Cumulative 600-mg Aspirin Oral Provocation Testing in Skin-Predominant NSAID Hypersensitivity: A Retrospective Cohort...

Aspirin oral provocation testing (OPT) is the reference standard for cross-reactive nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, but cumulative dose and observation duration remain unstandardized in skin-predominant phenotypes.

To evaluate diagnostic yield, dose- and time-to-reaction kinetics, severity, and safety of cumulative 600-mg aspirin OPT in adults with skin-predominant immediate NSAID hypersensitivity.

Adults undergoing cumulative 600-mg aspirin OPT using a 3-step (100, 200, and 300 mg) or 2-step (200 and 400 mg) schedule at one center from 2021 to 2024 were retrospectively evaluated.

Among 122 patients, aspirin OPT positivity was 63.1% (77/122) overall and 70.6% (77/109) in suspected cross-reactive phenotypes: 89.5% in NSAID-exacerbated cutaneous disease, 66.7% in NSAID-induced urticaria, angioedema, or anaphylaxis, and 0% in single NSAID-induced reactions. Most reactions occurred at cumulative 600 mg (60/77, 77.9%). Median elapsed time from the first dose was 227 minutes (IQR, 130-240); 75/77 reactions (97.4%) occurred within 6 hours. Modified Ring and Messmer grades 1, 2, and 3 occurred in 48 (62.3%), 11 (14.3%), and 18 (23.4%) reactors. Six patients received epinephrine; none required transfer from the clinic to an emergency department. Severity distributions (P = .07) and epinephrine use (3-step, 4/38; 2-step, 2/39; P = .43) did not differ significantly between protocols.

Cumulative 600-mg aspirin OPT captured most positive reactions only after the final dose, with nearly all reactions occurring within 6 hours. Testing should be performed with monitoring and rescue capability appropriate to individual patient risk.