HLA-B*1502 Strongly Predicts Carbamazepine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Thai Patients with Neuropathic Pain

Background: Carbamazepine (CBZ) is one of the standard pharmacological treatments for neuropathic pain. However, its serious adverse drug reactions include StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, HLA-B*1502 allele was implicated as a genetic marker of CBZ-induced SJS/TEN in some Asian epilepsy populations. Methods: This is a case control study to describe the clinical characteristics of SJS/TEN in Thai patients with neuropathic pain who were treated with CBZ, and to determine the association of HLA-B* 1502 in these patients, comparing with those who exposed to CBZ for at least 6 months without any cutaneous reactions. Results: Thirty-four SJS/TEN patients and 40 control patients were included in this study. Mean age of SJS/TEN patients was 47 years. SJS/TEN was developed in 10.8 +/- 1.4 days after initiation of CBZ. HLA-B* 1502 allele was found in 32 of 34 SJS/TEN patients (94.1%) but it was found only in 7 of 40 control patients (17.5%). The association was very strong with an odds ratio of 75.4. Sensitivity and specificity of this HLA-B* 1502 genotype test were 94.1% and 82.5%, respectively, while the positive predictive value and negative predictive value were 1.43% and 99.98%, respectively. Positive and negative likelihood ratios were 5.37 and 0.07, respectively. Conclusions: HLA-B* 1502 is a strong genetic marker for CBZ-induced SJS/TEN in Thai patients with neuropathic pain. The screening for this marker should be performed prior to initiation of CBZ treatment to assess the risk of this serious side effect.