosacea and seborrheic dermat it is. The rash may last for hours or days and has a t endency t o recur.
Rosacea is a chronic inflammat ory skin disorder t hat begins in early t o middle adult hood and is charact erized by cent ral t elangiect asis, flushing, and acneiform papules and
pust ules. Many pat ient s wit h rosacea are misdiagnosed as having SLE. However, t he nasolabial folds are not t ypically spared in rosacea, acne-like pust ules are more
prominent , and rosacea is not associat ed wit h ot her syst emic sympt oms, such as art hrit is.
Pat ient s wit h dermat omyosit is have pronounced proximal muscle weakness and elevat ed serum concent rat ions of muscle enzymes such as creat ine kinase. Pat ient s wit h
dermat omyosit is may have a facial rash t hat ext ends up t o t he eyelids, giving t hem a purplish (heliot rope) hue. Anot her charact erist ic finding is red t o purplish plaques on t he
dorsal hands, more prominent over t he joint s, and known as Got t ron papules.
The lesions of seborrheic dermat it is are ill defined (lack a dist inct border), yellowish-red, and of varying size, and are usually associat ed wit h a greasy or dandruff-like scale. It
occurs most commonly on t he scalp, cent ral face, upper mid-chest , and ot her oily areas of t he body, and is not relat ed t o sun exposure or associat ed wit h syst emic sympt oms.
Key Poi nt
The charact erist ic facial rash of syst emic lupus eryt hemat osus involves t he bridge of t he nose, malar areas, and forehead wit h eryt hemat osus plaques and a fine scale.
Bi bl i ography
Rot hfield N, Sont heimer RD, Bernst ein M. Lupus eryt hemat osus: syst emic and cut aneous manifest at ions. Clin Dermat ol. 2006;24:348-62. [PMID: 16966017]
Item 31 Answer: C
Educati onal Objecti ve: Diagnose dermatomyositis-related interstitial lung disease.
The most likely diagnosis is int erst it ial lung disease (ILD). ILD wit h progressive pulmonary fibrosis and secondary pulmonary art erial hypert ension is one of t he leading
causes of deat h in pat ient s wit h polymyosit is and dermat omyosit is. ILD may be prominent at t he onset of myopat hy or develop over t he course of t he disease. The presence
of ant i-Jo-1 ant ibodies is associat ed wit h an increased risk for ILD. Pat ient s wit h ILD have progressive dyspnea, basilar crackles, bibasilar infilt rat es on chest radiographs, and
rest rict ive changes on pulmonary funct ion st udies, including a decreased forced vit al capacit y, t ot al lung capacit y, and diffusing capacit y of t he lungs for carbon monoxide.
Chest radiographs demonst rat e an int erst it ial pat t ern, and high-resolut ion CT scans of t he chest most commonly suggest a diagnosis of nonspecific int erst it ial pneumonia.
Lung biopsy is generally not needed for diagnosis, but bronchoscopy may be needed t o exclude infect ion.
Typical communit y-acquired pneumonia is charact erized by rapid onset of high fever, product ive cough, and pleurit ic chest pain, all of which are absent in t his pat ient .
Cardiac involvement in pat ient s wit h an inflammat ory myopat hy is rare and includes arrhyt hmias and cardiomyopat hy. Furt hermore, t his pat ient has no findings t o support
heart failure, including an S
3
, jugular venous dist ent ion, or peripheral edema. Approximat ely 1% t o 2% of pat ient s wit h rheumat ic diseases can develop pneumocyst is
pneumonia, usually in pat ient s t aking combinat ion immunosuppressant t herapy t hat includes cort icost eroids. The risk may be higher in pat ient s wit h dermat omyosit is or
polymyosit is compared wit h ot her rheumat ic diseases. Most pat ient s wit h rheumat ic disease and pneumocyst is pneumonia have an abrupt onset of acut e respirat ory failure
and fever. This pat ient 's 6-week course of progressive dyspnea and absence of fever make pneumocyst is pneumonia an unlikely diagnosis.
Key Poi nt
Int erst it ial lung disease wit h progressive pulmonary fibrosis and secondary pulmonary art erial hypert ension is one of t he leading causes of deat h in pat ient s wit h polymyosit is
and dermat omyosit is.
Bi bl i ography
Fat hi M, Lundberg IE, Tornling G. Pulmonary complicat ions of polymyosit is and dermat omyosit is. Semin Respir Crit Care Med. 2007;28(4):451-8. [PMID: 17764062]
Item 32 Answer: A
Educati onal Objecti ve: Treat Raynaud phenomenon associated with systemic sclerosis.
