Clinical features of and genetic predisposition to drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a single Korean tertiary institution patients-investigating the relation between the HLA -B*4403 allele and lamotrigine

Eur J Clin Pharmacol. 2015 Jan;71(1):35-41. doi: 10.1007/s00228-014-1764-0. Epub 2014 Oct 21.

Abstract

Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but fatal adverse mucocutaneous reactions to certain drugs. Recent studies suggest that ethnicity and genetic predisposition may play a crucial role in the manifestation of the reaction. In this study, we described the role of human leukocyte antigen (HLA)-B alleles in the development of clinical characteristics and treatment outcomes of SJS/TEN in a single Korean tertiary hospital.

Methods: We retrospectively reviewed the medical records (from March 1, 2010 to February 28, 2014) of 30 patients diagnosed with SJS and/or TEN.

Results: The main causative drugs were anticonvulsants (26.7 %) and allopurinol (26.7 %), followed by antibiotics (16.7 %), acetazolamide (10.0 %), acetaminophen (10.0 %), and herbal medication (6.7 %). The mean latencies of these drugs were variable. Liver damage was the most common symptom (observed in 63.3 % of the patients). Of the five patients with lamotrigine-induced SJS/TEN, three expressed the HLA-B*4403 allele (60.0 %). Of the seven patients with allopurinol-induced SJS/TEN, five expressed the HLA-B*5801 allele (71.4 %).

Conclusions: The major SJS/TEN-inducing drugs were found to be allopurinol and anticonvulsants (such as lamotrigine). We speculated that Korean individuals expressing the HLA-B*4403 allele may be highly susceptible to lamotrigine-induced SJS/TEN.

MeSH terms

  • Acetaminophen / adverse effects
  • Acetazolamide / adverse effects
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Allopurinol / adverse effects
  • Anti-Bacterial Agents / adverse effects
  • Anticonvulsants / adverse effects*
  • Asian People / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • HLA-B Antigens / genetics*
  • Humans
  • Lamotrigine
  • Male
  • Middle Aged
  • Plants, Medicinal / adverse effects
  • Republic of Korea
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • Tertiary Care Centers
  • Triazines / adverse effects*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Anticonvulsants
  • HLA-B Antigens
  • Triazines
  • Acetaminophen
  • Allopurinol
  • Acetazolamide
  • Lamotrigine