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11 November 2001
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Fever of Unknown
KEY FACTS Origin: A Systematic
■ No single diagnostic algorithm
can be universally applied to all
patients with fever of unknown
Approach to Diagnosis
origin (FUO).
University of Wisconsin
■ Geographic location significantly Katharine F. Lunn, BVMS, MS, PhD, MRCVS, DACVIM
influences the diagnostic
differentials of FUO in any patient.
ABSTRACT: Fever of unknown origin (FUO) is by definition a diagnostic challenge. Fortunately,
a diagnosis can be made in most cases if a logical and thorough diagnostic plan is developed.
■ Arthrocentesis should be This article outlines the pathogenesis of fever and presents several options for the
performed in all dogs with FUO. development of an investigative approach to FUO. Data from several case series are compared
and show that infection, immune-mediated diseases, and neoplasia are important causes of
FUO in small animals. Finally, selected diagnostic tests are discussed in detail and therapeutic
approaches are reviewed.
F
ever of unknown origin (FUO) provides a significant diagnostic challenge
in both human and veterinary medicine. In human medicine, FUO was
originally defined as an illness of more than 3 weeks’ duration with a fever
higher than 101˚F (38.4˚C) on several occasions and an uncertain diagnosis after
1 week of hospital investigation. 1 The last component of this definition has
recently been modified to allow investigation as an outpatient or investigation for
at least 3 days as an inpatient.2 A more general definition of FUO is that it is
fever that does not resolve spontaneously in the period expected for self-limited
infection and its cause cannot be ascertained despite considerable diagnostic
effort.3 This definition emphasizes two important points about FUO:
Viral Infections
FeLV infection, feline immunodeficiency virus (FIV) Neoplasia
infection, FIP, canine distemper virus infection Hematopoietic Tumors
Lymphoma, leukemia, myeloma, malignant
Rickettsial, Chlamydial, and Mycoplasma Infections histiocytosis
Canine monocytic ehrlichiosis, canine granulocytic
ehrlichiosis, feline ehrlichiosis, Rocky Mountain spotted Solid Tumors
fever, haemobartonellosis, mycoplasma infections Hepatic tumors, gastric tumors, lung tumors,
metastatic disease, necrotic tumors
Fungal Infections
Blastomycosis, cryptococcosis, coccidioidomycosis,
histoplasmosis Miscellaneous Causes
Drug reactions, toxins, panosteitis, metaphyseal
Protozoal Diseases osteopathy, portosystemic shunt, hyperthyroidism,
Toxoplasmosis, neosporosis, hepatozoonosis, babesiosis, hypothalamic disease, shar-pei fever
leishmaniasis
Lymphoid Lymphoma, lymphadenitis, fungal infection Palpation of lymph nodes, lymph node
aspiration or biopsy
Nervous system Toxoplasmosis, fungal infection, steroid- Fundic and neurologic examination,
responsive meningitis radiography, CT, MRI, cerebrospinal fluid
analysis
pyrogens and appear to induce local release of system affected. This approach can be helpful in
prostaglandins in the hypothalamus, which then elevate choosing diagnostic tests, particularly if the clinical signs
the set point.6,11 of the body system involved are subtle or occult. By
combining a disease mechanism and body system
CAUSES OF FEVER OF UNKNOWN ORIGIN approach, clinicians can plan a diagnostic evaluation
The causes of FUO are often divided into categories that allows for the detection of most causes of FUO.
