Anticonvulsant hypersensitivity syndrome: a review.
Anticonvulsant hypersensitivity syndrome (AHS), characterised by fever, rash and internal organ involvement, is a rare, but potentially fatal adverse event that occurs most commonly with first-line aromatic anticonvulsants, but can also occur with non-aromatic anticonvulsants such as lamotrigine and valproic acid. AHS can begin anywhere from 1 to 12 weeks after commencement of therapy and has been estimated to occur at a frequency of 1/1000 to 1/10,000 exposures. Its true incidence, however, remains unknown due to under-reporting. The disease has protean manifestations mimicking several other conditions, and the diagnosis is thus difficult. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, graft versus host disease, antibody production and viral infections. The one based on toxic metabolites has found the greatest acceptance, perhaps due to the fact that it can be proven by an in vitro test; the lymphocyte toxicity assay. Discontinuation of the offending agent with supportive, symptomatic therapy forms the mainstay of management of AHS. In addition, counselling of both the patient and first degree relatives for susceptibility to AHS is an important aspect of management. In the last decade, several new anticonvulsants have been introduced for epilepsy. In addition, for resource-poor countries, inexpensive and effective first-line drugs such as phenytoin and phenobarbitone will continue to remain important treatment options. Thus, the problem of AHS will continue, and attempts should be made to further understand the molecular basis of and individual susceptibility to AHS. Adverse event monitoring programs must also actively seek AHS reports to estimate its true incidence.
Gogtay
Nithya J
NJ
Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel, Mumbai 400 012, India. njgogtay@hotmail.com
Bavdekar
Sandeep B
SB
Kshirsagar
Nilima A
NA
D000927:Anticonvulsants / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000503:physiopathology; D004827:Epilepsy / Q000188:drug therapy; D020022:Genetic Predisposition to Disease; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D013577:Syndrome; D013997:Time Factors
D000927:Anticonvulsants