ENHANCED DIFFERENTIAL-DIAGNOSIS OF ANTICONVULSANT HYPERSENSITIVITY REACTIONS BY AN INTEGRATED BAYESIAN AND BIOCHEMICAL APPROACH

Objective: The differential diagnosis of hypersensitivity reactions as sociated with anticonvulsants requires accuracy because of the many im plications for patient management. We tested an integrated Bayesian an d biochemical diagnostic approach. Methods: The patients were analyzed clinically by two tests. One test, the Bayesian Adverse Reaction Diag nostic Instrument (BARDI), calculates the posterior probability of a d rug being the cause based on epidemiologic and case data. The other, t he lymphocyte toxicity assay, is an in vitro rechallenge that determin es the percentage of cell death attributable to a drug's toxic metabol ites. The setting for the study was an adverse drug reaction clinic at Sunnybrook Health Science Centre and the Hospital for Sick Children, Toronto, Ontario, Canada. Fifty-one patients who had hypersensitivity reactions after receiving aromatic anticonvulsants were tested. Pour o f these patients had more than one reaction reported, with different a nticonvulsants generating 56 distinct events.Results: Compared to the lymphocyte toxicity assay, BARDI had 94% sensitivity, 93% accuracy, an d 50% specificity. When lymphocyte toxicity assay data were incorporat ed into BARDI, agreement rose from 93% to 100%. BARDI also identified which drug was a more likely cause for 11 patients receiving multiple anticonvulsants. Conclusion: These findings show that BARDI and the ly mphocyte toxicity assay have high concordance and, when used in an int egrated approach, these tests can improve the diagnostic accuracy and enhance the management of patients with hypersensitivity reactions.