Stevens-Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study
Stevens-Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study
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DOI：
10.1038/sj.jid.5701033
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发表时间：
2008-01-01
影响因子：
6.5
通讯作者：
Flahault, Antoine
中科院分区：
文献类型：
--
作者：
Mockenhaupt, Maja;Viboud, Cecile;Flahault, Antoine
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解（TEN）是罕见的，但严重的皮肤不良反应（SCAR）与多种药物有关。由于死亡率和发病率高，它们对公共卫生有重大影响。1997年至2001年间在欧洲进行的一项多国病例对照研究评估了药物诱导SCAR的风险。通过覆盖1亿多居民的医院网络积极发现病例。每个病例有三名年龄、性别和访谈日期相匹配的住院患者作为对照。经专家委员会对暴露进行盲法验证后，纳入379例SCAR病例和1505例对照。在最近进入市场的药物中，奈韦拉平（相对危险度bbbb22）和拉莫三嗪（相对危险度b>4）的相关性较强，舍曲林（相对危险度RR = 11[2.7-46]）、泮托拉唑（相对危险度RR = 18[3.9-85]）和曲马多（相对危险度RR = 20[4.4-93]）的相关性较弱。抗感染磺胺类药物、别嘌呤醇、卡马西平、苯巴比妥、苯妥英和奥昔康类非甾体抗炎药的相关性很强，暴露病例的相对数量也有一些变化。因此，许多病例仍然与少数已知高风险的“老”药物有关。风险仅限于药物摄入的前几周。应慎重考虑使用这类药物作为一线疗法，特别是在存在更安全的替代疗法的情况下。许多广泛使用的药物没有显示出对SJS和TEN有任何风险。
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions (SCAR) related to a variety of medications. They have a significant public health impact because of high mortality and morbidity. A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR. Cases were actively detected through a hospital network covering more than 100 million inhabitants. Three hospitalized patients per case matched on age, gender, and date of interview were enrolled as controls. After validation by an expert committee blinded to exposures, 379 SCAR cases and 1,505 controls were included. Among drugs recently introduced into the market, strong associations were documented for nevirapine (relative risk (RR) > 22) and lamotrigine (RR > 14), and weaker associations for sertraline (RR = 11 [2.7-46]), pantoprazole (RR = 18 [3.9-85]), and tramadol (RR = 20 [4.4-93]). Strong associations were confirmed for anti-infective sulfonamides, allopurinol, carbamazapine, phenobarbital, phenytoin, and oxicam-NSAIDs, with some changes in relative numbers of exposed cases. Thus, many cases were still related to a few "old'' drugs with a known high risk. Risk was restricted to the first few weeks of drug intake. The use of such drugs as first-line therapies should be considered carefully, especially when safer alternative treatments exist. A number of widely used drugs did not show any risk for SJS and TEN.