Medication Use and the Risk of Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis
Jean-Claude Roujeau, M.D., Judith P. Kelly, M.S., Luigi Naldi, M.D., Berthold Rzany, M.D., Robert S. Stern, M.D., Theresa Anderson, R.N., Ariane Auquier, M.S., Sylvie Bastuji-Garin, M.D., Osvaldo Correia, M.D., Francesco Locati, M.D., Maja Mockenhaupt, M.D., Catherine Paoletti, Samuel Shapiro, M.B., F.R.C.P.(E.), Neil Shear, M.D., Erwin Schöpf, M.D., and David W. Kaufman, Sc.D.
Background Toxic epidermal necrolysis and Stevens–Johnsonsyndrome are rare, life-threatening, drug-induced cutaneousreactions. We conducted a case–control study to quantifythe risks associated with the use of specific drugs.
Methods Data were obtained through surveillance networks inFrance, Germany, Italy, and Portugal. Drug use before the onsetof disease was compared in 245 people who were hospitalizedbecause of toxic epidermal necrolysis or Stevens–Johnsonsyndrome and 1147 patients hospitalized for other reasons (controls).Crude relative risks were calculated and adjusted for confoundingby multivariate methods when numbers were large enough.
Results Among drugs usually used for short periods, the riskswere increased for trimethoprim–sulfamethoxazole and othersulfonamide antibiotics (crude relative risk, 172; 95 percentconfidence interval, 75 to 396), chlormezanone (crude relativerisk, 62; 21 to 188), aminopenicillins (multivariate relativerisk, 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 relativerisk was 0.6 (95 percent confidence interval, 0.2 to 1.3) inFrance but 9.3 (3.9 to 22) in the other countries. Among drugsusually used for months or years, the increased risk was confinedlargely to the first two months of treatment, when crude relativerisks were as follows: carbamazepine, 90 (95 percent confidenceinterval, 19 to ); phenobarbital, 45 (19 to 108); phenytoin,53 (11 to ); valproic acid, 25 (4.3 to ); oxicam nonsteroidalantiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol,52 (16 to 167); and corticosteroids, 54 (23 to 124). For manydrugs, including thiazide diuretics and oral hypoglycemic agents,there was no significant increase in risk.
Conclusions The use of antibacterial sulfonamides, anticonvulsantagents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroidsis associated with large increases in the risk of Stevens–Johnsonsyndrome or toxic epidermal necrolysis. But for none of thedrugs does the excess risk exceed five cases per million usersper 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.
Toxic Epidermal Necrolysis
Wagner F. F., Flegel W. A., Feder H. M., Hoss D. M., Dimond R. L., Roujeau J.-C., Kaufman D. W.
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N Engl J Med 1996;
334:922-923, Apr 4, 1996.
Correspondence
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); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to 
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