HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

Br J Dermatol. 2013 Sep;169(3):660-5. doi: 10.1111/bjd.12389.


Background: HLA-B*58:01 is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied.

Objective: To study the association of HLA-B*58:01 with allopurinol-induced sCADR in a Portuguese population.

Methods: We studied 25 patients (11 male/14 female, mean age 67·4 years) with sCARD from allopurinol: 19 DRESS (drug reaction eosinophilia and systemic symptoms) and six Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). HLA was genotyped by reverse sequence-specific oligonucleotide-polymerase chain reaction and results compared statistically with a control group of 23 allopurinol-tolerant individuals and the control population.

Results: HLA-B*58:01 was present in 16 patients with sCADR (64%) [12 DRESS (63%), four SJS/TEN (67%)], one allopurinol-tolerant individual (4%) and 63 normal controls (1·96%), with a statistically significant difference between sCADR and the two control groups. When compared with the normal population, HLA-B*58:01 was associated with a higher risk of sCADR, both DRESS [odds ratio (OR) 85·36, 95% confidence interval (CI) 32·52-224·04] and SJS/TEN (OR 99·59, 95% CI 17·91-553·72). There was no statistically different risk between these two types of CADR.

Conclusions: Portuguese patients with sCADR from allopurinol, both DRESS and SJS/TEN, have a high frequency of HLA-B*58:01, with an OR similar to European patients with SJS/TEN. This study also extends this association to DRESS in Europeans. The recommendation to genotype systematically before therapy is controversial, particularly when HLA-B*58:01 prevalence in the normal population is low, as in Europe. However it could be an option for patients with other risks factors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allopurinol / adverse effects*
  • Female
  • Genotype
  • Gout Suppressants / adverse effects*
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / metabolism
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Portugal / ethnology
  • Prospective Studies
  • Retrospective Studies
  • Risk Factors
  • Stevens-Johnson Syndrome / ethnology
  • Stevens-Johnson Syndrome / genetics*
  • Young Adult


  • Gout Suppressants
  • HLA-B Antigens
  • HLA-B58 antigen
  • Allopurinol