Samter's Tiad

Samter’s triad, now more commonly called aspirin-exacerbated respiratory disease (AERD) or NSAID-exacerbated respiratory disease (N-ERD), is a chronic inflammatory respiratory disorder characterised by:

• 🫁 Asthma
• 👃 Chronic rhinosinusitis with recurrent nasal polyps
• 💊 Respiratory reactions following aspirin or other cyclo-oxygenase-1 (COX-1) inhibiting NSAIDs

The condition usually begins in adulthood. Persistent rhinosinusitis, loss of smell and recurrent nasal polyps often develop before asthma or NSAID sensitivity becomes apparent.

🧬 Pathophysiology

Samter’s triad is not usually an IgE-mediated drug allergy. Aspirin and non-selective NSAIDs inhibit COX-1, reducing production of protective prostaglandin E₂. Arachidonic acid metabolism is consequently diverted towards excessive production of cysteinyl leukotrienes.

Leukotrienes cause:

• Bronchoconstriction
• Nasal and bronchial mucosal oedema
• Eosinophilic inflammation
• Mucus production
• Recurrent nasal polyp formation

🤧 Clinical Features

• Persistent nasal obstruction and rhinorrhoea
• Reduced or absent sense of smell
• Recurrent nasal polyps despite previous surgery
• Adult-onset asthma
• Difficult-to-control asthma
• Wheeze, cough or chest tightness after aspirin or an NSAID
• Facial flushing or conjunctival irritation during a reaction

Symptoms usually occur within minutes to a few hours after taking a non-selective NSAID such as aspirin, ibuprofen, naproxen or diclofenac. Reactions may range from severe nasal congestion to marked bronchospasm and an acute asthma exacerbation.

🩺 Diagnosis

The diagnosis is usually clinical when the characteristic triad is present together with a convincing history of respiratory reactions to aspirin or NSAIDs.

There is no useful routine skin-prick test or serum-specific IgE test because the reaction is pharmacological rather than a conventional allergic response.

When the history is unclear, a supervised aspirin challenge may confirm the diagnosis. This must only be undertaken in a specialist setting because significant bronchospasm may occur.

💊 Management

• 🚫 Avoid aspirin and other non-selective COX-1 inhibiting NSAIDs.
• 🫁 Treat asthma with inhaled corticosteroids and additional controller therapy where required.
• 👃 Use intranasal corticosteroids and saline nasal irrigation for chronic rhinosinusitis.
• 💠 Consider a leukotriene receptor antagonist such as montelukast.
• 🏥 Refer to ENT for severe or recurrent nasal polyposis.
• 🔬 Consider respiratory, allergy or specialist rhinology referral in severe disease.
• 🧪 Consider biological therapy for severe type-2 asthma or chronic rhinosinusitis with nasal polyps.

🔄 Aspirin Desensitisation

Aspirin desensitisation involves giving gradually increasing doses of aspirin under specialist supervision. Once desensitisation has been achieved, aspirin must usually be taken continuously to maintain tolerance.

It may be considered when aspirin is medically necessary, or when severe asthma and recurrent nasal polyposis persist despite conventional treatment.

💉 Analgesia

Paracetamol is usually better tolerated, although high doses may occasionally provoke symptoms in very sensitive patients.

Selective COX-2 inhibitors, such as celecoxib, are generally better tolerated because they have little effect on COX-1. However, the first dose may need specialist supervision in patients with a history of severe reactions.

🧑‍⚕️ Case Example 1

A 42-year-old woman has adult-onset asthma, persistent nasal blockage and anosmia. She has undergone two previous operations for recurrent nasal polyps. Thirty minutes after taking ibuprofen for back pain, she develops severe nasal congestion, wheeze and chest tightness.

Diagnosis: Samter’s triad.

Reasoning: She has asthma, recurrent nasal polyposis and an acute respiratory reaction to a COX-1 inhibiting NSAID.

🧑‍⚕️ Case Example 2

A 55-year-old man with asthma and chronic rhinosinusitis takes aspirin for a headache. Within one hour, he develops facial flushing, rhinorrhoea, wheeze and a fall in peak expiratory flow. Skin-prick testing to aspirin is negative.

Diagnosis: Aspirin-exacerbated respiratory disease.

Reasoning: A negative skin-prick test does not exclude the condition because the reaction is not usually IgE-mediated.

🧑‍⚕️ Case Example 3

A 48-year-old woman with severe asthma and recurrent nasal polyps requires analgesia for osteoarthritis. She previously developed bronchospasm after naproxen.

Management: Avoid non-selective NSAIDs. Paracetamol may be used cautiously, and a selective COX-2 inhibitor may be considered following specialist advice. Her asthma and nasal disease should also be optimised.

⚠️ Clinical Pearl

Do not describe Samter’s triad simply as an “aspirin allergy”. It is a cross-reactive intolerance caused by COX-1 inhibition, so patients may react to several chemically unrelated NSAIDs.

⭐ Key Point

Suspect Samter’s triad in an adult with asthma, recurrent nasal polyps and deterioration after aspirin or another NSAID. The underlying mechanism is excessive leukotriene production following COX-1 inhibition rather than conventional IgE-mediated allergy.