Fever of Unknown Origin (FUO)
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- Classic definition
- Repeated fever >38.3°C
- Fever duration at least 3 weeks
- Diagnosis remains uncertain after 1 week of study in the hospital.
- The definition of fever of unknown origin (FUO) has evolved and is based on patient characteristics and presentation. The need for in-hospital evaluation has been eliminated in previously healthy people.
- Some expand the definition to include nosocomial, neutropenic (immunodeficient), and HIV-associated fevers.
Etiology and Pathophysiology
- >200 causes; each with prevalence of ≤5%
- Most commonly, FUO is an atypical presentation of a common condition.
- Spectrum of causes varies widely.
- Noninfectious inflammatory diseases are the most frequent causes in high-income countries. Common causes include temporal arteritis, polymyalgia rheumatica, or rheumatoid arthritis.
- Abdominal or pelvic abscesses
- Amebic hepatitis
- Catheter infections
- Dental abscesses
- HIV (advanced stage)
- Mycobacterial infection (often with advanced HIV)
- Pyelonephritis or renal abscess
- Wound infections
- Other miscellaneous infections
- Atrial myxoma
- Colorectal cancer and other GI malignancies
- Solid tumors (renal cell carcinoma)
- Noninfectious inflammatory disease
- Connective tissue diseases
- Adult Still disease
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Granulomatous disease
- Crohn disease
- Vasculitis syndromes
- Giant cell arteritis
- Polymyalgia rheumatica
- Connective tissue diseases
- Other causes
- Alcoholic hepatitis
- Cerebrovascular accident
- Allopurinol, captopril, carbamazepine, cephalosporins, cimetidine, clofibrate, erythromycin, heparin, hydralazine, hydrochlorothiazide, isoniazid, meperidine, methyldopa, nifedipine, nitrofurantoin, penicillin, phenytoin, procainamide, quinidine, sulfonamides
- Endocrine disease
- Factitious/fraudulent fever
- Occupational causes
- Periodic fever
- Pulmonary emboli/deep vein thrombosis
- Thermoregulatory disorders
- In up to 20–30% of cases, the cause of the fever is never identified despite a thorough workup.
- Recent travel (malaria, enteric fevers)
- Exposure to biologic or chemical agents
- HIV infection (particularly in acute infection and advanced stages)
- Drug abuse
- Young, (typically) female health care workers (factitious fever)
Common causes of geriatric infections include intra-abdominal abscess, urinary tract infection, tuberculosis, (TB) and endocarditis. Other common causes of FUO in patients >65 years include malignancies (particularly hematologic cancers) and drug-induced fever.
- ~50% of FUO in pediatric cases are infectious. Collagen vascular disease and malignancy are common.
- Inflammatory bowel disease is a common cause of FUO in older children and adolescents.