Eosinophilic esophagitis (“EoE”) is an increasingly prevalent allergic disease that is primarily triggered by food allergens which cause a delayed allergic reaction. The reaction creates inflammation in the esophagus and an influx of eosinophils in the tissue. Diagnosis currently requires sedated endoscopy, an invasive procedure requiring a hospital visit. EAT is funding research into noninvasive alternatives for diagnosing and monitoring this disease.
To learn more about EoE and diagnosis options, we interviewed Calies Menard-Katcher, MD, MSCS, Children’s Hospital of Colorado, and Amanda Muir, MD, Children’s Hospital of Philadelphia. Menard-Katcher and Muir are collaborators on the EAT-funded study, “Use of Esophageal String Test to Understand Symptoms, Inflammation, and Function in EoE.”
EAT: What is an eosinophil, and what is it its purpose in the body?
Menard-Katcher: An eosinophil is a type of white blood cell that is found in our blood and other areas of our body, typically in low numbers. They work with other white blood cells as an important part of our immune system. Eosinophils help fight parasitic infections as well as other bacterial or viral infections. They are also associated with allergic diseases.
EAT: What is eosinophilic esophagitis (“EoE”)?
Menard-Katcher: EoE is an inflammatory condition of the esophagus where we see an excess of eosinophils. Normally, eosinophils are not seen in the esophagus, as opposed to other parts of the gastrointestinal tract.
People with EoE have various symptoms, but most commonly experience heartburn and difficulty swallowing solids, such as feeling like food is getting lodged or is slow to go down the esophagus. In children, common symptoms include vomiting, feeding difficulties and feeding refusal.
EAT: How does EoE relate to food allergies?
Menard-Katcher: EoE occurs more commonly in people with food allergies and other atopic disorders. Exposure to certain food allergens drives the response. Removing specific foods can reduce inflammation and improve symptoms. While EoE is certainly more common in people with IgE mediated allergies (anywhere from 30 to 80% of people with EoE are reported to have IgE mediated food allergies), the current thinking is that it is a delayed hypersensitivity reaction that leads to inflammation. It’s not the same as immediate IgE reactions, such as anaphylaxis or immediate vomiting.
EAT: When was EoE first diagnosed?
Muir: It was first recognized in the early 1990’s by Dr. Alex Straumann and Dr. Stephen Attwood in Europe. They each described a group of patients with swallowing difficulties and increased eosinophils in their esophageal biopsies. In the United States, Dr. Kevin Kelly found that children with eosinophilic inflammation of the esophagus and uncontrolled reflux responded universally to a diet of hypoallergenic amino acid-based formula and relapsed when specific foods were reintroduced. Foods that trigger EoE are often one or many of the top eight allergens: milk, egg, peanut, tree nuts, fish, shellfish, soy, and wheat. This was the first time a connection was recognized between food allergens and this inflammation in the esophagus. We’re getting better at recognizing this disease and now know to recommend an endoscopy when patients present with these symptoms.
EAT: Is the incidence of EoE increasing?
Menard-Katcher: Even when we account for increased biopsy rates, it does seem that the incidence is increasing. There was a recent study in Denmark showing a 19.5 fold increase in EoE over the past 15 years, whereas the esophageal biopsy rate only increased 1.9 fold during the same time period. The current incidence in the United States is about 57 cases per 100,000 persons (approximately 1 in every 1,754 people).
EAT: How is EoE currently diagnosed?
Muir: Currently, the only way is by endoscopy, which is a special camera test that gastroenterologists use. Once the patient is sedated, the doctor puts the camera through the mouth and into the esophagus and takes mucosal scrapings called biopsies. Then, eosinophils are counted in the biopsy samples. Unfortunately, EoE patients require multiple endoscopies. The only way to determine triggers is through dietary elimination. Typically, a number of foods are eliminated. As patients add foods back, they undergo endoscopy to detect if inflammation is controlled. This can lead to a number of scopes in their lifetime.
EAT: Can you give us a brief overview of the string test you are researching as an alternative to endoscopy?
Menard-Katcher: The string test was developed by Dr. Glenn T. Furuta and Dr. Steven Ackerman as a way to measure inflammation that is less invasive than endoscopy. For the string test, you have a gelatin capsule filled with string that protrudes from one end of the capsule. The string end is taped to the cheek and the capsule is swallowed. The string unravels and goes through the mouth, into the esophagus, stomach and small intestine. The string is pulled out after an hour and analyzed. Proteins from eosinophils are captured on the string and can be measured as a marker of inflammation.