based on the underlying disease process.7,9 Table 1 shows In the human literature, 30% to 40% of cases of
typical disease categories, with examples of each. Similar FUO are caused by infection, 20% to 30% are caused
information is available from many sources4,7–9,12 (it is by neoplasia, 10% to 20% are the result of rheuma-
beyond the scope of this article to discuss in detail all tologic diseases, 15% to 20% have miscellaneous causes,
potential diagnostic differentials for FUO). Table 2 and 5% to 15% remain undiagnosed.3,13 A similar distri-
outlines a different approach that considers the bution has also been reported in veterinary patients.7
diagnostic differentials of FUO in terms of the body In 1995, Bennett8 noted that of 45 cases of FUO seen at a
Compendium November 2001 Small Animal/Exotics 979
veterinary referral hospital, 21 (47%) were due to infectious Table 3. Diagnoses in 24 Cases of Fever of
or parasitic causes and 18 (40%) were due to immune- Unknown Origin (23 Dogs and 1 Cat)
mediated polyarthritis. Of the remaining cases, 4 (9%) were
due to myeloproliferative disease and 2 (4%) were due to Number
metaphyseal osteopathy. In a larger canine case series, Dunn Diagnosis of Cases
and Dunn 14 reported that 22% of 101 patients with Immune-mediated polyarthritis 6 (25%)
unexplained pyrexia were diagnosed with immune-mediated Blastomycosis 6 (25%)
disease, with immune-mediated polyarthritis accounting for
Neoplasiaa 4 (17%)
20% of those cases. Another 22% of patients were diagnosed
with primary bone-marrow disease; 16% with infectious No diagnosis 2 (8%)
disease; 9.5% with neoplasia; and 11.5% with miscellaneous Peritonitis 1 (4%)
conditions, including metaphyseal osteopathy, meningitis, Endocarditis 1 (4%)
portosystemic shunt, and lymphadenitis. (A diagnosis was E. canis infection 1 (4%)
not established in the remaining 19%.) When considering
FIP 1 (4%)
these reports, it is important to recognize the influence of the
specific areas of interest of the authors and the particular Lymphadenitis 1 (4%)
areas of specialization of the referral centers to which the Panosteitis 1 (4%)
cases were presented. For example, Bennett has a specific a Included splenic hemangiosarcoma, splenic fibroma with a
interest in immune-mediated arthritis,8 and the cases necrotic center, lymphoblastic leukemia, and malignant
reported by Dunn and Dunn were investigated at a hospital histiocytosis.
with a large oncology caseload.14 However, while there may
be some differences in the distribution of cases seen by
different clinicians, the overall implication is that infection, • Tests may often be repeated several times.
immune-mediated disease, and neoplasia are important
causes of FUO in small animals. Table 3 summarizes 24 However, clinicians should also reassure clients of the
cases of FUO that I saw at an internal medicine referral following:
practice over approximately 3 years. For this small series,
infectious disease accounted for 42% (10 of 24) of the cases. • The fever itself is rarely harmful to patients.
These data emphasize the importance of geographic location • A diagnosis is ultimately obtained in most cases.
when considering infectious causes of fever. I practice in a
state with a high incidence of blastomycosis, which is • Many causes of FUO prove to be treatable or
manageable.14
reflected in the fact that 25% of the cases of FUO were
ultimately attributed to this fungal infection. In comparison, The importance of good client communication in these
systemic mycoses are extremely rare in the United Kingdom, cases cannot be overstated. The goal is not to dissuade
as demonstrated in the data of Dunn and Dunn14 and clients from pursuing an exhaustive workup but to
Bennett.8 ensure that the client is a willing partner who is prepared
for the necessary commitment of time and money.
DIAGNOSTIC APPROACH Four factors should be considered when developing a
In human medicine, it has been said that “patience, diagnostic plan for FUO:
compassion, equanimity, and intellectual flexibility are
indispensable attributes for clinicians in dealing 1. The plan should begin with tests that are safe,
successfully with FUO.”15 This statement is certainly simple, inexpensive, and easy to interpret.
also applicable to veterinarians dealing with FUO. It 2. Each clinician should choose a plan that minimizes
should also be remembered that the investigation of the chances of overlooking any potential diagnostic
FUO demands patience and equanimity from the pet differentials. Depending on the preferences of a
owner and often also requires considerable financial clinician, the plan may be based on the consid-
commitment. When planning the diagnostic investi- eration of disease processes (Table 1), a body-system
gation of a patient with FUO, it is essential for approach (Table 2), a stepwise approach to testing
clinicians to explain the following to clients: (Table 4), or a combination of these.
