PFAPA综合征的诊治进展

Advances in the Diagnosis and Management of PFAPA Syndrome

摘要: 本综述系统性总结PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis，周期性发热–阿弗他口炎–咽炎–淋巴结炎)综合征的流行病学、病因学、诊断与治疗进展。PFAPA综合征多见于儿童，通常为自限性良性病程，多数患儿在发病5年内或青春期前缓解；亦有少数病例成年后复发。MEFV、CARD8、NLRP3等基因变异与疾病表型可能存在相关性。发病机制涉及先天免疫失衡、IL-1、IFN相关通路与趋化因子(CXCL9、CXCL10、GCSF、IL-18)升高及抗mCRP介导的补体过度激活。诊断仍以临床标准为主(修订后马歇尔、Vanoni、Takeuchi、CARRA等)。治疗分急性期对症与长期维持治疗，其中秋水仙碱与扁桃体切除在多中心队列中显示较高应答率。其他治疗(沙利度胺、阿普米司特、益生菌、维生素D、西咪替丁等)证据有限。需进一步建立统一的诊断、分层策略及开展前瞻性研究，以指导个体化治疗与长期随访管理。

Abstract: This review provides a structured overview of recent progress in the epidemiology, aetiology, diagnosis and treatment of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis) syndrome. PFAPA predominantly affects children and usually follows a benign, self-limiting course. Most children achieve remission within five years of onset or before puberty, although a minority experience recurrence in adulthood. Genetic variation in MEFV, CARD8 and NLRP3 may contribute to phenotypic heterogeneity. Proposed mechanisms include innate immune imbalance, activation of IL-1- and IFN-associated pathways, elevated chemokines (CXCL9, CXCL10, G-CSF and IL-18), and anti-mCRP-mediated overactivation of the complement system. Diagnosis still relies mainly on clinical criteria, including the revised Marshall criteria and the Vanoni, Takeuchi and CARRA criteria. Management comprises symptomatic treatment during flares and longer-term maintenance strategies; colchicine and tonsillectomy have demonstrated comparatively high response rates in multicentre cohort studies. Evidence supporting other interventions—such as thalidomide, apremilast, probiotics, vitamin D and cimetidine—remains limited. Future priorities include harmonising diagnostic and risk-stratification approaches and conducting prospective studies to better inform individualised care and long-term follow-up.