12例伴疱疹病毒再激活的儿童药物超敏反应综合征回顾性分析  

Retrospectively Analysis of Drug-induced Hypersensitivity Syndrome(DIHS)Complicated with Herpesvirus Reactivation in 12 Pediatric Cases

作　　者：郑伟 莫小兰 汪雪莲 杨花梅 叶家卫 谭丽梅 徐翼 李旭芳 ZHENG Wei;MO Xiaolan;WANG Xuelian;YANG Huamei;YE Jiawei;TAN Limei;XU Yi;LI Xufang(Department of Pharmacy,Guangzhou Women and Children's Medical Center,Guangzhou 510120,China;Department of Infectious Diseases,Guangzhou Women and Children's Medical Center,Guangzhou 510120,China)

机构地区：[1]广州市妇女儿童医疗中心药学部,广州510120 [2]广州市妇女儿童医疗中心感染科,广州510120

出　　处：《医药导报》2024年第7期1139-1144,共6页Herald of Medicine

基　　金：广州市科技局2023年度农业和社会发展科技专题项目(SL2022B03J01382);十四五国家重点研发计划项目子课题(2021YFC2701801)。

摘　　要：目的总结儿童伴疱疹病毒再激活的药物超敏反应综合征(DIHS)临床特征,为儿童DIHS早期识别和诊治提供参考。方法回顾性分析2018年1月至2023年3月广州市妇女儿童医疗中心12例确诊为伴疱疹病毒再激活儿童DIHS病例的用药史、临床表现、治疗及预后。比较患儿出疹前5 d内、出疹后5 d内以及出疹后6~10 d的血液学指标、炎症指标和肝肾功能等变化。结果12例患儿男女比例5:1,中位年龄27个月(四分位数间距20.50~34.75)。发病前2~6周均应用≥2种抗菌药物,其中7例联合应用≥3种,5例联合或序贯应用2种抗菌药物。抗菌药物种类包括头孢菌素类(12例)、半合成青霉素(5例)、万古霉素(4例)、阿奇霉素(7例)。12例临床表现均有发热、皮疹和多器官受累。皮疹早期均为红色斑丘疹型,逐渐演变为超过全身面积50%且呈大片融合状。其中7例伴面部水肿,2例面部皮疹呈紫红色;11例后期表现为剥脱性皮炎。12例有明显淋巴结肿大。肝脏受累最常见(发生率100%,单纯转氨酶升高4例,胆汁淤积6例,肝衰竭2例),肺部受累9例。实验室检查显示出疹前5 d内白细胞、嗜酸粒细胞无明显升高,可有低水平异型淋巴细胞出现。出疹后白细胞、嗜酸粒细胞和异型淋巴细胞进行性升高。超敏C反应蛋白(Hs-CRP)、降钙素原(PCT)在出疹前后出现明显升高。所有患儿给予静脉注射免疫球蛋白(IVIG)和甲泼尼龙琥珀酸钠治疗,2例患儿给予抗病毒治疗,9例给予多次血浆置换。结果9例痊愈,1例出现免疫重建综合征,2例因肝衰竭死亡。结论抗菌药物是儿童DIHS常见致敏药物。临床表现发热、皮疹伴肝、肺等多器官受累,出疹后白细胞、嗜酸粒细胞和异型淋巴细胞进行性升高等时,应高度怀疑DIHS,应注意监测疱疹病毒活化情况并追朔用药史,早期积极免疫治疗,必要时抗病毒治疗。Objective To summarize the clinical characteristics of children with drug-induced hypersensitivity syndrome(DIHS)complicated with herpesvirus reactivation,and to promote the early and accurate identification,diagnosis,and treatment of DIHS in children.Methods The medication history,clinical manifestations,treatment,and prognosis of 12 children confirmed DIHS complicated with herpesvirus reactivation in Guangzhou Women and Children's Medical Center between January 2018 and March 2023 were retrospectively analyzed.The changes in hematological parameters,inflammatory indexes,and hepatic and renal function within 5 d before the eruption,5 d,and 6-10 d after eruption were compared.Results Of the 12 patients,the male-to-female ratio was 5:1,with a median age of 27(interquartile range 20.50-34.75)months.Two or more antibiotics were used at least two to six weeks before onset,with a combination of 3 or more antibiotics in 7 children,and a combined or sequential application of 2 antibiotics in 5 children.The antibiotics included cephalosporins(n=12),semisynthetic penicillins(n=5),vancomycin(n=4)and azithromycins(n=7).All 12 patients presented fever,rashes,and multiple organ involvement.The rashes were red maculopapules in the early stage and then gradually developed into massive fusion exceeding 50%of the whole body.Among them,seven children were accompanied by facial edema,and two had purplish-red facial rashes.11 children suffered from exfoliative dermatitis in the later stage.12 children presented obviously enlarged lymph nodes.Liver involvement was the most common(100%,simple increase of transaminase in four children,cholestasis in six children,and hepatic failure in two children),and lung involvement was found in nine children.Laboratory examination showed no significant increase in leukocytes or eosinophils within 5 d before the eruption,but low levels of atypical lymphocytes.After the eruption,leukocytes,eosinophils,and atypical lymphocytes increased progressively.Inflammatory indexes of hypersensitive C-reactive p

关 键 词：药物超敏反应综合征 儿童 嗜酸粒细胞 异型淋巴细胞 疱疹病毒 

分 类 号：R978.1[医药卫生—药品] R969[医药卫生—药学]