Suchergebnisse

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 male ; mean (SD) age was 36.01 [15.42] years. HLA-A*66: 01 (odds ratio [OR], 24.0 ; 95% CI, 2.79-206.0 ; P < 001), HLA-B*44: 03 (OR, 2.71 ; 95% CI, 1.11-6.65 ; P = 04), and HLA-C*12: 03 (OR, 5.6 ; 95% CI, 1.67-18.80 ; P = 006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11: 01 (OR, 0.074 ; 95% CI, 0.004-1.26 ; P = 008), HLA-B*08: 01 (OR, 0.15 ; 95% CI, 0.02-1.15 ; P = 048), and HLA-B*51: 01 (OR, 0.23 ; 95% CI, 0.05-1.03 ; P = 045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry ; 14 males and 25 females ; age, 35.2 [14.4] years ; and 133 controls: 66 Pardo and 61 European ancestry ; 55 males and 78 females ; age, 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, 12.2 ; 95% CI, 1.19-125.0 ; P = 03 ; and European: OR, 21.2 ; 95% CI, 0.97-465.0 ; P = 04). An association was observed only in the European cohort for HLA-B*44: 03 (OR, 5.50 ; 95% CI, 1.47-20.50 ; P = 01) and HLA-C*12: 03 (OR, 8.79 ; 95% CI, 1.83-42.20 ; P = 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 government ; Japan Society for the Promotion of Science Core-to-Core Program Advanced Research Networks ; Japanese Ministry of Health, Labor and Welfare ; Kyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of Medicine ; Ministry of Education, Brazil-Japan ; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo ; Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil ; Prefectural Univ Med, Dept Frontier Med Sci & Technol Ophthalmol, Kyoto, Japan ; Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, Japan ; Osaka Univ, Dept Stat Genet, Osaka, Japan ; RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan ; Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan ; Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil ; Web of Science