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Mediators of Inflammation
Volume 2015, Article ID 563876, 6 pages
Review Article

The Pathogenesis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: A Review of Current Research

Department and Clinic of Pediatric Infectious Diseases, Wroclaw Medical University, 2-2A Chałubińskiego, 50-368 Wroclaw, Poland

Received 31 July 2015; Accepted 8 September 2015

Academic Editor: Ariadne Malamitsi-Puchner

Copyright © 2015 Barbara Kraszewska-Głomba et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.