HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.
OBJECTIVE
The carbonic anhydrase inhibitor methazolamide infrequently causes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). An association between these diseases and the HLA-B59 serotype has been suggested in case reports. This study examined the disease-associated B*59 allele and investigated the association of these diseases with other HLA class I alleles.


METHODS
We performed high-resolution HLA-A, -B and -C genotyping in five patients with methazolamide-induced SJS/TEN using a PCR-sequencing-based typing method and analyzed the association between HLA-class I alleles and occurrence of methazolamide-induced SJS/TEN.


RESULTS
B*5901 and Cw*0102 alleles were observed in all patients and A*2402 was observed in four patients. The B*5901 allele showed the strongest association with methazolamide-induced SJS/TEN (p < 0.001; odds ratio: 249.8; 95% CI: 13.4-4813.5), followed by Cw*0102 (p = 0.004; odds ratio: 22.1; 95% CI: 1.2-414.3), when compared with the general population as a control. The frequency of the patients carrying B*5901, Cw*0102 and A*2402 simultaneously was significantly higher than that in the general population (p < 0.001; odds ratio: 110.1; 95% CI: 11.7-1038.6).


CONCLUSIONS
A strong association was observed between HLA-B*5901 and methazolamide-induced SJS/TEN in Korean patients. HLA-B*5901 may be a useful screening marker for predicting methazolamide-induced SJS/TEN in patients of Korean and Japanese ancestry.
Kim
Sae-Hoon
SH
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Kim
Myunghwa
M
Lee
Kyung Wha
KW
Kim
Sang-Heon
SH
Kang
Hye-Ryun
HR
Park
Heung-Woo
HW
Jee
Young-Koo
YK
D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008704:Methazolamide / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D056910:Republic of Korea; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000276:immunology
D015235:HLA-B Antigens; D008704:Methazolamide