Blended reactions and angioedema are common in patients with cross-reactive nonsteroidal anti-inflammatory drug hypersensitivity

Background: The European Academy of Allergology and Clinical Immunology (EAACI)/The Global Allergy and Asthma European Network (GA²LEN) guidelines recognize 3 phenotypes of cross-reactive nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (NHS): NSAID-induced urticaria/angioedema (NIUA), NSAID-exacerbated cutaneous disease (NECD), and NSAID-exacerbated respiratory disease (NERD). However, numerous cases cannot be neatly classified into any of these groups. Objective: This study investigated the phenotypes of cross-reactive NHS in Vietnamese patients. Methods: Our retrospective study of 141 patients with cross-reactive NHS was conducted at the Allergy and Clinical Immunology Unit, University Medical Center Ho Chi Minh City, Vietnam. Patients were diagnosed with cross-reactive NHS if they had 3 or more reactions involving 3 or more different NSAIDs. Patients with an unclear history underwent single-blind oral challenge tests with aspirin to diagnose cross-reactive NHS. Reactions that did not align with any of the 3 standard phenotypes were defined as blended reactions (BRs). Results: Among the 125 patients with cross-reactive NHS who exhibited cutaneous symptoms, 113 (90.4%) had angioedema with or without wheals and 12 (9.6%) had isolated wheals. However, the most common phenotype according to the EAACI classification was NIUA (66/141, 46.8%), followed by NECD (8/141, 5.7%) and NERD (4/141, 2.8%). BRs were determined in 63 patients (44.7%). The most common causative drug was paracetamol (63.8%). The alternative NSAIDs tolerated by most of the patients were etoricoxib (97.2%), celecoxib (95.9%), and meloxicam (94.3%). Conclusions: BRs are a common phenotype in patients with cross-reactive NHS. Angioedema, with or without wheals, is an important clinical manifestation suggesting a cross-reactive NHS response. Highly selective COX-2 inhibitors are likely to be tolerated by most patients with cross-reactive NHS.