Identifying Those at Risk
With millions of patients being newly prescribed ASMs annually, accurately screening out all people at risk of severe cutaneous adverse reactions based on available genetic information is impossible. The complexity of evolving recommendations for HLA testing makes them hard to remember, Dr. Mani said. “Development and better use of clinical decision support systems can help.”
Accordingly, he starts with a thorough history and physical examination, inquiring about prior skin reactions or hypersensitivity, which are risk factors for future reactions to drugs such as carbamazepine, phenytoin, phenobarbital, oxcarbazepine, lamotrigine, rufinamide, and zonisamide. “Most of the medicines that the HLA tests are being done for are not the initial medicines I typically prescribe for a patient with newly diagnosed epilepsy,” said Dr. Mani. For ASM-naive patients with moderate or high risk of skin hypersensitivity reactions, he usually starts with lacosamide, levetiracetam, or brivaracetam. Additional low-risk drugs he considers in more complex cases include valproate, topiramate, and clobazam.
Only if a patient’s initial ASM causes problems will Dr. Mani consider higher-risk options and order HLA tests for patients belonging to indicated groups — such as testing for HLA-B*15:02 in Asian patients being considered for carbamazepine. About once weekly, he must put a patient on a potentially higher-risk drug before test results are available. If after a thorough risk-benefit discussion, he and the patient agree that the higher-risk drug is warranted, Dr. Mani starts at a lower-than-labeled dose, with a slower titration schedule that typically extends the ramp-up period by 1 week.
Fortunately, Dr. Mani said that, in 20 years of practice, he has seen more misdiagnoses — involving rashes from poison ivy, viral infections, or allergies — than actual ASM-induced reactions. “That’s why the patient, family, and practitioner need to be open-minded about what could be causing the rash.”
Dr. Mani reported no relevant conflicts. The study authors reported no funding sources.
