Selective NSAID Induced Urticaria and Anaphylaxis

Selective NSAID-induced urticaria and anaphylaxis is an IgE-mediated allergy to a single NSAID (or a chemically related group), with tolerance of other NSAIDs. It differs from cross-reactive NSAID hypersensitivity, which involves all COX-1 inhibitors.

Pathophysiology. A specific IgE antibody binds one drug or its metabolite and causes mast cell activation. Pyrazolones (metamizole, propyphenazone), ibuprofen, naproxen, diclofenac and paracetamol are the usual culprits.

The reaction recurs on re-exposure to the same drug, but not to structurally different NSAIDs or to aspirin.

Onset is within minutes to 1 hour. Patients may have atopy, and reactions may be severe.

• Urticaria, angio oedema, flushing within 1 hour of one NSAID
• Wheeze, throat tightness, hypotension, anaphylaxis
• Reactions on every exposure to the same drug
• Tolerance of aspirin and unrelated NSAIDs
• No underlying chronic urticaria or asthma tied to NSAID intake
• Cofactors in some: exercise, alcohol, infection

• History: the drug, timing, features, repeat reactions, and tolerance of other NSAIDs.
• Skin prick and intradermal tests with the culprit (metamizole, propyphenazone, paracetamol) are positive in some, and specific IgE is available for few drugs.
• Basophil activation test where available.
• Serum tryptase after a reaction.
• Oral challenge with the culprit (to confirm), and with an alternative NSAID (to find a safe one), in a monitored setting with graded doses (for example ibuprofen 50 mg, 100 mg, 200 mg and 400 mg at 60 minute intervals).
• Distinguish from cross-reactive hypersensitivity by challenge with aspirin: no reaction means selective disease.

Differential diagnosis.

• NSAID-exacerbated cutaneous disease (chronic urticaria)
• Cross-reactive NSAID-induced urticaria and angio oedema in people without chronic urticaria
• NSAID-exacerbated respiratory disease
• Food dependent and exercise induced anaphylaxis with NSAID as a cofactor
• Idiopathic anaphylaxis
• Reaction to a drug excipient or co-administered drug

• Avoid the culprit drug and structurally related drugs (for example other pyrazolones, or other propionic acids if ibuprofen is the culprit).
• Safe alternatives confirmed by challenge: aspirin, a structurally unrelated NSAID, celecoxib 100 to 200 mg orally twice daily (maximum 400 mg daily), or paracetamol 1 g orally up to four times daily (maximum 4 g daily; 3 g daily if under 50 kg or hepatic impairment).
• Anaphylaxis: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen and intravenous fluids, and observation for at least 6 hours.
• Adrenaline auto injector after anaphylaxis: 150 microgram for 7.5 to 25 kg, 300 microgram for 25 to 50 kg, 500 microgram for over 50 kg, with a written action plan and training.
• Mild reactions: cetirizine 10 mg orally once daily in adults (children 1 to 5 years 2.5 mg twice daily; 6 to 11 years 5 mg twice daily).
• Medical alert naming the culprit and tolerated alternatives.

Special groups.

• Children with ibuprofen reaction: confirm by challenge, since many are not allergic and need an alternative analgesic.

Monitoring. Observation for 1 to 2 hours after challenge. Review yearly. Update the allergy record with tolerated drugs.

Referral and escalation. Refer to allergy for any NSAID reaction with systemic features. Emergency for anaphylaxis.