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


CONCLUSIONS
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.
Lonjou
Christine
C
INSERM, U563 Paul Sabatier University III, Toulouse, France.
Borot
Nicolas
N
Sekula
Peggy
P
Ledger
Neil
N
Thomas
Laure
L
Halevy
Sima
S
Naldi
Luigi
L
Bouwes-Bavinck
Jan-Nico
JN
Sidoroff
Alexis
A
de Toma
Claudia
C
Schumacher
Martin
M
Roujeau
Jean-Claude
JC
Hovnanian
Alain
A
Mockenhaupt
Maja
M
D000328:Adult; D000368:Aged; D001483:Base Sequence; D017931:DNA Primers; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*
D017931:DNA Primers; D015235:HLA-B Antigens