3. The plan should evolve as results of each diagnostic
• Investigation of FUO can be time consuming and
test become available. For example, bone marrow
frustrating.
aspiration should be performed early in the course
• Many diagnostic tests may be necessary. of investigation if a CBC reveals cytopenia. This
980 Small Animal/Exotics Compendium November 2001
same test is likely to be conducted at a later stage in nodes, bones and joints, rectum, mouth, and skin.
a patient with FUO and an unremarkable CBC. Repeated fundic examinations are also essential as they
4. The plan should allow for repetition of simple and may reveal evidence of infectious disease (Figure 1). For
basic diagnostic tests, including physical hospitalized patients, physical examinations should be
examinations, in-depth history taking, CBCs, fine- performed at least twice daily. For outpatients, a
needle aspiration, cultures of fluids, radiography, complete physical examination should be performed at
and infectious disease titers. every hospital visit and an appointment should be
scheduled whenever a client observes a change in a
Table 4 outlines my approach to diagnostic testing in patient’s status. Clients should be advised to watch for
patients with FUO. Similar staged approaches are the development of skin lesions, masses or swellings,
available from other sources,4,9 and the exact details are lameness, and changes in urination or defecation habits.
likely to depend on clinician preference, geographic
location, client compliance, and whether the cases are Complete Blood Cell Count
investigated in a primary care or referral setting. The The CBC should always be accompanied by an
stages should not be rigidly defined, and the timing of examination of the blood smear. This will allow
specific tests should primarily be dictated by the
abnormalities detected in a patient.
Figure 2—Morulae within the neutrophils of a dog infected Figure 3—Lateral thoracic radiograph from a 5-year-old golden
with E. canis. retriever with fever due to blastomycosis. There is a marked
increase in soft-tissue density in the perihilar region, with
detection of morphologic abnormalities in blood cells compression of the caudal trachea and main-stem bronchi
as well as the possible detection of organisms (Figure suggestive of tracheobronchial lymphadenopathy. There is also
a diffuse interstitial pattern throughout the lung fields.
2). The latter may require the careful examination of
repeated blood smears. Many patients with inflam-
matory or infectious causes of fever may have a Figure 3 illustrates an example of a dog with blasto-
neutrophilia with a left shift,7 but this finding does not mycosis. The patient had no historical or physical
help to localize the problem of fever. Although the examination findings of respiratory tract disease, but
CBC findings rarely lead directly to a specific diagnosis, thoracic radiographs revealed marked hilar
they may provide diagnostic clues that can be pursued lymphadenopathy. This problem was then used to
with further testing. Dramatic changes in the CBC generate a new list of diagnostic differentials and a more
(e.g., evidence of immune-mediated hemolytic anemia) focused diagnostic plan. Because immune-mediated
usually do not meet the criteria for FUO. polyarthritis is a common finding in patients with
FUO,8,14 I also obtain radiographs of multiple joints
Urine Culture and Evaluation during the second stage of the diagnostic plan. Additional
of the Urogenital Tract radiographic studies that may be useful include long bone
Urine should be obtained by cystocentesis whenever (particularly in young dogs), vertebral, dental, and
possible and submitted for aerobic bacterial culture with contrast radiography of specific body systems.
antibiotic sensitivity testing. Urine cultures should be
performed in all cases of FUO, even if the urine Ultrasonography and Echocardiography
sediment appears inactive. Urine cultures are usually Abdominal ultrasonography is a valuable tool for
used to detect pyelonephritis or prostatitis. However, a evaluating patients with FUO and is becoming more
single negative culture does not rule out these diagnostic widely available in veterinary practice. A skilled
differentials. If there is a history of lower urinary tract ultrasonographer can examine most abdominal organs
infection or other evidence suggesting the presence of and often detect lesions that are not demonstrated by
pyelonephritis, repeated urine cultures should be radiography (Figure 4). Ultrasonography of the
conducted in addition to ultrasonography and contrast thoracic cavity may be useful when effusions or masses
radiographic evaluation of the renal collecting system. are present. Ultrasonography can also be used to
Similarly, if prostatitis is suspected, further testing may investigate the retrobulbar area or any other large mass
include prostatic wash, ejaculate evaluation, or swelling that is not confined to a body cavity. This
ultrasonography, and prostatic aspiration or biopsy. technique can facilitate the acquisition of fine-needle
aspirates or biopsies from many sites.