This pat ient has Raynaud phenomenon, which is present in more t han 95% of pat ient s wit h syst emic sclerosis and is part icularly likely t o develop in pat ient s wit h limit ed
cut aneous disease. The most appropriat e t reat ment for t his pat ient is amlodipine.
Syst emic sclerosis is classified according t o t he degree of skin involvement . Syst emic sclerosis wit h limit ed cut aneous involvement , or CREST syndrome (calcinosis, Raynaud
phenomenon, esophageal dysmot ilit y, sclerodact yly, and t elangiect asia), manifest s as skin t hickening dist al t o t he elbows and knees. Conversely, syst emic sclerosis wit h
diffuse cut aneous involvement is associat ed wit h skin t hickening proximal t o t he elbows and knees. Diffuse and limit ed cut aneous syst emic sclerosis may affect t he face.
Episodes of Raynaud phenomenon are oft en precipit at ed by cold exposure or st ress and usually involve t he ext remit ies. In pat ient s wit h Raynaud phenomenon, cigaret t e
smoking is cont raindicat ed and avoidance of cold is recommended; pharmacologic t herapy is warrant ed for pat ient s in whom t hese int ervent ions do not provide sufficient
relief. Dihydropyridine calcium channel blockers such as amlodipine have been shown t o reduce t he frequency and severit y of at t acks in pat ient s wit h bot h primary and
secondary Raynaud phenomenon, and t hese agent s are frequent ly used as first -line t reat ment in t his condit ion. Ot her agent s used t o manage Raynaud phenomenon include
peripherally act ing -1 blockers, phosphodiest erase inhibit ors, and endot helin recept or ant agonist s.
Topical nit rat es applied t o t he finger webs are oft en used in t he t reat ment of Raynaud phenomenon but are usually used as second-line t herapy. Oral t herapy wit h
nit roglycerin is less effect ive and less well t olerat ed t han amlodipine and is not indicat ed as a first -line drug for t his condit ion.
Raynaud phenomenon is caused by microvascular involvement in pat ient s wit h syst emic sclerosis and is charact erized by int imal proliferat ion and progressive luminal
oblit erat ion, as well as digit al spasm. This process does not respond t o ant i-inflammat ory agent s; t herefore, prednisone is not indicat ed in t he t reat ment of Raynaud
phenomenon.
-Blockers such as propranolol are not indicat ed in t he t reat ment of Raynaud phenomenon and may act ually worsen sympt oms by prevent ing -adrenergic-mediat ed
vasodilat ion.
Key Poi nt
Use of a dihydropyridine calcium channel blocker is warrant ed in pat ient s wit h Raynaud phenomenon in whom cold avoidance does not provide sufficient relief.
Bi bl i ography
Henness S, Wigley FM. Current drug t herapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review. Curr Opin Rheumat ol. 2007;19(6):611-618.
[PMID: 17917543]
Item 33 Answer: A
Educati onal Objecti ve: Diagnose fibromyalgia.
This pat ient most likely has fibromyalgia. This condit ion is charact erized by diffuse pain on bot h sides of t he body and above and below t he waist as well as axial skelet al pain,
or, according t o t he original American College of Rheumat ology crit eria, t he presence of pain in at least 11 of 18 specified pot ent ial t ender point s. However, expert opinion
now st at es t hat t hese t ender point s are arbit rary and not essent ial in t he diagnosis of fibromyalgia.
Most pat ient s wit h t his condit ion have fat igue and sleep dist urbance. Fibromyalgia also may be associat ed wit h dry eyes and mout h. St udies t hat have assessed t he comorbidit y
of fibromyalgia wit h ot her sympt om-defined syndromes have found high rat es of chronic fat igue syndrome, migraine, irrit able bowel syndrome, pelvic pain, and
t emporomandibular joint pain in pat ient s wit h fibromyalgia.
Polymyosit is may manifest as muscle pain and fat igue but is unlikely in t he absence of significant proximal muscle weakness or an elevat ed creat ine kinase level.
