HYPERSENSITIVITY SYNDROME TO ANTICONVULSANTS ASSOCIATED WITH REACTIVATION OF EPSTEIN-BARR-VIRAL INFECTION

Abstract

SUMMARY. Hypersensitivity syndrome to anticonvulsants is a dangerous reaction caused by taking aromatic anticonvulsants, namely: phenytoin, carbamazepine, phenobarbital. Clinical signs include rash, fever, lymphadenopathy, internal organ involvement (hepatitis, carditis, internal nephritis or interstitial pneumonitis), and hematological abnormalities such as leukocytosis with eosinophilia or atypical lymphocytosis. The syndrome occurs after prolonged exposure to anticonvulsants on the body.

The aim is to establish the regularity of the anticonvulsant drug side effects on the patients’ body present with latent human HHV-4 infection (Epstein-Barr virus). To evaluate the importance of applying an alternative treatment plan for patients, which limits the use of aromatic anticonvulsants by doctors due to herpes virus latent infection.

Patients and methods: analysis of clinical cases, articles and cohort studies related to the confirmation of the trigger action of anticonvulsants as factors in human HHV-4 (Epstein-Barr) reactivation.

Results and discussion. A genetic deficiency of detoxifying enzymes such as epoxide hydrolase, which leads to the accumulation of toxic metabolites, or a virus-drug interaction, as seen in the cases of human immunodeficiency virus and human herpesvirus, are thought to be possible causes of ADS. Aromatic anticonvulsants are metabolized by cytochrome P-450 to intermediate metabolites such as arene oxides. If metabolic defects are present, these toxic metabolites can cause cell necrosis or apoptosis and induce secondary immunological responses. The clinical case described below characterizes the symptoms of the syndrome, diagnostic criteria and confirms the feasibility of treating the syndrome with glucocorticosteroids. The HLA-A-3101 genetic allele has been shown to be associated with carbamazepine-induced skin reactions in patients with anticonvulsant hypersensitivity syndrome.

Conclusions. Arenoxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may participate in the pathogenesis of hypersensitivity reactions and reactivation of latent HHV-4. Cross-reactivity among major anticonvulsants is common and should be considered before deciding on alternative therapy. Considering the high level of HLA-A-3101 carriers worldwide, increasing the awareness of health professionals about anticonvulsant hypersensitivity syndrome is important to reduce the percentage of clinical reactivation of latent human HHV-4 (Epstein-Barr) and prevent possible serious complications.