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Abstract: Purpose: Oxcarbazepine (OXC) is a promising alternative for patients who cannot tolerate carbamazepine. Recently, however, it has been reported that OXC-induced cutaneous adverse drug reactions (cADRs) are prevalent and may lead to drug discontinuation. Additionally, these reactions are thought to be associated with HLA-B*1502. This study aims to investigate the incidence, features and risk factors of OXC-cADRs, and to explore their relation to HLA-B alleles in Southern Han Chinese. Methods: A prospective study was performed to investigate the incidence, features and risk factors of OXC-cADRs, in which 252 new users were recruited. To examine the association between OXC-cADRs and HLA-B alleles, 14 maculopapular eruption (MPE) cases, including 9 additional cases beyond this prospective observation, were genotyped by PCR-SSP and sequencing. Thirty-five OXC-tolerant patients served as controls. Results: Five patients (2.0%) developed an OXC-cADR, and all were mild MPE. History of other AED allergy (p =0.005, OR=121.23) and non-AED allergy (p =0.006, OR=59.92) were significant risk factors for OXC-cADRs in multivariate logistic regression analysis. Only one patient with OXC-MPE was positive for HLA-B*1502; and the frequency of HLA-B*1502 in OXC-MPE did not differ significantly from that in OXC-tolerant controls. Four HLA-B*1302 alleles were detected in OXC-MPE cases, which was significantly different from that in general population of southern Han Chinese (p =0.001, OR=7.83). Conclusions: The incidence of OXC-induced cADRs was low, and no severe reactions occurred. Patients with a history of allergy are more susceptible to OXC-cADRs. No significant association between HLA-B*1502 and OXC-MPE was found. The associations between OXC-MPE and HLA alleles warrant further studies. [Copyright &y& Elsevier]

Abstract: Recent studies associated the HLA-B∗1502 allele with carbamazepine (CBZ)-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients from China, Thailand and Malaysia. No association has been found in patients from Europe or Japan. Linkage summary reports from East and South-east Asia predict a highly significant odds ratio (OR) of 84.75 (95% confidence interval [CI]=42.53–168.91; p =8.96×10[–15]) with sensitivity and negative predictive values of 92% and 98%, respectively. The higher prevalence of HLA-B∗1502 allele among certain Asian populations (10–15%) compared to Caucasians (1–2%) may explain a 10-fold to 25-fold higher incidence of CBZ-SJS/TEN in patients from Asia. Screening for HLA-B∗1502 before using CBZ can prevent SJS/TEN in certain populations, but screening may be less beneficial in populations with low HLA-B∗1502 allele frequency and in patients exposed to CBZ for more than 2 months. A retrospective study demonstrated that the costs of HLA-B∗1502 screening were less than those of SJS treatment. This article reviews possible benefits and concerns of HLA-B∗1502 screening in clinical practice. [Copyright &y& Elsevier]

Abstract: Previous studies have found a strong association between HLA-B*1502 and carbamazepine-induced Stevens–Johnson syndrome in Asian areas including Taiwan, Hongkong and Thailand. This study explores the association between HLA-B*1502 allele and carbamazepine-induced cutaneous adverse reactions in Han Chinese of southern China mainland, and find the genetic marker that can predict carbamazepine-induced cutaneous adverse reactions. HLA-B*1502 allele genotyping was performed by a polymerase chain reaction–sequence specific primers (PCR–SSP) method in 48 Han Chinese subjects who had carbamazepine-induced cutaneous adverse reactions, including 9 severe cutaneous adverse reaction patients with Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and 39 cutaneous adverse reaction patients with maculopapular eruption (MPE). Meanwhile 80 carbamazepine-tolerant controls and 62 healthy individuals were also tested. The frequency of HLA-B*1502 allele among SJS/TEN patients (100%) is significantly higher than carbamazepine-tolerant controls (13.75%, P <0.001) and healthy individuals (17.74%, P <0.001). But the frequency between MPE patients and carbamazepine-tolerant controls (25.64% vs.13.75%, P =0.110) did not have any significant difference. The data showed that HLA-B*1502 allele is strongly associated with carbamazepine-induced SJS/TEN but not MPE in Han Chinese of southern China mainland. [Copyright &y& Elsevier]

