Evaluation of fever of unknown origin in adults

Fever of unknown origin (FUO) occurs across all age groups. However, age, together with epidemiologic considerations, are important factors in forming a differential diagnosis.

In 1961, the first formal criteria for FUO were published, based on a prospective trial.[1]Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb;40:1-30. http://www.ncbi.nlm.nih.gov/pubmed/13734791?tool=bestpractice.com The criteria defined FUO as a fever higher than 100.9°F (38.3°C) on several occasions, persisting without a diagnosis for at least three weeks, despite having investigations for at least one week in hospital.[1]Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb;40:1-30. http://www.ncbi.nlm.nih.gov/pubmed/13734791?tool=bestpractice.com

With subsequent advancements in medical care, a revised definition for classic FUO was published in 1991, including a proviso for patients with an uncertain diagnosis despite three days in hospital or three outpatient visits.[2]Durack DT, Street AC. Fever of unknown origin - reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35-51. http://www.ncbi.nlm.nih.gov/pubmed/1651090?tool=bestpractice.com The revised definition also outlined three additional groups of FUO: nosocomial (healthcare-associated), neutropenic (immune-deficient), and HIV-related. 

In 1997, a prospective study advised replacing the time-based criteria with a standardized diagnostic protocol to minimize differences in diagnostic workup and unintended biases that could influence outcomes.[3]De Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever of unknown origin (FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. Medicine (Baltimore). 1997 Nov;76(6):392-400. http://www.ncbi.nlm.nih.gov/pubmed/9413425?tool=bestpractice.com This FUO definition is now termed the qualitative FUO criteria, and is detailed in the Diagnostic approach.[3]De Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever of unknown origin (FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. Medicine (Baltimore). 1997 Nov;76(6):392-400. http://www.ncbi.nlm.nih.gov/pubmed/9413425?tool=bestpractice.com [4]Wright WF, Mulders-Manders CM, Auwaerter PG, et al. Fever of unknown origin (FUO) - a call for new research standards and updated clinical management. Am J Med. 2022 Feb;135(2):173-8. http://www.ncbi.nlm.nih.gov/pubmed/34437835?tool=bestpractice.com