What is Samter's Triad?

Also known as Aspirin-Exacerbated Respiratory Disease (AERD)

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Samter's Triad, also know as aspirin-exacerbated respiratory disease, is a condition of asthma, nasal polyps, and sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). It is named after the allergist Max Samter, who published research on the topic in the 1950s and suggested that the symptoms were due to a disease of the entire respiratory tract.

Read on to learn more about this condition, its symptoms, and management.

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Samter's Triad Symptoms

Aspirin-exacerbated respiratory disease is known as Samter's "Triad" because of the classic three findings of NSAID sensitivity, nasal polyps, and asthma.

Signs and symptoms include the following:

  • Nasal polyps, which are extra growths of tissue in the nasal cavity, which can be associated with runny nose and discomfort
  • NSAID sensitivity, with symptoms such as difficulty breathing, cough, rash, itching, and red and watery eyes after taking NSAIDs
  • Rhinosinusitis, or inflammation of the nasal passages
  • Asthma, which usually starts later on in the teenage years or adulthood, later than is typical of asthma
  • Decreased sense of smell
  • High levels of blood cells called eosinophils, which are involved in inflammation and allergic responses

Samter's triad is more common in women and is estimated to affect less than 1% of people but up to 10% of people with adult-onset asthma.


What are NSAIDs?

NSAIDs are medications with anti-inflammatory, pain-relieving, and fever-reducing properties. Commonly used NSAIDs include aspirin (acetylsalicylic acid), Alleve (naproxen), Motrin and Advil (ibuprofen). NSAIDs work by blocking an enzyme called cyclooxygenase (COX), which is involved in activation of proteins involved in inflammation, blood clotting, and pain sensation, among other roles.

Causes

The cause of aspirin-exacerbated respiratory disease still remains somewhat unclear. Scientists have discovered that people with AERD have differing levels of various inflammatory proteins, including cysteinyl leukotriene (CysLT) and prostaglandin D2.

Only 1-2% of people with AERD appear to have a number of family members affected, suggesting the possibility of an inherited genetic cause. Another explanation that can explain the lack of inheritance in most people and the later onset of symptoms may be epigenetic changes. Epigenetics refers to changes in the expression of genes that can be thought of as an on/off switch for making or not making specific proteins.

Diagnosis

Unlike many allergic syndromes diagnosed with skin testing, AERD does not typically show abnormalities on skin testing. It instead requires a medical history, physical examination, and an "NSAID challenge test."

When taking a medical history, a healthcare provider will ask about symptoms, reactions to medications, like aspirin and other NSAIDs, and family history. The physical examination will include an examination of the nasal cavity to look for polyps.

In an NSAID challenge test, Aspirin or another NSAID is given in a monitored setting. Symptoms usually are evident in 30min to 3 hours. Pulmonary function testing, which requires measuring lung volumes and force of exhalation, is done as part of challenge testing.

Treatment

Treatment of AERD involves avoiding triggers, taking medications to relieve symptoms, and possible surgery.

Avoiding Triggers

NSAID sensitivity is a hallmark of AERD, so these medications must be avoided. If you have AERD, make sure to pay close attention to the ingredients in medications. Look for NSAIDs that are often found in cough and cold medications and headache medication. Tylenol (acetaminophen) can be a good alternative to NSAIDs when needed for pain or fever. However, some people with AERD can also have sensitivity to Tylenol.


Avoiding medications isn't always enough. Certain spices, foods, and beverages can also trigger unwelcome symptoms in those with AERD. Keeping a log of your diet and symptoms can help uncover aggravating foods.

