Recurrent (or episodic) fever of unknown origin (FUO) as a variant subgroup of classical FUO: a French Multicenter Retrospective study of 170 patients

Background Recurrent-FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking. Methods We performed a retrospective multicentre study of patients with recurrent-FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical, and prognostic variables independently associated with final diagnosis and mortality. Results Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR=5.2; p<0.001), contributory history (OR=10.4; p < 0.001), and abnormal clinical examination (OR=4.0; p=0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p=0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death. Conclusion This study extends the known yield of recurrent-FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow- up. Moreover, their overall prognosis is excellent.