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

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Wakamatsu, Tais H. [UNIFESP]
Ueta, Mayumi
Tokunaga, Katsushi
Okada, Yukinori
Loureiro, Renata R. [UNIFESP]
Costa, Karita A. [UNIFESP]
Sallum, Juliana Maria F. [UNIFESP]
Milhomens, Jose Arthur [UNIFESP]
Inoue, Chikara
Sotozono, Chie
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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.
Jama Ophthalmology. Chicago, v. 135, n. 4, p. 355-360, 2017.