Investigating the association of Lamotrigine and Phenytoin-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis with HLA-B*1502 in Iranian population

Exp Dermatol. 2021 Feb;30(2):284-287. doi: 10.1111/exd.14240. Epub 2020 Dec 4.

Abstract

Previous studies have found an association between HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS)/ toxic epidermal necrosis (TEN) spectrum in Han Chinese populations. This study aims to investigate the association between HLA-B*1502 and lamotrigine- or phenytoin- induced SJS/TEN in an Iranian population. The medical records of twenty-eight lamotrigine-induced SJS/TEN patients and twenty-five lamotrigine-tolerant controls as well as eight phenytoin-induced SJS/TEN and twelve phenytoin-tolerant controls were extracted between March 2013 and March 2019 from the university hospitals in Mashhad, Iran. The presence of HLA-B*1502 allele was determined using real-time polymerase chain reaction (PCR). Among lamotrigine-induced patients with SJS/TEN, 11 (39.3%) patients tested positive for the HLA-B*1502 while only 3 (12.0%) of the lamotrigine-tolerant controls tested positive for this allele. The risk of lamotrigine-induced SJS/TEN was significantly higher in patients with HLA-B*1502, with an odds ratio (OR) of 4.74 [95% confidence interval (CI) 1.14-19.73, p = 0.032]. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HLA-B*1502 for lamotrigine-induced SJS/TEN was 39.29%, 88.00%, 78.57% and 56.41%, respectively. The HLA-B*1502 allele was present in 2 (25.0%) of phenytoin-induced SJS/TEN cases and 5 (41.7%) of the phenytoin-tolerant controls tested positive for HLA-B*1502 allele. The risk of phenytoin-induced SJS/TEN was not higher in the patients with HLA-B*1502 (OR = 0.467 [95% confidence interval (CI) 0.065-3.34, p = 0.642]). Lamotrigine-induced SJS/TEN is associated with HLA-B*1502 allele in an Iranian population but this is not the case for phenytoin-induced SJS/TEN.

Keywords: HLA-B Antigens; Stevens-Johnson Syndrome; lamotrigine; pharmacogenetics; phenytoin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anticonvulsants / adverse effects*
  • Case-Control Studies
  • Female
  • HLA-B15 Antigen / genetics*
  • Humans
  • Iran
  • Lamotrigine / adverse effects*
  • Male
  • Middle Aged
  • Phenytoin / adverse effects*
  • Predictive Value of Tests
  • Risk Factors
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • Young Adult

Substances

  • Anticonvulsants
  • HLA-B*15:02 antigen
  • HLA-B15 Antigen
  • Phenytoin
  • Lamotrigine