Radiography Echocardiography should be used to evaluate the
I routinely obtain thoracic and abdominal radiographs pericardium, myocardium, endocardium, heart valves,
in the first stage of evaluating patients with FUO. These and great vessels during the early stages of the
radiographs are simple to obtain and relatively diagnostic plan for a febrile patient with a heart
inexpensive, and if abnormalities are detected, they can murmur. This modality is often used to look for
facilitate the rapid localization of the source of fever. vegetative valvular lesions when endocarditis is
984 Small Animal/Exotics Compendium November 2001
Figure 4—Abdominal ultrasound image from a 10-year-old Figure 5—Fine-needle aspirate from a skin nodule in a dog
mixed breed dog with fever. There is a 4-cm diameter mass of with blastomycosis. Cytology demonstrates the typical broad-
mixed echogenicity within the spleen. This was subsequently based budding yeast organisms with associated pyogranulo-
found to be a fibroma with a necrotic center. matous inflammation.
suspected; however, it should be noted that this test is aspirates of masses, abnormal organs, or fluid accumu-
neither sensitive nor specific for this diagnosis.16 False- lations that are detected on physical examination or
positive results may occur because other valve lesions imaging studies. Joint fluid and lymph node cytology
(e.g., endocardiosis) may resemble vegetations. False- may be informative in patients with FUO when less
negative results occur when the vegetative lesions are invasive tests do not localize the source of the fever
very small or absent (due to embolization), when (Figure 6). Bone marrow aspiration is indicated early in
infection exists without vegetation, and when infection the diagnostic plan if there are CBC changes suggestive
is localized to the mural endocardium.13 Therefore, the of bone marrow disease. Even in the absence of such
results of echocardiography should be interpreted in changes, bone marrow aspiration should be considered
light of a patient’s signalment, the time of onset of the in the later stages of the diagnostic plan because bone
heart murmur, and the results of blood cultures. marrow disease (e.g., lymphoid leukemia, myeloma,
malignant histiocytosis) has been reported to be a
Advanced Imaging relatively common cause of FUO. 14 In cats, bone
In human medicine, advanced imaging modalities marrow slides should also be reserved for feline
have markedly reduced the need for exploratory surgeries leukemia virus (FeLV) immunofluorescent antibody
in patients with FUO.13,15 In addition to ultrasonog- (IFA) testing as this may occasionally reveal the
raphy, computed tomography (CT) and magnetic presence of viral antigen in the marrow despite negative
resonance imaging (MRI) are increasingly used in tests on peripheral blood.
veterinary practice. These imaging modalities are often
selected with regard to specific areas or body systems of Arthrocentesis
interest. For example, CT is considered to be more In my practice and according to previously reported
sensitive than standard radiographic techniques17 for case studies, 8,14 immune-mediated polyarthritis is a
detecting several types of pulmonary lesions and MRI is common cause of canine FUO. Since affected patients
often used to evaluate the central nervous system.18 In do not consistently demonstrate lameness or significant
human medicine, nuclear medicine is increasingly used periarticular pain or swelling on physical examination,
to evaluate patients with FUO.19 A technique for the use arthrocentesis is recommended in the second stage of
of scintigraphy in localizing abscesses with labeled canine the diagnostic plan for all cases of FUO. Several joints
neutrophils has been described but has not yet been should be sampled; I generally obtain synovial fluid
adapted for use in clinical veterinary practice.20 from at least the carpi and tarsi. Arthrocentesis is well
described elsewhere. 4 Samples obtained should be
Cytology and Bone Marrow Evaluation inspected for cloudiness, discoloration, or loss of
Cytology is an essential tool for evaluating patients normal viscosity. If small fluid samples are collected,
with FUO,14 particularly if it reveals the presence of the highest priority is to make direct smears for
abnormal cells or infectious agents (Figure 5). cytologic examination. Larger samples can be
Cytologic preparations should always be made from transferred to EDTA tubes (taking care to use the
986 Small Animal/Exotics Compendium November 2001
Figure 6—Joint fluid from a dog with immune-mediated Figure 7—Blood culture bottle containing 70 ml of culture
polyarthritis. Cytology demonstrated the presence of large medium with resins.
