Roujeau J C, Kelly J P, Naldi L, Rzany B, Stern R S, Anderson T, Auquier A, Bastuji-Garin S, Correia O, Locati F
Department of Dermatology, Université Paris XII, Créteil, France.
N Engl J Med. 1995 Dec 14;333(24):1600-7. doi: 10.1056/NEJM199512143332404.
Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case-control study to quantify the risks associated with the use of specific drugs.
Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough.
Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk.
The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week.
中毒性表皮坏死松解症和史蒂文斯 - 约翰逊综合征是罕见的、危及生命的药物性皮肤反应。我们进行了一项病例对照研究，以量化使用特定药物相关的风险。
数据通过法国、德国、意大利和葡萄牙的监测网络获取。比较了245例因中毒性表皮坏死松解症或史蒂文斯 - 约翰逊综合征住院的患者和1147例因其他原因住院的患者（对照组）发病前的用药情况。计算了粗略相对风险，并在数量足够大时通过多变量方法对混杂因素进行调整。
在通常短期使用的药物中，甲氧苄啶 - 磺胺甲恶唑和其他磺胺类抗生素（粗略相对风险，172；95%置信区间，75至396）、氯美扎酮（粗略相对风险，62；21至188）、氨基青霉素（多变量相对风险，6.7；2.5至18）、喹诺酮类（多变量相对风险，10；2.6至38）和头孢菌素（多变量相对风险，14；3.2至59）的风险增加。对于对乙酰氨基酚，在法国多变量相对风险为0.6（95%置信区间，0.2至1.3），但在其他国家为9.3（3.9至22）。在通常使用数月或数年的药物中，风险增加主要局限于治疗的前两个月，此时粗略相对风险如下：卡马西平，90（95%置信区间，19至无穷大）；苯巴比妥，45（19至108）；苯妥英，53（11至无穷大）；丙戊酸，25（4.3至无穷大）；奥昔康类非甾体抗炎药（NSAIDs），72（25至209）；别嘌醇，52（小括号内16至167）；以及皮质类固醇，54（23至124）。对于许多药物，包括噻嗪类利尿剂和口服降糖药，风险没有显著增加。
使用抗菌磺胺类药物、抗惊厥药、奥昔康类NSAIDs、别嘌醇、氯美扎酮和皮质类固醇与史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症风险大幅增加有关。但对于任何一种药物，额外风险均未超过每百万使用者每周5例。
