Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B¹13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10⁻⁴, Pc = 0.0126). Moreover, the HLA-C¹08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10⁻⁴, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.     

突发性聋患者耳蜗死区分布及预后分析

目的：采用阈值均衡噪声检测法研究耳蜗死区在突发性聋患者中的分布情况,探讨耳蜗死区与突发性聋预后的关系。方法采用阈值均衡噪声检测法检测138例（149耳）突发性聋患者,综合治疗2周后,再次行听力检测,分析耳蜗死区和突发性聋预后的相关性。结果138例（149耳）突发性聋患者中39例患者（45耳）单或双耳存在一个或多个频率的耳蜗死区,耳蜗死区检出率为30.20%（45/149）;耳蜗死区在突发性聋患者主要分布在2000～4000 Hz的高频区域;检测有听力下降的频率993个,其中有耳蜗死区的频率103个,治疗后有效率29.13％（30/103）;经检测无耳蜗死区的频率890个,治疗后有效率54.38％（484/890）。两组有效率进行比较,差异具有统计学意义（χ2=23.58,P<0.05）。结论耳蜗死区与突发性聋预后密切相关。     

The thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation

Background

In severe drug eruptions, precise evaluation of disease severity at an early stage is needed to start appropriate treatment. It is not always easy to diagnose these conditions at their early stage. In addition, there are no reported prognostic biomarkers of disease severity in drug eruptions. The aim of this study was to test whether the thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption can serve as a prognostic biomarker of systemic inflammation.

p38 MAPK在自体移植静脉中的表达及其意义

目的　研究丝裂原活化蛋白激酶p3 8MAPK信号传导通路在自体移植静脉中的表达。方法　Wistar大鼠 80只 ,建立自体移植静脉模型。术后随机分为 6,2 4h ,3 ,7d和 2 ,4,6,8周等 8组 ,于相应时点取材 ,半定量逆转录PCR检测移植血管中p3 8MAPK的mRNA表达 ,Western蛋白印迹定量检测 p3 8的蛋白产物及磷酸化蛋白产物表达 ,原位杂交和免疫组化方法定位p3 8mRNA及蛋白表达。结果　移植静脉术后 6hp3 8的mRNA表达即较正常静脉明显增强 (P <0 .0 1) ,并于术后 2周达高峰 ,表达值为 (59± 2 6) % ,与 4,6,8周比较差异极显著 (P <0 .0 1)。Western蛋白印迹提示 p3 8在移植 2～ 4周达高峰 ,之后开始减少 ,8周时仍维持一定表达量 (1/4～ 1/2 )。原位杂交及免疫组化提示阳性表达多定位于移植血管中层或增生内膜中的血管平滑肌细胞 (VSMCs)。结论　p3 8MAPK通路的激活参与了移植静脉的内膜增生以及血管重塑 ,可望成为防治移植静脉狭窄闭塞的治疗靶点     

Association between the HLA-B*15:02 allele and carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han individuals of northeastern China

BackgroundThis study examined the significant association between carbamazepine (CBZ)-induced Stevens–Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) and HLA-B*15:02 in epilepsy patients of Han ethnicity living in northeastern China.MethodsCBZ–SJS/TEN patients and CBZ-tolerant control patients were genotyped for HLA-B*15:02 by PCR amplification using sequence-specific primers. Patients then were evaluated for HLA genotypes using PCR with sequence-based typing.ResultsEight of 35 CBZ–SJS/TEN patients carried HLA-B*15:02 (22.9%) versus 2 of 125 in CBZ-tolerant control patients (OR = 18.222, 95% CI = 3.662–90.662, p = 0.000). Our results suggest that HLA-B*15:02 is necessary but is not sufficient to produce SJS/TEN following CBZ treatment among Han individuals from northeastern China. Other HLA alleles, including A*33:03, B*58:01, C*03:02, DQB1*03:03, and DRB1*07:01 may be associated weakly with CBZ–SJS/TENConclusionOur results are not consistent with previous studies reporting a strong association between HLA-B*15:02 and CBZ–SJS/TEN among individuals from southern, southwestern, and central China. Other genes may be more tightly associated with CBZ–SJS/TEN. Screening for HLA-B*15:02 still may be recommended for patients in northeastern China before starting CBZ.     

Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications

Introduction: Stevens-Johnson syndrome (SJS) and its severe phenotype, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucosa. Approximately 50% of SJS/TEN patients diagnosed by dermatologists and in burn units suffer from severe ocular complications (SOC) in the acute stage.

Areas covered: Earlier studies on patients with SJS/TEN with SOC identified cold medicines including multi-ingredient cold medications and non-steroidal anti-inflammatory drugs as the main eliciting drugs. HLA analyzes showed that genetic predisposition might play a role in the response to these drugs. Our analysis of the association between HLA genotypes and cold medicine-related SJS/TEN (CM-SJS/TEN) with SOC revealed that certain HLA genotypes play a role in the development of SJS/TEN with SOC. Genetic predisposition and other factors contributing to the elicitation of CM-SJS/TEN with SOC and the management of patients in the acute and chronic stage of the disease are discussed.

Expert opinion: The main sequelae of SJS/TEN are ocular sequelae with visual disturbance. SJS/TEN with SOC needs ophthalmic treatment in addition to systemic treatment from the onset time to reduce the ophthalmic sequelae. In addition, HLA examination and public awareness of SJS/TEN with SOC due to cold medicine use might contribute to preventing visual disturbance due to SJS/TEN.

Abbreviations: SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis; SOC: severe ocular complications     

喹诺酮类药物致Stevens-Johnson综合征和中毒性表皮坏死松解症文献分析

目的:分析喹诺酮类药物致Stevens-Johnson综合征(SJS)和中毒性表皮坏死松解症(TEN)不良反应的发生情况,为临床合理用药提供参考.方法:通过PubMed、Web of Science、Springer、Embase、Scopus、万方期刊论文数据库、维普期刊数据库、中国知网(CNKI)、中国生物医学文献...