Generalized Rash and Angioedema During Triple Antiepileptic Therapy: A Case Report

We present the case of a 42-year-old woman with drug-resistant symptomatic focal epilepsy secondary to focal cortical dysplasia, first diagnosed at the age of 15. The patient was on triple antiepileptic drug (AED) therapy: levetiracetam (LEV), lamotrigine (LTG), and oxcarbazepine (OxCBZ). Three months after the introduction of oxcarbazepine, she developed a generalized skin rash accompanied by episodic angioedema, manifesting as lip swelling and intermittent dyspnea. Oxcarbazepine was initially discontinued, as it was the most recently introduced drug, but the rash persisted. Lamotrigine was then withdrawn and replaced with lacosamide (LCZ), without significant improvement. Finally, levetiracetam was discontinued and substituted with zonisamide (ZON), resulting in the complete resolution of the cutaneous symptoms. The patient continued to experience two focal seizures per week, consistent with her baseline seizure frequency prior to medication adjustments. This case underscores the importance of recognizing cutaneous adverse effects associated with AEDs and illustrates the therapeutic challenges in managing patients with pharmacoresistant epilepsy, particularly when adverse drug reactions complicate polytherapy.