Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in childhood. Recent studies report genetic susceptibility variants for PFAPA syndrome and the efficacy of tonsillectomy in a broader cohort of patients with recurrent stereotypical fever. In this review, we highlight the findings of these studies and what they may reveal about the pathogenesis of PFAPA.

Newly identified genetic susceptibility loci for PFAPA suggest that it is a complex genetic disorder linked to Behçet's disease and recurrent aphthous ulcers. Patients who have PFAPA with some features of Behçet's disease have been reported. Moreover, the efficacy of tonsillectomy has now been described in patients who do not meet the full diagnostic criteria for PFAPA, although the immunologic profile in the tonsils is different from those with PFAPA. Factors that predict response to tonsillectomy are also reported.

These findings highlight the heterogeneous phenotypes that may be related to PFAPA due to common genetic susceptibility or response to therapy. These relationships raise questions about how to define PFAPA and highlight the importance of understanding of the genetic architecture of PFAPA and related diseases.