Background/aims Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by cold medicine (CM) may result in severe ocular complications (SOCs). The purpose of this study was to investigate the human leucocyte antigen (HLA) polymorphism pattern in CM-induced patients with SJS/TEN developing SOCs.
Methods All participants, including patients with SJS/TEN (n=33) and control patients (n=98), were enrolled through visits to the clinic from 2016 to 2017. SOCs were diagnosed (n=26) via a chart review or eye examination. Patient saliva was collected with commercialised kits and genotyped with PCR assays followed by hybridisation with sequence-specific oligonucleotide (SSO) probes (PCR-SSO) using commercial bead-based typing kits.
Results In all patients with SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was significantly higher than that in controls (OR=3.24, 95% CI=1.09 to 9.60, p=0.049), as was the genotype frequency (OR=3.89, 95% CI=1.49 to 10.16, p=0.007). In patients with CM-SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was higher than that in controls (OR=5.56, 95% CI=1.52 to 20.00, p=0.016), as was the allele frequency (OR=6.67, 95% CI=2.33 to 20.00, p=0.001). In patients with CM-SJS/TEN with SOCs, the HLA-B*46:01 allele frequency was significantly higher than that in controls (OR=3.85, 95% CI=1.52 to 10.00, p=0.008).
Conclusions The HLA-A*02:07 and HLA-B*46:01 alleles were significantly associated with SOCs among Han Chinese patients with CM-SJS/TEN. These findings demonstrate the genetic diversity in SJS pathogenesis among different ethnic groups.
- ocular surface
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Contributors KS-KM—data analysis and writing of the manuscript. WHC—providing study subjects and contributing opinion in Discussion. Y-JH—IRB application and subsequent inspection. S-YC—patient examination and recording. KT—HLA genotyping and analysis. SK—contributing opinion in Discussion. DHKM—patient collection, supervising manuscript preparation, fund provider and corresponding author. MU—study design, sample handling, fund provider and corresponding author.
Funding This work was supported by Chang Gung Memorial Hospital grants (CMRPG3G0021-3, CMRPG1H0091) and the Japan Society for the Promotion of Science (JSPS) Core-to-Core Program grants-in-aid Type A Advanced Research Networks.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study procedure used to collect SJS/TEN and control patient genomes for HLA analysis was approved by the Institutional Review Boards of Chang Gung Medical Foundation (IRB approval number: 104-0927B) and of Kyoto Prefectural University of Medicine. All experimental procedures were conducted in accordance with the principles set forth in the Helsinki Declaration.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information.
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