药物所致重症多形红斑和中毒性表皮坏死松解症的临床研究

对药物所致征症多形红斑（ＳＪＳ）和中毒性表皮松解症（ＴＥＮ）进行了对比研究。两者最常见的致敏解药物是解镇痛药，其次是抗生素类和镇静抗癫痫药。ＳＪＳ和ＴＥＮ的发病年龄、性别和潜伏期无差异，但ＴＥＮＲ 发热时间、急性期和恢复期时间明显长于ＳＪＳ，发热程度、粘膜损害程度和合并症发生率明显高于ＳＪＳ。ＳＪＳ预后良好，无１例死亡，ＴＥＮ的死亡率高达３９％。关于皮质类固醇激素在治疗ＴＥＮ中的应用，我们认为早期     

帕博利珠单抗致严重免疫相关皮肤不良反应的文献分析

目的: 探讨帕博利珠单抗致Stevens-Johnson综合征(SJS)、中毒性表皮坏死松懈症(TEN)严重皮肤反应的临床特点,旨在为临床合理使用帕博利珠单抗提供参考。方法: 检索中国知网、维普、万方、PubMed、Web of Science 和Medline 等数据库,收集整理自数据库建库至2022年2月关于帕博利珠单抗致SJS/TEN的个案报道,分析该药致SJS/TEN的临床特点。结果: 共收集25例病例,其中帕博利珠单抗致SJS病例13例,TEN7例,SJS/TEN重叠征5例。3种类型SJS/TEN反应中TEN发生最早,中位发生时间为16(3,39)d;其次为SJS/TEN重叠征,发生时间为30(22.5,115)d;SJS反应最晚为55(7,106.5)d。25例中有22例(88.0%)伴随着黏膜受累,17例(68.0%)在黏膜受累或皮肤脱落之前出现前驱性皮疹。25例患者24例(96.0%)接受了全身性糖皮质激素治疗,9例(36.0%)接受静脉注射免疫球蛋白,4例(16.0%)接受免疫抑制剂。最终,25例患者中17例(68.0%)好转或痊愈,5例(20.0%)死亡,3例(12.0%)预后未知。结论: 帕博利珠单抗可诱发SJS/TEN,应注意黏膜损伤,异常皮疹等可能为SJS/TEN发生信号,除了全身性糖皮质激素治疗以外,静脉注射免疫球蛋白和环孢素治疗证实是有益补充。     

孟氏架结合TEN治疗大龄儿童胫腓骨骨折

目的:评价孟氏架结合TEN治疗大龄儿童胫腓骨骨折的临床疗效。方法:随访该疗法治疗的胫腓骨骨折患者18例,观察其治疗效果。结果:术后采用Johner-Wruhs评价标准,优16例,良2例,中0例,差0例。结论:本疗法符合生物学固定原则,具有操作简单、固定牢靠、创伤小、骨折愈合快、功能恢复好、并发症少等优点,是治疗大龄儿童胫腓骨骨折的有效疗法之一。     

重症多形红斑型药疹52例和中毒性表皮坏死松解症31例回顾性分析

目的比较重症多形红斑(SJS)和中毒性表皮坏死松解症(TEN)的临床特征和实验室检查指标的差异。方法对2000年7月-2012年2月本院收治的83例SJS和TEN患者的临床资料进行回顾性分析,用SCORTEN评分系统对疾病的严重程度和病人的预后进行评估。结果引起SJS和TEN的药物以抗生素为主,其次是非甾体类抗炎药。TEN组的电解质异常的例数明显高于SJS组(P<0.05);肝功能损害是SJS和TEN最常见的并发症;SJS组和TEN组共有81例给予系统用糖皮质激素治疗,2例仅用人免疫球蛋白治疗,SJS组7例和TEN组15例给予激素联合人免疫球蛋白治疗。SCORTEN评分超过3分的有4例,其中1例死亡。结论抗生素是引起重症药疹最常见的药物,系统应用糖皮质激素尤其是联合人免疫球蛋白治疗可能是降低SJS和TEN死亡率的有效手段之一。     

Association between HLA‐B*1502 and carbamazepine‐induced severe cutaneous adverse drug reactions in a Thai population

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA‐B*1502 and CBZ‐induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case–control study was conducted to determine whether HLA‐B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ‐induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA‐B*1502 while only 5 (11.90%) of the CBZ‐tolerant controls had this allele. The risk of CBZ‐induced SJS/TEN was significantly higher in the patients with HLA‐B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62–205.13, p = 2.89 × 10^?12]. The sensitivity and specificity of HLA‐B*1502 for prediction of CBZ‐induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ‐induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA‐B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA‐B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ‐induced SJS and TEN.     

Human leukocyte antigen and idiosyncratic adverse drug reactions

A clinical association between a specific human leukocyte antigen (HLA) allele and idiosyncratic adverse drug reactions (IADRs) is a strong indication that IADRs are mediated by the adaptive immune system. For example, it is well-established that HLA-B*15:02 and HLA-B*57:01 are associated with carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, respectively. Drug-specific T-cells whose response is restricted by specific HLA risk alleles have been detected from IADR patients, also suggesting an adaptive immune pathogenesis. T-cells from carbamazepine SJS/TEN patients are activated by direct pharmacological interaction between carbamazepine and HLA-B*15:02 expressed on antigen presenting cells (APCs). Abacavir-specific, HLA-B*57:01-restricted T-cells are activated by APCs presenting peptides which are only displayed by the HLA molecule when abacavir is bound during peptide loading. Finally, HLA-B*57:01-restricted activation of T-cells from patients with flucloxacillin-induced liver injury is dependent on processing of drug protein adducts. Based on these observations, it is now possible to utilize blood from healthy drug-naïve volunteers to study the priming of naïve T-cells to drugs. Future development of these methodologies may lead to the development of assays that predict intrinsic immunogenicity of drugs and chemicals at the preclinical stage of drug development.