Abstract

BackgroundThe relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China.MethodsWe enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test.ResultsWe found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found.ConclusionsIn northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Highlights

  • The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated

  • Depending on the severity of the drug eruption, the main symptoms are maculopapular exanthema (MPE) and severe cutaneous adverse reactions (SCARs) with potentially life-threatening consequences, including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); the mortality rate for the latter two diseases is as high as 30 %, and the fatality rate is very high [4, 5]

  • Of the 165 patients with EP treated with AEDs (N = 165), nine patients who had been diagnosed with AEDMPE were treated with aromatic AEDs (CBZ/OXC)

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Summary

Introduction

The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. We investigated the association between AEDinduced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China. As a derivative of CBZ, OXC is relatively safe to use, whereas some studies have shown that OXC-induced cutaneous adverse drug reactions (CADRs) are related to HLA-B*1502, of which MPE is the most common [8]. Some studies have found no correlation between the HLA-B*1502 gene and OXC-induced MPE (OXC-MPE) in northern and southern China [9, 10]. This study was conducted because these current results are controversial and because no studies on the HLA-B*1502 gene and AEDinduced MPE (AED-MPE) have been previously conducted in northwest China

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