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News
The genetic panels routinely ordered before prescribing lamotrigine — a drug taken by ~2.5 million Americans — are testing for the wrong markers. A new study found that HLA-A*32:01, not the variants currently screened, is strongly linked to a rare but potentially fatal drug reaction called DRESS. The good news? A rapid, inexpensive test for this marker already exists.
Clinicians prescribing lamotrigine — a first-line treatment for epilepsy and bipolar disorder taken by an estimated 2.5 million Americans — routinely order pharmacogenomic panels to screen for dangerous drug reactions. But a new Vanderbilt Health-led study published in JAMA Network Open reveals those panels are testing the wrong genetic markers, potentially giving patients a false sense of safety.
The study focused on DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), a severe hypersensitivity reaction that can escalate from rash and fever to organ failure, carrying a 3–10% mortality rate. Lamotrigine is among the top five global causes of DRESS. Researchers found that HLA-A32:01 — a marker already used to flag vancomycin-related DRESS — was present in 41.4% of lamotrigine-DRESS cases vs. just 4.1% of tolerant controls, a 16.4-fold higher odds ratio. Meanwhile, the two variants currently screened (HLA-B15:02 and HLA-A*31:01) showed no significant association in a U.S. population.
By the Numbers:
Why it matters: A rapid PCR test for HLA-A*32:01 already exists and is inexpensive — meaning this finding could be quickly translated into clinical practice to better protect patients from a life-threatening and preventable drug reaction.
