Aspirin-Exacerbated Respiratory Disease (AERD)

What AERD is

AERD is not an allergy in the usual sense. People with AERD have an imbalance in how their bodies process arachidonic acid, a fat used to make inflammatory signaling molecules. They overproduce leukotrienes, which inflame the airways, and underproduce protective prostaglandin E2. Aspirin and NSAIDs that block the COX-1 enzyme reduce prostaglandin E2 further, releasing the brake on leukotriene production and on mast cells. This triggers a surge of inflammation in the nose and lungs.

The disease continues even if NSAIDs are avoided: polyps and asthma persist, because the underlying inflammation is always present.

Symptoms

Ongoing symptoms

• chronic nasal congestion and a runny nose
• recurring nasal polyps, often needing repeated surgery
• reduced or lost sense of smell (anosmia)
• chronic sinusitis with facial pressure and repeated infections
• asthma, often moderate to severe, frequently starting in the 20s to 40s

Reactions to NSAIDs

Within 30 minutes to 3 hours of taking aspirin, ibuprofen, naproxen or similar drugs:

• sudden worsening of nasal congestion and runny nose
• watery, red eyes
• flushing of the face and chest
• wheezing, coughing, chest tightness and breathlessness
• sometimes hives, stomach pain or nausea

Reactions can be severe and life-threatening, and are sometimes mistaken for anaphylaxis.

Other features

• about 3 in 4 people with AERD react to alcohol with nasal congestion or wheezing
• a history of severe asthma attacks needing emergency care or steroid courses

Typical progression

AERD usually develops in adulthood, around age 30 on average, often after a bad cold. A common sequence is persistent nasal congestion and loss of smell, followed by asthma, then nasal polyps, and then the recognition of NSAID reactions. It is not usually inherited and is slightly more common in women.

Diagnosis

There is no blood test for AERD. Diagnosis is based on:

1. History: asthma, nasal polyps and a clear reaction to aspirin or an NSAID. Two or more reactions make the diagnosis likely.
2. Nasal examination and CT of the sinuses: show polyps and sinus disease.
3. Blood tests: a raised eosinophil count is common.
4. Aspirin challenge: gradually increasing doses of aspirin given under close supervision in a specialist clinic or hospital. It confirms the diagnosis when the history is unclear, and is often combined with desensitization.

Treatment

Avoiding NSAIDs (or desensitizing)

Without desensitization, avoid all COX-1 inhibiting NSAIDs:

Check labels of combination products, which often contain aspirin or ibuprofen. Wear a medical alert bracelet.

Aspirin desensitization and daily aspirin

Under specialist supervision, aspirin is given in gradually increasing doses over 1 to 2 days until the body tolerates it. Taking aspirin every day afterward reduces polyp regrowth, improves smell and sinus symptoms, lowers the need for steroids and surgery, and lets people safely take NSAIDs. It is often done a few weeks after polyp surgery. Daily aspirin can cause stomach irritation and bleeding, and the daily dose must not be missed for more than a day or two, or desensitization is lost.

Asthma treatment

Inhaled corticosteroids and long-acting bronchodilators, as in other asthma. Leukotriene modifiers such as montelukast or zileuton are particularly useful in AERD.

Nasal and sinus treatment

• steroid nasal sprays or rinses
• saline irrigation
• short courses of oral steroids for flares
• endoscopic sinus surgery to remove nasal polyps and open the sinuses; polyps commonly return without additional treatment

Biologic medicines

Biologics that target type 2 inflammation, such as dupilumab, mepolizumab or omalizumab, reduce polyp size, improve smell and asthma control, and are often used when polyps keep returning. Some people with AERD have dramatic responses to these treatments.

Diet and alcohol

Some studies suggest a low omega-6, high omega-3 diet may reduce symptoms. Avoid alcohol if it triggers reactions.

Outlook

AERD is lifelong, but with modern treatments most people achieve good control of asthma and sinus symptoms. Combining surgery with aspirin therapy or biologics greatly reduces polyp recurrence and the need for repeat operations.

Frequently asked questions

What is Samter's triad?

Samter's triad is another name for aspirin-exacerbated respiratory disease. The triad is asthma, chronic sinusitis with nasal polyps, and reactions to aspirin and other NSAIDs. Reactions cause congestion and wheezing, sometimes severe, within a few hours of taking the drug.

What pain relievers are safe with AERD?

Acetaminophen (paracetamol) is usually safe at standard doses. Celecoxib, a COX-2 selective NSAID, is usually tolerated, ideally tried first under medical supervision. Aspirin, ibuprofen, naproxen and most other NSAIDs should be avoided unless you have been desensitized.

What is aspirin desensitization?

It is a supervised procedure in which aspirin is given in gradually increasing doses until your body tolerates it without reacting. You then take aspirin every day, which reduces polyp regrowth and improves sinus and asthma symptoms. It must be continued daily to stay effective.

Is AERD an allergy?

No. AERD is not an IgE-mediated allergy. It is caused by an abnormality in how the body produces inflammatory chemicals. NSAIDs that block the COX-1 enzyme tip this balance and cause reactions. Allergy skin tests do not diagnose it.

Can AERD go away?

AERD does not go away on its own and usually persists for life, even if NSAIDs are avoided. However, it can be well controlled with medicines, surgery, aspirin desensitization and biologic treatments.