Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity

Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be cofactors for other clinically relevant conditions, especially food-dependent exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is required for the correct diagnosis, classification, and treatment of affected patients.