Up t o 25% of pat ient s wit h syst emic inflammat ory condit ions, such as syst emic lupus eryt hemat osus (SLE) and rheumat oid art hrit is, have sympt oms consist ent wit h
fibromyalgia in t he init ial st ages of t heir illness. This pat ient 's fat igue, polyart hralgia, dry eyes and mout h, and st rongly posit ive t it ers of ant inuclear ant ibodies are consist ent
wit h SLE and Sjogren syndrome. However, pat ient s wit h SLE usually have anemia, leukopenia, or lymphopenia. Similarly, joint involvement in Sjogren syndrome t ypically
manifest s as inflammat ory art hrit is. Furt hermore, pat ient s wit h SLE and Sjogren syndrome may have syst emic manifest at ions, including cut aneous, neurologic, and renal
involvement , which are absent in t his pat ient .
The presence of ant inuclear ant ibodies is not diagnost ic of SLE or Sjogren syndrome. These ant ibodies are oft en present in t he general populat ion and part icularly in pat ient s
wit h aut oimmune t hyroid disease or in first -degree relat ives of pat ient s wit h SLE. In addit ion, high t it ers of ant inuclear ant ibodies do not necessarily indicat e t he presence of
aut oimmune disease.
Key Poi nt
Fibromyalgia is charact erized by diffuse pain on bot h sides of t he body and above and below t he waist as well as axial skelet al pain.
Bi bl i ography
Chakrabart y S, Zoorob R. Fibromyalgia. Am Fam Physician. 2007;76(2):247-254. [PMID: 17695569]
Item 34 Answer: C
Educati onal Objecti ve: Diagnose Sjogren syndrome.
This pat ient has Sjogren's syndrome. Sjogren's syndrome is an aut oimmune disease charact erized by kerat oconjunct ivit is sicca, xerost omia, and t he presence of mult iple
aut oant ibodies. This condit ion may occur as a primary disease process or may be associat ed wit h anot her aut oimmune disease. Primary Sjogren's syndrome usually is diagnosed
in pat ient s bet ween 40 and 60 years of age, and t his condit ion has a 9:1 female predominance. The charact erist ic manifest at ions of Sjogren's syndrome are sympt omat ic oral
and ocular dryness. Lymphocyt ic inflammat ion of t he lacrimal glands causes an aqueous t ear deficiency wit h result ant kerat oconjunct ivit is sicca, whereas lymphocyt ic
inflammat ion of t he major and minor salivary glands is associat ed wit h salivary gland enlargement and xerost omia. A cardinal feat ure of Sjogren's syndrome is t he presence of
aut oant ibodies, which may include ant ibodies t o Ro/SSA and La/SSB. These aut oant ibodies are not specific for Sjogren's syndrome; t hey may also occur in subset s of pat ient s
wit h syst emic lupus eryt hemat osus and in asympt omat ic women. Ant inuclear ant ibodies and rheumat oid fact or also frequent ly are present in pat ient s wit h t his condit ion, as is
hypergammaglobulinemia.
Hodgkin disease is an aggressive lymphoid malignancy t hat t ypically present s wit h rapidly progressive, sympt omat ic disease, oft en init ially localized t o one organ or
compart ment (for example, bone marrow).
Sarcoidosis is a mult isyst em, granulomat ous inflammat ory disease of unknown cause. It occurs most commonly in young and middle-aged adult s, wit h a peak incidence in t he
t hird decade. The most common present ing manifest at ions involve t he lymphat ic and pulmonary syst ems, along wit h t he eyes and skin.
Syst emic lupus eryt hemat osus (SLE) is a chronic mult isyst em aut oimmune disease of unknown cause. Manifest at ions of t his het erogeneous syndrome range from mild t o
severe and life t hreat ening and most commonly involve t he skin and joint s. Ot her manifest at ions include cyt openias, hemolyt ic anemia, serosit is, apht hous ulcers, and kidney
disease.
The syndrome of dry eyes, parot id gland enlargement and art hrit is is not found in syst emic lupus eryt hemat osus, lymphoma, or sarcoidosis.
Key Poi nt
Sjogren syndrome is an aut oimmune disease charact erized by kerat oconjunct ivit is sicca, xerost omia, and t he presence of mult iple aut oant ibodies.
Bi bl i ography
Tzioufas AG, Voulgarelis M. Updat e on Sjogren's syndrome aut oimmune epit helit is: from classificat ion t o increased neoplasias. Best Pract Res Clin Rheumat ol. 2007;21:989-
1010. [PMID: 18068857]
Item 35 Answer: B
Educati onal Objecti ve: Diagnose polyarteritis nodosa as a cause of kidney failure.
