Fever of Unknown Origin
Amit Kalra
Jonathan P. Moorman
DEFINITION
Fever of unknown origin (FUO) was defined by Petersdorf and Beeson in 1962:
1. Temperature of >101°F (38.3°C) on several occasions
2. Duration of fever >3 weeks
3. Failure to reach diagnosis despite 1 week of inpatient investigations
Durack and Street recommended another revised system of classification of FUO:
1. Classic
2. Nosocomial
3. Neutropenic
4. HIV-associated FUO
Newer definition of FUO outlines describes three outpatient visits or 3 days in the hospital without finding the cause for fever, or 1 week of intensive investigations.
ETIOLOGIES
1. Infections: (most common cause)
A. Bacterial: localized or systemic
Pyogenic infections: appendicitis, cholecystitis, diverticulitis, dental abscess, liver abscess, osteomyelitis, pelvic inflammatory disease, pancreatitis abscess, perirectal abscess, sinusitis, suppurative thrombophlebitis, recurrent aspiration
Systemic infections: subacute bacterial endocarditis, gonococcemia, Lyme disease, Legionnaires disease, leptospirosis, borreliosis, salmonellosis
B. Mycobacterial: tuberculosis
C. Fungal: cryptococcus, histoplasmosis
D. Rickettsial
E. Mycoplasma
F. Chlamydia
G. Viral: CMV, EBV, HIV, viral hepatitis
H. Parasitic: malaria, toxoplasmosis, trypanosomiasis
2. Neoplasms: benign or malignant
A. Lymphoma
B. Leukemia
C. Renal cell carcinoma
D. Hepatocellular carcinoma
E. Atrial myxoma
3. Connective tissue disorders: lupus, polymyalgia rheumatica, giant cell arteritis
4. Granulomatous disease: sarcoidosis, granulomatous hepatitis
5. Metabolic and inherited diseases including endocrine causes: thyroiditis, pheochromocytoma
6. Thermoregulatory disorder
7. Miscellaneous causes:
A. Drugs, including allopurinol, antihistamine, aspirin, clofibrate, erythromycin, captopril, quinidine, nitrofurantoin, penicillins
B. Deep vein thrombosis
C. Pulmonary embolism
D. Superficial thrombophlebitis
E. Factitious fever
F. Postmyocardial infarction
G. Hematoma
H. Periodic fever
I. Gout/pseudogout
J. Familial Mediterranean fever
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