HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese
10.5415/apallergy.2015.5.2.68
- Author:
Dinh Van NGUYEN
1
;
Hieu Chi CHU
;
Doan Van NGUYEN
;
Minh Hong PHAN
;
Timothy CRAIG
;
Karl BAUMGART
;
Sheryl VAN NUNEN
Author Information
1. Department of Allergy and Clinical Immunology, Hanoi Medical University, Hanoi 10000, Vietnam. vngu3162@uni.sydney.edu.au
- Publication Type:Original Article
- Keywords:
HLA-B antigens;
Carbamazepine;
Drug-related side effects and adverse reactions;
Pharmacogenomics
- MeSH:
Academic Medical Centers;
Alleles;
Asian Continental Ancestry Group;
Carbamazepine;
Case-Control Studies;
Cicatrix;
DNA;
Drug-Related Side Effects and Adverse Reactions;
Eosinophilia;
Epilepsy;
Exanthema;
Flow Cytometry;
HLA-B Antigens;
Humans;
Hypersensitivity;
Incidence;
Microspheres;
Odds Ratio;
Oligonucleotide Probes;
Oligonucleotides;
Pharmacogenetics;
Polymerase Chain Reaction;
Risk Factors;
Sensitivity and Specificity;
Skin;
Vietnam
- From:
Asia Pacific Allergy
2015;5(2):68-77
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: In Vietnam, we observed a high incidence of carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs)-Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity rash with eosinophilia and systemic symptoms (DRESS). In other Asian countries, HLA-B*1502 is an established risk factor for SCARs. OBJECTIVE: The aim of our study was to determine the frequency of HLA-B*1502 in SCARs patients at a large University Medical Center in Hanoi, Vietnam. METHODS: Thirty-eight cases of SCARs caused by CBZ and 25 patients with epilepsy tolerating CBZ were enrolled in a case-controlled study. Clinical manifestations and laboratory findings were recorded for each subject. Genomic DNA was isolated using the QIAamp DNA purification system. The combination of polymerase chain reaction and sequence specific oligonucleotide probes with the Luminex 100×MAP flow cytometry dual laser system was then used to quantitate fluorescently labelled oligonucleotides attached to colour-coded microbeads. RESULTS: Cases comprised 20 SJS (52.6%), 7 TEN (18.4%), 8 overlap syndrome (21.1%), and 3 DRESS patients (7.9%). A strong association between HLA B*1502 and bullous skin reactions such as SJS/TEN and overlap was confirmed with an odds ratio (OR) of 33.78 (95% confidence interval [CI], 7.55-151.03), p < 0.0001, Sensitivity 91.4%, Specificity 76.0%, positive predictive value 84.2%, and negative predictive value 86.4%. We did not, however, observe any correlation between the presence of this allele and CBZ-induced nonbullous skin reactions (DRESS) (OR, 6.33; 95% CI, 0.48-82.74; p = 0.1592). CONCLUSION: Our results indicate the presence of HLA-B*1502 in Vietnamese is a pharmacogenetic risk factor for developing CBZ-induced SJS/TEN.
