title: HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population.
abstract: 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.
authors.affiliation: Clinic of Dermatology, Coimbra University Hospital, Praceta Mota Pinto, P-3000-075, Coimbra, Portugal; Department of Dermatology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Gonçalo
authors.forename: I
authors.initials: I
authors.lastname: Coutinho
authors.forename: V
authors.initials: V
authors.lastname: Teixeira
authors.forename: A R
authors.initials: AR
authors.lastname: Gameiro
authors.forename: M M
authors.initials: MM
authors.lastname: Brites
authors.forename: R
authors.initials: R
authors.lastname: Nunes
authors.forename: A
authors.initials: A
authors.lastname: Martinho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011174:Portugal / Q000208:ethnology; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D006074:Gout Suppressants; D015235:HLA-B Antigens; C041533:HLA-B58 antigen; D000493:Allopurinol