This pat ient most likely has polyart erit is nodosa, which is charact erized by a necrot izing inflammat ion of t he medium-sized or small art eries wit hout glomerulonephrit is or
vasculit is of t he art erioles, capillaries, or venules. Clinical manifest at ions of t his condit ion include fever; musculoskelet al sympt oms; and vasculit is involving t he nervous
syst em, gast roint est inal t ract , heart , and nonglomerular renal vessels t hat is associat ed wit h hypert ension, kidney insufficiency, prot einuria, and hemat uria.
Polyart erit is nodosa most commonly affect s t he kidneys and may cause significant hypert ension, kidney insufficiency, and renal vasculit is associat ed wit h prot einuria and
hemat uria. Prompt immunosuppressive t herapy is crit ical t o reduce t he risk of irreversible kidney failure, but a definit ive diagnosis must be est ablished before beginning t his
t reat ment .
Sural nerve biopsy may est ablish t he diagnosis of polyart erit is nodosa, and kidney angiography can support t his diagnosis. Aft er exclusion of ot her causes of medium- or
small-vessel vasculit is, angiography of t he renal art eries is oft en performed when t here is no appropriat e t issue t o biopsy. Specific angiographic findings in pat ient s wit h
polyart erit is nodosa include microaneurysms or a beaded pat t ern wit h areas of art erial narrowing and dilat ion.
Abdominal fat pad aspirat ion may help t o diagnose AL amyloidosis, but t his condit ion is unlikely in a pat ient wit h normal result s on serum and urine immunoelect rophoreses.
Kidney biopsy may yield a false-negat ive result for polyart erit is nodosa and is associat ed wit h an increased risk for bleeding secondary t o t ranssect ion of an int rarenal
aneurysm. Biopsy of normal skin has a low diagnost ic yield for polyart erit is nodosa because of t he minimal hist ologic abnormalit ies associat ed wit h t his condit ion.
Key Poi nt
Polyart erit is nodosa most commonly affect s t he kidneys and may cause significant hypert ension, kidney insufficiency, and renal vasculit is wit h classic angiographic findings.
Bi bl i ography
Schmidt WA. Use of imaging st udies in t he diagnosis of vasculit is. Curr Rheumat ol Rep. 2004;6(3):203-211. [PMID: 15134599]
Item 36 Answer: D
Educati onal Objecti ve: Diagnose Wegener granulomatosis.
This pat ient most likely has Wegener granulomat osis, a necrot izing vasculit is t hat t ypically affect s t he upper- and lower-respirat ory t ract and t he kidneys. This pat ient 's
purpura is consist ent wit h vasculit is. His diffuse pulmonary infilt rat es (generally associat ed wit h alveolar hemorrhage), hist ory of refract ory ot it is media, renal failure, and
urinalysis findings t hat suggest glomerulonephrit is part icularly raise suspicion for Wegener granulomat osis.
Wegener granulomat osis may be associat ed wit h inflammat ory art hrit is involving t he small and large joint s and joint effusions. The presence of c-ANCA and ant iprot einase-3
ant ibodies is approximat ely 90% specific for t his condit ion. The present at ion of Wegener granulomat osis is highly nonspecific and evolves slowly over a period of mont hs;
t herefore, diagnosis of t his condit ion is oft en delayed by several mont hs.
Pat ient s wit h severe, long-st anding rheumat oid art hrit is may develop int erst it ial pneumonit is, and t his condit ion is part icularly likely t o develop in men. Radiographs of
pat ient s wit h t his condit ion usually show bibasilar int erst it ial markings. Int erst it ial lung disease associat ed wit h rheumat oid art hrit is most charact erist ically has an insidious
onset and is associat ed wit h seroposit ive, erosive joint disease. In most pat ient s, t he lung disease appears 5 years or more aft er t he diagnosis of rheumat oid art hrit is.
Met hot rexat e-induced pneumonit is can occur at any t ime in t he course of t herapy wit h t his agent , regardless of t he dosage or durat ion of t reat ment . However, t his condit ion
would not explain t his pat ient 's ent ire clinical pict ure, including c-ANCA posit ivit y, vasculit is, renal failure, and his urinalysis findings.
Pneumocystis pneumonia may manifest as fever, dyspnea, t achypnea, and crackles heard on pulmonary examinat ion. However, dyspnea is t ypically progressive and not acut e
and would not result in rapid pulmonary failure. Chest radiography in pat ient s wit h t his condit ion may show diffuse infilt rat es. Pneumocystis pneumonia also usually develops
in pat ient s who are significant ly immunosuppressed, whereas t his pat ient has received only a short course of low-dose met hot rexat e. Furt hermore, Pneumocystis pneumonia
would not explain t his pat ient 's addit ional findings.
