Anticonvulsant-induced cutaneous reactions - Incidence, mechanisms and management

Management of patients receiving anticonvulsant drugs is often a matter of balancing medication efficacy against untoward effects. Cutaneous drug reac tions (CDRs! to anticonvulsants are a widely recognised idiosyncratic effec t, In spite of almost 60 years' experience with phenytoin and greater than 80 years' experience with phenobarbital (phenobarbitone), anticonvulsant-in duced CDRs remain one of the most difficult challenges in optimising the ca re of patients with epilepsy and mood disorders. Epidemiological evaluation is complicated by lack of consensus on reporting and systematic classification of these reactions. Many clinicians choose t o discontinue a suspected agent at the first sign of a skin eruption, witho ut confirmation. Time-honoured catalogues are useful for identification of common skin reactions. Broad classification of CDR as mild vs severe reacti ons seems to aid the clinician in managing the patient. Both immunological and non-immunological factors contribute to CDRs. Immuno logical mechanisms consist of 4 types (types I through IV reactions). The m ost serious eruptions result from a type I or type IV immunological process . Non-immunological mechanisms have great variability, but are believed to include activation of effector pathways, as well as the alteration of pharm acodynamic and pharmacokinetic variables. Epidemiological data suggest that nonimmunological CDRs are more predominant and largely reflect the inciden ce of mild CDRs. While there is general agreement about discontinuation of suspected agents, issues pertaining to rechallenge and management of seven life-threatening reactions remain controversial. Of the new anticonvulsants, lamotrigine has received much attention following CDR reports. While rare severe CDRs with lamotrigine have been reported, the drug has been successfully reintroduce d without precipitation of CDRs. Severe CDRs require the successful management of fluids, nutrition and infe ction, and can be best managed in burn centres. Fluid and nutrition balance an typically well controlled with close monitoring of hydration and labora tory values. Prophylactic antibacterial administration is not recommended. Immunosuppressive therapy with corticosteroids to limit the extent of CDRs has received much attention. General recommendations from burn centres sugg est this approach may actually promote a negative patient outcome.