The following foods and drinks may contain salicylates and cause symptoms in some people with AERD:

  • Alcohol (especially red wine and beer)
  • Certain vegetables like broccoli, peas, radish, and dried tomatoes
  • Certain fruits like avocado, cranberries, raisins, and pineapple
  • Herbs and spices like cinnamon, paprika, and rosemary
  • Seeds and nuts like almonds, pine nuts, and pistachios

Medications

Symptoms of AERD can be drastically improved with certain medications. Your allergist may prescribe the following medications to help:

  • Nasal corticosteroids, given as a nasal spray, for symptoms of rhinosinusitis.
  • Asthma medications, including steroid and rescue inhalers.
  • Biologic therapies are reserved for more severe cases of AERD that don't respond to other therapies. These medications alter the immune system and can be very effective, but come at the cost of immunosuppression.

Nasal Surgery

Nasal polyps can not only be uncomfortable, but can cause problems with breathing and sleep. For those with significant symptoms from nasal polyps, surgery to remove them can be done. Nasal polyps can grow back, so repeat surgery may be needed.

Desensitization Therapy

It's not always possible to avoid NSAIDs, such as when aspirin is needed to treat certain forms of heart disease. In these cases, desensitization is performed under medical observation by introducing very small doses of aspirin and increasing the dose slowly over time. Once the required dose is reached, it must be taken every day without missing a dose, or the process must start over.

Desensitization has also been shown to delay nasal polyp growth and improve other AERD symptoms.

Summary

Samter's triad, also known as AERD, is an immune condition characterized by nasal polyps, asthma, and sensitivity to NSAIDs. While Samter's triad is rare in the general population, those with asthma starting in adulthood, particularly those with nasal polyps, have a much higher likelihood of having this condition.

The causes of AERD are unclear, but epigenetic factors seem to play a role in abnormal levels of specific proteins with roles in the immune response. Treatment can involve medications, surgery to remove nasal polyps, and avoidance or desensitization to NSAIDs.

A Word from Verywell

Drug sensitivities can be extremely scary, particularly when they cause symptoms like shortness of breath with airway obstruction, which can be life-threatening. If you have concern about NSAID sensitivity or have been diagnosed with AERD, know what medications and foods to avoid. Since asthma in Samter's triad can be severe, it is essential to have an asthma action plan and carry prescribed rescue inhalers at all times.

10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. The Samter's Society. The history of AERD (Samter's Triad).

  2. Taniguchi M, Mitsui C, Hayashi H, et al. Aspirin-exacerbated respiratory disease (AERD): Current understanding of AERD. Allergol Int. 2019 Jul;68(3):289-295. doi:10.1016/j.alit.2019.05.001

  3. American Academy of Allergy, Asthma & Immunology. Nasal polyps.

  4. Kim SD, Cho KS. Samter's triad: tate of the artClin Exp Otorhinolaryngol. 2018;11(2):71-80. doi:10.21053/ceo.2017.01606

  5. American College of Rheumatology. NSAIDs (Nonsteroidal anti-inflammatory drugs).

  6. Badrani JH, Doherty TA. Cellular interactions in aspirin-exacerbated respiratory disease. Curr Opin Allergy Clin Immunol. 2021;21(1):65-70. doi:10.1097/ACI.0000000000000712

  7. Centers for Disease Control and Prevention. What is epigenetics?

  8. The Samter's Society. Avoiding NSAIDs.

  9. Workman AD, Bleier BS. Biologic therapies versus surgical management for aspirin-exacerbated respiratory disease: A review of preliminary data, efficacy, and cost. World J Otorhinolaryngol Head Neck Surg. 2020;6(4):230-234. doi:10.1016/j.wjorl.2020.06.002

  10. American Academy of Allergy, Asthma & Immunology. Aspirin-exacerbated respiratory disease.

By Angela Ryan Lee, MD
Angela Ryan Lee, MD, is board-certified in cardiovascular diseases and internal medicine. She is a fellow of the American College of Cardiology and holds board certifications from the American Society of Nuclear Cardiology and the National Board of Echocardiography. She completed undergraduate studies at the University of Virginia with a B.S. in Biology, medical school at Jefferson Medical College, and internal medicine residency and cardiovascular diseases fellowship at the George Washington University Hospital. Her professional interests include preventive cardiology, medical journalism, and health policy.