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Previous Volume 333:1600-1608 December 14, 1995 Number 24 Next

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ABSTRACT

Background 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.

Methods 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.

Results 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 ); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to ); valproic acid, 25 (4.3 to ); 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.

Conclusions 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.

Source Information

From the Groupe Epidemiologie LY Stevens–Johnson (ELYS), Department of Dermatology (J.-C.R.), and the Department of Public Health (S.B.-G.), Université Paris XII, Créteil, France; the Slone Epidemiology Unit, Boston University School of Medicine, Boston (J.P.K., T.A., S.S., D.W.K.); Gruppo Italiano Studi Epidemiologici in Dermatologia, Department of Dermatology, Università degli Studi di Milano, Bergamo, Italy (L.N., F.L.); Dokumentationszentrum schwerer Hautreaktionen, Department of Dermatology, Albert-Ludwigs-Universität, Freiburg, Germany (B.R., M.M., E.S.); the Department of Dermatology, Beth Israel Hospital, Harvard Medical School, Boston (R.S.S.); the Department of Biostatistics and Epidemiology, INSERM Unité 351, Institut Gustave-Roussy, Villejuif, France (A.A., C.P.); Grupo Português ELYS, Department of Dermatology and Immunology, Hospital S. João, Faculdade de Medicina, Porto, Portugal (O.C.); and the Department of Pharmacology, Sunnybrook Health Science Centre, Toronto (N.S.).

Address reprint requests to Dr. Roujeau at the Service de Dermatologie, Hôpital H. Mondor, 94010 Créteil, France.

Full Text of this Article

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