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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
    • Uncertain diagnosis 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 geographically and temporally.
    • 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 female health care workers (consider factitious fever)

Geriatric Considerations
Common causes of geriatric infections include intra-abdominal abscess, urinary tract infection, tuberculosis, 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, malignancy are common.
  • Inflammatory bowel disease is a common cause of FUO in older children and adolescents.

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Stephens, Mark B., et al., editors. "Fever of Unknown Origin (FUO)." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816017/all/Fever_of_Unknown_Origin__FUO_.
Fever of Unknown Origin (FUO). In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816017/all/Fever_of_Unknown_Origin__FUO_. Accessed April 26, 2019.
Fever of Unknown Origin (FUO). (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816017/all/Fever_of_Unknown_Origin__FUO_
Fever of Unknown Origin (FUO) [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 26]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816017/all/Fever_of_Unknown_Origin__FUO_.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Fever of Unknown Origin (FUO) ID - 816017 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816017/all/Fever_of_Unknown_Origin__FUO_ PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -