Valproic acid-induced pancreatitis in an adult.

Ribeirão Preto School of Medicine, University of São Paulo, São Paulo SP, Brazil: Physician Resident in Neurology, Department of Neurosciences and Behaviour Sciences; Neurologist and Associated Professor, Department of Neurosciences and Behaviour Sciences; Emergencist Physician, Departament of Internal Medicine. Idiosyncratic reactions to drugs are adverse effects not straightly related with pharmacodynamic mechanisms of the drug and they can take place on unpredictable way by abnormal interaction between the drug and the organism, usually mediated by immunologic or cytotoxic effects triggered by the drug or its metabolites. Even being responsible for 6-10 % of all the adverse reactions to drugs, the idiosyncratic effects can be important sources of morbidity and mortality, mainly in children. The anti-epileptic drugs (AED) also can cause adverse effects by these mechanisms, which impairs the seizure control and obliges the physician to use second line drugs. A study in epileptic patients showed that 10 to 27 % stopped their first treatment with AED on account of the adverse effects, being several of them idiosyncratic. Valproic acid (VPA) is a carboxylic acid used as anti-epileptic in idiopathic and symptomatic generalized epilepsies and in some cases of symptomatic focal epilepsies, as well as for trigeminal neuralgia, migraine and bipolar disorders. Its mechanism is unknown, however it is probably associated with the metabolism of the neurotransmitter GABA. The toxic effects it provokes can be dose-dependent or idiosyncratic. There are several VPA-related idiosyncrasies, being the most noteworthy alopecia, bone marrow aplasia, immune-mediated hepatotoxicity and pancreatitis. The acute pancreatitis is a disease of several etiologies, sometimes caused by use of determined drugs. The pancreatitis provoked by VPA is a rare entity, with estimated incidence of 1:40000, occurring mainly during the first year of treatment or after increase in the dose, with higher incidence in young individuals, in polytherapy (mainly with carbamazepine, phenytoin, phenobarbital and some benzodiazepines), with chronic encephalopathies and in dialysis treatment. The supposed pathogenic mechanism is by direct toxic effect of free radicals in the membranes of the pancreatic cells. The onset can be a slight asymptomatic hyperamylasemia up to a fatal necrohemorragic pancreatitis, and the mortality varies from 17 to 20%, with many complications in the non-lethal cases (pseudocysts, infections, septic shock, chronic pancreatitis, endocrine pancreatic insufficiency). The treatment is based on the immediate withdrawal of the drug, general clinical support and specific treatment of the possible complications. We present the case of a patient who, in less than 2 months of treatment with appropriate dose of VPA, evolved to pancreatitis.