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Fever of Unknown Origin
JANUARY 26, 2015 | THE CHIEFS | 1 COMMENT
“The mark of a good ID clinician is not how many antibiotics he or she starts but how many he or she stops.” — Brad Cutrell
Definitions
“Classic” definition of FUO
Fever > 38.3 C
Duration > 3 weeks
Unknown etiology after > 1 week hospital evaluation
Revised Classification: proposed revisions decreased duration and removed inpt evaluation criteria
Classic Definition: temperature higher than 38.0 °C (100.4 °F) for more than 3 weeks and either more than 3 days of hospital investigation or more than two outpatient visits
without determination of the cause.
Health care–associated FUO: temperature higher than 38.0 °C (100.4 °F) for more than 3 days in a hospitalized patient receiving acute care with infection not present or incubating
on admission.
Immune-deficient (neutropenic) FUO: temperature higher than 38.0 °C (100.4 °F) in a patient in with ANC < 500 in whom the diagnosis remains uncertain after more than 3
days despite appropriate investigation, including at least 48 hours’ incubation of microbiologic cultures.
HIV-related FUO: temperature higher than 38.0 °C (100.4 °F) in a patient with confirmed HIV infection for more than 3 weeks in outpatients or more than 3 days in inpatients.
Epidemiology
Classic FUO etiologies fall into 5 major categories: Infection, Malignancy, Inflammatory, Miscellaneous, Unknown
Distribution depends on decade, patient age, geography, and type of practice
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Etiology
Infections
Tuberculosis (extrapulmonary, miliary, IC hosts)
Occult abscess (abd/pelvic)
Complicated UTI
Osteomyelitis
Culture-negative endocarditis
Malaria
Typhoid fever
Visceral Leishmaniasis
Malignancies
Lymphoma (esp. NHL)
Leukemia
Renal Cell carcinoma
Hepatocellular carcinoma or liver metastases
Inflammatory Disorders
Adult-onset Still’s Disease
RA
SLE
Temporal arteritis (Giant Cell arteritis)
Polymyalgia rheumatica
Miscellaneous
Drug Fever (abx, anti-seizure meds, NSAIDs, anti-arrhythmics)
Alcoholic hepatitis
Venous thromboembolic disease
Endocrine disease (hyperT, adrenal insufficiency, pheo)
Disordered heat homeostasis (“central fever”)
Factitious Fever (Munchausen)
Special Populations
Pediatrics
Infectious most often, particularly viral and respiratory
CTD: Kawasaki in younger, AOSD in older children
Geriatrics
CTD (GCA and PMR) and malignancy more common than in < 65 age group
Returning Traveler
Malaria, typhoid fever, amebic liver abscess, acute HIV
Diagnostic Evaluation
History and Physical!
Recent prospective Dutch series found average of 10.5 potential diagnostic clues per pt from history/exam and only 3 per pt from lab testing (81% misleading)
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Laboratory Testing
Best guided by history/exam clues, not “shotgun” approach
Laboratory testing yields diagnosis in 25% of cases
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15/01/labs.png)
Recent meta-analysis showed pooled sens. 98% and spec. 86% for FDG-PET, arguing for role if initial w/u negative
Invasive Testing
BM evaluation useful, especially if abnormal CBC or immunocompromised host
Biopsy of sites with suspected involvement in select cases
Management and Prognosis
Management
Therapeutic trials of abx generally not recommended
“Non-specific Rx rarely cures FUO but may delay Dx.”
Exceptions: empiric steroids for suspected GCA or empiric abx in neutropenic patients
Prognosis
Depends on age and etiology of FUO (worse with elderly and malignancy as etiology)
Most without Dx after extensive evaluation have good prognosis with low mortality and fever resolution
Imaging
CXR and CT abdomen/pelvis part of
initial tests
MRI/MRA good for CNS, spine, and
vasculitis evaluation
Older nuclear tagged scans and
Gallium scans have been largely
replaced by FDG-PET scans
Remember: The cause is more likely a common diagnosis presenting in an atypical fashion than a rare disease presenting in a typical fashion.
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