儿童NLRP12-自身炎症性疾病临床特征分析

Clinical characteristics of NLRP12-related auto-inflammatory diseases in children

目的探讨儿童NLRP12-自身炎症性疾病(NLRP12-AD)的临床表现、免疫学特点、基因型、诊治过程及预后,加强儿科医师对本病认识。方法回顾性分析2016年深圳市儿童医院诊治NLRP12-AD 1例患儿的临床特征,并以NLRP12-AD为检索词,检索PubMed、中国知网、重庆维普及万方数据库2008年1月至2019年1月相关文献,总结儿童期发病NLRP12-AD患者的临床资料及基因变异特点。结果本组为首例伴发巨噬细胞活化综合征患儿。回顾本组及儿童期发病NLRP12-AD(33例)共34例患儿,总结临床特征如下:儿童期各年龄均可发病,无性别差异,可无阳性家族史。几乎全部以发热为首发症状,近半数由寒冷诱发(44%),常见症状为周期性发热(100%)、肌痛(53%)、皮疹(38%)、关节炎(35%)、腹痛及腹泻(50%),其他症状有头痛、口腔溃疡、淋巴结肿大和肝脾大等。约50%患者发作时红细胞沉降率(ESR)和C反应蛋白(CRP)异常升高,并伴有白介素(IL)-1、IL-6、IL-18升高。约48%患者激素和抗组胺药物治疗有效,但其中5例严重病例单用激素效果不佳,联合使用托珠单抗等新型生物制剂疗效显著。结论儿童NLRP12-AD临床表型多样,易被误诊为全身型幼年特发性关节炎(SoJIA)或感染性疾病,如能早期诊治,大部分患者预后良好。

Objective To investigate the clinical manifestations,immunological features,genotypes,diagnosis,treatment and prognosis of NLRP12-autoinflammatory disease(NLRP12-AD)in children.Methods The clinical characteristics of 1 case of NLRP12-AD patient admitted in 2016 in Shenzhen Children’s Hospital were analyzed retrospectively,and using NLRP12-AD as the search term,we searched PubMed,CNKI,Chongqing Weipu and Wanfang database from January 2008 to January 2019 to summarize the clinical data and genetic variation characteristics of NLRP12-AD patients with the onset in childhood.Results By literature review of NLRP12-AD,34 cases of NLRP12-AD were included.The clinical characteristics were summarized as follows:the children of all ages might suffer from this disease,without gender difference.There can be no positive family history.Fever was the first symptom in almost all cases,and nearly half of them were induced by cold(44%).The common symptoms included periodic fever(100%),myalgia(53%),rash(38%),arthritis(35%),and abdominal pain/diarrhea(50%).Some patients had headache,oral ulcers,lymphadenopathy,and hepatosplenomegaly,etc..During disease attack,half patients would show increased acute phase reactions,including ESR and CRP,and the levels of IL-1,IL-6 and IL-18 increased,especially IL-6.Hormones and antihistamines were effective in most patients,but hormones alone were ineffective in 5 severe cases,and combined use of new biological agents such as tropizumab was effective.Conclusion The clinical phenotypes of NLRP12-AD in children are diverse and the disease is easily misdiagnosed as SoJIA or infectious diseases.If early diagnosis and treatment can be made,the prognosis of most patients is good.