Can Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) cause angioedema?

From the Guidelines

NSAIDs can cause angioedema, a potentially life-threatening condition that requires immediate medical attention. According to the most recent study published in the Journal of Allergy and Clinical Immunology in 2022 1, single NSAID-induced urticaria, angioedema, and anaphylaxis can occur, and the underlying etiology of these reactions is not fully understood. The study suggests that any NSAID, including selective COX-2 inhibitors, may be responsible for this reaction.

Key Points to Consider

• The risk of angioedema from NSAIDs varies among individuals, but those with a history of allergic reactions to NSAIDs are at higher risk 1.
• Angioedema from NSAIDs typically develops within minutes to hours after taking the medication.
• Some people may experience cross-reactivity between different NSAIDs, making it essential to determine the culprit NSAID in single NSAID reactors 1.
• Management of single NSAID reactors is contingent on determining the culprit NSAID, and challenge to NSAIDs in a different structural class would provide options for as-needed pain control 1.

Recommendations

• If you develop swelling of the face, lips, tongue, or throat after taking an NSAID, seek immediate medical attention as severe angioedema can compromise breathing.
• For those with known NSAID sensitivity, acetaminophen (Tylenol) may be a safer alternative for pain relief, though you should always consult with a healthcare provider before switching medications.
• Direct aspirin challenges should be performed to allow future aspirin use, and skin testing is generally not recommended in the evaluation of single NSAID reactors due to the lack of parenteral forms of most NSAIDs and unknown positive predictive value (PPV) and negative predictive value (NPV) 1.

From the Research

NSAIDs and Angioedema

• Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with numerous adverse drug reactions, including angioedema 2, 3, 4.
• Angioedema induced by NSAIDs can be life-threatening and is often due to increased leukotriene production from COX pathway inhibition 2.
• The pathogenesis of NSAID-induced angioedema involves mast cells and basophil degranulation, and its clinical presentation can include facial (periorbital) angioedema and respiratory symptoms 3.
• The prevalence of NSAID-induced urticaria and angioedema ranges from 0.1-0.3%, and some predisposing factors have been identified, such as atopic diathesis, female sex, and young adulthood 3.

Diagnosis and Management

• Diagnosis of NSAID-induced angioedema can be confirmed by controlled peroral drug challenges, and management involves strict avoidance of the culprit drug and the use of alternative tolerated medications 3.
• Prompt recognition and immediate cessation of the NSAID, along with the administration of corticosteroids and antihistamines, are essential in treating angioedema caused by NSAIDs 2.
• The classification and diagnosis of angioedema exacerbated or induced by NSAIDs are critical for its management, and the pathophysiology and pharmacogenetics of angioedema have been reviewed in the literature 4.

Other Considerations

• While angioedema is a known adverse effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the focus of the question is on NSAIDs, and therefore, ACEIs and ARBs are not directly relevant to this discussion 5.
• The use of NSAIDs is associated with an increased risk of adverse cardiovascular events, and their use should be optimized by using the lowest effective dose for the shortest amount of time, especially among individuals with increased cardiovascular risk 6.