Cysteinyl‐leukotriene release test (CAST) in the diagnosis of immediate drug reactions

Background: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross‐linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys‐LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy. Methods: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to β‐lactams, six to acetaminophen, and 19 to aspirin) and 64 drug‐exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys‐LT release was determined after drug‐allergen stimulation by the cellular antigen stimulation test (CAST®) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti‐FcεRIα‐induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated. Results: Net Cys‐LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low. Conclusions: Thus, in most cases, the in vitro Cys‐LT test has little or no diagnostic utility and is not superior to histamine release.