Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel - 24/04/13
, Pierre-Dominique Ghislain, MD b, Maja Mockenhaupt, MD, PhD c, Jean-Paul Fagot, PharmD d, Jan Nico Bouwes Bavinck, MD, PhD e, Alexis Sidoroff, MD f, Luigi Naldi, MD g, Ariane Dunant, MS b, h, Cecile Viboud, PhD d, Jean-Claude Roujeau, MD bEuroSCAR Study Group
Reprint requests: Sima Halevy, MD, Department of Dermatology, Soroka University Medical Center, Beer-Sheva 84101, Israel.Abstract |
Background |
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions.
Objectives |
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.
Methods |
We conducted a multinational case-control study.
Results |
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.
Limitations |
Nonsystematic recording of the indications for allopurinol use was a limitation.
Conclusions |
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.
Le texte complet de cet article est disponible en PDF.Abbreviations used : CI, NSAID, OR, SCAR, SJS, TEN
Plan
| Dr Ghislain is currently affiliated with St-Luc University Hospital, UCL, Brussels, Belgium, and Dr Viboud is currently affiliated with Fogarty International Center, National Institutes of Health, Bethesda, Maryland. |
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| Supported by the following institutions/companies (unrestricted grants): ADIR and Cie, Bayer Pharma/AG/Vital, Boehringer Ingelheim, Cassenne, Ciba Geigy/Novartis, Cilag GmbH, Dr Willmar Schwabe, Goedecke Parke Davis, Glaxo Wellcome/Glaxo SmithKline, Hoechst AG/Hoechst Marion Roussel/Aventis, Hoffmann-La-Roche, IRIS Servier, Jouveinal Lab, LEO, LILLY, MSD Sharp and Dohme, Pfizer, Rhone Poulenc Rorer, Sanofi Winthrop/Sanofi Synthelabo GmbH, and Schering AG. Funding from pharmaceutical companies in France was managed through contract with Institut National de la Santé et de la Recherche Médicale, French Ministry of Health (PHRC AOM 98027). |
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| Conflicts of interest: None declared. |
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| Previously presented as: Roujeau JC, Ghislain PD, Mockenhaupt M, Bouwes Bavinck JN, Naldi L, Sidoroff A, Halevy S, Paty C. Dose-effect relation in SJS or TEN related to allopurinol. 5th International Congress on Cutaneous Adverse Drug Reactions, Satellite Congress of the 32nd ESDR Annual Meeting, Palexpo Geneva, Switzerland, September 18-19, 2002 [abstract]. J Invest Dermatol 2002;119:725; and Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Schlingmann J, Roujeau JC. Allopurinol is the medication most frequently associated with Stevens-Johnson syndrome or toxic epidermal necrolysis in Europe. International Investigative Dermatology (IID-03), Fontainebleau Hilton, Miami Beach, Florida, April 30-May 4, 2003 [abstract]. J Invest Dermatol 2003;121:72. |
Vol 58 - N° 1
P. 25-32 - janvier 2008 Retour au numéro
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