numbers of neutrophils, some of which are seen here. Some
of these cells contain phagocytosed nuclear debris. If the size of the patient allows, a second blood sample
is immediately drawn from a different site and again
optimum fluid:anticoagulant ratio) and used for both divided between aerobic and anaerobic culture bottles.
cytology and cell counts. If larger samples are obtained, The use of separate sites assists in determining whether
it is also advisable to submit joint fluid for aerobic, positive cultures are due to true bacteremia or contami-
anaerobic, and mycoplasma culture. nation. Contamination should be minimized by proper
sterile technique, and identification of the organisms
Blood Culture cultured also assists in identifying contaminants. For
Blood cultures are recommended for evaluating all patients that have recently received antibiotic therapy,
patients with unexplained pyrexia. 14 The goal is to blood culture bottles containing resins are used (Figure
detect bacteremia associated with endocarditis, 7; BBLTM SEPTI-CHEKTM with Resins Culture Bottle).
discospondylitis, or other foci of infection.14 In human
medicine, it has been convincingly demonstrated that Serology
the volume of blood drawn is the single most important Antibody titers (and sometimes antigen tests) are
factor influencing the sensitivity of blood cultures for frequently obtained to look for evidence of infectious
detecting bloodstream infections.21 As the volume of disease in patients with FUO. When selecting and
blood drawn is increased, the number of positive interpreting these tests, it is important to consider the
cultures increases; this effect is the same whether all the clinical signs in the patient (although these are often
blood is drawn at one time or serially over 24 hours.21 not present in FUO) and understand the sensitivity
Similar studies have not been performed in veterinary and specificity of the tests selected.22 For example, in
patients, but there is no reason to expect that the results diagnosing fungal disease, cryptococcal antigen titers
would be different in dogs and cats. Therefore, it is are sensitive and specific.23 In contrast, I have detected
recommended that blood culture techniques should be Blastomyces dermatitidis in many patients with negative
optimized for the collection of adequately large volumes antibody titers, implying that this test is not very
of blood, rather than focusing on the timing of blood sensitive. An example of low specificity is the use of
collections. In my practice, patient size and the size of feline coronavirus titers in diagnosing feline infectious
the blood culture bottles are used to determine the peritonitis (FIP). Positive titers imply exposure to one
volume of blood collected. For large dogs, 16 to 20 ml of several related coronaviruses but cannot be used to
of blood is collected from a single site during a febrile make a specific diagnosis of FIP.24 Low specificity can
episode and 8 to 10 ml is inoculated into an aerobic and be advantageous in some tests. For example, antibodies
an anaerobic culture bottle (BBLTM SEPTI-CHEKTM to Ehrlichia canis cross-react with Ehrlichia ewingii and
with Trypticase TM Soy Broth, Becton Dickinson Ehrlichia chaffeensis; thus E. canis serology can be used
Microbiology Systems, Sparks, Maryland [70 ml]). For to detect infection with any one of these organisms.25
cats and small dogs, approximately 5 ml of blood is Specificity, sensitivity, and disease prevalence in the
collected and divided between blood culture bottles population of interest determine the predictive value of
designed for pediatric patients (BBLTM SEPTI-CHEKTM a test. 22 Disease prevalence is often influenced by
with Brain Heart Infusion [20 ml]). geographic location. It should also be remembered that
988 Small Animal/Exotics Compendium November 2001
For example, if immune-mediated polyarthritis is Table 5. Risks Associated with Therapeutic Trials
suspected, immunosuppressive doses of corticosteroids
should be used and a dramatic response should be • Exacerbating an undiagnosed disease is a risk,
expected within 24 to 48 hours. These patients should particularly when using corticosteroids (e.g.,
be hospitalized during this period to allow for administering immunosuppressive doses of
corticosteroids to a patient with an undiagnosed
detection of infectious disease that may be worsened
fungal infection could lead to marked clinical
by the therapy. If fungal disease is suspected, the deterioration or even death).
