儿童药物超敏反应相关噬血细胞综合征9例分析  

Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis

作　　者：赵云泽 马宏浩[1] 王冬[1] 廉红云[1] 王天有[1] 张蕊[1] Zhao Yunze;Ma Honghao;Wang Dong;Lian Hongyun;Wang Tianyou;Zhang Rui(Hematology Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing 100045,China)

机构地区：[1]国家儿童医学中心、首都医科大学附属北京儿童医院血液病中心、儿童血液病与肿瘤分子分型北京市重点实验室、儿科学国家重点学科、儿科重大疾病研究教育部重点实验室,北京100045

出　　处：《中华儿科杂志》2024年第1期60-65,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金(82200203);北京市教育委员会科研计划(KM202110025011);首都临床特色诊疗技术研究及转化应用(Z221100007422054);北京市医院管理中心“青苗”人才项目(QML20231210);首都医科大学附属北京儿童医院研究型病房项目(BCRW202101)。

摘　　要：目的探讨儿童药物超敏反应相关噬血细胞综合征(DIHS-HLH)的临床特征、治疗及预后。方法回顾性病例分析。以2020年1月至2022年12月就诊于首都医科大学附属北京儿童医院的9例DIHS-HLH患儿为研究对象,总结患儿的临床表现、实验室检查、治疗及预后情况。使用Kaplan-Meier法计算总生存率。结果9例患儿男6例、女3例,年龄0.8~3.1岁,均有发热、皮疹、肝肿大和2个及以上部位淋巴结肿大,其他表现包括脾肿大4例、肺部影像学改变6例、中枢神经系统表现3例、水样便3例等。实验室检查以可溶性CD25升高(8例)、肝功能损伤(7例)、高铁蛋白血症(7例)较为突出,其他包括骨髓噬血现象5例、低纤维蛋白原血症3例、高甘油三酯血症2例、细胞因子以白细胞介素(IL)5、IL-8、干扰素γ(IFN-γ)升高(分别有6、7、6例)为著。所有患儿均应用足量免疫球蛋白、激素和芦可替尼治疗,其中4例应用大剂量甲泼尼龙冲击,2例应用依托泊苷,2例应用环孢素。随访0.2~38.6个月,7例存活,1年总生存率为(78±14)%。2例死亡患儿均为病初应用足量免疫球蛋白、甲泼尼龙2 mg/(kg·d)联合芦可替尼病情控制不佳者。2例死亡患儿均有水样便、IL-5和IL-8升高、IgM减低。结论对于发热、皮疹并有可疑用药史的患儿,如存在肝肿大及肝功能损伤、IL-5和IL-8升高,需高度警惕DIHS-HLH,及时停用可疑药物,应用足量免疫球蛋白、激素联合芦可替尼有助于疾病控制。Objective To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis(DIHS-HLH).Methods This was a retrospective case study.Clinical characteristics,laboratory results,treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized.Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results Among all 9 cases,there were 6 males and 3 females,with the age ranged from 0.8 to 3.1 years.All patients had fever,rash,hepatomegaly and multiple lymph node enlargement.Other manifestations included splenomegaly(4 cases),pulmonary imaging abnormalities(6 cases),central nervous system symptoms(3 cases),and watery diarrhea(3 cases).Most patients showed high levels of soluble-CD25(8 cases),hepatic dysfunction(7 cases)and hyperferritinemia(7 cases).Other laboratory abnormalities included hemophagocytosis in bone marrow(5 cases),hypofibrinogenemia(3 cases)and hypertriglyceridemia(2 cases).Ascending levels of interleukin(IL)5,IL-8 and interferon-γ(IFN-γ)were detected in more than 6 patients.All patients received high dose intravenous immunoglobulin,corticosteroid and ruxolitinib,among which 4 patients were also treated with high dose methylprednisolone,2 patients with etoposide and 2 patients with cyclosporin A.After following up for 0.2-38.6 months,7 patients survived,and the 1-year overall survival rate was(78±14)%.Two patients who had no response to high dose immunoglobulin,methylprednisolone 2 mg/(kg·d)and ruxolitinib died.Watery diarrhea,increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions For children with fever,rash and a suspicious medication history,when complicated with hepatomegaly,impaired liver function and high levels of IL-5 and IL-8,DIHS-HLH should be considered.Once diagnosed with DIHS-HLH,suspicious drugs should be stopped immediately,and high dose intrave

关 键 词：淋巴组织细胞增多症 嗜血细胞性 超敏反应 儿童 

分 类 号：R725.9[医药卫生—儿科]