Survey the association of Carbamazepine and Lamotrigine induced drug skin reaction and HLA-B*1502 status

Abstract

Anticonvulsant drugs are a valuable treatment to control seizures and epilepsy. Carbamazepine and lamotrigine are antiepileptic and mood stabilizing drugs that are used to treat these diseases and cases such as trigeminal neuralgia and chronic pain. Considering the numerous studies in different regions and races to determine the relationship between HLA-B*1502 and HLA-A31:01 with complications caused by carbamazepine and lamotrigine consumption, so far there has been no study to determine the relationship between these factors in the country and region-northwest of Iran- has not been done. Therefore, we decided to conduct a study with the aim of investigating the relationship between the side effects of carbamazepine and lamotrigine and HLA-B*1502 and HLA-A31:01 genes in patients with seizure disorder. Methods This cross-sectional study was conducted on patients diagnosed with convulsions who visited the Imam Reza or Razi Educational-Therapeutic Center, affiliated to Tabriz University of Medical Sciences, between March 2018 and March 2022. Patients were divided into 2 groups with and without skin complications caused by carbamazepine or lamotrigine. Various parameters such as age, gender, type and dose of the used drug, as well as the severity of the hypersensitivity reaction were completed according to the questionnaire. A blood sample of 5 cc was collected from all subjects and kept at -70 degrees until the tests were performed. Finally, the blood samples of two groups were examined by polymerase chain reaction (PCR) method for the presence or absence of HLA-B*1502 and HLA-A31:01 and the resulting data were analyzed using IBM SPSS software (ver24, SPSS; Chicago, IL) was analyzed.

Results 97 patients who were divided into 2 groups, case group (48 patients) and control group (49 patients), participated in this study. In 48 patients of the case group, the severity of allergic reaction was mild in 43 patients (89.6%) and SJS in 5 patients (10.4%). There was no significant difference between the patients of the 2 groups in terms of age (p=0.47), gender (p=0.12) and seizure type (p=0.74). 67 (69.1%) patients received carbamazepine and 30 (30.9%) patients received lamotrigine, so that 31 (64.6%) patients from the case group received carbamazepine and 17 (35.4%) patients from this group received lamotrigine. There was no statistically significant difference between the case and control groups in terms of the type of drug used (p=0.34). In HLA genetic analysis, the prevalence of HLA-A31:01 was found to be 3.1%, and all three HLA-A31:01 patients were in the case group; however, the difference between the case and control groups was not statistically significant (p=0.07). The prevalence of HLA-B 1502 gene in low resolution was 5.2%, which included 2 (4.2%) patients in the case group and 3 (6.1%) patients in the control group (p=0.66). None of these patients carried the HLA-B 1502 genotype in the high-resolution analysis. In the subgroup of carbamazepine recipients in the HLA genetic study, the prevalence of HLA-A31:01 was found to be 4.5%, and all three HLA-A31:01 patients were in the case group; however, the difference between the case and control groups was not statistically significant (p=0.05). The prevalence of HLA-B 1502 gene was 6.0% in the low-resolution study, which included 2 (6.5%) patients in the case group and 2 (5.6%) patients in the control group (p=0.87). In the lamotrigine subgroup, HLA-B15:02 was present in only 1 (7.7%) patient in the control group in the low-resolution analysis, which did not indicate a significant difference between the 2 groups (p=0.24).