title: Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis.
abstract: PFAPA syndrome represents the most common cause of recurrent fever in children in European populations, and it is characterized by recurrent episodes of high fever, pharyngitis, cervical adenitis, and aphthous stomatitis. Many possible causative factors have been explored so far, including infectious agents, immunologic mechanisms and genetic predisposition, but the exact etiology remains unclear. Recent findings demonstrate a dysregulation of different components of innate immunity during PFAPA flares, such as monocytes, neutrophils, complement, and pro-inflammatory cytokines, especially IL-1β, suggesting an inflammasome-mediated innate immune system activation and supporting the hypothesis of an autoinflammatory disease. Moreover, in contrast with previous considerations, the strong familial clustering suggests a potential genetic origin rather than a sporadic disease. In addition, the presence of variants in inflammasome-related genes, mostly in NLRP3 and MEFV, suggests a possible role of inflammasome-composing genes in PFAPA pathogenesis. However, none of these variants seem to be relevant, alone, to its etiology, indicating a high genetic heterogeneity as well as an oligogenic or polygenic genetic background.
authors.affiliation: Pediatric Rheumatology Unit of Western Switzerland, Pediatric Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland. aikaterini.theodoropoulou@chuv.ch.|Geneva University Hospital (HUG), Geneva, Switzerland. aikaterini.theodoropoulou@chuv.ch.
authors.forename: Katerina
authors.initials: K
authors.lastname: Theodoropoulou
authors.affiliation: Pediatric Rheumatology Unit of Western Switzerland, Pediatric Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland.|Geneva University Hospital (HUG), Geneva, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Vanoni
authors.affiliation: Pediatric Rheumatology Unit of Western Switzerland, Pediatric Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland.|Geneva University Hospital (HUG), Geneva, Switzerland.
authors.forename: Michaël
authors.initials: M
authors.lastname: Hofer
mesh_terms: D005334:Fever / Q000209:etiology* / Q000628:therapy; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000235:genetics; D008199:Lymphadenitis / Q000209:etiology* / Q000628:therapy; D010612:Pharyngitis / Q000209:etiology* / Q000628:therapy; D012008:Recurrence; D013281:Stomatitis, Aphthous / Q000209:etiology* / Q000628:therapy; D013577:Syndrome
chemical_list: D058847:Inflammasomes
keywords: Autoinflammation; Inflammasome-related genes; Innate immunity; PFAPA