Predictive value of the lymphocyte toxicity assay in the diagnosis of drug hypersensitivity syndrome

Abstract

Background: Drug hypersensitivity syndrome (DHS) is a rare but potentially fatal adverse drug reaction that develops in susceptible patients following exposure to certain drugs. Because of the variable clinical picture of DHS and its resemblance to other diseases, the diagnosis of DHS is challenging. The lymphocyte toxicity assay (LTA) is an in vitro test that has been used in the diagnosis of DHS. However, its predictive values are still controversial because of the lack of a 'gold standard' test to measure it against.

Objectives: To determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the LTA in the diagnosis of DHS due to different classes of drugs, based on systemic re-exposure as a gold standard, and to evaluate the current clinical utility of the LTA in clinical practice.

Methods: Potential participants were identified from their medical records and contacted to obtain their consent to participate in the study. One hundred forty-seven patients were recruited and interviewed by telephone to identify events of re-exposure and their consequences. These data were used to determine true positive, false positive, true negative, and false negative results of the test, which were then used to estimate the predictive value of the test.

Results: We identified 26 re-exposure events in 22 patients: 4 were true positives, 17 were true negatives, 1 was a false positive, and 4 were false negatives, as determined by systemic re-exposure. Although the number of identified re-exposures limited the ability to calculate the predictive values, our data provide an estimate of the clinical value of the test for the diagnosis of DHS. The data also highlight the effect of the type of drug involved in the reaction on the predictive value of the test.

Conclusion: The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.