Anticonvulsant hypersensitivity syndrome - Incidence, prevention and management

Although the anticonvulsant hypersensitivity syndrome was first described i n 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1000 to 10 000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (pheno barbitone) and carbamazepine] are the most frequently involved drugs; howev er, there have also been several cases of anticonvulsant hypersensitivity s yndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign . This is followed by a rash which can range from a simple exanthem to toxi c epidermal necrolysis. Internal organ involvement usually involves the liv er, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 mon ths after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compo unds, such as arene oxides. If detoxification of this toxic metabolite is i nsufficient, the: toxic metabolite may bind to cellular macromolecules caus ing cell necrosis or a secondary immunological response. Cross-reactivity a mong the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimu m battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticoster oids are usually administered if symptoms are severe. Patients with anticon vulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants ; valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic acid should be used very cau tiously in the presence of hepatitis. There is no evidence that lamotrigine crossreacts with aromatic anticonvulsants. In addition, family counselling is a vital component of patient management.