Antiepileptic Drug-Induced Skin Rash Revealing a Cross-Reactivity between Antiepileptic Drugs in a Patient with Anticonvulsant Polypharmacy

Aims: The cross-reactivity of antiepileptic drugs (AEDs) in the occurrence of drug eruption makes intrinsic accountability difficult. We are reporting on a case of drug eruption that occurred in a patient treated with four AEDs who had previously developed rashes with two other AEDs.

Presentation of Case: A 17-year-old epileptic patient with a history of rashes induced by phenobarbital and carbamazepine three years ago, and since ceased. Two months before admission, levetiracetam was added. Lamotrigine and clobazam were then added for generalized seizures. Two weeks later, a rash appeared on the neck, trunk and face with extension to limbs associated with pruritus and fever. On admission, the patient was febrile with tachycardia. Skin examination revealed a maculo-papular exanthema on the limbs, trunk and puffy face with negative Nikolski's sign. Biological assessment: leukopenia, thrombocytopenia and elevated CRP. The skin biopsy was in favor of toxiderma. The patient received paracetamol; imputability scores of the 4 antiepileptic drugs were calculated; and incriminated latromigine (C3S2B4) which was stopped with progressive increase of levetiracetam. The evolution was marked by a clinical and biological improvement.

Discussion: The incidence of AED-induced drug eruption ranged from 1.7 to 8.8%. The AEDs most at risk are aromatic AEDs. A high initial dose and rapid dose escalation are risk factors, especially for lamotrigine when metabolism is inhibited by valproic acid.

Conclusion: During anticonvulsant polypharmacy, caution should be taken when administering some AEDs to ensure that clinicians safely prescribe appropriate anti-epileptic medications considering the history of previous AED-related skin reactions.