儿童周期性发热-阿弗他口炎-咽炎-淋巴结炎综合征13例临床特点分析

Clinical features of children with periodic fever,aphthous stomatitis,pharyngitis,and adenitis syndrome:an analysis of 13 cases

摘要:

目的 周期性发热-阿弗他口炎-咽炎-淋巴结炎（PFAPA）综合征是一种发病机制不明的多基因多因素自身炎症性疾病。该研究旨在分析儿童PFAPA综合征的临床特点。方法 回顾性分析13例PFAPA综合征患儿的临床资料。结果 13例均在3岁内起病，平均发病年龄（14±10）个月。13例均有周期性发热表现，年发作次数8~18次。发热间歇期平均（30±5）d。三大主要症状，即咽炎、颈淋巴结炎和阿弗他口炎的发生率分别为100%（13例）、85%（11例）和38%（5例）。发热期均伴白细胞、C反应蛋白、红细胞沉降率等炎性指标升高。13例中6例行医学全外显子基因测序，7例行自身炎症性疾病panel基因检测，6例（46%）检测出MEFV基因杂合突变。所有患儿的反复发热在不使用抗生素的情况下可逐渐退至正常。使用单剂量糖皮质激素治疗10例，治疗后当次发热均迅速缓解。使用西咪替丁治疗4例，2例有效。使用秋水仙碱4例，2例有效；2例因不良反应停用。扁桃体切除2例，1例已随访3年，无再次发作；1例仍有反复发作。结论 对于年幼起病的不明原因周期性发热伴咽炎、颈淋巴结炎和阿弗他口炎，伴有炎性指标升高，且对激素反应良好的患儿，临床医师应警惕PFAPA综合征；PFAPA综合征预后良好；早期诊断可避免患儿反复使用抗生素。

Abstract:

Objective To study the clinical features of children with periodic fever,aphthous stomatitis,pharyngitis,and adenitis(PFAPA)syndrome,a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis.Methods A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome.Results All 13 children had disease onset within the age of 3 years,with a mean age of onset of(14±10)months.They all had periodic fever,with 8-18 attacks each year.The mean interictal period of fever was(30±5)days.Pharyngitis,cervical adenitis,and aphthous stomatitis were the three cardinal symptoms,with incidence rates of 100%(13/13),85%(11/13),and 38%(5/13)respectively.There were increases in white blood cells,C-reactive protein,and erythrocyte sedimentation rate during fever.Of all the 13 children,6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease,and the results showed single heterozygous mutations in the MEFV gene in 6 children(46%).Recurrent fever in all children gradually returned to normal without antibiotics.Ten children were treated with a single dose of glucocorticoids,and fever was relieved after treatment.Of all the children,4 were treated with cimetidine,among whom 2 had response;4 children were treated with colchicine,among whom 2 had response and 2 were withdrawn from the drug due to adverse reactions.Tonsillectomy was performed for 2 children,among whom 1 was followed up for 3 years without recurrence and 1 still had recurrence.Conclusions For children with unexplained periodic fever with early onset accompanied by pharyngitis,cervical adenitis,aphthous stomatitis,elevated inflammatory indices,and good response to glucocorticoids,PFAPA syndrome should be considered.This disorder has good prognosis,and early diagnosis can avoid the long-term repeated use of antibiotics.