A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs

Christine Lonjou, Nicolas Borot, Peggy Sekula, Neil Ledger, Laure Thomas, Sima Halevy, Luigi Naldi, Jan Nico Bouwes-Bavinck, Alexis Sidoroff, Claudia De Toma, Martin Schumacher, Jean Claude Roujeau, Alain Hovnanian, Maja Mockenhaupt

Research output: Contribution to journalArticlepeer-review

488 Scopus citations

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) 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.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalPharmacogenetics and Genomics
Volume18
Issue number2
DOIs
StatePublished - 1 Jan 2008
Externally publishedYes

Keywords

  • Adverse drug reactions
  • Allopurinol
  • Europe
  • HLA-B
  • HLAB*5801
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis

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