Key Poi nt
Wegener granulomat osis should be considered in pat ient s wit h upper- and lower-airway manifest at ions, renal involvement , and inflammat ory art hrit is.
Bi bl i ography
Bosch X, Guilabert A, Font J. Ant ineut rophil cyt oplasmic ant ibodies. Lancet . 2006;368(9533):404-418. [PMID: 16876669]
Item 37 Answer: B
Educati onal Objecti ve: Manage giant cell arteritis.
This pat ient 's headache, t emporal art ery t enderness, acut e visual loss, fever, and mild anemia are st rongly suggest ive of giant cell art erit is (GCA). Immediat e high-dose
int ravenous met hylprednisolone is indicat ed for t his pat ient . Pain in t he shoulder and hip girdle accompanied by a significant elevat ion in t he eryt hrocyt e sediment at ion rat e
is consist ent wit h polymyalgia rheumat ica, which is present in approximat ely 33% of pat ient s wit h GCA. Ant erior ischemic opt ic neuropat hy usually causes acut e and
complet e visual loss in pat ient s wit h GCA, and funduscopic examinat ion of t hese pat ient s t ypically reveals a pale, swollen opt ic nerve.
Rarely, pat ient s wit h GCA regain vision if t reat ed immediat ely wit h high doses of an int ravenous cort icost eroid such as met hylprednisolone (1 g/d or 100 mg every 8 hours
for 3 days) followed by oral prednisone (1 t o 2 mg/kg/d). More import ant ly, t his aggressive regimen helps t o prevent blindness in t he cont ralat eral eye. Therefore, alt hough
t emporal art ery biopsy is t he gold st andard for diagnosing GCA, diagnost ic t est ing should not precede t reat ment in pat ient s whose clinical present at ion is suspicious for t his
condit ion.
Even in t he absence of visual loss, GCA is a medical emergency. In a pat ient whose condit ion is suspicious for GCA but who does not have visual loss, immediat e init iat ion of
high-dose oral prednisone before diagnost ic t est ing is performed also is indicat ed. Whet her int ravenous cort icost eroid t herapy is more effect ive t han oral administ rat ion of
prednisone for pat ient s wit h GCA and visual loss remains uncert ain. Nevert heless, int ravenous t herapy seems reasonable in t his circumst ance and is recommended by many
expert s, even t hough rigorous st udies have not validat ed t his approach. However, it is clear t hat low-dose oral prednisone, which is an adequat e t reat ment for isolat ed
polymyalgia rheumat ica, does not sufficient ly t reat GCA.
A process in t he brain is unlikely t o cause monocular visual loss, and pat ient s wit h GCA t ypically have normal findings on brain MRI. Therefore, t his st udy would most likely
be unhelpful in t his pat ient .
In pat ient s whose condit ion raises a st rong suspicion of GCA, t emporal art ery biopsy should be performed aft er cort icost eroid t herapy is begun. Cort icost eroid t herapy will
not affect t he result s of t emporal art ery biopsy as long as biopsy is performed wit hin 2 weeks of init iat ing t his t herapy; posit ive biopsy result s have been seen as lat e as 6
weeks aft er inst it ut ion of high-dose cort icost eroid t herapy, but t he yield of biopsy is higher when t his st udy is performed sooner.
Key Poi nt
In pat ient s whose clinical present at ion is suspicious for giant cell art erit is, cort icost eroid t herapy should be inst it ut ed immediat ely, before diagnost ic t est ing is performed.
Bi bl i ography
Fraser JA, Weyand CM, Newman NJ, Biousse V. The t reat ment of giant cell art erit is. Rev Neurol Dis. 2008;5(3):140-152. [PMID: 18838954]
Normal Laboratory Val ues
Note
U.S. t radit ional unit s are followed in parent heses by equivalent values expressed in S.I. unit s.
