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Association between HLA-B*44:03-HLA-C*07:01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand
  1. Passara Jongkhajornpong, MD1,
  2. Kaevalin Lekhanont, MD1,
  3. Phattrawan Pisuchpen, MD2,
  4. Patchima Chantaren, MD2,
  5. Vilavun Puangsricharern, MD2,
  6. Pinnita Prabhasawat, MD3,
  7. Kanya Suphapeetiporn, MD4,
  8. Shigeru Kinoshita, MD, PhD5,
  9. Mayumi Ueta, MD, PhD5
  1. 1 Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  2. 2 Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  3. 3 Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
  4. 4 Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  5. 5 Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  1. Correspondence to Dr Mayumi Ueta, Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan; mueta{at}koto.kpu-m.ac.jp

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.

  • Stevens-Johnson syndrome
  • cold medicine
  • severe ocular complications
  • human leucocyte antigen

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Footnotes

  • Funding This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government (BioBank Japan Project), and by the JSPS Core-to-Core Program, A. Advanced Research Networks.

  • Competing interests None declared.

  • Ethics approval The study was approved by the institutional review board of all institutes of Mahidol University and Chulalongkorn University in Thailand and Kyoto Prefectural University of Medicine in Japan.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Presented at The Third International Stevens-Johnson Syndrome Symposium, Kyoto, Japan.

  • Patient consent Not required.

  • Contributors MU planned the research design. PJ, KL, PhP, PC, VP, PiP and KS collected samples. SK and MU analysed the data. PJ and MU wrote the paper.

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