The following is a summary of “Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation,” published in the May 2024 issue of Pediatrics by Vyzhga et al.

Systemic autoinflammatory disorders (SAIDs) encompass a diverse range of conditions characterized by dysregulation of the innate immune system. While Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome constitutes a well-defined pediatric autoinflammatory fever syndrome, a subset of patients presents with recurrent fevers that do not meet PFAPA criteria, classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES and supported through the EMERGE fellowship program, aimed to investigate the clinical evolution of undifferentiated recurrent fevers within the context of uAID, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data extracted from European autoinflammatory disease registries.

Data were gathered from three registries detailing epidemiological, demographic, and clinical profiles and genetic and laboratory findings. The study retrospectively applied modified Marshall criteria to the PFAPA cohort and preliminary SURF criteria to patients classified under uSAID/SURF.

Clinical manifestations of PFAPA were found to be variable, with some patients not conforming to traditional diagnostic criteria and exhibiting diverse symptomatology. Furthermore, a subset of patients did not fit the PFAPA or SURF categories, underscoring significant heterogeneity within these groups. Overlaps between PFAPA and SURF/uAID were also explored, revealing instances where patients displayed symptoms characteristic of both conditions, highlighting the complexity of classification.

Patients experiencing recurrent fevers without a molecular diagnosis represent a clinically heterogeneous population. The study underscores the imperative for enhanced classification criteria for both PFAPA and SURF/uAID to accurately characterize and manage these individuals, ultimately aiming to improve clinical outcomes in this challenging patient group.

Source: ped-rheum.biomedcentral.com/articles/10.1186/s12969-024-00987-z