The Link between HLA-B Alleles and Causative Drugs in Vietnamese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Abstract

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Human leukocyte antigens (HLA) may play an important role in the pathogenesis of SJS/TEN.
 AIMS: This study aims to identify HLA-B alleles in Vietnamese patients with SJS/TEN and to investigate the possible link between HLA-B alleles and causative drugs.
 MATERIALS AND METHODS: Sixty patients including SJS (30 patients) and TEN (30 patients) were enrolled in a cross-sectional descriptive study at two hospitals in Hanoi, Vietnam, from July 2018 to July 2019. Clinical features and laboratory findings were noted, HLA-B alleles were analyzed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide assay and LuminexTM Multiplex Technology.
 RESULTS: The most common HLA-B allele was HLA-B*15:02 (41.7%) followed by HLA-B*58:01 (25%) and HLA-B*46:01 (15%). Of the 25 patients possessing HLA-B*15:02 allele, culprit medicines were carbamazepine (13 patients; 52%), traditional medicine (two patients; 8%), and unknown drugs (seven patients; 28%). Of the 15 patients carrying HLA-B*58:01 allele, there were 13 patients whose offending medicine was allopurinol. Of the eight patients whose culprit drug was traditional medicine, there were 6 patients (75%) carrying HLA-B*51:02. Patients who carry HLA-B*15:02 were found to have 4 times higher risk of developing carbamazepine-induced SJS/TEN as compared with the tolerant control group (OR=4.17; 95% CI=2.07–8.37; p < 0.001).
 CONCLUSION: HLA-B*15:02 was the most common HLA-B allele in Vietnamese patients with SJS/TEN. In traditional medicine-induced SJS/TEN patients, HLA-B*51:02 allele might play an important role. The link between the HLA-B genotypes and causative drugs may suggest physicians to avoid risk medications for certain patients.

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…The remaining 4467 studies were screened for title, abstract, and full text, and 64 potentially relevant studies were identified. Of the 64 studies that underwent data extraction, 3 studies described the same study population and were excluded from the meta-analysis. Furthermore, there were 23 studies that did not count the SJS/TEN associations at the patient level and thus were excluded.…”

“…In the end, the meta-analysis included 38 retrospective observational studies with 2917 patients from more than 20 countries . There were 16 studies from Asia (1298 patients), 14 studies from North America (932 patients), 4 studies from Europe (208 patients), 3 studies from Africa (437 patients), and 1 study from Australia (42 patients).…”

“…The pooled proportion of antibiotics associated with SJS/TEN (38 studies; 2917 patients) was 28% (95% CI, 24%-33%), with moderate certainty of evidence (Figure 2). There was no evidence of publication bias (eFigure 2 in Supplement 1).…”

Stevens–Johnson Syndrome in an Adult Filipino Male Positive for HLA‐B*38:16 and B*58:17, Associated With Allopurinol: A Case Report

“…In SJS, HLA genetic variations contribute to its development by making the HLA molecule, bound with the culprit drug or a drug metabolite, susceptible to T‐cell recognition 1 . The presence of HLA‐B*58:01 alleles and its association in allopurinol‐induced SJS have been detected in multiple ethnicities, including Chinese, Thai, Korean, Vietnamese, and Japanese populations 3,5 . Given this association, genetic screening has been employed in several countries to limit the incidence of allopurinol‐induced SJS since 2012 3 .…”

“…1 The presence of HLA-B*58:01 alleles and its association in allopurinolinduced SJS have been detected in multiple ethnicities, including Chinese, Thai, Korean, Vietnamese, and Japanese populations. 3,5 Given this association, genetic screening has been employed in several countries to limit the incidence of allopurinol-induced SJS since 2012. 3 The present case demonstrates novel HLA alleles that may predispose Filipino patients to developing allopurinol-induced SJS.…”