Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population

IMPORTANCE Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). OBJECTIVE To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs. DESIGN, SETTING, AND PARTICIPANTS This case-control studywas conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014. MAIN OUTCOMES AND MEASURES Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes. RESULTS Of 74 patients included in the analysis, 32 (43%) were malemean (SD) age was 36.01 [15.42] years. HLA-A*66: 01 (odds ratio [OR], 24.095% CI, 2.79-206.0P < 001), HLA-B*44: 03 (OR, 2.7195% CI, 1.11-6.65P = 04), and HLA-C*12: 03 (OR, 5.695% CI, 1.67-18.80P = 006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11: 01 (OR, 0.07495% CI, 0.004-1.26P = 008), HLA-B*08: 01 (OR, 0.1595% CI, 0.02-1.15P = 048), and HLA-B*51: 01 (OR, 0.2395% CI, 0.05-1.03P = 045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry14 males and 25 femalesage, 35.2 [14.4] yearsand 133 controls: 66 Pardo and 61 European ancestry55 males and 78 femalesage, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66: 01 and HLA-C*12: 03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66: 01 was associated with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 12.295% CI, 1.19-125.0P = 03and European: OR, 21.295% CI, 0.97-465.0P = 04). An association was observed only in the European cohort for HLA-B*44: 03 (OR, 5.5095% CI, 1.47-20.50P = 01) and HLA-C*12: 03 (OR, 8.7995% CI, 1.83-42.20P = 008). CONCLUSIONS AND RELEVANCE This study suggests that HLA-A*66: 01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44: 03 and HLA-C*12: 03 might be markers only in those of European ancestry. Moreover, HLA-A*11: 01 might be a marker of resistance to CM-SJS/TEN with SOCs.Ministry of Education, Culture, Sports, Science and Technology of the Japanese governmentJapan Society for the Promotion of Science Core-to-Core Program Advanced Research NetworksJapanese Ministry of Health, Labor and WelfareKyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of MedicineMinistry of Education, Brazil-JapanFundacao de Amparo a Pesquisa do Estado de Sao PauloUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilPrefectural Univ Med, Dept Frontier Med Sci & Technol Ophthalmol, Kyoto, JapanUniv Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, JapanOsaka Univ, Dept Stat Genet, Osaka, JapanRIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, JapanKyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, JapanUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilWeb of Scienc