Carbamazepine and phenytoin induced Stevens‐Johnson syndrome is associated with HLA‐B*1502 allele in Thai population

Abstract

Summary Purpose: Previous studies found a strong association between HLA‐B*1502 and carbamazepine (CBZ)‐induced Stevens‐Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations. Even in Han Chinese, the HLA‐B*1502 was not associated with CBZ‐induced maculopapular eruptions (MPE). This study seeks to identify whether HLA‐B*1502 is associated with CBZ‐ or phenytoin (PHT)‐induced SJS or MPE in a Thai population. Methods: Eighty‐one Thai epileptic patients between 1994 and 2007 from the Chulalongkorn Comprehensive Epilepsy Program were recruited. Thirty‐one subjects had antiepileptic drug (AED)‐induced SJS or MPE (6 CBZ‐SJS, 4 PHT‐SJS, 9 CBZ‐MPE, 12 PHT‐MPE), and 50 were AED‐tolerant controls. Results: For the first time, a strong association between HLA‐B*1502 and PHT‐induced SJS was found (p = 0.005). A strong association was also found between the HLA‐B*1502 and CBZ‐induced SJS (p = 0.0005), making Thai the first non‐Chinese population demonstrating such an association. Some patients, who were HLA‐B*1502 and suffered from CBZ‐induced SJS, could be tolerant to PHT and vice versa. This suggests that HLA‐B*1502 may be a common attribute required for a Thai patient to develop SJS from these two AEDs; other different elements, however, are also needed for each AED. In addition, no association between HLA‐B alleles and CBZ‐ or PHT‐induced MPE was found. Conclusions: CBZ‐ and PHT‐induced SJS, but not MPE, is associated with HLA‐B*1502 allele in Thai population.

Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs

“…49 Similar findings emerged from other Han Chinese populations. [68][69][70][71] A significant association between CBZ-SJS/TEN and HLA-B*1502 was also found in Thai, 72,73 Malay 74 and, to a lesser degree, Indian patients. 75 In a European study, the only HLA-B*1502-positive CBZ-SJS patients were of East Asian descent.…”

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“…Cytotoxic molecules-FasL and granulysin are thought to be responsible for the disseminated keratinocyte apoptosis in SJS/TEN. 19 In fact the HLAB*1502 allele 20 Additionally. Phenytoin being a strong inducer of CYP450, is linked to induction of oxidative stress and generation of reactive oxygen species.…”

Valproate-Induced Reversible Brain Atrophy and Cognitive Deterioration

“…The US FDA cautions that phenytoin or fosphenytoin should not be prescribed as an alternative to carbamazepine in patients who carry HLA-B*15.02, although the association with severe cutaneous reactions in Asians is weaker than that found with carbamazepine [5]. Current studies find that the HLA-DRB1*15.01 allele is a risk factor for AED-induced SJS/TEN among Han Chinese, whereas HLA-A*33.03, HLA-B*58.01, and HLA-DRB1*03.01 alleles may be protectors against AED-induced skin reactions, especially CBZ-SJS/TEN [6].…”

“…Erythema multiforme as a synergistic side effect to a combination of phenytoin therapy and cranial radiotherapy is also reported [2]. The routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures is discouraged [3][4].The US FDA cautions that phenytoin or fosphenytoin should not be prescribed as an alternative to carbamazepine in patients who carry HLA-B*15.02, although the association with severe cutaneous reactions in Asians is weaker than that found with carbamazepine [5]. Current studies find that the HLA-DRB1*15.01 allele is a risk factor for AED-induced SJS/TEN among Han Chinese, whereas HLA-A*33.03, HLA-B*58.01, and HLA-DRB1*03.01 alleles may be protectors against AED-induced skin reactions, especially CBZ-SJS/TEN [6].…”