Yawalkar Nikhil
Department of Dermatology, Inselspital, CH-3010 Bern, Switzerland.
Toxicology. 2005 Apr 15;209(2):131-4. doi: 10.1016/j.tox.2004.12.023.
Cutaneous adverse reactions to drugs can comprise a broad spectrum of clinical and histopathological features. Recent evidence from immunohistological and functional studies of drug-reactive T cells suggest that distinct T-cell functions may be responsible for this broad spectrum of different clinical reactions. Maculopapular exanthems represent the most commonly encountered cutaneous drug eruption. Previous studies on maculopapular exanthems indicate that drug-specific CD4+ T cells expressing cytotoxic granule proteins such as perforin and granzyme B are critically involved in killing activated keratinocytes. These cells are particularly found at the dermo-epidermal junction and may contribute to the generation of vacuolar alteration and destruction of basal keratinocytes, which are typical found in drug-induced maculopapular exanthems. In contrast to maculopapular exanthems, the preferential activation of drug-specific cytotoxic CD8+ T cells may lead to more severe reactions like bullous drug eruptions. Furthermore, activation of drug-specific T with distinct cytokine and chemokines profiles may also explain the different clinical features of drug-induced exanthems. IL-5 and eotaxin are upregulated in maculopapular exanthems and explain the eosinophilia often found in these reactions.
药物引起的皮肤不良反应可表现出广泛的临床和组织病理学特征。近期关于药物反应性T细胞的免疫组织学和功能研究证据表明,不同的T细胞功能可能是导致这种广泛的不同临床反应的原因。斑丘疹是最常见的皮肤药物疹。以往关于斑丘疹的研究表明,表达细胞毒性颗粒蛋白(如穿孔素和颗粒酶B)的药物特异性CD4+ T细胞在杀死活化的角质形成细胞中起关键作用。这些细胞尤其存在于真皮-表皮交界处,可能导致空泡改变和基底角质形成细胞的破坏,这在药物性斑丘疹中很常见。与斑丘疹不同,药物特异性细胞毒性CD8+ T细胞的优先活化可能导致更严重的反应,如大疱性药物疹。此外,具有不同细胞因子和趋化因子谱的药物特异性T细胞的活化也可能解释药物性皮疹的不同临床特征。白细胞介素-5和嗜酸性粒细胞趋化因子在斑丘疹中上调,这解释了这些反应中常见的嗜酸性粒细胞增多现象。