Hematol ogy
Acti vated parti al thrombopl asti n ti me 25-35 s
Bl eedi ng ti me less t han 10 min
Erythrocyte count 4.2-5.9 10
6
/L (4.2-5.9 10
12
/L)
Erythrocyte sedi mentati on rate
Male 0-15 mm/h
Female 0-20 mm/h
Erythropoi eti n less t han 30 mU/mL (30 U/L)
D-Di mer less t han 0.5 g/mL (0.5 mg/L)
Ferri ti n, serum 15-200 ng/mL (15-200 g/L)
Haptogl obi n, serum 50-150 mg/dL (500-1500 mg/L)
Hematocri t
Male 41%-51%
Female 36%-47%
Hemogl obi n, blood
Male 14-17 g/dL (140-170 g/L)
Female 12-16 g/dL (120-160 g/L)
Leukocyte al kal i ne phosphatase 15-40 mg of phosphorus liberat ed/h per 10
10
cells; score = 13-130/100 polymorphonuclear neut rophils and band forms
Leukocyte count 4000-10,000/L (4.0-10 10
9
/L)
Mean corpuscul ar hemogl obi n 28-32 pg
Mean corpuscul ar hemogl obi n concentrati on 32-36 g/dL (320-360 g/L)
Mean corpuscul ar vol ume 80-100 fL
Pl atel et count 150,000-350,000/L (150-350 10
9
/L)
Prothrombi n ti me 11-13 s
Reti cul ocyte count 0.5%-1.5% of eryt hrocyt es; absolut e: 23,000-90,000/L (23-90 10
9
/L)
Bl ood, Pl asma, and Serum Chemi stry Studi es
Al bumi n, serum 3.5-5.5 g/dL (35-55 g/L)
Al kal i ne phosphatase, serum 36-92 U/L
-Fetoprotei n, serum 0-20 ng/mL (0-20 g/L)
Ami notransferase, al ani ne (ALT) 0-35 U/L
Ami notransferase, aspartate (AST) 0-35 U/L
Ammoni a, plasma 40-80 g/dL (23-47 mol/L)
Amyl ase, serum 0-130 U/L
Bi carbonate, serum see Carbon dioxide
Bi l i rubi n, serum
Total 0.3-1.2 mg/dL (5.1-20.5 mol/L)
Di rect 0-0.3 mg/dL (0-5.1 mol/L)
Bl ood gases, art erial (ambient air)
pH 7.38-7.44
PCO
2
35-45 mm Hg (4.7-6.0 kPa)
PO
2
80-100 mm Hg (10.6-13.3 kPa)
Oxygen saturati on 95% or great er
Bl ood urea ni trogen 8-20 mg/dL (2.9-7.1 mmol/L)
C-reacti ve protei n 0.0-0.8 mg/dL (0.0-8.0 mg/L)
Cal ci um, serum 9-10.5 mg/dL (2.2-2.6 mmol/L)
Carbon di oxi de content, serum 23-28 meq/L (23-28 mmol/L)
Chl ori de, serum 98-106 meq/L (98-106 mmol/L)
Chol esterol , plasma
Total 150-199 mg/dL (3.88-5.15 mmol/L), desirable
Low-densi ty l i poprotei n (LDL) less t han or equal t o 130 mg/dL (3.36 mmol/L), desirable
Hi gh-densi ty l i poprotei n (HDL) great er t han or equal t o 40 mg/dL (1.04 mmol/L), desirable
Compl ement, serum
C3 55-120 mg/dL (550-1200 mg/L)
Total (CH
50
) 37-55 U/mL (37-55 kU/L)
Creati ne ki nase, serum 30-170 U/L
Creati ni ne, serum 0.7-1.3 mg/dL (61.9-115 mol/L)
El ectrol ytes, serum
Sodi um 136-145 meq/L (136-145 mmol/L)
Potassi um 3.5-5.0 meq/L (3.5-5.0 mmol/L)
Chl ori de 98-106 meq/L (98-106 mmol/L)
Carbon di oxi de 23-28 meq/L (23-28 mmol/L)
Fi bri nogen, plasma 150-350 mg/dL (1.5-3.5 g/L)
Fol ate, red cell 160-855 ng/mL (362-1937 nmol/L)
Fol ate, serum 2.5-20 ng/mL (5.7-45.3 nmol/L)
Gl ucose, plasma fast ing, 70-100 mg/dL (3.9-5.6 mmol/L)
-Gl utamyl transferase, serum 0-30 U/L
Homocystei ne, plasma
Male 0.54-2.16 mg/L (4-16 mol/L)
Female 0.41-1.89 mg/L (3-14 mol/L)
Immunogl obul i ns
Gl obul i ns, t ot al 2.5-3.5 g/dL (25-35 g/L)
IgG 640-1430 mg/dL (6.4-14.3 g/L)
