One specific gene variation increases a patient’s risk of a rare but life-threatening hypersensitivity reaction to the mood-stabilizing drug lamotrigine—but that information is not included on current commercially available pharmacogenomic panels, according to a study published today in JAMA Psychiatry.Why It’s Relevant
Widely prescribed for bipolar and seizure disorders, lamotrigine has emerged as a common trigger for a drug reaction with eosinophilia and systemic symptoms (DRESS)—a rare but severe cutaneous adverse reaction that causes widespread, measles-like rashes, fever, swollen lymph nodes, and internal organ impairment. About 10% of patients who develop this hypersensitivity reaction die, and survivors face serious ongoing health challenges.
Practice guidelines recommend the use of pharmacogenomic testing for specific gene variations (HLA-B*15:02 and HLA-A*31:01) before prescribing the antiseizure medication carbamazepine to help prevent DRESS and other hypersensitivity reactions. However, no reliable pharmacogenomic biomarkers have been identified for lamotrigine.
By the Numbers
- Genetic testing was performed on 29 patients who experienced lamotrigine-induced DRESS (86% female, 79% White) along with 290 patients who tolerated at least 90 days of lamotrigine treatment with no adverse reaction.
- The researchers found that individuals who carried the HLA-A*32:01 variant had 16 times the odds of developing lamotrigine-induced DRESS than non-carriers.
- The prevalence of the HLA-A*32:01 allele was 41% among those who had lamotrigine-induced DRESS versus 4% among those who tolerated lamotrigine.
- The HLA-A*31:01 allele wasn’t significantly more common in participants with DRESS compared with those who tolerated lamotrigine (7% versus 4%, respectively), and HLA-B*15:02 wasn’t identified in either group.
The Other Side
The study was limited by its small size and the predominantly White composition of its cohort. It’s also not yet known if this genetic variant increases risk for other severe drug-induced reactions such as Stevens-Johnson syndrome.
Takeaway Message
“This study provides a foundation for evaluating genotype-guided risk stratification; however, because DRESS is rare and the allele was present in fewer than half of cases, its clinical utility remains uncertain,” Kun Lin Lu, M.D., of Keelung Chang Gung Memorial Hospital in Keelung City, Taiwan, wrote in an invited commentary. “Independent replication across ancestries, prospective evaluation of genotype-guided prescribing, and assessment of treatment alternatives and cost-effectiveness are needed before routine implementation.”
Related Information
Source
Matthew S. Krantz. HLA-A*32:01 and lamotrigine-induced drug reaction with eosinophilia and systemic symptoms. JAMA Network Open. Published September 2, 2026. doi:10.1001/jamanetworkopen.2026.31291
(Image: Getty Images/iStock/Alena Butusava)