Abstract: Background: Recent study demonstrated that HLA-B*1502 was a common risk allele in aromatic antiepileptic drugs (AEDs) induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Han Chinese. However, the association of AEDs-induced mild maculopapular eruption (MPE) with HLA-B*1502 remains unclear until recently. In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population. Methods: We enrolled 90 subjects involving 9 patients with OXC-induced MPE and two groups of controls, 9 OXC-tolerant and 72 normal controls. High-resolution HLA genotyping was performed by specific kit. The results of HLA genotyping are expressed as positive or negative for HLA-B*1502 allele. Differences in genotype frequencies between groups were assessed by the Fisher''s exact test. Results: Four cases were detected as positive for HLA-B*1502 amongst 9 patients. However, only 1 subject was positive amongst 9 tolerant controls, and 6 subjects were positive amongst 72 normal controls. The difference in HLA-B*1502 allele frequencies between the MPE group and normal controls was statistically significant (OR: 8.8; 95% CI: 1.853–41.790; P =0.011). In addition, we also observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P =0.294). Conclusions: Our findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population. In order to safer AEDs use, we recommend that HLA-B*1502 allele should be tested for patients with OXC-induced MPE before changing to other AEDs, and AEDs with similar chemical structure should be avoided in individuals who test positive for HLA-B*1502 allele. It should be pointed out that, however, our results may well be just by chance owing to the small sample size and should be further confirmed in future studies. [Copyright &y& Elsevier]

Eslicarbazepine acetate (ESL) is an anticonvulsant drug approved for the treatment of focal epilepsies, and related to oxcarbazepine and carbamazepine (CBZ), which are also derivatives of the dibenzazepine family. ESL is contraindicated in patients with hypersensitivity reactions to CBZ.We report a patient with frontal lobe epilepsy responding to treatment with ESL without any serious adverse effects after developing a severe skin rash following treatment with CBZ. HLA testing revealed an HLA-A*31:01 haplotype, that increases the risk of CBZ-induced cutaneous reactions.This case study shows that, in clinical practice, ESL may be considered in a patient with the HLA-A*31:01 haplotype and a hypersensitivity reaction to CBZ. [ABSTRACT FROM AUTHOR]

We describe a 28-year-old Malaysian Australian man of Han Chinese descent with toxic epidermal necrolysis (TEN), occurring 2 weeks after commencing carbamazepine. He was subsequently found to be positive for human leukocyte antigen (HLA)-B*1502. Carbamazepine-induced Stevens–Johnson syndrome/TEN is strongly associated with the HLA-B*1502 allele, which is highly prevalent in Han Chinese, Malay, Thai and Indian populations. Prospective screening for the allele may prevent this cutaneous adverse drug reaction from occurring, but many neurologists and other medical practitioners are still unaware of the medico-legal risks of prescribing carbamazepine in susceptible populations and the availability of HLA-B*1502 testing. Performing HLA-B*1502 genotyping and avoiding carbamazepine in at-risk individuals has been proven to decrease incidences of drug-induced TEN. This test is widely available at most large pathology services in Australia, with results available within 2 weeks. The recommendation by regulatory bodies should be strengthened to ensure that the broad medical community is made more aware of this pertinent issue. [ABSTRACT FROM AUTHOR]

Abstract: Antiepileptic drugs-induced Stevens–Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction. Recent studies in Thailand and Taiwan showed a significant association between phenytoin (PHT)-induced SJS and human leucocyte antigen HLA-B*1502 allele. Although the US FDA had issued an alert to clinicians, insufficient information is available to recommend testing for HLA-B*1502 in Asian patients in line for PHT treatment. Therefore, extended studies are necessary to further evaluate the potential association between PHT-induced SJS and HLA-B*1502 allele in various populations. To date, no similar data exist in mainland China. Here, we describe two Chinese Han cases of PHT-induced SJS with negative HLA-B*1502 allele, in which HLA high-resolution genotyping showed two heterozygous HLA-B*4601/B*5102 and HLA-B*3701/B*4601 allele, respectively. Our findings provide evidence to support that other genetic markers or nongenetic factors could contribute to the susceptibility of PHT-induced SJS, except for HLA-B*1502 allele. Further studies are encouraged to investigate the genetic link with PHT-induced serious skin reactions in future. [Copyright &y& Elsevier]