Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens–Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human leukocyte antigens (HLAs) play a key role in the immunopathogenesis of severe cutaneous reactions induced by several drugs. This study investigated the association between the HLA class I and HLA-DRB1 polymorphisms and co-trimoxazole-induced SJS/TEN in a Thai population.
Forty-three patients with co-trimoxazole-induced SJS/TEN and 91 co-trimoxazole-tolerant patients were enrolled in the study. HLA class I and HLA-DRB1 were genotyped using the reverse sequence-specific oligonucleotide probe method.
The frequencies of three alleles of HLA, namely HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01, were significantly higher in the co-trimoxazole-induced SJS/TEN group compared with controls. The risks for co-trimoxazole-induced SJS/TEN in patients with the HLA-B*15:02, HLA-C*06:02, or HLA-C*08:01 allele were about 3–11-fold higher when compared with those who did not carry one of these alleles. Individuals who carried the HLA-B*15:02-C*08:01 haplotype had a 14-fold higher risk for co-trimoxazole-induced SJS/TEN.
Evidence of associations between co-trimoxazole-induced SJS/TEN and HLA alleles including HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 were found in the study population. These findings may suggest that apart from the HLA molecules, other molecules involved in the molecular pathogenesis of these severe cutaneous adverse drug reactions may play an important role in the susceptibility of individuals to SJS/TEN caused by co-trimoxazole.
aDepartment of Pharmacology
cDepartment of Medicine, Faculty of Medicine
dFaculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen
eMedical Genetics Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health
fHealth Product Vigilance Center, Food and Drug Administration, Ministry of Public Health, Nonthaburi
hDepartment of Medicine, Udon Thani Hospital, Udon Thani
iBuddhachinaraj Hospital, Phitsanulok
jLampang Hospital, Lampang
kRayong Hospital, Rayong
lSongkhla Hospital, Songkhla
mChiangraiprachanukroh Hospital, Chiangrai, Thailand
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Correspondence to Wichittra Tassaneeyakul, PhD, Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand Tel: +66 81 6594623; fax: +66 43 348397; e-mails: firstname.lastname@example.org, email@example.com
Received January 24, 2015
Accepted May 18, 2015