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Fever of unknown origin 

Fever of unknown origin
Fever of unknown origin

Steven Vanderschueren

and Daniël Knockaert


July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


HIV serology should be a routine investigation.

Allergy testing sometimes used to confirm drug fever/reactions.

Minor editorial amendments.

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date: 21 October 2021

Fever of unknown origin (FUO) refers to a prolonged febrile illness that persists without diagnosis after careful initial assessment. Although over 200 causes have been described, including rare diseases, most cases are due to familiar entities presenting in an atypical fashion.

Causes of FUO—The ‘big three’ are (1) infections—including tuberculosis, endocarditis, abdominal and hepatobiliary infections and abscesses, complicated genitourinary tract infections, pleuropulmonary infections, bone and joint infections, salmonellosis, cytomegalovirus, Epstein–Barr virus and HIV; (2) tumours—including lymphoma; and (3) multisystem inflammatory conditions—including connective tissue diseases, vasculitic syndromes and granulomatous disorders. A miscellaneous category including factitious fever, habitual hyperthermia, and drug fever deserves consideration early in a patient’s workup, since timely recognition may avert invasive and expensive procedures....

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