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Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis

  • Pediatric Rheumatology (S Ozen, Section Editor)
  • Published:
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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.

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Authors and Affiliations

  1. Pediatric Rheumatology Unit of Western Switzerland, Pediatric Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    Katerina Theodoropoulou, Federica Vanoni & Michaël Hofer

  2. Geneva University Hospital (HUG), Geneva, Switzerland

    Katerina Theodoropoulou, Federica Vanoni & Michaël Hofer

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  1. Katerina Theodoropoulou
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  2. Federica Vanoni
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  3. Michaël Hofer
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Correspondence to Katerina Theodoropoulou.

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Katerina Theodoropoulou and Federica Vanoni declare that they have no conflicts of interest. Michaël Hofer reports grants from Novartis, grants and personal fees from Abbvie, grants from Pfizer, and grants from Roche, outside the submitted work.

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Theodoropoulou, K., Vanoni, F. & Hofer, M. Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis. Curr Rheumatol Rep 18, 18 (2016). https://doi.org/10.1007/s11926-016-0567-y

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