IgA 70-300 mg/dL (0.7-3.0 g/L)
IgM 20-140 mg/dL (0.2-1.4 g/L)
IgD less t han 8 mg/dL (80 mg/L)
IgE 0.01-0.04 mg/dL (0.1-0.4 mg/L)
Iron studi es
Ferri ti n, serum 15-200 ng/mL (15-200 g/L)
Iron, serum 60-160 g/dL (11-29 mol/L)
Iron-bi ndi ng capaci ty, total , serum 250-460 g/dL (45-82 mol/L)
Transferri n saturati on 20%-50%
Lactate dehydrogenase, serum 60-100 U/L
Lacti c aci d, venous blood 6-16 mg/dL (0.67-1.8 mmol/L)
Li pase, serum less t han 95 U/L
Magnesi um, serum 1.5-2.4 mg/dL (0.62-0.99 mmol/L)
Methyl mal oni c aci d, serum 150-370 nmol/L
Osmol al i ty, plasma 275-295 mosm/kg H
2
O
Phosphatase, al kal i ne, serum 36-92 U/L
Phosphorus, serum 3-4.5 mg/dL (0.97-1.45 mmol/L)
Potassi um, serum 3.5-5.0 meq/L (3.5-5.0 mmol/L)
Prostate-speci fi c anti gen, serum - less t han 4 ng/mL (4 g/L)
Protei n, serum
Total 6.0-7.8 g/dL (60-78 g/L)
Al bumi n 3.5-5.5 g/dL (35-55 g/L)
Gl obul i ns, total 2.5-3.5 g/dL (25-35 g/L)
Rheumatoi d factor less t han 40 U/mL (40 kU/L)
Sodi um, serum 136-145 meq/L (136-145 mmol/L)
Transferri n saturati on 20%-50%
Tri gl yceri des less t han 150 mg/dL (1.69 mmol/L), desirable
Troponi ns, serum
Troponi n I 0-0.5 ng/mL (0-0.5 g/L)
Troponi n T 0-0.10 ng/mL (0-0.10 g/L)
Urea ni trogen, blood 8-20 mg/dL (2.9-7.1 mmol/L)
Uri c aci d, serum 2.5-8 mg/dL (0.15-0.47 mmol/L)
Vi tami n B
12
, serum 200-800 pg/mL (148-590 pmol/L)
Endocri ne
Adrenocorti cotropi c hormone (ACTH), serum 9-52 pg/mL (2-11 pmol/L)
Al dosterone, serum
Supine 2-5 ng/dL (55-138 pmol/L)
St anding 7-20 ng/dL (194-554 pmol/L)
Al dosterone, urine 5-19 g/24 h (13.9-52.6 nmol/24 h)
Catechol ami nes
Epi nephri ne, plasma (supine) less t han 75 ng/L (410 pmol/L)
Norepi nephri ne, plasma (supine) 50-440 ng/L (296-2600 pmol/L)
Catechol ami nes, 24-hour, urine less t han 100 g/m
2
per 24 h (591 nmol/m
2
per 24 h)
Corti sol , free, urine - less t han 50 g/24 h (138 nmol/24 h)
Dehydroepi androsterone sul fate (DHEA), plasma
Male 1.3-5.5 g/mL (3.5-14.9 mol/L)
Female 0.6-3.3 g/mL (1.6-8.9 mol/L)
Epi nephri ne, plasma (supine) less t han 75 ng/L (410 pmol/L)
Estradi ol , serum
Male 10-30 pg/mL (37-110 pmol/L);
Female day 1-10, 14-27 pg/mL (50-100 pmol/L); day 11-20, 14-54 pg/mL (50-200 pmol/L); day 21-30, 19-41 pg/mL (70-150 pmol/L)
Fol l i cl e-sti mul ati ng hormone, serum
Male (adult ) 5-15 mU/mL (5-15 U/L)
Female follicular or lut eal phase, 5-20 mU/mL (5-20 U/L); midcycle peak, 30-50 mU/mL (30-50 U/L); post menopausal, great er t han 35 mU/mL (35 U/L)
Growth hormone, plasma aft er oral glucose: less t han 2 ng/mL (2 g/L); response t o provocat ive st imuli: great er t han 7 ng/mL (7 g/L)
Lutei ni zi ng hormone, serum
Male 3-15 mU/mL (3-15 U/L)
Female follicular or lut eal phase, 5-22 mU/mL (5-22 U/L); midcycle peak, 30-250 mU/mL (30-250 U/L); post menopausal, great er t han 30 mU/mL (30 U/L)
Metanephri ne, urine less t han 1.2 mg/24 h (6.1 mmol/24 h)
Norepi nephri ne, plasma (supine) 50-440 ng/L (296-2600 pmol/L)
