Association between HLA-B*44:03-HLA-C*07:01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand

Br J Ophthalmol. 2018 Sep;102(9):1303-1307. doi: 10.1136/bjophthalmol-2017-311823. Epub 2018 Apr 29.

Abstract

Background: Polymorphisms in human leucocyte antigen (HLA) class I genes have been found to be associated with cold medicine (CM)-related Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). Because ethnic differences in genetic predisposition to SJS/TEN among different populations have been proposed, we focused on Thai patients and investigated the association between HLA class I genotypes and CM-SJS/TEN with SOC.

Methods: This multicentre case-control study was conducted between September 2014 and August 2017. Seventy-one Thai patients with SJS/TEN with SOC and 159 healthy Thai controls were enrolled. HLA typing was performed. Genetic relationships were analysed using Fisher's exact test.

Results: Of 71 patients with SJS/TEN with SOC (28 male, 43 female), 49 (69%) had a history of taking cold medications prior to SJS/TEN onset. The mean age of onset was 26.7±17.1 years (range, 2-77 years). HLA-B*44:03 (OR, 7.2, p=5.5×10-6, pc=1.1×10-4) and HLA-C*07:01 (OR, 6.1, p=7.1×10-6, pc=1.1×10-4) showed significant positive associations with Thai patients with CM-SJS/TEN with SOC. Additionally, 17 of 49 patients with CM-SJS/TEN with SOC (34.7%) significantly harboured the HLA-B*44:03 and HLA-C*07:01 haplotype compared with only 11 of 159 healthy controls (6.9%) (OR=7.1, p=5.5×10-6).

Conclusions: HLA-B*44:03-HLA-C*07:01 haplotype is a potential risk factor for CM-SJS/TEN with SOC in the Thai population. This study supports that HLA-B*44:03 might be a common marker for CM-SJS/TEN with SOC in Eurasia populations, including European, Indian, Japanese and Thai.

Keywords: Stevens-Johnson syndrome; cold medicine; human leucocyte antigen; severe ocular complications.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Eye Diseases / epidemiology
  • Eye Diseases / etiology*
  • Eye Diseases / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-B Antigens / genetics*
  • HLA-C Antigens / genetics*
  • Haplotypes
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Stevens-Johnson Syndrome / complications
  • Stevens-Johnson Syndrome / genetics*
  • Thailand / epidemiology
  • Young Adult

Substances

  • HLA-B Antigens
  • HLA-C Antigens