One of the main objectives of this study is to determine whether the string test is an adequate marker that correlates with patients’ symptoms and biopsies.
EAT: How comfortable is the test for patients?
Menard-Katcher: It is most often very well tolerated. Some smaller kids or people with a very strong gag reflex may have difficulty. For the vast majority of kids and adults that does not happen. As part of this study, we are collecting information on how well subjects tolerate the string test and whether they would choose it over endoscopy. When given a choice, patients more commonly prefer methods that don’t require anesthesia and IVs.
EAT: How would patients and physicians benefit from having the string test as an alternative to endoscopy? How might it improve care and quality of life?
Muir: Patients with EoE often have so many endoscopies, and it does affect their quality of life. Patients and physicians would benefit from a less invasive diagnosis, avoiding anesthesia, medicines, IVs, and the loss of an entire day of work or school.
The string test would also allow a more timely assessment of inflammation. Scheduling an endoscopy takes two to four weeks, or even longer. Having the string test could allow for more real-time correlation of symptom flares with eosinophilic inflammation.
EAT: Can the string test be performed in a doctor’s office instead of a hospital?
Muir: For the string test, it absolutely could be used in a doctor’s office instead of a hospital. Now it is used only in research centers, but our hope is that it will be used in the doctor’s office. We’re hoping this study will help bring the string test to the marketplace.
EAT: A recent study from the Children’s Hospital of Philadelphia (CHOP) found that children with other allergic conditions are at much higher risk for EoE and recommends early screening for allergic children. What would that screening look like now?
Muir: This paper taps into the idea of the allergic march and the evidence that EoE is more prevalent in kids with atopic dermatitis, asthma, and IgE mediated food allergies. The study suggests that EoE may be part of that atopic march. When looking at the medical history of patients with IgE allergies, there does seem to be a large number of kids diagnosed with EoE later on.
Right now, there really is no screening. Primary care doctors have to have a high index of suspicion when kids with IgE allergies have vomiting, feeding refusal, and dysphagia (i.e. difficulty swallowing).
EAT: How would a noninvasive diagnostic method like the string test help further the recommendation for screening?
Menard-Katcher: When you consider a recommendation for screening, you have to look at practical use. It needs to be low-risk, cost-conscious, and accurately recognize disease in high-risk population. Screening means testing patients with no symptoms, and that is not practical right now since the only diagnostic method for EoE is sedated upper endoscopy. With the development of non-invasive screening tools, we could start making recommendations for screening the at-risk patient population. So, one potential use of the string test is the possibility of appropriate screening. The next step would be to determine what is the right group to screen.
EAT: Do you have any theories on why some kids with food allergies develop EoE while others do not?
Muir: This is one thing we’re really working on. We are trying to recapitulate the disease in a test tube. We take tissue from healthy controls and people with EoE. We stimulate the tissue in the lab and examine if barrier function of the tissue remains intact. We add different foods and see what happens. There is an interplay with genetic and environmental factors and we are trying to tease these factors apart.
Some kids with IgE mediated disease, after they have outgrown the allergy and reintroduce the food, have later on developed EoE. So, there is some connection between the two, but we don’t understand the immune system well enough yet to explain why.
EAT: Are there any recommendations for preventing EoE?
Muir: We don’t really have ways at this time. There are whole bodies of research trying to identify potential risk factors and what may be avoidable, but at this time, no.
EAT: Why did you choose to go into this area of practice and research?
Menard-Katcher: We both trained at CHOP. As fellows, Amanda and I had desks next to each other in the lab. It is there that I had my first exposure to EoE. As an impressionable young doctor, it was an exciting time to be part of the discussions and research on EoE. Really, it was the energy of the mentors and the patients I was exposed to as a trainee. My goal is to further understand the natural history of EoE and related disease and improve our management of eosinophilic gastrointestinal disease.
Muir: We were lucky enough to be at a hospital that had a center for eosinophilic disorders, with nutrition, gastroenterology, allergy, and pathology, all working together to figure it out. As we start to learn more and more, I would like to look at the mechanisms behind the evolution of this disease into a fibrotic disease and what makes that happen.
EAT: Thank you so much for your time.