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儿童严重皮肤不良反应的流行病学及其与人类白细胞抗原的关联

Epidemiology of Severe Cutaneous Adverse Drug Reaction and Its HLA Association among Pediatrics.

作者信息

Esmaeilzadeh Hossein, Farjadian Shirin, Alyasin Soheila, Nemati Hamid, Nabavizadeh Hesamodin, Esmaeilzadeh Elmira

机构信息

Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Allergy and Clinical Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Iran J Pharm Res. 2019 Winter;18(1):506-522.

Abstract

Severe cutaneous adverse drug reaction (SCAR) is considered to be a multifactorial drug side effect. This study was designed to investigate the epidemiology and human leukocyte antigen (HLA)-A and -B gene polymorphisms in pediatric patients with SCAR admitted in tertiary referral center, southwestern of Iran from 2013 to 2017. Demographic data, past allergy and autoimmune history, clinical presentations, drugs confirmed to be the cause of SCAR as well as its therapy were reviewed for each patient. HLA-A and -B allele frequencies were determined in 40 of the patients using polymerase chain reaction based on sequence specific primers (PCR-SSP) and compared with 40 healthy individuals as control group. Sixty-one patients with mean age of 6 years old and boy to girl ratio was 1.2/1 in this study. The most common type of SCAR in our patients was Steven Johnson Syndrome (SJS)/Toxic Epidermal Necrosis (TEN) mainly caused by beta-lactam antibiotics. Carbamazepine was the second cause of drug-induced SCAR. Moreover, HLA-A02:01 and A51:01 were related to the increased risk of SCAR while A11:01 seemed to be protective against SCAR. HLA-A02:01, HLA-A24:02, and HLA-B51:01 showed associations to the increased risk of SJS. Based on our results, beta-lactam antibiotics and antiepileptic drugs are the most common causes of severe adverse drug reaction in southwestern Iranian pediatric patients. Moreover, some HLA-A alleles can influence risk of SCAR.

摘要

严重皮肤药物不良反应(SCAR)被认为是一种多因素药物副作用。本研究旨在调查2013年至2017年在伊朗西南部三级转诊中心收治的SCAR儿科患者的流行病学以及人类白细胞抗原(HLA)-A和-B基因多态性。回顾了每位患者的人口统计学数据、既往过敏和自身免疫病史、临床表现、确诊为SCAR病因的药物及其治疗情况。使用基于序列特异性引物的聚合酶链反应(PCR-SSP)测定了40例患者的HLA-A和-B等位基因频率,并与40名健康个体作为对照组进行比较。本研究中61例患者的平均年龄为6岁,男女比例为1.2/1。我们患者中最常见的SCAR类型是史蒂文斯-约翰逊综合征(SJS)/中毒性表皮坏死松解症(TEN),主要由β-内酰胺类抗生素引起。卡马西平是药物性SCAR的第二大病因。此外,HLA-A02:01和A51:01与SCAR风险增加相关,而A1:01似乎对SCAR有保护作用。HLA-A02:01、HLA-A24:02和HLA-B51:01与SJS风险增加相关。根据我们的结果,β-内酰胺类抗生素和抗癫痫药物是伊朗西南部儿科患者严重药物不良反应的最常见原因。此外,一些HLA-A等位基因可影响SCAR风险。

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