Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis

N Engl J Med. 1995 Dec 14;333(24):1600-7. doi: 10.1056/NEJM199512143332404.


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 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.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Allopurinol / adverse effects
  • Anti-Bacterial Agents / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anticonvulsants / adverse effects
  • Case-Control Studies
  • Chlormezanone / adverse effects
  • Humans
  • Multivariate Analysis
  • Risk
  • Stevens-Johnson Syndrome / chemically induced*
  • Stevens-Johnson Syndrome / etiology*
  • Sulfonamides / adverse effects


  • Adrenal Cortex Hormones
  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticonvulsants
  • Sulfonamides
  • Allopurinol
  • Chlormezanone