A European study of HLA-B in Stevens–Johnson syndrome and... : Pharmacogenetics and Genomics (original) (raw)

ORIGINAL ARTICLES

Lonjou, Christinea b; Borot, Nicolasa b; Sekula, Peggye; Ledger, Neila b; Thomas, Laureg; Halevy, Simah; Naldi, Luigii; Bouwes-Bavinck, Jan-Nicoj; Sidoroff, Alexisk; de Toma, Claudiac; Schumacher, Martine; Roujeau, Jean-Clauded; Hovnanian, Alaina b; Mockenhaupt, Majaf for the RegiSCAR study group

aINSERM, U563

bPaul Sabatier University III, Toulouse

cJean Dausset Fundation-CEPH, Paris

dDepartment of Dermatology, Henri Mondor Hospital, Paris XII University, Créteil, France

eInstitute of Medical, Biometry, Informatics, University Medical Center Freiburg

fDokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany

gDepartment of Pharmacovigilance, Henri Mondor Hospital, Créteil cedex

hDepartment of Dermatology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel

iDepartment of Dermatology, Azienda Ospedaleria Ospedali Riuniti di Bergamo, Milano University, Bergamo, Italy

jDepartment of Dermatology, Leiden University Medical Center, ZA Leiden

kDepartment of Dermatology (Universitätsklinik für Dermatologie und Venerologie), Innsbruck University, Innsbruck, Austria

Correspondence to Professor Jean-Claude Roujeau, Department of Dermatology, Hôpital Henri Mondor, F-94010 Créteil, France

Tel: +33149812512; fax: +33149812508; e-mail: [email protected]

Received 30 May 2007 Accepted 31 October 2007

Abstract

Background

Stevens–Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine. Recently, a strong association between carbamazepine and allopurinol induced SJS or TEN has been described with respectively, HLA-B*1502 and HLA-B*5801 in a Han Chinese population from Taiwan and other Asian countries.

Objective

The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population.

Methods

HLA-B genotyping was performed on 150 patients included in a European study (RegiSCAR) of SJS and TEN. We focused on patients related to ‘high-risk’ drugs including: 31 cases related to allopurinol, 28 to sulfamethoxazole, 19 to lamotrigine and 14 to oxicam.

Results

Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry [odds ratio=80 (34–187)], (P<10−6) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfamethoxazole or lamotrigine-related patients, and B*73 for oxicam.

Conclusion

At variance with prior results in Asia, this study shows that even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease. Further investigations are necessary to delineate the exact role of the HLA region in SJS/TEN, and to look for other associations in other regions of the genome.