PDF(Pubmed)
Abstract：
Cutaneous hypersensitivity reactions represent the most common manifestation of drug allergy seen in the clinic, with 25% of all adverse drug reactions appearing in the skin. The severity of cutaneous eruptions can vastly differ depending on the cellular mechanisms involved from a minor, self-resolving maculopapular rash to major, life-threatening pathologies such as the T-cell mediated bullous eruptions, i.e., Stevens Johnson syndrome/toxic epidermal necrolysis. It remains a significant question as to why these reactions are so frequently associated with the skin and what factors polarise these reactions towards more serious disease states. The barrier function which the skin performs means it is constantly subject to a barrage of danger signals, creating an environment that favors elicitation. Therefore, a critical question is what drives the expansion of cutaneous lymphocyte antigen positive, skin homing, T-cell sub-populations in draining lymph nodes. One answer could be the heterologous immunity hypothesis whereby tissue resident memory T-cells that express T-cell receptors (TCRs) for pathogen derived antigens cross-react with drug antigen. A significant amount of research has been conducted on skin immunity in the context of contact allergy and the role of tissue specific antigen presenting cells in presenting drug antigen to T-cells, but it is unclear how this relates to epitopes derived from circulation. Studies have shown that the skin is a metabolically active organ, capable of generating reactive drug metabolites. However, we know that drug antigens are displayed systemically so what factors permit tolerance in one part of the body, but reactivity in the skin. Most adverse drug reactions are mild, and skin eruptions tend to be visible to the patient, whereas minor organ injury such as transient transaminase elevation is often not apparent. Systemic hypersensitivity reactions tend to have early cutaneous manifestations, the progression of which is halted by early diagnosis and treatment. It is apparent that the preference for cutaneous involvement of drug hypersensitivity reactions is multi-faceted, therefore this review aims to abridge the findings from literature on the current state of the field and provide insight into the cellular and metabolic mechanisms which may contribute to severe cutaneous adverse reactions.
摘要：
皮肤超敏反应是临床上最常见的药物过敏表现，25％的药物不良反应出现在皮肤上。皮肤爆发的严重程度可能会有很大的不同，这取决于未成年人所涉及的细胞机制，自我解决的斑丘疹到主要，危及生命的病理，如T细胞介导的大疱性爆发，即，史蒂文斯·约翰逊综合征/中毒性表皮坏死松解症。关于为什么这些反应如此频繁地与皮肤相关联以及哪些因素使这些反应朝向更严重的疾病状态,这仍然是一个重要的问题。皮肤执行的屏障功能意味着它不断受到危险信号的影响，创造一个有利于启发的环境。因此,一个关键问题是什么驱动皮肤淋巴细胞抗原阳性的扩大，皮肤归巢,引流淋巴结中的T细胞亚群。一个答案可能是异源免疫假设，即表达病原体衍生抗原的T细胞受体（TCR）的组织驻留记忆T细胞与药物抗原发生交叉反应。在接触变态反应和组织特异性抗原呈递细胞在将药物抗原呈递至T细胞中的作用的背景下，已经进行了大量的皮肤免疫研究。但目前尚不清楚这与来自循环的表位有何关系。研究表明皮肤是代谢活跃的器官,能够产生反应性药物代谢物。然而,我们知道药物抗原是全身性展示的，那么什么因素允许身体的一个部位耐受，而是皮肤的反应性。大多数药物不良反应是轻微的，皮肤喷发对病人来说是可见的，而轻微的器官损伤，如短暂的转氨酶升高往往不明显。全身性超敏反应往往有早期皮肤表现，其进展通过早期诊断和治疗而停止。很明显，对药物超敏反应的皮肤参与的偏好是多方面的，因此，这篇综述旨在总结有关该领域现状的文献发现，并提供对可能导致严重皮肤不良反应的细胞和代谢机制的见解。
