John Bartlett, MD


July 23, 2003

In This Article

Fever of Unknown Origin (FUO)

Vanderschueren S, Knockaert D, Adriaenssens T, et al. From prolonged febrile illness to fever of unknown origin: the challenge continues. Arch Intern Med. 2003;163:1033-1041. Abstract This is a report from the University Hospital Leuven in Belgium that prospectively evaluated patients with FUO to determine final diagnosis. The criteria for inclusion were: illness exceeding 3 weeks in duration and repeatedly documented body temperature exceeding 38.3° C. The authors evaluated 200 immunocompetent patients between 1990 and 1999. There were 4 groups according to the timing of diagnosis: early diagnosis (within 3 hospital days or 3 outpatient visits), intermediate (4-7 days), late diagnosis (> 7 days), or no diagnosis with the initial evaluation or with follow-up. No diagnosis was made in 98 (34%), including 50 (48%) of 105 patients with episodic fever and 48 (30%) of 185 patients with continuous fever.

Among the 192 patients with a final diagnosis, the most frequent causes were noninfectious inflammatory diseases accounting for 35%, infections in 30%, malignancies in 15%, and miscellaneous causes in 20%. Follow-up information was available for 80 of the 95 patients without a definitive diagnosis. Three died, but in no case was the death attributed to the febrile illness. The authors conclude that FUO remains an elusive diagnosis at the present time despite progress in diagnostic methods made in the 20th century. The breakdown of causes of FUO in this series among those who had an identifiable cause is provided below ( Table 11 ), and a comparison of findings in this study with other major reports is provided in Table 12 .

Comment: This is a report from Belgium, which is a sequel to a prior report by this group for a review from the same hospital for 1980-89 with 199 patients.[24] One important difference with this more recent report is the change in the classic definition that required the absence of a diagnosis after at least 1 week of diagnostic testing in the hospital; in this report the diagnosis was established in 67 patients within 1-3 days and in an additional 38 within 4-7 days. Highlights of this series are the large number of patients who had no diagnosis, confirmation of previous reports showing the benign long-term outcome in patients with no diagnosis, and an increase in patients with noninfectious inflammatory conditions.

Durack DT, Street AC. Fever of unknown origin--reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35-51. Abstract The authors make 3 suggestions regarding fever of unknown origin (FUO):

  1. The classic definition requires fever of at least 3 weeks' duration, but the authors suggest the better term is "prolonged FUO" to accept the fact that there are cases of "acute FUO."

  2. Durack and Street have suggested subtypes of FUO including classic FUO, nosocomial FUO, immunodeficient FUO, and HIV-related FUO. The recommendation here is to change the appellation to patient populations such as: "FUO in the elderly," "FUO in travelers," "FUO in natives of India," etc.

  3. Episodic or periodic fever should be a recognized subtype since it does not involve the classic categories (infection, tumors, and multisystem inflammatory diseases) and most patients with this diagnosis do well even in the absence of a diagnosis.[24,25]


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