Diagnosis of immediate-type ß-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production: A multicenter study

Introduction: This multicenter study aimed to evaluate the diagnostic value of 2 cellular tests based on basophil reactivity-the basophil activation test (BAT, Flow-CAST) and the sulfidoleukotriene release assay (CAST-ELISA)-in immediate-type 6-lactam allergy, particularly in patients with a clinical history of allergy and a negative skin test result. Material and Methods: In a multicenter study encompassing 10 European centers, 181 patients with a history of immediate-type ß-lactam allergy, and 81 controls, we evaluated the diagnostic efficiency of specific IgE determinations and of 2 cellular tests based on basophil reactivity, the BAT and the sulfidoleukotriene release assay. Results: With Flow-CAST, sensitivity varied for individual ß-lactam allergens from 16% for penicilloyl-polylysine to 33% for amoxicillin, reaching 50% when all 5 allergens were considered. In ß-lactam-allergic patients with negative skin test results (22.8%), Flow-CAST showed positive results for at least 1 of the 5 allergens in 37%. Specificity varied from 89% to 97%, depending on the allergens used. In CAST-ELISA, the overall sensitivity in skin test-positive patients was 41.7%; in patients with negative skin test results it was 27.9%. Both tests were not absolutely correlated, so that when all the results were considered together, sensitivity increased to 64.3% and specificity varied for both tests combined from 73% to 92%. In contrast, specific IgE determinations in the same population yielded a lower sensitivity (28.3%). Conclusions: A diagnostic algorithm including skin tests and specific IgE, followed by cellular tests in negative patients and controlled challenge enabled us to confirm ß-lactam allergy in 92% of cases. This procedure would also allow us to avoid two-thirds of the required controlled challenges.