Clinical characteristics associated with spontaneous resolution of classical fever of unknown origin in outpatients: a retrospective observational study

Although fever of unknown origin (FUO) remains a challenging clinical problem in general medicine, factors associated with spontaneous resolution without a definitive diagnosis, particularly in outpatient settings, remain unclear. The aim of this study was to identify clinical and laboratory factors associated with spontaneous resolution of classical FUO in adult outpatients. We conducted a retrospective observational study of 71 consecutive adult outpatients who fulfilled criteria for classical FUO at a tertiary-care university hospital in Japan between 2018 and 2024. Patients whose fever resolved spontaneously without identification of an underlying cause were compared with those in whom a definitive diagnosis was established. Multivariable logistic regression analysis based on 68 patients with complete data was performed to identify factors associated with spontaneous resolution. Spontaneous resolution of fever occurred in 43 patients (60.6%). Patients with spontaneous resolution showed lower levels of systemic inflammation than the established diagnosis group. In multivariable analysis, erythrocyte sedimentation rate (ESR) < 100 mm/h was independently associated with spontaneous resolution of FUO in outpatients (odds ratio 12.53, 95% confidence interval 3.36–46.70). Lower ESR may characterize outpatients with classical FUO who are more likely to experience spontaneous resolution. Further prospective studies are needed to validate this association. Clinical trial registration none.