Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel

• Published in: Journal of the American Academy of Dermatology Vol. 58; no. 1; pp. 25 - 32
• Main Authors: Halevy, Sima, Ghislain, Pierre-Dominique, Mockenhaupt, Maja, Fagot, Jean-Paul, Bouwes Bavinck, Jan Nico, Sidoroff, Alexis, Naldi, Luigi, Dunant, Ariane, Viboud, Cecile, Roujeau, Jean-Claude
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 2008; Elsevier
• Subjects: Adult; Aged; Allopurinol - administration & dosage; Allopurinol - adverse effects; Allopurinol - therapeutic use; Biological and medical sciences; Bullous diseases of the skin; Case-Control Studies; Demography; Dermatology; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Europe - epidemiology; Female; Gout Suppressants - administration & dosage; Gout Suppressants - adverse effects; Gout Suppressants - therapeutic use; Humans; Incidence; Israel - epidemiology; Male; Medical sciences; Middle Aged; Population Surveillance; Stevens-Johnson Syndrome - chemically induced; Stevens-Johnson Syndrome - epidemiology; Stevens-Johnson Syndrome - etiology; Asia; Europe; Israel; OR; TEN; SJS; CI; NSAID; SCAR; Stevens-Johnson syndrome; severe cutaneous adverse reactions; confidence interval; odds ratio; nonsteroidal anti-inflammatory drug; toxic epidermal necrolysis; Bullous dermatosis; Skin disease; Hypouricemic agent; Enzyme; Erythroderma; Stomatology; Dermatology; Allopurinol; Enzyme inhibitor; Eye disease; Pyrazolopyrimidine derivatives; Xanthine oxidase; Oxidoreductases; Lyell syndrome
• ISSN: 0190-9622; 1097-6787; 1097-6787
• DOI: 10.1016/j.jaad.2007.08.036

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions. We sought to update knowledge on the causes of SJS or TEN with a focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN. We conducted a multinational case-control study. In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (≤8 weeks). The use of comedications did not increase the risk. Nonsystematic recording of the indications for allopurinol use was a limitation. Results of this multinational study (EuroSCAR) revealed that allopurinol is the drug most commonly associated with SJS or TEN. The incidence of allopurinol-associated SJS or TEN has increased possibly because of increased use and dosages of this drug.