Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications

Abstract

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02:06 and HLA-B*44:03 in the Japanese. In this study, to determine whether HLA-B*44:03 is a common risk factor for CM-SJS/TEN with SOC in different ethnic groups we used samples from Indian, Brazilian, and Korean patients with CM-SJS/TEN with SOC, and investigated the association between CM-SJS/TEN with SOC and HLA-B*44:03 and/or HLA-A*02:06. We found that HLA-B*44:03 was significantly associated with CM-SJS/TEN with SOC in the Indian and Brazilian but not the Korean population, and that HLA-A*02:06 might be weakly associated in the Korean- but not the Indian and Brazilian population.

Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens–Johnson syndrome with severe ocular complications

“…This is consistent with findings reported in our earlier studies; they had shown a strong association between SJS/TEN with SOC and HLA-A*02:06. 8,9,[17][18][19] Outside of the HLA region, there were 82 polymorphisms manifesting associations with Po10 − 7 in the allele frequency model. Of these, four exhibited MAF40.05 and they were located on chromosome 16.…”

“…2 Among SJS and TEN patients, especially those with SJS/TEN with SOC, cold medicines (CM), including multi-ingredient cold medications and non-steroidal anti-inflammatory drugs, were identified as causative. 2,[6][7][8][9] We reported that in the Japanese, CM-related SJS/TEN (CM-SJS/TEN) with SOC was strongly associated with HLA-A*02:06 and significantly associated with HLA-B*44:03. 9 In our first genome-wide association study (GWAS), we analyzed SJS/TEN with SOC patients using the Affymetrix GeneChip Mapping 500 K array set (Affymetrix, Santa Clara, CA, USA).…”

IKZF1, a new susceptibility gene for cold medicine–related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement

“…1,14,[16][17][18][19][20][21][22][23] Usually, ophthalmologists encounter patients with SJS/TEN in the chronic rather than acute stage, and therefore many of our patients had SJS/TEN many years before recruitment for this study. The samples from the National Institute of Health Sciences represented only patients with SJS/TEN in the acute stage, and the criteria proposed by Bastuji-Garin et al 24 were used for a diagnosis of SJS/TEN for these patients in the acute stage.…”

“…We also reported that CM-SJS/TEN with SMI was significantly associated with HLA-B*44:03 in Indian (cases, n 5 20; control subjects [normal], n 5 55; OR, 12.3; P 5 1.1 3 10 25 ) and Brazilian (especially Brazilian white; cases, n 5 15; control subjects [normal], n 5 62; OR, 6.2; P 5 3.7 3 10 23 ) subjects. 17 Here we performed a genome-wide association study (GWAS) to identify genetic factors associated with CM-SJS/TEN with SMI; cold medicines included NSAIDs and multi-ingredient cold medications, and SMIs included severe ocular surface complications. We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects.…”

Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions

“…Furthermore, they found that HLA-B*44:03 was significantly associated with cold medicine-induced SJS/TEN with severe ocular surface involvement in Indian and Brazilian populations, but not in a Korean population, and that HLA-A*02:06 may be weakly associated with the conditions in Korean, but not Indian or Brazilian, populations. 12 Taken together, these data suggest an association between HLA genotypes and acetaminophen in patients with SJS/TEN. Our patient had been treated with systemic steroid therapy for UC.…”