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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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    Basics

    Description

    • 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.

    Epidemiology

    Incidence
    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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    Citation

    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 -