Etiological spectrum and outcome of fever and inflammation of unknown origin. Does symptom duration matter?

Abstract

Objective: Evidence suggests that the symptom duration may affect the occurrence of certain fever (FUO) and inflammation (IUO) of unknown origin associated conditions. It is unclear if this could potentially guide diagnostic evaluations. We examined the association between symptom duration and diagnostic and prognostic outcomes in FUO/IUO.

Methods: We retrospectively analyzed a cohort of adult patients meeting criteria for FUO/IUO from a tertiary care center in Belgium between 2000 and 2019. The association between symptom duration and outcomes of interest were estimated by Cox proportional hazards models.

Results: Among 602 patients who met criteria for FUO/IUO (mean age 54 years, 43% female), 132 (22%) and 68 (11%) had symptoms for 3-12 months and >12 months, respectively. There were no significant differences in diagnosis or all-cause mortality between a symptom duration of <3 months and 3-12 months. In contrast, those who had a symptom duration of >12 months were less likely to receive a final diagnosis (aHR 0.42, 95% CI 0.30-0.60), in particular a diagnosis of infectious disorders (aHR 0.29, 95% CI 0.12-0.74), malignancies (aHR 0.11, 95% CI 0.03-0.46), and miscellaneous conditions (aHR 0.22, 95% CI 0.07-0.71), but no significant differences were seen in noninfectious inflammatory disorders (aHR 0.74, 95% CI 0.48-1.15) or all-cause mortality (aHR 0.55, 95% CI 0.19-1.54).

Conclusions: The symptom duration may be used to guide the diagnostic workup among patients with FUO and IUO, in particular those with longstanding symptoms.

Keywords: FUO; Fever of unknown origin; IUO; Inflammation of unknown origin; Time to diagnosis.