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

Abstract

BackgroundIn 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.ObjectiveThe 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.MethodsThirty-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.ResultsCases 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).ConclusionOur results indicate the presence of HLA-B*1502 in Vietnamese is a pharmacogenetic risk factor for developing CBZ-induced SJS/TEN.

The Genetics of Drug Hypersensitivity Reactions

“…One of the first studies demonstrating a strong association between a genetic marker, the HLA-B*1502 allele, and carbamazepine-induced SJS-TEN was performed in Han Chinese in 2004 [51] and has been further replicated by other studies performed in the same ethnic group [52,53] and in other Asian populations [54][55][56][57], but not in Japanese [58,59] or Europeans [60,61]. In contrast to the association between the HLA-B*5801 allele and allopurinol-induced SJS-TEN in various populations [41], the association between carbamazepine-induced SJS-TEN and HLA-B*1502 appears to be ethnicity-specific and has led the United States Food and Drug Administration to recommend screening for this allele in patients of Asian descent before initiating carbamazepine [62][63][64].…”

HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study

“…There have been studies reporting an association between HLA alleles and drug allergy, which were primarily related to the alleles of HLA-A and HLA-B (32). HLA-B*1502 were reported to be associated with carbamazepine-induced Stevens-Johnson syndrome in Asian populations (33)(34)(35) and HLA-A*3101 in European, North American, and Mexican mestizo populations (36)(37)(38). HLA-B*5801 were reported to be associated with allopurinol-induced Stevens-Johnson syndrome or drug-induced hypersensitivity syndrome (39,40), and HLA-B*5701 were reported to be associated with abacavir-induced hypersensitivity reaction (41,42).…”

Update on the Genetic Basis of Drug Hypersensitivity Reactions

“…Multiple studies have found an association between the HLA-B*1502 allele and carbamazepine-induced SJS/TEN in Han Chinese [38][39][40][41] and other Asian populations [42][43][44][45]. The strength of such associations has led to the recommendation to screen for this variant in patients with Asian ancestry before starting treatment [46,47].…”