N-ERD

A guide developed by patients of the Samter’s Society

Hopkins C, Surda P, Walker A, Wolf A, Speth M, Jacques T, et al. EPOS 4 patients. Rhinology. 2021 Suppl. 30: 1-57.

ERS logoWeb.png

http://www.samterssociety.org

 

 

What is N-ERD?

Non-steroidal Exacerbated Respiratory Disease (also called N-ERD, Aspirin exacerbated respiratory disease, AERD or

Samter’s Triad) is a chronic disorder of the immune system. The main symptoms of the disease are asthma, nasal polyps, and respiratory reactions to aspirin and NSAID medications such as ibuprofen. The disease usually develops in adulthood, although cases have also been reported in children and adolescents. N-ERD is most commonly diagnosed between ages 30 and 40. Avoiding aspirin and NSAID medications is not enough to control the symptoms of the disease.

 

Do I have N-ERD?

Because of the above situation, it is common for patients to suspect that they have the disease before a doctor diagnoses them.

 

Signs that you might have N-ERD:

  • Asthma or nasal polyps that began in adulthood

  • Asthma or nose and sinus symptoms after taking aspirin or NSAIDs

  • Asthma or nose and sinus symptoms after drinking alcohol

  • Nasal polyps that return quickly after surgery

  • A complete loss of sense of smell

Not all N-ERD patients have asthma. Asthma in N-ERD can range from non-existent to very severe and difficult to treat. About 5% of N-ERD patients never develop asthma or have asthma symptoms only after ingesting an aspirin or NSAID medication. If you think that you might have N-ERD but haven’t been diagnosed yet, you may wish to avoid aspirin and NSAID medications until you are able to be seen by an expert on the disease. If you have some of the symptoms of N-ERD but aren’t sure if you have reactions to aspirin or NSAID medications, you may need to undergo an aspirin challenge with an allergist to receive a diagnosis. Don’t attempt to take aspirin or NSAIDs on your own to see if you would have a reaction. N-ERD can cause life-threatening reactions and a challenge needs to be done under medical supervision.

 

Finding a doctor who understands N-ERD

Research has found that around 7% of adults with asthma have N-ERD. In patients with both nasal polyps and asthma, the percentage is much higher – around 40%. The disease is not uncommon, but many patients go undiagnosed due to a lack of awareness of the disease in the medical community. Doctors who don’t specialize in the disease such as primary care physicians and emergency personnel are often unfamiliar with it. Specialists such as ENTs and allergists are more likely to have heard of the disease, but not all of them are familiar with current knowledge on how to treat it.

Unfortunately, it is common for patients to have difficulty finding a doctor knowledgeable about N-ERD and the recommended treatments. It can make a big difference in your quality of life if you are able to be seen by a doctor who specializes in N-ERD. There is a map of physicians who specialize in N-ERD and other patient-recommended doctors available on the website www.samterssociety.org. It can also help to educate yourself on the disease so that you can better advocate for yourself. Many doctors will be willing to learn about the disease in order to help you feel better. If your doctor is not familiar with N-ERD, one step you can take is to print some medical literature for them to review. There are also a variety of printable handouts available on The Samter’s Society website. When talking to your doctor, don’t be afraid to be assertive. Many physicians don’t understand the impact that smell loss has on quality of life, but smell loss is the symptom that N-ERD patients report impacts their quality of life the most. Sense of smell is important for the enjoyment of food, detecting danger, and even plays an important role in memory and social bonding.

 

Finding effective treatments

There are treatments that can help, but they aren’t always easy for patients to access. The most important thing you can do to improve your quality of life is to be seen by a doctor who specializes in N-ERD. Most patients will need to be on an asthma controller medication such as an inhaled steroid or an inhaler that combines a steroid with a bronchodilator. Generally, N-ERD patients have a more difficult time accessing effective treatments for sinus disease than asthma. Asthma can be life-threatening and most doctors take uncontrolled asthma seriously. Sinus symptoms like smell loss and nasal congestion are often seen as less important, even though they can make life miserable for patients. Allergy treatments like antihistamines and allergy shots are not usually very effective. Only about half of N-ERD patients also have environmental allergies and allergies aren’t the cause of N-ERD symptoms. Even when environmental allergies are controlled, patients will continue with asthma, nasal polyps, and chronic sinus inflammation without additional treatments. Fortunately, there are a variety of treatments that can be beneficial for N-ERD including anti-leukotriene medications, aspirin desensitization, effective nasal steroids, and biologic medications. We will address a few of the most important N-ERD treatments below.