response to antifungal therapy may take days to
• Continued progression of an undiagnosed
weeks and changes in radiographic or ophthalmologic
disease occurs when the therapeutic trial is
findings may occur very slowly. It is also important to unsuccessful (e.g., use of an ineffective antibiotic in
remember that the response to therapy may be coinci- a patient with pyelonephritis; failure to treat
dental or nonspecific. For example, fever may wax and appropriately could ultimately lead to irreversible
wane in a patient with FUO7,12; therefore, monitoring organ damage).
should continue for sufficient time to confirm that • Drug toxicity (e.g., nephrotoxicity of gentamicin or
resolution of the fever can be attributed to the amphotericin, central nervous system toxicity of
selected therapy. Corticosteroids have antiinflam- metronidazole) may occur.
matory effects that may be of nonspecific benefit in • Undesirable side effects (e.g., polyuria, polydipsia,
many cases of FUO, metronidazole is known to have and polyphagia associated with corticosteroid
immunomodulatory properties, 30 and doxycycline therapy) are possible. It can be difficult for clients to
may have beneficial effects in certain patients with comply with treatment recommendations when side
noninfectious arthritis. 31 These effects may further effects are intolerable and there is no clear diagnosis
confuse the interpretation of the response to a or endpoint to define the course of therapy.
therapeutic trial. • Inducing antibiotic resistance is a concern when
When selecting a treatment for any problem or for a using trial courses of antibiotics in patients with
specific disease, it is important to consider the risks and suspected bacterial infection. If antibiotic selection is
benefits of therapy. For patients with FUO, potential not based on culture and sensitivity results and
benefits include the possibility of a resolution or an inappropriate antibiotic or dose is selected, this
control of the underlying disease, the chance to rule may contribute to antibiotic resistance in bacterial
populations.32 This is now recognized as an increasing
out certain diagnostic differentials, and the relief of
problem in both human and veterinary medicine.
clinical signs associated with fever or the underlying
disease. However, the many risks associated with • Interfering with future diagnostic tests or
therapies is a particular concern when diagnosing
therapeutic trials in patients with FUO should be
neoplasia (e.g., use of corticosteroids in a patient
considered carefully before therapy (Table 5).32,33 with lymphoma). Therapy may be successful in the
short term but could interfere with future attempts
NONSPECIFIC THERAPY to confirm the diagnosis and also lead to resistance
Body temperatures in excess of 106 ˚F (41.1˚C) may to other chemotherapeutic agents.33
cause organ damage, electrolyte and acid–base distur- • Poor owner compliance due to the expense of
bances, disseminated intravascular coagulopathy, and therapy is a particular concern with antifungal
death.8,34 Fortunately, temperature elevations of this agents and certain antibiotics (e.g., third-generation
magnitude are more likely to be associated with cephalosporins). This is a significant risk for some
nonfebrile causes of hyperthermia and are not common patients with FUO because many clients have
in patients with FUO. 9 It is likely that fever has already made a significant financial investment in
beneficial effects in patients with infectious disease, the rest of the diagnostic evaluation. A trial course
leading to enhanced resistance to infection and of therapy with an expensive medication and
improved immune function. 11 However, in some without a confirmed diagnosis may, therefore, be
unacceptable in some cases.
patients, fever can also lead to reduced appetite,
dehydration due to reduced fluid intake and increased
insensible losses, and significant lethargy or of improving patient comfort or quality of life, while
obtundation. The common medical advice to “get lots working through a diagnostic plan. For hospitalized
of rest and drink plenty of fluids” is not always easy to patients, I routinely use intravenous (IV) crystalloid
apply to veterinary patients. Therefore, clinicians may fluid therapy in patients with FUO with a body
need to select nonspecific therapies for canine and temperature above 103.5˚F (39.8˚C). Fluids are given
feline patients with FUO, specifically for the purpose at a rate of 1.5 to 2 times maintenance to allow for
990 Small Animal/Exotics Compendium November 2001
increased water requirements and insensible losses 14. Dunn KJ, Dunn JK: Diagnostic investigations in 101 dogs with
pyrexia of unknown origin. J Small Anim Pract 39:574–580, 1998.
