Aspirin-induced asthma

Samter's triad
Aspirin in tablets
Classification and external resources
ICD-10	J45.1, J45.8
ICD-9	493.1
OMIM	208550
MeSH	D055963

Samter's triad is a medical condition consisting of asthma, aspirin and NSAID sensitivity, and nasal/ethmoidal polyposis.^[1] It usually begins in young adulthood^[2] (twenties and thirties are the most common onset times)^[3] and may not include any other allergies.

Signs and symptoms

Most commonly the first symptom is rhinitis (inflammation or irritation of the nasal mucosa), which can manifest as sneezing, runny nose, or congestion. The disorder typically progresses to asthma, then nasal polyposis, with aspirin sensitivity coming last. The reactions to aspirin vary in severity, ranging from mild nasal congestion and eye watering to lower respiratory symptoms including wheezing, coughing, an asthma attack, anaphylaxis, and urticaria in some cases. In addition to aspirin, patients usually also react to other NSAIDs such as ibuprofen, and to any medication that inhibits the cyclooxygenase-1 (COX-1) enzyme, although paracetamol (acetaminophen) in low doses^[4] is generally considered safe.

Anosmia (lack of smell) is also common, as inflammation within the nose and sinuses likely reaches the olfactory receptors.

In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients.^[5]

Cause

The disorder is caused by an anomaly in the arachidonic acid cascade which leads to increased production of cysteinyl leukotrienes, a series of chemicals involved in the body's inflammatory response. When medications like NSAIDs or aspirin block the COX-1 enzyme, production of thromboxane and some prostaglandins is decreased, and in patients with aspirin-induced asthma this results in the overproduction of leukotrienes and produces the severe asthma and allergy-like effects.^[6] The underlying cause of the disorder is not fully understood, but there have been several important findings:

• Abnormally low levels of prostaglandin E₂ (PGE₂), which is protective for the lungs, has been found in patients with aspirin-induced asthma and may worsen their lung inflammation.^[7]
• Overexpression of both the cysteinyl leukotriene receptor 1^[8] and the leukotriene C₄ synthase^[9] enzyme has been shown in respiratory tissue from patients with aspirin-induced asthma, which likely relates to the increased response to leukotrienes and increased production of leukotrienes seen in the disorder.
• The attachment of platelets to certain leukocytes in the blood of patients with aspirin-sensitive asthma has also been shown to contribute to the overproduction of leukotrienes.^[10]
• There may be a relationship between aspirin-induced asthma and TBX21, PTGER2, and LTC4S.^[11]

Treatment

Medication

The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. In the United States, the Scripps Clinic in San Diego, CA,^[12] the Massachusetts General Hospital in Boston, MA,^[13] the Brigham and Women's Hospital in Boston, MA,^[14] National Jewish Hospital in Denver ^[15] and Stanford University Adult ENT Clinic have allergists who routinely perform aspirin desensitization procedures for patients with aspirin-induced asthma. Patients who are desensitized then take a maintenance dose of aspirin daily and while on daily aspirin they often have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and many have an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence, and can slow the regrowth of nasal polyps. Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists.

Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) are often helpful in treating the symptoms of aspirin-induced asthma. Some patients require oral steroids to alleviate asthma and congestion, and most patients will have recurring or chronic sinusitis due to the nasal inflammation.

Surgery

Often surgery is required to remove nasal polyps,^[16] although they typically recur, particularly if aspirin desensitization is not undertaken.

Diet

A diet low in omega-6 oils (precursors of arachidonic acid), and high in omega-3 oils, may also help.

Some people have reported relief of symptoms by following a low-salicylate diet such as the Feingold diet. However, there is little evidence that a low-salicylate diet is beneficial for patients with AERD,^[17] and current clinical trials are underway to determine whether or not the difficult dietary changes truly provide worthwhile therapeutic improvement for these patients.^[18]

Alternate and related names

Samter's triad goes by several other names:

• Acetylsalicylic acid triad ^[19]
• Widal's triad
• Francis' triad
• Aspirin triad
• Aspirin-exacerbated respiratory disease (AERD).^[20]
• Aspirin-induced asthma and rhinitis (AIAR)^[21]

A sufferer who has not yet experienced asthma or aspirin sensitivity might be diagnosed as having:

• Non-allergic rhinitis
• Non-allergic rhinitis with eosinophilia syndrome (NARES)

History

It is named for Max Samter.^[22]

Initial reports on the link between asthma, aspirin and nasal polyposis were made by Widal in 1922.^[23] Further studies were done by Samter & Beers in reports published in 1968.^[24]

See also

• Salicylate sensitivity
• Drug intolerance

References