Journal of Pharmacogenomics & Pharmacoproteomics

Pharmacogenomic Insights into HLA-B*15:02 Mediated Carbamazepine-Induced Stevens-Johnson Syndrome

Arvind Nair^* Department of Clinical Genomics, Trivandrum Institute of Medical Research, Trivandrum University, Trivandrum, India
^*Correspondence: Arvind Nair, Department of Clinical Genomics, Trivandrum Institute of Medical Research, Trivandrum University, Trivandrum, India, Email:

Received: 26-Feb-2025, Manuscript No. JPP-25-29330; Editor assigned: 28-Feb-2025, Pre QC No. JPP-25-29330(PQ); Reviewed: 14-Mar-2025, QC No. JPP-25-29330; Revised: 21-Mar-2025, Manuscript No. JPP-25-29330(R); Published: 28-Mar-2025, DOI: 10.4172/2153-0645.25.16.128

Description

Carbamazepine is a widely prescribed antiepileptic and mood- stabilizing agent used in the treatment of epilepsy, bipolar disorder, and trigeminal neuralgia. Despite its effectiveness, the drug is associated with Severe Cutaneous Adverse Reactions (SCARs), particularly Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). These hypersensitivity reactions, although rare, are life-threatening and have been strongly linked to specific genetic markers. One of the most clinically relevant pharmacogenomics associations is between the HLA-B*15:02 allele and carbamazepine-induced SJS, particularly in individuals of Asian descent.

HLA-B*15:02 is a variant of the human leukocyte antigen system that plays a key role in immune recognition. This allele has been found to predispose carriers to inappropriate immune responses upon exposure to carbamazepine, resulting in widespread epidermal necrosis and mucosal ulceration. The prevalence of HLA-B*15:02 varies significantly across ethnic groups, being particularly high in populations from Southeast Asia, Southern India, and Han Chinese regions, and virtually absent in individuals of European and African ancestry. These findings prompted regulatory and clinical policy changes. The U.S. Food and Drug Administration (FDA) and several Asian health authorities now recommend genetic screening for HLA-B*15:02 in individuals of Asian ancestry before initiating carbamazepine. The Clinical Pharmacogenetics Implementation Consortium (CPIC) also provides guidelines advising the use of alternative medications in allele carriers. Such pharmacogenomics screening has been shown to dramatically reduce the incidence of SCARs, thereby improving drug safety and patient outcomes.

Despite these advancements, implementation remains uneven. In India, while major hospitals in urban centers offer HLA-B*15:02 testing, access in rural areas remains limited. Challenges include cost barriers, lack of infrastructure, and limited awareness among general practitioners. However, initiatives by public health authorities and nonprofit organizations are gradually expanding the availability of pharmacogenomics testing through mobile labs and digital health platforms. This immune response targets keratinocytes, resulting in massive apoptosis and the clinical presentation of SJS. Ongoing structural immunology studies are using crystallography and molecular docking simulations to better understand the specificity of this interaction, with the goal of developing safer drug analogs or desensitization strategies.

In addition to genotyping, Pharmacoproteomic approaches are now being investigated to assess immune activation biomarkers in patients at risk. Proteomic profiling of blood samples from SJS patients has revealed elevated levels of granulizing, a cytotoxic protein that contributes to keratinocyte death. Such biomarkers could potentially serve as early indicators of immune activation or as endpoints in clinical trials evaluating new preventive strategies. From a public health standpoint, integrating HLA-B*15:02 screening into standard epilepsy care protocols represents a cost-effective strategy. Economic models have shown that routine testing before carbamazepine initiation, particularly in high-prevalence regions, reduces overall healthcare expenditures by preventing hospitalization, intensive care admission, and long-term rehabilitation associated with SCARs.

The association between HLA-B*15:02 and carbamazepine- induced SJS exemplifies the critical role of pharmacogenomics in personalized medicine. Pre-treatment genotyping offers a powerful tool to enhance drug safety and efficacy, especially in populations with known genetic risk. As pharmacogenomics awareness and infrastructure expand, it is anticipated that such testing will become an integral part of standard clinical workflows, ensuring safer prescribing practices and better patient outcomes in the management of epilepsy and related disorders.