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Background: The 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.Methods: We 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.Results: We 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.Conclusions: In 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. [ABSTRACT FROM AUTHOR]

Objective: Carbamazepine, widely used in the treatment of partial and generalized tonic–clonic seizures, has been associated with life‐threatening Stevens‐Johnson syndrome/toxic epidermal necrolysis among some Asians. The HLA‐B*1502 genotype that occurs with varying frequency among Asians is recommended for screening prior to starting carbamazepine. Our goal is to explore the cost‐effectiveness of screening for the presence of this genetic allele. Methods: We constructed a Markov model in a hypothetical cohort of adult Asian patients with epilepsy in the United States being considered for carbamazepine to investigate the cost‐effectiveness of two alternative strategies: (1) no HLA‐B*1502 gene allele screening and using carbamazepine and (2) HLA‐B*1502 gene allele screening and starting levetiracetam in the case of a positive screen. Results: For the lifetime horizon, HLA‐B*1502 gene screening was the cost‐effective choice compared to no gene screening, with an incremental cost‐effectiveness ratio of $27 058 per quality‐adjusted life‐year (QALY), below the $50 000/QALY threshold in 99.69% of probabilistic sensitivity analyses. Although gene screening strategy was more expensive than a no screening strategy, it was more effective, yielding more QALYs, across all Asian ethnic groups. Significance: Our analysis confirms the 2007 US Food and Drug Administration recommendation to screen for HLA‐B*1502 allele before starting treatment with carbamazepine in patients of Asian ancestry in the United States. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B*1502 in Han Chinese. Here, we extended the study of HLA-B*1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobabital (PB). In addition, we genotyped HLA-B*1511 in a case of CBZ-induced SJS with genotype negative for HLA-B*1502. The presence of HLA-B*1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B*1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant ( n=32) and normal controls ( n=38) in the central region of China. The data showed that HLA-B*1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B*1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06-36.74) and 4.86 (95% CI: 1.01-23.47). The sensitivity and specificity of HLA-B*1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B*1502 was not found in 11 children with maculopapular exanthema (MPE) ( n=9) and hypersensitivity syndrome (HSS) ( n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B*1502 but carried HLA-B*1511. It was suggested that the association between the CBZ-induced SJS and HLA-B*1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B*1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B*1502. [ABSTRACT FROM AUTHOR]

Background Carbamazepine (CBZ) is broadly used for the treatment of epilepsy, neuropathic pain and other neurological diseases, owing to its effectiveness and low price. CBZ can induce Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). There are several studies that found an association between HLA-B*1502 and CBZ-induced SJS/TEN, especially in people of Thai origin. In Thailand the prevalence of HLA-B*1502 was found to be in the range 8.1-14 %. Objective This study aimed to determine if screening for HLA-B*1502 in Thai patients who were to receive CBZ is cost effective. Setting Srinagarind Hospital, Khon Kaen University, Thailand. Method A comparison between treatment cost of CBZ induced SJS/TEN and the HLAB*1502 screening costs in the Thai population. Main outcome measure Comparison of the costs of treatment of CBZ induced SJS/TEN and costs of HLA-B*1502 screening test. Results When persons having the HLA-B*1502 allele receive CBZ, the chance of developing SJS/TEN is as high as 88.1 %, while persons without the HLA-B*1502 allele do not develop SJS/TEN. Therefore, a model was calculated to compare the cost of treatment between HLA-B*1502 testing before giving CBZ and if the patients were not tested for HLAB*1502. It was found that screening 100 patients before giving CBZ would save an amount of 98,549.94 baht per 100 cases of CBZ-prescribed patients. Conclusion The screening for HLA-B*1502 allele before giving carbamazepine is cost effective. The results of the present study may also apply to other populations if the HLA-B*1502 frequency is high enough. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between oxcarbazepine (OXC)-induced maculopapular eruption (MPE) and HLA-B alleles in a northern Han Chinese population, and conducted an analysis of clinical risk factors for OXC-MPE. Methods: Forty-two northern Han Chinese patients who had been treated with OXC in Changchun, China were genotyped. Among them were 14 cases with OXC-induced MPE; the remaining 28 were OXC-tolerant. The HLA-B allele frequencies of the normal control group were found in the Allele Frequency Net Database. Polymerase chain reaction-sequence specific primer( PCR-SSP )was used for HLA-B"1502 testing and direct sequencing for four-digit genotype determination. Results: Four-digit allele sequencing showed that there was no statistically significant difference in the frequency of the HLA-B"1502 allele between the OXC-MPE and OXC-tolerant controls (3.6% versus 7.5%, OR = 0.38, 95% CI = 0.04-3.40, P = 0.65), as well as between OXC-MPE and normal controls (3.6% versus 2.4%, OR = 1.54, 95% CI = 0.20-11.73, P = 0.49). However, a significant difference in the frequency of HLA-B"3802 alleles was found between the MPE group and normal controls (10.7% versus 1.9%, OR = 6.329, 95% CI = 1.783-22.460, P = 0.018). There was no significant difference in terms of age, gender, or final OXC dose between the OXC-MPE and OXC-tolerant groups. Conclusions: There was no significant association between OXC-MPE and HLA-B"1502 in the northern Han Chinese population in our study. Instead, HLA-B"3802 was found to be a potential risk factor for OXC-MPE. [ABSTRACT FROM AUTHOR]