 

Effective nasal steroids

Regular nasal sprays aren’t very effective for nasal polyps since they aren’t able to penetrate the sinuses deeply. There are more effective nasal steroids available that can be added to a sinus rinse or used to soak nasal polyps. One such medication is budesonide (Pulmicort) which is a steroid liquid that is designed for use in an asthma nebulizer. This medication can be added to a sinus rinse or used in a more concentrated soak to treat nasal polyps. There is a similar medication available in some countries called Flixonase Nasules.

 

Anti-leukotriene medications

Patients with N-ERD produce high levels of inflammatory sub- stances called leukotrienes and these contribute to many of our symptoms. Anti-leukotriene medications like montelukast, zafirlukast and zilueton may be helpful for both asthma and sinus symptoms, however, there are not sufficient trials evaluating their effectiveness in CRSwNP, particularly in the presence of N-ERD, to recommend as an add on treatment to nasal corticosteroids at the current time.

 

Aspirin desensitisation

Physician-supervised aspirin desensitisation followed by daily high-dose aspirin is an effective treatment for many N-ERD patients. The maintenance dose that works best for most patients ranges from 650mg to 1300mg aspirin daily. Taking high-dose aspirin can improve sinus and asthma symptoms and slows polyp regrowth after surgery. Aspirin desensitisation

appears to have the best outcomes when it closely follows sinus surgery.

Desensitisation MUST be undertaken in a healthcare setting – DO NOT attempt to do this at home as life-threatening reactions to aspirin can occur

 

Biologic medications

Biologic medications can be effective for treating both asthma and sinus disease. These medications include omalizumab, mepolizumab, benralizumab, and dupilumab. These are medications that are administered by injection, usually once every 2 to 8 weeks. Due to the cost of the medications, there are limitations on who can receive them, and they may not be available in all countries at the current time, or only offered to very severe cases. Dupixent is already being used to treat nasal polyps in the United States and Europe and it is expected to become more widely available for this indication in the future.

 

Coordinating care

One of the biggest challenges faced by N-ERD patients is the need to coordinate care between various specialists. Ideally, we need to be treated by a surgical specialist like an ENT or rhinologist as well as a doctor who specializes in allergy and immunology. Surgical specialists can fully evaluate nasal polyps, remove them, and can provide treatments such as topical steroid rinses. Immunologists typically handle other treatments such as aspirin desensitisation and biologic medications. There are some comprehensive medical centres where your doctors will work together to coordinate your care plan – but this isn’t always the case. If your doctors don’t seem to be in agreement on your treatment plan, it may be up to you to help get them on the same page. This can be a frustrating experience. When doctors disagree with one another about the best course of action, it can be difficult as a patient to know what to do. This is one reason it’s important to be educated on your own disease – it will empower you to speak up for yourself and help guide your own treatment plan.

 

Living with N-ERD

A life-changing diagnosis

Living with N-ERD can be a challenge. For most of us, coming to terms with the fact that we have a chronic condition is disheartening. Many of us enjoyed good health before developing N-ERD. Many of us are in the prime of our lives enjoying good health when everything suddenly goes downhill. N-ERD is a frustrating disease to manage because it can be difficult to find a doctor who understands the disease and how to treat it. Most of us see several doctors before being diagnosed, and even then, the doctor who diagnoses us may not know the best treatments. Steps to Take; Learn about the disease so that you can be your own advocate. If you haven’t been offered helpful treatments, seeing an expert on the disease could make a big difference for you.

 

N-ERD can be dangerous

There is a real risk of life-threatening reactions with N-ERD. It is not uncommon for N-ERD patients to accidentally ingest NSAID containing medications. Many patients are never provided with basic tools such as a list of medications that must be avoided. There are hundreds of over-the-counter medications that contain NSAIDs and it’s not always an easy task understanding what medications are safe for us. Patients often face significant anxiety about taking new medications and have a sense that they can’t trust their doctor to know what medications are safe for them. This anxiety is not unfounded – research has found that many patients have been prescribed NSAID containing medications by a doctor despite being diagnosed with N-ERD. Due to a lack of awareness of N-ERD, doctors who don’t specialize in the disease are not always familiar with which medications are safe for us.

 

Steps to Take; Be your own advocate. Print the list of medications to avoid and provide a copy to every doctor who treats you. Read labels on over-the-counter medications carefully. There is a printable wallet card available that you can carry with you. Having this information easily accessible in an emergency situation could be lifesaving. Printable versions of the medication list and wallet card are available on The Samter’s Society website.

 

Most common medications to avoid

Aspirin - Excedrin, Alka-Seltzer, Anadin

Ibuprofen - Motrin, Advil, Brufen

Naproxen - Aleve, Anaprox

Salsalate - Amigesic, Salflex, Argesic

Flurbiprofen - Ansaid

Ketorolac - Toradol

Diclofenac – Arthrotec, Voltarol

 

What pain medications can I take?

