Greenberger Paul A
Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N. Clair Street #14018, Chicago, IL 60611, USA.
J Allergy Clin Immunol. 2006 Feb;117(2 Suppl Mini-Primer):S464-70. doi: 10.1016/j.jaci.2005.11.002.
Drug reactions can be considered as being either predictable or unpredictable. A predictable reaction would be the result of the pharmacologic action of the medication. An unpredictable reaction might be idiosyncratic, might be drug intolerance, or might have or imply an immunologic basis, such as being IgE mediated. Immediate reactions that are not IgE mediated can be considered as pseudoallergic (non-IgE-mediated mast cell activation). This review will discuss allergic and immunologic reactions to immunomodulators, penicillins and cephalosporins, sulfonamides, aspirin, and nonselective nonsteroidal anti-inflammatory drugs and consider the serious drug-related conditions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The field of drug "allergy" has expanded to include adverse reactions associated with immunosuppressive medications, anticytokine therapies, and mAbs. The cytokine release reaction that occurs with anti-CD20 antibody infusions in patients with leukemia and white blood cell counts of greater than 50 x 10(9)/L is associated with high concentrations of TNF, IL-6, and IL-8. Because of the findings of fever, dyspnea, rigors, and hypotension, this reaction resembles the Jarisch-Herxheimer reaction that occurs 60 to 90 minutes after penicillin administration in patients with secondary syphilis. Furthermore, the care of the patient with penicillin allergy has been made more difficult in the absence of the major determinant, penicilloyl-polylysine, in that from 34% to 84% of patients who have positive skin test reactions to penicillin have exclusively positive reactions to the major determinant. SJS and TEN typically are caused by medications within 1 to 8 weeks of initiation of therapy. Evidence for death of the keratinocytes through (1) drug-specific cytotoxicity with the perforin-granzyme B-mediated killing and (2) activation of Fas on keratinocytes have provided explanations for the sloughing of skin. Unfortunately, intravenous immunoglobulin therapy for SJS and TEN has been disappointing.
药物反应可被认为是可预测的或不可预测的。可预测的反应是药物药理作用的结果。不可预测的反应可能是特异反应性的，可能是药物不耐受，或者可能有或暗示免疫基础，例如由IgE介导。非IgE介导的即刻反应可被视为假过敏反应（非IgE介导的肥大细胞活化）。本综述将讨论对免疫调节剂、青霉素和头孢菌素、磺胺类药物、阿司匹林以及非选择性非甾体抗炎药的过敏和免疫反应，并考虑严重的药物相关病症，如史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）。药物“过敏”领域已扩展到包括与免疫抑制药物、抗细胞因子疗法和单克隆抗体相关的不良反应。白血病患者且白细胞计数大于50×10⁹/L时，输注抗CD20抗体所发生的细胞因子释放反应与高浓度的肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）和白细胞介素-8有关。由于出现发热、呼吸困难、寒战和低血压等表现，这种反应类似于二期梅毒患者使用青霉素后60至90分钟发生的雅里希-赫克斯海默反应。此外，在缺乏主要决定簇青霉素酰聚赖氨酸的情况下，对青霉素过敏患者的护理变得更加困难，因为对青霉素皮肤试验反应呈阳性的患者中，有34%至84%仅对主要决定簇呈阳性反应。SJS和TEN通常由治疗开始后1至8周内的药物引起。通过（1）穿孔素-颗粒酶B介导的杀伤作用导致的药物特异性细胞毒性和（2）角质形成细胞上Fas的激活，角质形成细胞死亡的证据为皮肤脱落提供了解释。不幸的是，SJS和TEN的静脉注射免疫球蛋白治疗效果并不理想。
