Fever of Unknown Origin (FUO)

Fever of Unknown Origin (FUO) is a topic covered in the 5-Minute Clinical Consult.

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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.


Incidence unclear

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.
  • Infection
    • Abdominal or pelvic abscesses
    • Amebic hepatitis
    • Catheter infections
    • Cytomegalovirus
    • Dental abscesses
    • Endocarditis/pericarditis
    • HIV (advanced stage)
    • Mycobacterial infection (often with advanced HIV)
    • Osteomyelitis
    • Pyelonephritis or renal abscess
    • Sinusitis
    • Wound infections
    • Other miscellaneous infections
  • Neoplasms
    • Atrial myxoma
    • Colorectal cancer and other GI malignancies
    • Hepatoma
    • Lymphoma
    • Leukemia
    • Solid tumors (renal cell carcinoma)
  • Noninfectious inflammatory disease
    • Connective tissue diseases
      • Adult Still disease
      • Rheumatoid arthritis
      • Systemic lupus erythematosus
    • Granulomatous disease
      • Crohn disease
      • Sarcoidosis
    • Vasculitis syndromes
      • Giant cell arteritis
      • Polymyalgia rheumatica
  • Other causes
    • Alcoholic hepatitis
    • Cerebrovascular accident
    • Cirrhosis
    • Medications
      • 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.

Risk Factors

  • Recent travel (malaria, enteric fevers)
  • Exposure to biologic or chemical agents
  • HIV infection (particularly in acute infection and advanced stages)
  • Elderly
  • Drug abuse
  • Immigrants
  • Young, (typically) female health care workers (factitious fever)

Geriatric Considerations
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.

Pediatric Considerations
  • ~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.

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