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 pr ovocation tests. Cross-linking of IgE on basophils is known to cause the re lease of both cysteinyl leukotriene (Cys-LT) and histamine. We aimed to eva luate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfoleukotrienes in drug allergy. Methods: We performed a prospective study in 55 patients with proven immedi ate adverse reactions to drugs (30 to beta -lactams, six to acetaminophen, and 19 to aspirin) and 64 drug-exposed nonallergic controls. Positive diagn osis was established by history, skin tests, and, if needed, oral provocati on tests. Cys-LT release was determined after drug-allergen stimulation by the cellular antigen stimulation test (CAST(R)) technique. Histamine releas e was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti-Fc epsilon RI alpha -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 man ufacturer 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. T he 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.