Immunological Adverse Effects of Anticonvulsants

Abstract

Long term administration of anticonvulsants is sometimes associated with impairment of the humoral and/or cellular immune response. Furthermore, certain well known adverse reactions to antiepileptics may have an immunotoxicological origin e.g. lymphadenopathy, pseudolymphoma and systemic lupus erythematosus. However, two important questions remain unresolved. First, the possibility that epilepsy per se might be primarily associated with immune alterations makes it difficult to assess the pathogenetic role of a specific drug, especially in a patient population usually on multiple drug therapy. Secondly, the clinical relevance of some of the observed immunological abnormalities is still highly controversial. This review is intended to give an outline of the present state of knowledge on the effects of anticonvulsants on humoral, cellular and nonspecific immunity, with particular regard to some of the major clinical conditions that have been ascribed to drug-induced immune dysregulation, such as pseudolymphoma and systemic autoimmune diseases. The immunotoxic potential of anticonvulsants appears to be low, and immunological monitoring is not usually required except in patients with known immune defects.

Epilepsy: an autoimmune disease?

“…However, epilepsy itself and antiepileptic drugs are reported to alter immune responses45 46 57 and it is not clear which autoantibodies arise as a consequence and which are causative. Furthermore the mechanisms of action of the putative pathogenic antibodies are not well understood.…”

Autoimmunity and inflammation in status epilepticus: from concepts to therapies

“…The modulation of various 'classic' AEDs of the humoral and cellular immune system has been investigated in an important number of studies [21][22][23][24][25]. De Sarro and colleagues, for example, showed in 1998 that the chronic use of carbamazepine (CBZ), phenobarbital, phenytoin, valproic acid (VPA) or clobazam, alone or in various combinations, was associated with a decrease in IgA, IgG or IgM serum levels and an increase in TNF-a or IL-2 receptor in some of their patients [25].…”

Anticardiolipin, glutamic acid decarboxylase, and antinuclear antibodies in epileptic patients

“…Immunoglobulin A (IgA) deficiency has been detected in up to 25% of patients with epilepsy, and imbalance of other immunoglobulin subclasses also occurs [4]. These changes have, however, been traditionally associated with either antiepileptic drug exposure (e.g., phenytoin), autoimmune diseases, or recurrent infections [4][5][6]. More recently, serum antiphospholipid antibodies have been observed in 19%-26% of adult [7][8][9] and pediatric [10][11][12] patients with both chronic epilepsy and newly diagnosed seizure disorders.…”