Parathyroi d hormone, serum 10-65 pg/mL (10-65 ng/L)
Prol acti n, serum
Male less t han 15 ng/mL (15 g/L)
Female less t han 20 ng/mL (20 g/L)
Testosterone, serum
Male (adult ) 300-1200 ng/dL (10-42 nmol/L)
Female 20-75 ng/dL (0.7-2.6 nmol/L)
Thyroi d functi on tests
Thyroi d i odi ne (
131
I) uptake 10%-30% of administ ered dose at 24 h
Thyroi d-sti mul ati ng hormone (TSH) 0.5-5.0 U/mL (0.5-5.0 mU/L)
Thyroxi ne (T
4
), serum
Tot al 5-12 g/dL (64-155 nmol/L)
Free 0.9-2.4 ng/dL (12-31 pmol/L)
Free T
4
index 4-11
Tri i odothyroni ne, free (T
3
) 3.6-5.6 ng/L (5.6-8.6 pmol/L)
Tri i odothyroni ne, resi n (T
3
) 25%-35%
Tri i odothyroni ne, serum (T
3
) 70-195 ng/dL (1.1-3.0 nmol/L)
Vani l l yl mandel i c aci d, urine less t han 8 mg/24 h (40.4 mol/24 h)
Vi tami n D
1,25-di hydroxy, serum 25-65 pg/mL (60-156 pmol/L)
25-hydroxy, serum 25-80 ng/mL (62-200 nmol/L)
Uri ne
Al bumi n-creati ni ne rati o less t han 30 mg/g
Cal ci um 100-300 mg/24 h (2.5-7.5 mmol/24 h) on unrest rict ed diet
Creati ni ne 15-25 mg/kg per 24 h (133-221 mmol/kg per 24 h)
Gl omerul ar fi l trati on rate (GFR)
Normal
Male 130 mL/min/1.73 m
2
Female 120 mL/min/1.73 m
2
Stages of Chroni c Ki dney Di sease
St age 1 great er t han or equal t o 90 mL/min/1.73 m
2
St age 2 60-89 mL/min/1.73 m
2
St age 3 30-59 mL/min/1.73 m
2
St age 4 15-29 mL/min/1.73 m
2
St age 5 less t han 15 mL/min/1.73 m
2
5-Hydroxyi ndol eaceti c aci d (5-HIAA) 2-9 mg/24 h (10.4-46.8 mol/24 h)
Protei n-creati ni ne rati o - less t han or equal t o 0.2 mg/mg
Sodi um 100-260 meq/24 h (100-260 mmol/24 h) (varies wit h int ake)
Uri c aci d 250-750 mg/24 h (1.48-4.43 mmol/24 h) (varies wit h diet )
Gastroi ntesti nal
Gastri n, serum 0-180 pg/mL (0-180 ng/L)
Stool fat less t han 5 g/d on a 100-g fat diet
Stool wei ght less t han 200 g/d
Pul monary
Forced expi ratory vol ume i n 1 second (FEV
1
) great er t han 80% of predict ed
Forced vi tal capaci ty (FVC) great er t han 80% of predict ed
FEV
1
/FVC great er t han 75%
Cerebrospi nal Fl ui d
Cel l count 0-5/L (0-5 10
6
/L)
Gl ucose 40-80 mg/dL (2.2-4.4 mmol/L); less t han 40% of simult aneous plasma concent rat ion is abnormal
Pressure (openi ng) 70-200 mm H
2
O
Protei n 15-60 mg/dL (150-600 mg/L)
Hemodynami c Measurements
Cardi ac i ndex 2.5-4.2 L/min/m
2
Left ventri cul ar ejecti on fracti on great er t han 55%
Pressures
Pul monary artery
Syst olic 20-25 mm Hg
Diast olic 5-10 mm Hg
Mean 9-16 mm Hg
Pul monary capi l l ary wedge 6-12 mm Hg
Ri ght atri um mean 0-5 mm Hg
Ri ght ventri cl e
Syst olic 20-25 mm Hg
Diast olic 0-5 mm Hg
Pl ate 1. Gast roent erology and Hepat ology, It em 46
Pl ate 2. General Int ernal Medicine, It em 55
Pl ate 11. Hemat ology, It em 4
Pl ate 21. Infect ious Disease Medicine, It em 21
Pl ate 22. Infect ious Disease Medicine, It em 26
Pl ate 23. Oncology, It em 2
Pl ate 29. Rheumat ology, It em 2

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FOR STUDENTS 5 (2011)

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