药疹发病机理研究的几个热点

Advanced studies on the pathogenesis of drug eruption

人类疱疹病毒6型(HHV6)和EB病毒在药疹的发生与发展中起重要作用,由于部分患者只能检测到显著升高的IgG抗体,因此潜伏病毒感染可能更重要。T细胞可直接识别药物非肽类抗原,药物特异性CD4+T细胞可损伤角质形成细胞(keratinocyte,KC)导致药疹发生。红斑或斑丘疹性药疹的浸润细胞为CD4+T细胞,而中毒性表皮坏死松解型药疹(toxic epidermal necrolysis,TEN)却以CD8+T细胞为主。细胞因子、粘附分子是药疹中的毒性因子,尤其是IFN-γ、TNF-α、IL-5和嗜酸性粒细胞活性趋化因子。广泛的KC凋亡是多形性红斑型药疹(Stevens-Johnson syndrome,SJS)和TEN主要组织学特征,是静脉注射大剂量免疫球蛋白(intravenous immunoglobulin,IVIg)治疗的主要机理之一。药物代谢酶谷胱甘肽S-转移酶基因在药疹患者中有多态性。

Viral infection,especially HHV6 and EB viruses plays an important role in the incidence and development of drug eruption.Since only a significant increase in IgG antibodies can be detected in some patients,the latent infection should be considered with more importance.T cells can directly identify the drug non-peptide antigen,drug-specific CD4+T cells may damage KC which leads to drug eruption.CD4+ cells are main infiltrating cells in erythema or maculopapular eruptions,but in TEN,CD8+ cells are more prevalent.Cytokines,adhesion molecules act like toxic factors in the development of drug eruption,particularly IFN-g,TNF-α,IL-5 and eosinophil activation chemokine.A wide range of KC apoptosis is the main histologic characteristic in SJS and TEN.Also,it is one of the main mechanisms in high-dose IVIg treatment.Drug metabolic enzyme,GST gene shows polymorphism in patients with drug eruption.