Search

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.The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population.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.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)], (P10(-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.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.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, which can be caused by a certain number of specific drugs among which is carbamazepine, an antiepileptic agent. A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population. Here in, we report preliminary results from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine French and three German). Among these only four had a HLA-B*1502 allele. Remarkably, these four patients had an Asian ancestry, whereas the others did not as far as we have ascertained. This shows that although the HLA region may contain important genes for SJS, the HLA-B*1502 allele is not a universal marker for this disease and that ethnicity matters.

Two yeast artificial chromosomes of the HLA class I region were subcloned. Four of the subclones studied displayed restriction polymorphisms that corresponded to six bi-allelic series. Allelic distribution of the anonymous markers was then studied by comparing a control population with a group of patients with familial haemochromatosis. Only one marker presents an unequivocal association with the haemochromatosis gene and is 100 kb centromeric to HLA-A. This association however is not as strong as with HLA-A3. The results suggest two possible locations for the haemochromatosis gene: less than 100 kb centromeric to the HLA-A locus, or on the telomeric side.

HLA typing, demographic and immunological risk factors for nevirapine and efavirenz reactions were studied in a French cohort of HIV patients. Cases with isolated rash were significantly associated with HLA-DRB1*01 allele. No liver toxicity was observed and no association was detected with the percentage of CD4 T-cells. This study suggests that HLA-DRB1*01 allele plays an important role in susceptibility to cutaneous reactions associated with nevirapine and efavirenz in HIV patients.