associated with fever. For outpatients, low doses of
aspirin can be used (10 mg/kg bid for dogs; 10 mg/kg 15. Gelfand JA, Dinarello CA: Fever of unknown origin, in Fauci
AS, Braunwald E, Isselbacher KJ, et al (eds): Harrison’s Principles
q48h for cats).4,35 Use of dipyrone or flunixin is not of Internal Medicine. New York, McGraw-Hill, 1998, pp
recommended in either species. For hyperthermia with 780–785.
temperatures in excess of 106˚F (41.1˚C), mechanical 16. DeFrancesco TC: CVT update: Infectious endocarditis, in
cooling methods such as cool water baths and fans Bonagura JD (ed): Kirk’s Current Veterinary Therapy XIII (Small
should accompany IV fluid support.8,9 Animal Practice). Philadelphia, WB Saunders Co, 2000, pp
768–772.
SUMMARY 17. Schwarz LA, Tidwell AS: Alternative imaging of the lung. Clin
Techniques Small Anim Pract 14(4):187–206, 1999.
The problem-oriented approach to medicine involves
18. Thomson CE, Kornegay JN, Burn RA, et al: Magnetic
identifying and verifying a problem, localizing the resonance imaging: A general overview of principles and
problem, and considering the appropriate diagnostic examples in veterinary neurolodiagnosis. Vet Radiol Ultrasound
differentials, 36 which are then used to generate the 34(1):2–17, 1993.
diagnostic plan. Because FUO is, by definition, not 19. Corstens FHM, van der Meer JWM: Nuclear medicine’s role in
easily localized, there are no simple algorithms that infection and inflammation. Lancet 354:765–770, 1999.
provide an inclusive approach to diagnosing all 20. Moon ML, Hinkle GN, Krakowka GS: Scintigraphic imaging
of technetium 99m-labeled neutrophils in the dog. Am J Vet Res
patients.10,37 The goal of the diagnostic plan should be 49(6):950–955, 1988.
to use simple tests to identify an abnormality and then
21. Li J, Plorde JJ, Carlson LG: Effects of volume and periodicity
use that as the basis for targeted diagnostic testing. on blood cultures. J Clin Microbiol 32(11):2829–2831, 1994.
With this approach, clinicians should be able to replace 22. Lappin MR: ELISA tests: Methods and interpretation, in
the problem of FUO with a more specific diagnosis. Bonagura JD (ed): Kirk’s Current Veterinary Therapy XIII (Small
Animal Practice). Philadelphia, WB Saunders Co, 2000, pp 8–11.
ACKNOWLEDGMENTS 23. Jacobs GJ, Medleau L: Cryptococcosis, in Greene CE (ed):
The author thanks Dr. P. S. MacWilliams for the cytology Infectious Diseases of the Dog and Cat. Philadelphia, WB
slides, the Department of Radiology at the University of Saunders Co, 1998.
Wisconsin–Madison School of Veterinary Medicine for 24. McReynolds C, Macy D: Feline infectious peritonitis. Part I.
Etiology and diagnosis. Compend Contin Educ Pract Vet
the radiographic and ultrasound images, and Faye 19(9):1007–1016, 1997.
Hartmann for discussion of blood culture techniques. 25. Neer TM: Canine monocytic and granulocytic ehrlichiosis, in
Greene CE (ed): Infectious Diseases of the Dog and Cat.
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cats. J Small Anim Pract 28:167–181, 1987. leukemias, in Withrow SJ, MacEwen EG (eds): Small Animal
13. Hirschman JV: Fever of unknown origin in adults. Clin Infect Clinical Oncology. Philadelphia, WB Saunders Co, 1996, pp
Dis 24:291–302, 1997. 451–479.
