Antiepilepsy drugs and the immune system

To alert physicians about the peculiar adverse effects of antiepilepsy drugs (AEDs) on the immune system.

PubMed literature during the past 25 years.

Reports and review articles on the hypersensitivities of AEDs and their effect on immunity.

AEDs have significant effects on the immune system in the form of hypersensitivity or immune suppression. IgE-mediated reactions can be urticaria, angioedema, bronchospasm, or anaphylaxis. Non-IgE-mediated reactions, more commonly associated with aromatic AEDs, can be in the form of nonspecific rashes or serious reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptom syndrome, and acute generalized exanthematous pustulosis. Because of strong genetic predispositions for certain AEDs in causing severe reactions, HLA analysis before initiation of the drug is advised in certain populations. Immunoglobulin levels can be reduced to various degrees, particularly by carbamazepine, valproate, phenytoin, levetiracetam, zonisamide, and lamotrigine. Spontaneous return to normal levels can be rapid or take months to a few years, and intravenous immunoglobulin supplementation may be needed. Cellular effects can be in the form of cytopenias, inhibition of lymphocyte function, or cytokine dysregulation.

When prescribing AEDs, physicians should pay special attention to their potential adverse effects on immunity or hypersensitivity, which can be severe and even fatal. For early recognition and intervention, monitoring such patients is necessary. The cornerstone of management is discontinued use of the suspected medication and avoidance of drugs of similar structure, particularly among members of the aromatic group.