HLA-B58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

Summary 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 Portu...

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Bibliographic Details
Published in:British journal of dermatology (1951) 2013-09, Vol.169 (3), p.660-665
Main Authors: Gonçalo, M., Coutinho, I., Teixeira, V., Gameiro, A.R., Brites, M.M., Nunes, R., Martinho, A.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Allopurinol - adverse effects
Biological and medical sciences
Bullous diseases of the skin
Dermatology
Drug toxicity and drugs side effects treatment
Female
Genotype
Gout Suppressants - adverse effects
HLA-B Antigens - genetics
HLA-B Antigens - metabolism
Homozygote
Humans
Male
Medical sciences
Middle Aged
Miscellaneous (drug allergy, mutagens, teratogens...)
Pharmacology. Drug treatments
Portugal - ethnology
Prospective Studies
Retrospective Studies
Risk Factors
Stevens-Johnson Syndrome - ethnology
Stevens-Johnson Syndrome - genetics
Young Adult
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Summary:Summary 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. What's already known about this topic? Allopurinol‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS in Han Chinese occur almost exclusively in HLA‐B*58:01‐positve individuals. A less strong association with HLA‐B*58:01 and allopurinol‐induced SJS/TEN is observed in Europeans. What does this study add? In a European population, HLA‐B*58:01 is also associated with DRESS, with a similar strength as for SJS/TEN. With a low prevalence of HLA‐B*58:01 in Europeans and a less strong association, systematic genotyping before allopurinol therapy remains controversial.
ISSN:0007-0963
1365-2133
DOI:10.1111/bjd.12389