Hunziker T, Künzi U P, Braunschweig S, Zehnder D, Hoigné R
Dermatological Clinic, University of Berne, Switzerland.
Allergy. 1997 Apr;52(4):388-93. doi: 10.1111/j.1398-9995.1997.tb01017.x.
Studies on the epidemiology of common adverse cutaneous drug reactions have rarely been reported, since they can only be successfully conducted in clinics of internal medicine employing consultant dermatologists and having a comprehensive or intensive system of monitoring. Between 1974 and 1993, the adverse skin reactions occurring in divisions of general internal medicine of three different hospitals were monitored by a computerized comprehensive system. The "drug-monitoring patient" was defined as the recipient of at least one drug during hospitalization. The relationship of the skin reactions to drug causality in these patients had to be either definite (proven by re-exposure) or probable (drug relation greater than that of nondrug causality). The skin reactions were classified into four diagnostic groups. Maculopapular exanthema, urticaria, and vasculitis were the three main groups. The fourth group comprised cases of nonhomogeneous but clinically well-defined special exanthema. For selected drugs and years of observation, special emphasis was placed on the study of time patterns (reaction time, exposure time). A total of 1317 definite or probable drug-induced skin reactions occurred during the hospitalization of 48,005 consecutively admitted "drug-monitoring patients": 1201 cases of maculopapular exanthema, 78 cases of urticaria, 18 cases of cutaneous vasculitis, and 20 cases of special exanthema (five of erythema multiforme minor, six of fixed eruption, one of photosensitivity reaction, and eight of acneiform eruption). The main drugs involved did not differ for the three main types of skin reactions, penicillins ranking in the first place, followed by sulfonamides--most often combined with trimethoprim--and in the third place nonsteroidal anti-inflammatory drugs. The reaction time (time from last drug exposure to first skin manifestation) for urticaria showed a relevant proportion of the acute type (within 1 h) and most of the subacute type (1-24 h). For maculopapular exanthema, the subacute or, rarely, the latent type (1-8 days, exceptionally more than 8 days) predominated. For aminopenicillins, the rate of occurrence of skin reactions increased with increasing exposure time up to 12 days, and then markedly diminished. Possibly due to the tendency to withdraw suspected drugs even in the case of minor (e.g., maculopapular) skin reactions, no severe events such as erythema multiforme major/Stevens-Johnson syndrome or toxic epidermal necrolysis occurred.
关于常见皮肤药物不良反应的流行病学研究鲜有报道，因为此类研究只有在内科诊所由皮肤科会诊医生参与并具备全面或强化监测系统的情况下才能成功开展。1974年至1993年间，通过计算机化综合系统对三家不同医院普通内科病房中发生的皮肤不良反应进行了监测。“药物监测患者”定义为住院期间至少接受过一种药物治疗的患者。这些患者皮肤反应与药物因果关系必须明确（经再次用药证实）或很可能存在（药物关联大于非药物因果关系）。皮肤反应分为四个诊断组。斑丘疹、荨麻疹和血管炎是三个主要组。第四组包括非均质但临床明确的特殊皮疹病例。对于选定的药物和观察年份，特别着重研究时间模式（反应时间、暴露时间）。在48005例连续入院的“药物监测患者”住院期间，共发生了1317例明确或很可能由药物引起的皮肤反应：1201例斑丘疹，78例荨麻疹，18例皮肤血管炎，20例特殊皮疹（5例轻症多形红斑，6例固定性药疹，1例光敏反应，8例痤疮样疹）。三种主要类型皮肤反应所涉及的主要药物并无差异，青霉素位居首位，其次是磺胺类药物（最常与甲氧苄啶联用），第三位是非甾体抗炎药。荨麻疹的反应时间（从最后一次用药到首次出现皮肤表现的时间）显示急性型（1小时内）占相当比例，且大部分为亚急性型（1至24小时）。对于斑丘疹，亚急性型或很少见的潜伏型（1至8天，极少数超过8天）占主导。对于氨基青霉素，皮肤反应发生率随暴露时间增加至12天而上升，之后明显下降。可能由于即使出现轻微（如斑丘疹）皮肤反应也倾向于停用可疑药物，未发生严重事件，如重症多形红斑/史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症。
