Abstract
Stevens Johnson syndrome (SJS) is part of a spectrum of adverse drug reactions resulting in the destruction of skin, mucous membranes, and the ocular surface. A similar, more severe form of the disorder included in this spectrum is toxic epidermal necrolysis (TEN). Approximately 35% of patients suffer chronic sequelae such as vascularization, corneal scarring, conjunctival inversion to the cornea, keratinization, symblepharon, scarring of the palpebral conjunctiva, trichiasis, and severe dry eye. We focused on 80 Indian patients with SJS/TEN with severe ocular complications (SOC) and investigated the association of alleles at HLA -A, HLA-B and HLA-C loci; the controls were 50 healthy Indian volunteers. Genotyping at HLA-A, HLA-B, and HLA-C loci showed a significant positive association with HLA-A*33:03, HLA-B*44:03, and HLA-C*07:01 alleles, and a significant negative association with HLA-B*57:01 and HLA-C*06:02. This indicates that HLA-A*33:03, HLA-B*44:03 and HLA-C*07:01 are risk alleles, and HLA-B*57:01 and HLA-C*06:02 are protective alleles in this population. We also found that the haplotypes consisting of HLA-B*44:03 and HLA-C*07:01 were strongly associated with SJS/TEN with SOC in our Indian population (p = 1.1 × 10−7, odds ratio = 11.0). Describing the association of the haplotype could facilitate the understanding of increased risk factors for developing SJS/TEN with SOC.
Highlights
Common acute ocular manifestations are bilateral severe conjunctivitis, pseudomembrane, and corneal and conjunctival epithelial defects[4]
human leukocyte antigen (HLA) antigens associated with Stevens Johnson syndrome (SJS) with ocular complications include HLAB12 or its sub-group HLABw44 in Caucasians[10,11]; an association has been reported in a French population with TEN12
Elsewhere we reported that in Japanese patients with SJS/toxic epidermal necrolysis (TEN) with severe ocular complications (SOC), the disease was associated with specific alleles at various HLA loci including HLA-A*02:0613 and that HLA-B*44:03 was an independent risk allele for cold-medicine-induced SJS14
Summary
Received: 23 August 2017 Accepted: 3 November 2017 Published: xx xx xxxx ocular complications in an Indian population. We focused on 80 Indian patients with SJS/TEN with severe ocular complications (SOC) and investigated the association of alleles at HLA -A, HLA-B and HLA-C loci; the controls were 50 healthy Indian volunteers. Common chronic ocular manifestations include vascularization, corneal scarring, conjunctival inversion to the cornea, keratinization, symblepharon, scarring of the palpebral conjunctiva, trichiasis, and severe dry eye[6]. Significant risk factors for ocular involvement in SJS include exposure to drugs such as NSAIDs and cold medications[5,7]. Elsewhere we reported that in Japanese patients with SJS/TEN with SOC, the disease was associated with specific alleles at various HLA loci including HLA-A*02:0613 and that HLA-B*44:03 was an independent risk allele for cold-medicine-induced SJS14. We examined genetic factors by investigating the association of alleles at HLA-A, HLA-B, and HLA-C loci
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