Asia Pac Allergy.  2015 Apr;5(2):68-77. 10.5415/apallergy.2015.5.2.68.

HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese

• Nguyen DV
• Chu HC
• Nguyen DV
• Phan MH
• Craig T
• Baumgart K
• van Nunen

• KMID: 2397053
• DOI: http://doi.org/10.5415/apallergy.2015.5.2.68

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.

Keyword

HLA-B antigens; Carbamazepine; Drug-related side effects and adverse reactions; Pharmacogenomics

MeSH Terms

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
Carbamazepine
DNA
HLA-B Antigens
Oligonucleotide Probes
Oligonucleotides

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