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Recently, strong associations of HLA-B*1502 with carbamazepine-induced SJS/TEN have been found in Han Chinese patients. These associations have been confirmed in several Asian populations, excluding Japanese. SJS patients carrying HLA-B*1508, HLA-B*1511, or HLA-B*1521, which are members of the HLA-B75 type along with HLA-B*1502, were detected in studies in India and Thailand. In the current study, we genotyped the HLA-B locus from 14 Japanese typical and atypical SJS/TEN patients in whom carbamazepine was considered to be involved in the onset of adverse reactions. Although there were no HLA-B*1502 carriers, four patients had HLA-B*1511. Our data suggest that HLA-B*1511, a member of HLA-B75, is a risk factor for carbamazepine-induced SJS/TEN in Japanese. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case–control study was conducted to determine whether HLA-B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ-induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA-B*1502 while only 5 (11.90%) of the CBZ-tolerant controls had this allele. The risk of CBZ-induced SJS/TEN was significantly higher in the patients with HLA-B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62–205.13, p = 2.89 × 10−12]. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ-induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA-B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA-B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ-induced SJS and TEN. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-B*1502 is not a universal marker but is ethnicity-specific for Asians. Aim: To study the association between HLA-B*1502 and carbamazepine-induced SJS in Indian patients. Methods: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. Results: Out of eight patients studied for genotype, six patients were found to have the HLA-B*1502 allele. Conclusion: This study suggests an association between HLA-B*1502 and carbamazepineinduced SJS in Indian patients. [ABSTRACT FROM AUTHOR]

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. 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. 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. CBZ- and PHT-induced SJS, but not MPE, is associated with HLA-B*1502 allele in Thai population. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the association of HLA-B*1502 allele with CBZ-induced SJS/TEN in the mainland Han Chinese population. Methods: HLA-B*1502 genotyping with sequence-specific primer polymerase chain reaction (PCR-SSP) and PCR-sequencing based typing (PCR-SBT) was performed on 17 CBZ-induced SJS/TEN patients, 21 CBZ-tolerant controls, and 185 healthy controls recruited during 2008-2010. Results: HLA-B*1502 allele was present in 94.1% (16/17) of CBZ-SJS/TEN patients, 9.5% (2/21) of CBZ-tolerant patients, and 9.2% (17/185) of healthy controls. The risk of CBZ-induced SJS/TEN was significantly higher ( P < 0.01) in the patients with HLA-B*1502. One CBZ-induced SJS patient tested negative for HLA-B*1502, and the test result showed HLA-B*3503/B*4601. Conclusions: We found a strong association between HLA-B*1502 and CBZ-induced SJS/TEN in the Han Chinese population from central and northern China. Combined with previous studies of the southern Han Chinese subpopulation, our results suggest that HLA-B*1502 is strongly associated with CBZ-induced SJS/TEN in the whole Han Chinese population. [ABSTRACT FROM AUTHOR]