Roychowdhury Sanjoy, Svensson Craig K
Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
AAPS J. 2005 Dec 9;7(4):E834-46. doi: 10.1208/aapsj070480.
Cutaneous drug reactions (CDRs) are the most commonly reported adverse drug reactions. These reactions can range from mildly discomforting to life threatening. CDRs can arise either from immunological or nonimmunological mechanisms, though the preponderance of evidence suggests an important role for immunological responses. Some cutaneous eruptions appear shortly after drug intake, while others are not manifested until 7 to 10 days after initiation of therapy and are consistent with delayed-type hypersensitivity. This review discusses critical steps in the initiation of delayed-type hypersensitivity reactions in the skin, which include protein haptenation, dendritic cell activation/migration and T-cell propagation. Recently, an alternative mechanism of drug presentation has been postulated that does not require bioactivation of the parent drug or antigen processing to elicit a drug-specific T-cell response. This review also discusses the role of various immune-mediators, such as cytokines, nitric oxide, and reactive oxygen species, in the development of delayed-type drug hypersensitivity reactions in skin. As keratinocytes have been shown to play a crucial role in the initiation and propagation of cutaneous immune responses, we also discuss the means by which these cells may initiate or modulate CDRs.
皮肤药物反应（CDRs）是最常报告的药物不良反应。这些反应的程度从轻微不适到危及生命不等。CDRs可由免疫或非免疫机制引起，不过大量证据表明免疫反应起重要作用。一些皮肤疹在服药后不久出现，而另一些直到治疗开始后7至10天才显现，这与迟发型超敏反应一致。本综述讨论了皮肤中迟发型超敏反应起始的关键步骤，包括蛋白质半抗原化、树突状细胞激活/迁移和T细胞增殖。最近，有人提出了一种药物呈递的替代机制，该机制不需要母药的生物活化或抗原加工就能引发药物特异性T细胞反应。本综述还讨论了各种免疫介质，如细胞因子、一氧化氮和活性氧在皮肤迟发型药物超敏反应发生中的作用。由于角质形成细胞已被证明在皮肤免疫反应的起始和传播中起关键作用，我们也讨论了这些细胞引发或调节CDRs的方式。