992 Small Animal/Exotics Compendium November 2001
34. Boothe DM: Therapy of cardiovascular diseases, in Boothe DM active urine sediment.
(ed): Small Animal Clinical Pharmacology and Therapeutics. b. Fundic examinations should always be performed.
Philadelphia, WB Saunders Co, 2001, pp 553–601.
c. Thoracic radiographs are indicated only when signs
35. Boothe DM: Anti-inflammatory drugs, in Boothe DM (ed):
Small Animal Clinical Pharmacolog y and Therapeutics. of respiratory disease are present.
Philadelphia, WB Saunders Co, 2001, pp 281–311. d. Bone marrow cytology is not recommended if the
36. Osborne CA: Diagnosis by rule-out: Judgment in the absence of CBC is normal.
certainty, in Bonagura JD (ed): Kirk’s Current Veterinary Therapy
XII (Small Animal Practice). Philadelphia, WB Saunders Co, 7. Which of the following statements regarding the use of
1995, pp 11–13.
echocardiography in diagnosing endocarditis is true?
37. Brusch JL, Weinstein L: Fever of unknown origin. Med Clin a. Echocardiography is highly sensitive but not
North Am 72(5):1247–1261, 1988.
specific for diagnosing endocarditis.
b. Echocardiography is highly specific but not
sensitive for diagnosing endocarditis.
ARTICLE #3 CE TEST
CE
c. Echocardiography is neither sensitive nor specific
The article you have read qualifies for 1.5 con- for diagnosing endocarditis.
tact hours of Continuing Education Credit from d. none of the above
the Auburn University College of Veterinary Med-
icine. Choose the best answer to each of the follow- 8. Which of the following statements regarding immune-
ing questions; then mark your answers on the mediated polyarthritis is false?
postage-paid envelope inserted in Compendium. a. Cytologic examination of joint fluid can be
performed on direct smears or on samples preserved
in EDTA.
1. Which of the following statements about FUO is true? b. Dogs with immune-mediated polyarthritis always
a. FUO can be diagnosed only in a hospitalized patient. have lameness and joint swelling on physical
b. The pattern of fever in FUO is very useful in examination.
determining the underlying cause. c. Immune-mediated polyarthritis is a common cause
c. In human medicine, 5% to 15% of cases of FUO of canine FUO.
remain undiagnosed. d. If immune-mediated polyarthritis is suspected,
d. Neoplasia rarely causes fever in humans or dogs. arthrocentesis should be performed on more than
one joint.
2. Which of the following is an example of true fever?
a. elevated body temperature after prolonged seizure 9. Which of the following statements regarding blood
activity cultures is true?
b. elevated body temperature associated with necrosis a. Studies in humans have shown that the sensitivity
of a tumor of blood cultures in detecting bloodstream
c. elevated body temperature due to heat stroke infections is greatest when blood samples are evenly
d. malignant hyperthermia spaced throughout a 24-hour period.
b. Blood cultures should never be conducted in
3. Which of the following are involved in the patients on antibiotic therapy.
pathogenesis of fever? c. Volume of blood drawn is the most important
a. IL-1 b. IL-6 factor in determining the sensitivity of blood
c. prostaglandins d. all of the above cultures for detecting bloodstream infections in
humans.
4. Which of the following have been reported to cause d. Blood cultures are rarely indicated in the workup of
fever in dogs? dogs with FUO.
a. portosystemic shunt c. lymphadenitis
b. metaphyseal osteopathy d. all of the above 10. Which of the following statements regarding serologic
testing is true?
5. Which of the following tests are useful in investigating a. A negative Blastomyces dermatitidis titer rules out
suspected prostatitis? the diagnosis of blastomycosis.
a. abdominal ultrasonography c. urine culture b. An abnormal ANA titer can be detected in patients
b. evaluating ejaculate d. all of the above that do not have SLE.
c. Elevated IgG titers are seen only after recent
6. Which of the following statements regarding the exposure to toxoplasmosis.
evaluation of FUO patients is true? d. An elevated Borrelia burgdorferi titer is diagnostic
a. Urine culture is indicated only in the presence of an for Lyme disease.