The following are key points to remember from a state-of-the-art review on aspirin hypersensitivity. This guide offers a practical approach to distinguishing and managing different types of aspirin reactions and highlights the role of interdisciplinary collaboration:

1. Aspirin is a cornerstone of therapy for many cardiovascular disease states, particularly coronary artery disease (CAD), and exerts anti-inflammatory effects by inhibition of cyclooxygenase (COX)-2 and antiplatelet effects through inhibition of COX-1. Aspirin hypersensitivity has an estimated prevalence of 0.6-2.5% in the general population.
2. A careful medical history reviewing the symptoms associated with a reported aspirin allergy are essential, as correct classification of the reaction is used to determine management and prevent unnecessary aspirin avoidance. Aspirin reactions range from hypersensitivity either pharmacological or immunological, intolerance, and rare reactions.
3. Cross-reactive or pharmacological reactions can result in aspirin or nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (AERD/NERD) characterized by the respiratory triad of rhinitis, nasal polyps, and asthma as well as cutaneous disease (NECD), urticaria or angioedema (NIUA), or anaphylaxis. Reaction may be triggered by chemically unrelated NSAIDs and is mediated by COX-1 induced downstream overproduction of leukotrienes, which leads to vasoconstriction, bronchoconstriction, and pro-inflammatory effects. Desensitization is recommended for patients experiencing NERD, less effective for those with urticaria, and not recommended for patients with severe anaphylaxis.
4. Selective or immunological reactions can result in immediate or delayed symptoms including asthma, urticaria, angioedema, anaphylaxis, or maculopapular exanthemas. Reaction may be triggered by NSAIDs in the same chemical group and this immune system response is mediated by immunoglobulin E (IgE) for Type I hypersensitivity reactions or T cells in the delayed Type IV reaction. Desensitization can be performed for asthma, urticaria, or angioedema; however, it is not recommended for severe anaphylaxis or delayed reactions.
5. Type I hypersensitivity includes single NSAID-induced urticaria, angioedema, and anaphylaxis (SNIUAA), which may range from mild to severe and occurs within 1 hour of NSAID administration after a previous exposure. This IgE response is mediated by histamine, which results in vasodilation, bronchial and smooth muscle contraction, glandular secretion, and pruritus within minutes. Single NSAID-induced delayed hypersensitivity reaction (SNIDHR) may occur within several hours to days after re-exposure and results in T cell and other immune cell activation resulting in inflammation and/or cell lysis.
6. Intolerance or pseudo-allergy may be reported as dyspepsia or gastrointestinal bleeding. The mechanism of this reaction is through COX-1 induced hypoproduction of prostaglandins or may be psychosomatic. Desensitization is not needed, although a proton pump inhibitor or aspirin dose reduction can be considered.
7. Rare reactions to aspirin include aseptic meningitis, Stevens-Johnson syndrome, and erythema multiforme. These may be selective for specific NSAIDs with a variable and typically idiopathic reaction mechanism. Desensitization is not recommended.
8. Proposed desensitization protocols vary; however, most involve administering increasing doses of aspirin over a time period (typically hours ranging to days) with or without pretreatment with agents such as antihistamines, antileukotrienes, and corticosteroids. Response is evaluated by measuring vitals, symptoms, and/or spirometry. Symptomatic treatment should be provided if a reaction is observed. Success of various desensitization procedures with protocols ranging from 1 to 5.5 hours has been reported as 87.5% to 100%. Aspirin tolerance is only achieved for the dose reached during the successful desensitization procedure.
9. For the nonacute setting, patients with CAD and suspected true aspirin hypersensitivity should undergo a desensitization protocol after consult with an allergist/immunologist. For nonemergent percutaneous coronary intervention (PCI), aspirin desensitization is recommended prior to coronary angiography. For patients requiring an emergent PCI, angiography and/or PCI should be performed with a P2Y12 inhibitor and/or glycoprotein IIb/IIIa inhibitor with aspirin desensitization started immediately after the procedure.
10. An interdisciplinary approach promoting collaboration between cardiologists, immunologists/allergists, and other members of the care team is recommended when possible. Counseling and follow-up are critical to ensure uninterrupted continuation of aspirin, as cessation would increase prothrombotic risk and require another desensitization.

Clinical Topics: Cardiovascular Care Team, Prevention

Keywords: Aspirin, Hypersensitivity

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