From prolonged febrile illness to fever of unknown origin - The challenge continues

Background: Epidemiological changes and the ongoing expansion of the diagnostic armamentarium warrant a regular update of the spectrum of diseases that present as prolonged febrile illnesses. Methods: We prospectively collected a series of 290 immunocompetent patients referred to our university hospital between 1990 and 1999 with a febrile illness (temperature >38.3degreesC) of uncertain cause, lasting at least 3 weeks. Patients were categorized in 4 groups according to the timing of diagnosis: early diagnosis (within 3 in-hospital days or 3 outpatient visits), intermediate diagnosis (between days 4 and 7), late diagnosis (after day 7), and no diagnosis during index contact or follow-up. Results: A final diagnosis was established early in 67 patients (23.1%), intermediate in 38 (13.1%), and late in 87 (30.0%). In the remaining 98 (33.8%), no diagnosis was made. The cause of the fever remained obscure in 50 (47.6%) of 105 patients with episodic fever vs 48 (25.9%) of 185 patients with continuous fever (P<.001). Among the 192 patients with a final diagnosis, noninfectious inflammatory diseases represented the most prevalent diagnostic category (35.4%), surpassing infections (29.7%), miscellaneous causes (19.8%), and malignancies (15.1%). Fourteen disorders accounted for over 59% of diagnoses, whether diagnosis was reached early, intermediate, or late. Hematological malignancies made: up 11.5% of diagnoses, but were responsible for 14. (58.3%) of the 24 fatalities related to the febrile illness. Of the 80 patients discharged alive without diagnosis and for whom follow-up was available, 3 died, but the deaths were considered to be unrelated to the feverish illness. Conclusions: Prolonged febrile illnesses remain a diagnostic-challenge: Despite the technological progress of the late 20th century; the origin of the fever remains elusive in many patients, especially in those with episodic. fevers. Noninfectious inflammatory diseases emerge as the most prevalent diagnostic category.