Distinguishing Benign Rashes From Severe Skin Reactions From Anti-Seizure Medications

Purpose of review: This review describes risk factors for severe skin reactions to antiseizure medications (ASMs), the usage of updated tests to predict those with increased risk of a severe cutaneous reaction, and guides how to choose specific ASMs and dosing to lower the risk for these reactions. Information is given regarding specific mild versus severe reactions, initial diagnostic evaluation, and treatment. A table listing the risk of mild and severe cutaneous reaction risks as well as the management of potential seizures that may occur while stopping the culprit ASM are provided. Recent findings: Five new ASMs have joined the total of 26 FDA-approved ASMs since 2018. Cenobamate had three patients develop a drug reaction with eosinophilia and systemic symptoms. A lower starting dosing and slower titration have resulted in no further published cases. Based on limited data, rash risk is low for fenfluramine, ganaxalone, and stiripentol. It is low-moderate for Epidiolex. Molecular tests can predict severe reactions. Summary: Skin reactions are a relatively common side effect of ASMs with aromatic ASMs having the greatest risk. Identifying and informing high-risk patients when to seek medical attention, stopping the culprit ASM when a severe reaction looks possible, and providing appropriate medical triage can reduce morbidity and mortality from severe skin and systemic reactions.