Utility of basophil activation tests in the diagnosis of cross-intolerance to nonsteroidal anti-inflammatory drug reactions

Background: Nonsteroidal anti-inflammatory drugs (NSAID) are the second most frequent cause of drug-induced hypersensitivity after β-lactam antibiotics. Diagnosing cross-intolerance reactions to NSAIDs remains challenging because conventional allergy tests are not useful and drug provocation tests (DPT), the current criterion standard, are resource-intensive and carry risk of severe reactions. Basophil activation testing (BAT) has emerged as a potential ex vivo diagnostic alternative. Objective: This study aimed to evaluate the diagnostic utility of the BAT for cross-intolerance reactions to NSAIDs among Vietnamese patients, including the identification of optimal drug type, concentration, and cutoff values. Methods: This validation study used a case-control design that involved 38 patients previously diagnosed with cross-intolerance to NSAIDs and 34 healthy controls. The diagnosis of NSAID cross-intolerance was established according to the international consensus guidelines, based on a detailed clinical history and, when indicated, a DPT. Both groups underwent BAT by using two NSAIDs at two concentrations each: acetylsalicylic acid (ASA) at 1.25 mg/mL and 0.5 mg/mL, and ketorolac at 1.25 mg/mL and 0.5 mg/mL. Flow cytometric analysis was performed to assess basophil activation based on CD63 and CD203c expression. Results: ASA 1.25 mg/mL showed the best BAT diagnostic performance for cross-intolerance, achieving 55.3% sensitivity and 91.2% specificity by using cutoffs of ≥4% activated basophils and stimulation index (SI) ≥ 1.5. Conclusion: BAT demonstrates moderate sensitivity but high specificity for NSAID cross-intolerance, particularly when ASA is used as the stimulant. These findings support BAT as a complementary confirmatory tool in selected patients at high risk, although negative results do not exclude hypersensitivity and DPT remains necessary when diagnostic confirmation is required. Further validation in clinically relevant populations is needed before routine clinical implementation.