Acetaminophen (paracetamol) is a safer choice for pain relief than aspirin or other NSAIDs, but it can still provoke reactions in some N-ERD patients, particularly when used at high doses. Research has found that 34% of N-ERD patients will have reactions to doses of acetaminophen 1000mg or higher. These reactions are typically milder than reactions to other NSAIDs, but severe reactions have also occurred. If other pain relief options are needed, COX-2 inhibiting medications like Celebrex (celecoxib) are considered safe for N-ERD.

 

People don't understand

Having a disease that so few people know about can be isolating. It's common for N-ERD patients to feel frustrated when trying to explain this disease to others. N-ERD is not an autoimmune disease, but in many ways, it is more similar to one than an allergic disorder. Most people who have allergies cannot identify with the intense inflammation that we experience on a daily basis. The name of the disease can confuse people. Many people hear “aspirin-exacerbated” and think that as long as aspirin is avoided symptoms should be under control. Every N-ERD patients know that this isn’t the case, but it can be a difficult thing to explain to other people. It’s a chronic immune disorder and avoiding aspirin and NSAIDs does not treat it.

Steps to Take; Having a good support system can make a big difference. There are support groups for patients such as The Samter’s Society, where thousands of patients share their experiences and support one another. Being able to communicate with other patients who understand what you’re going through can be life-changing. You don’t have to struggle with symptoms alone – join the patient community. It’s also important to educate yourself on the disease. The better you understand it yourself, the more empowered you will feel to be able to explain it to other people. Many patients have said that they tell people in their lives that they simply have allergies because it’s easier than trying to explain what N-ERD is. While it might be easier, patients should not feel that they have to hide the fact that they have a serious chronic illness. Explaining the disease to others helps spread awareness and can give the people in your life a better understanding of what you’re going through.

 

Can diet changes help?

This is one of the most frequently asked questions in our support group. Many patients are eager to learn about ways that they can help control the disease without so many medications. It’s important to understand that the disease isn’t caused by something you’re eating. Many patients go through phases of avoiding various foods in the process of trying to figure out why they are so sick all the time. This can actually be harmful and lead to patients following unnecessarily strict diets in an attempt to avoid anything that may trigger symptoms.

 

Dietary fatty acid modification

There is a dietary strategy developed by experts on the disease that may be helpful – it involves reducing omega 6 fatty acids in the diet and increasing omega 3. In our support group, we recommend that patients try this diet before other diets they may read about on the internet. There is an overwhelming amount of information on the internet about various diets that claim to help treat diseases, but this diet was developed by N-ERD experts specifically to address inflammation caused by N-ERD; a small pilot study suggests benefit but more evidence is needed in this area.

 

N-ERD and alcohol

Research has found that about 80% of N-ERD patients report sinus or asthma reactions to alcoholic beverages. These reactions can occur with any type of alcohol but are usually most pronounced with wine and beer. The cause of these reactions is not entirely understood, but experts believe that the high polyphenol content in these beverages may have a similar effect to NSAIDs. Polyphenols are found in red wine, where they come from the grape skin and in beer, where they come from barley and hops. White wine and liquor can also contain polyphenols, derived from the oak barrels in which they are sometimes aged. In general, liquor contains fewer of these substances than wine or beer.

Abstaining from alcohol or reducing your alcohol consumption is likely to have a benefit on symptoms. If you wish to have a drink, you may find that you have less of a reaction to alcoholic beverages that have a lower polyphenol content. Types of alcohol that are frequently recommended in our support group include drinks made with vodka or gin, as well as white wines aged in steel containers rather than oak. Aspirin desensitisation has been found to improve tolerance to alcohol for over 80% of patients.

 

What about dietary salicylates?

Decades ago, before much was known about N-ERD, researchers did think that dietary salicylates might be causing N-ERD symptoms. Today much more is understood about the disease and N-ERD experts discourage patients from trying to avoid dietary salicylates.

 

Inhibition of the COX-1 enzyme is the mechanism by which aspirin and other NSAIDs cause N-ERD reactions. N-ERD experts do not recommend a low salicylate diet because dietary salicylates do not inhibit the COX-1 enzyme-like aspirin does. The chemical name for aspirin is acetyl-salicylate (ASA). The chemical structure of ASA is the reason that it inhibits COX-1. It does this by means of the acetyl group attached to its chemical structure. Dietary salicylates have a different chemical structure and therefore do not have the same effect. Therefore, there is no scientific reason why avoiding dietary salicylates would have any benefit. In addition to this, avoiding dietary salicylates may not be healthy. Most fruits and vegetables contain salicylates. Attempts to avoid dietary salicylates may result in nutritional deficiencies.