Sánchez-Borges Mario, Capriles-Hulett Arnaldo, Caballero-Fonseca Fernan
Allergy-Immunology Service, Centro Médico-Docente La Trinidad, Caracas, Venezuela.
Am J Clin Dermatol. 2002;3(9):599-607. doi: 10.2165/00128071-200203090-00002.
Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in urticaria and angioedema, is being observed with increasing frequency. Prevalence rates range from 0.1-0.3%, which is partly due to the large size of the exposed (at risk) population. Some predisposing factors for these cutaneous reactions have been identified, among them atopic diathesis, female sex, young adulthood, a history of chronic urticaria and the use of the NSAID for the relief of acute pain. The description of two different arachidonic acid cyclo-oxygenases (COX) about a decade ago, designated COX-1 and COX-2, and the incorporation into the therapeutic armamentarium of more selective enzyme inhibitors for the control of inflammation and pain, has led to an improved understanding of the pathogenesis of adverse reactions to NSAIDs. This has allowed investigators to study 'sensitive' individuals to see if they can safely receive these new pharmaceutical compounds. The reasons why some people react to NSAIDs are not completely clarified. The prevalent theory about the pathogenesis of urticaria and angioedema due to NSAIDs in cross-reactive patients assumes that the inhibition of COX-1 leads to a shunting of arachidonic acid metabolism towards the 5-lipoxygenase pathway, which results in an increased synthesis and release of cysteinyl leukotrienes. Although COX-2 inhibitors are well tolerated by the majority of classic NSAID-sensitive patients, cutaneous reactions to highly selective inhibitors of COX-2 have been described in some of these individuals, casting some doubts about the relevance of such hypotheses. On the other hand, in patients who react to a single NSAID and chemically similar products (single-reactors), specific immunoglobulin E antibodies to haptenated NSAID metabolites have been suspected, although these metabolites are not easily demonstrated by means of routine in vivo or in vitro techniques. Facial (periorbital) angioedema constitutes the most common form of clinical presentation, and one-third of the patients show a mixed clinical pattern of cutaneous (urticaria and/or angioedema) and respiratory symptoms which include upper respiratory tract edema, rhinorrhea, cough, breathlessness and tearing. When necessary, diagnosis is confirmed by means of controlled peroral drug challenges done by experienced physicians in the hospital setting and test results are helpful for clinical management, which will be based on strict avoidance, and the use of alternative tolerated medications. This approach is specially indicated in hypersensitive patients with chronic medical conditions who require continuous NSAID therapy, such as those with arthritis and coronary heart disease.
对非甾体抗炎药（NSAIDs）过敏导致荨麻疹和血管性水肿的情况越来越常见。患病率在0.1%至0.3%之间，部分原因是暴露（有风险）人群规模庞大。已确定了一些导致这些皮肤反应的易感因素，其中包括特应性素质、女性、青年、慢性荨麻疹病史以及使用NSAIDs缓解急性疼痛。大约十年前对两种不同的花生四烯酸环氧化酶（COX）的描述，即COX - 1和COX - 2，以及将更具选择性的酶抑制剂纳入治疗药物库以控制炎症和疼痛，使人们对NSAIDs不良反应的发病机制有了更好的理解。这使得研究人员能够研究“敏感”个体，看他们是否能安全地接受这些新的药物化合物。有些人对NSAIDs产生反应的原因尚未完全阐明。关于交叉反应患者中因NSAIDs导致荨麻疹和血管性水肿的发病机制的普遍理论认为，COX - 1的抑制会导致花生四烯酸代谢转向5 - 脂氧合酶途径，从而导致半胱氨酰白三烯的合成和释放增加。尽管大多数对经典NSAIDs敏感的患者对COX - 2抑制剂耐受性良好，但在其中一些个体中已描述了对COX - 2高度选择性抑制剂的皮肤反应，这对这些假说的相关性产生了一些怀疑。另一方面，在对单一NSAID及其化学相似产品有反应的患者（单一反应者）中，怀疑存在针对半抗原化NSAID代谢物的特异性免疫球蛋白E抗体，尽管这些代谢物不易通过常规体内或体外技术检测到。面部（眶周）血管性水肿是最常见的临床表现形式，三分之一的患者表现出皮肤（荨麻疹和/或血管性水肿）和呼吸道症状的混合临床模式，包括上呼吸道水肿、鼻漏、咳嗽、呼吸急促和流泪。必要时，由经验丰富的医生在医院环境中通过口服药物激发试验来确诊，试验结果有助于临床管理，临床管理将基于严格避免使用，并使用替代的耐受性药物。这种方法特别适用于患有慢性疾病需要持续NSAIDs治疗的过敏患者，如关节炎和冠心病患者。
