Background: PFAPA syndrome is a chronic disease that is characterized by recurrent episodes of high fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Knowledge regarding the etiology of PFAPA is limited.
Objectives: To provide up-to-date information considering etiology of PFAPA syndrome, by summarizing what has been explored and established in this area so far.
Materials and methods: PubMed, Web of Science, and Scopus databases were searched for pertinent reports. Eventually 19 articles were selected. The results were classified into categories regarding three areas of interest: familial occurrence, genetic basis, and immunological mechanisms of PFAPA.
Results: Recent findings suggest that there is a familial tendency to PFAPA but the level of evidence does not warrant definite conclusions. The absence of a clear monogenic trait indicates a heterogenous, polygenic, or complex inheritance of PFAPA syndrome. As two mutations with a possible functional effect on the inflammasomes (MEFV E148Q and NLRP3 Q703K) have been found in several PFAPA cohorts, the role of inflammasome-related genes in PFAPA pathogenesis cannot be excluded. Immunological mechanisms of PFAPA involve an abnormal, IL-1β dependent innate immune response to an environmental trigger, which leads to Th1-driven inflammation expressed by recruitment of T-cells to the periphery.