Theodoropoulou Katerina, Vanoni Federica, Hofer Michaël
Pediatric Rheumatology Unit of Western Switzerland, Pediatric Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
Geneva University Hospital (HUG), Geneva, Switzerland.
Curr Rheumatol Rep. 2016 Apr;18(4):18. doi: 10.1007/s11926-016-0567-y.
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.
PFAPA综合征是欧洲人群中儿童反复发热最常见的病因，其特征为高热、咽炎、颈淋巴结炎和阿弗他口炎反复发作。迄今为止，人们已经探讨了许多可能的致病因素，包括感染因子、免疫机制和遗传易感性，但确切病因仍不清楚。最近的研究结果表明，在PFAPA发作期间，先天性免疫的不同组成部分存在失调，如单核细胞、中性粒细胞、补体和促炎细胞因子，尤其是白细胞介素-1β，这表明炎性小体介导的先天性免疫系统激活，并支持自身炎症性疾病的假说。此外，与之前的观点相反，强烈的家族聚集性表明其潜在的遗传起源，而非散发性疾病。此外，炎性小体相关基因存在变异，主要在NLRP3和MEFV中，这表明构成炎性小体的基因在PFAPA发病机制中可能起作用。然而，这些变异似乎都与病因无关，这表明其存在高度的遗传异质性以及寡基因或多基因的遗传背景。
