Evaluation of fever of unknown origin in adults

Fever of unknown origin (FUO) has been defined as a temperature >100.9°F (>38.3°C) on several occasions lasting for more than 3 weeks, with no obvious source despite evaluation of at least 1 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 A revised frequency/duration of evaluation has been proposed: "at least 3 outpatient visits or 3 days in hospital".[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 Subsequent authors have suggested quantitative criteria (i.e., diagnosis uncertain after 1 week or 3 days of investigation) with a qualitative requirement, namely that the fever remains undiagnosed after a minimal diagnostic work-up has been performed.​[3]Fusco FM, Pisapia R, Nardiello S, et al. Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review. BMC Infect Dis. 2019 Jul 22;19(1):653. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-4285-8 http://www.ncbi.nlm.nih.gov/pubmed/31331269?tool=bestpractice.com [4]Bleeker-Rovers CP, Vos FJ, de Kleijn EMHA, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore). 2007 Jan;86(1):26-38. https://journals.lww.com/md-journal/Fulltext/2007/01000/A_Prospective_Multicenter_Study_on_Fever_of.3.aspx http://www.ncbi.nlm.nih.gov/pubmed/17220753?tool=bestpractice.com [5]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 [6]Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med. 2003 Mar;253(3):263-75. https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2796.2003.01120.x?sid=nlm%3Apubmed http://www.ncbi.nlm.nih.gov/pubmed/12603493?tool=bestpractice.com [7]Petersdorf RG. Fever of unknown origin. An old friend revisited. Arch Intern Med. 1992 Jan;152(1):21-2. http://www.ncbi.nlm.nih.gov/pubmed/1728921?tool=bestpractice.com ​​​​​​

Fluctuations in body temperature of up to 2°F (1.1°C) are normal. Elevated body temperature can be physiologic, or caused by pathologic processes such as infection, inflammation, or malignancy. The diagnosis occurs across all age groups and affects both sexes equally. However, age is an important factor in forming a differential diagnosis. Epidemiologic trends in the etiology of FUO vary throughout the world. A careful history includes recent travel. Infections remain a leading cause of FUO, with tuberculosis and intra-abdominal and pelvic abscesses now being more commonly implicated than infective endocarditis.​​[8]Varghese GM, Trowbridge P, Doherty T. Investigating and managing pyrexia of unknown origin in adults. BMJ. 2010;341:C5470. http://www.ncbi.nlm.nih.gov/pubmed/22312655?tool=bestpractice.com ​​ Local epidemiologic data must be taken into account.

The differential diagnoses of FUO may be grouped into infections, malignancies, autoimmune diseases, and other miscellaneous.