Follow-up, diagnosis, and outcomes of fever of unknown origin cases in whom no diagnosis was established after initial evaluation: an ID-IRI (Infectious Diseases - International Research Initiative) observational retrospective cohort study

BACKGROUND/AIM: In fever of unknown origin (FUO), despite comprehensive evaluation a substantial proportion of patients may remain without a definitive diagnosis. Herein, we aimed to analyse the disease course, mortality rate, final diagnosis, and the workup performed to reach final diagnosis in fever of unknown origin without final diagnoses (FUOWFD) cases. MATERIALS AND METHODS: The roster of patients with FUOWFD was obtained from a previously published multicenter study. Subsequently, additional data was gathered retrospectively from each cooperating center. RESULTS: The follow-up data for 79 cases from 11 centers were included. While being considered as FUOWFD: 100% were performed biochemistry and microbiology, 78.5% for rheumatological markers, 33% for oncological markers, and 97.5% for radiological investigations. Other medical departments were consulted in 64.5% of the cases and invasive diagnostic procedures were performed in 27.8%. During the follow-up, 73 cases (92.4%) saw their fever resolve. Among these, 70 cases' fever resolved within the first three months. In total, two patients (2.5%) received a definitive diagnosis during the follow-up period. After 6 months and 12 months follow up, the all-cause mortality rate was 3.8%. Notably, none of the three cases that experienced mortality by day 365 had received a final diagnosis for FUO. CONCLUSION: The diagnostic process for FUO cases who remain undiagnosed exhibits substantial heterogeneity. The majority of patients experience spontaneous recovery, and the mortality rate is relatively low. Infectious causes are the most frequently encountered contributors to the FUO cases who remain undiagnosed. CLINICAL TRIAL NUMBER: Not applicable.