Comparing Pediatric and Adult EoE

Description:

Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED’s Health Sciences Advisory Council, interview Dr. Melanie Ruffner, an Attending Physician with the Division of Allergy and Immunology and the Center for Pediatric Eosinophilic Disorders at Children’s Hospital of Philadelphia. Dr. Ruffner describes her work in clinic and the paper she co-authored about pediatric and adult eosinophilic esophagitis (EoE). She covers the questions they considered in the paper and the conclusions they reached.

Disclaimer: The information provided in this podcast is designed to support, not replace the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.

 

Key Takeaways:

[:49] Co-host Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda. Ryan introduces co-host Holly Knotowicz.

 

[1:17] Holly introduces today’s topic, pediatric and adult eosinophilic esophagitis (EoE), and introduces today’s guest, Dr. Melanie Ruffner.

 

[1:23] Dr. Melanie Ruffner is an attending physician with the Division of Allergy and Immunology in the Center for Pediatric Eosinophilic Disorders at Children’s Hospital of Philadelphia. Holly welcomes Dr. Ruffner to Real Talk.

 

[1:50] As an attending physician in the Center for Pediatric Eosinophilic Disorders at Children’s Hospital of Philadelphia, Dr. Ruffner sees patients who have eosinophilic esophagitis and other eosinophilic disorders, including eosinophilic GI tract disorders.

 

[2:09] Dr. Ruffner also leads a research group that studies how the immune system causes inflammation in response to certain foods, leading to EoE.

 

[2:20] Inflammation in the esophagus is tied to other diseases like epithelial barrier dysfunction and fibrosis.

 

[2:28] Our bodies use many different proteins that allow cells to communicate with one another. One type of signaling protein that causes inflammation is called cytokines.

 

[2:41] Dr. Ruffner’s group is interested in how these signaling proteins called cytokines interact with epithelial cells and how that impacts the oral function of the esophagus in patients with EoE.

 

[3:02] In training, Dr. Ruffner became interested in eosinophilic esophagitis and other non-IgE-mediated food allergies because we don’t have a lot of clear treatments or clear mechanisms that cause them.

 

[3:21] Dr. Ruffner felt there was a lot of work to be done in that area. It was rewarding to be in clinical encounters with those patients. Often, patients had spent a long time trying to find out what was happening and to find a treatment plan that worked for them.

 

[4:31] Dr. Ruffner’s group sees some patients who have eosinophilic gastroenteritis and patients who are referred for hypereosinophilia with impacts of inflammation in other organ systems.

 

[5:06] Dr. Ruffner co-authored a paper about pediatric and adult EoE published in the Journal of Allergy and Clinical Immunology. It explored if EoE in pediatric patients and adult patients is a spectrum or distinct diseases.

 

[5:29] EoE is a chronic allergic condition that affects the esophagus. The esophagus carries food from the mouth to the stomach. In people with EoE, the immune system overreacts to foods and causes inflammation in the esophagus.

 

[5:47] Eosinophils are a type of white blood cell. Eosinophils infiltrate the tissue in the esophagus of people with EoE. Doctors look for eosinophils in the tissue of the esophagus as a sign that inflammation in the esophagus is EoE.

 

[6:04] The symptoms of EoE can vary in children and adults. That was one of the things the doctors were interested in when they were thinking about this paper. There are no blood or allergy tests that make it easy to diagnose EoE, which requires an endoscopy.

 

[6:31] An endoscopy is performed by a gastroenterologist. The gastroenterologists look at the appearance of the esophagus and take biopsies.

 

[6:49] A pathologist counts the eosinophils in the tissue to determine if there are eosinophils present. If there are more than 15 eosinophils in the high-powered field of the microscope and symptoms and clinical conditions are present, EoE is diagnosed.

 

[7:25] One of the variables Dr. Ruffner considers is that symptoms can be different in children versus adults. In older adolescents and adults, the classic symptom is difficulty swallowing or dysphagia. That is often caused by fibrosis in the esophagus.

 

[7:54] In younger children this is often not how EoE presents. They may vomit or refuse food. They may experience more weight loss. Symptoms vary over the lifespan. Pediatric EoE symptoms of nausea and abdominal pain can also show up in adults.

 

[9:54] Atopy refers to allergic conditions. In the paper, a history of atopy means a history of allergic conditions, like atopic dermatitis, IgE-mediated food allergy, allergic rhinitis, or asthma.

 

[10:37] These disorders tend to cluster together, over time, because they share many common genetic risks. They cluster in families because some of the genetic risks are the same. Not every family member will have the same atopic or allergic conditions.

 

[11:07] In families, perhaps one person will have atopic dermatitis and allergic rhinitis while another will have atopic dermatitis, allergic rhinitis, asthma, and EoE. They may have inherited different genetics or had different environmental exposures.

 

[11:50] Ryan says that describes his family. They each have different atopic conditions. Ryan got them all! Dr. Ruffner says it describes her family, as well.

 

[12:26] Dr. Ruffner says it’s understandable for families to stress about atopic conditions. Unfortunately, right now, there’s no way to predict who will develop which atopic conditions. It’s on the minds of the medical and research communities.

 

[13:10] IgE is an antibody that binds to food allergens and mediates anaphylaxis, usually within 30 minutes, with hives, vomiting, and difficulty breathing. Not everyone with a diagnosed food allergy will be given an epinephrine auto-injector.

 

[13:44] IgE-mediated food allergies are influenced by type 2 cytokines. Cytokines are immune system signaling proteins that have been labeled as groups. The group that is involved in allergy most heavily is under the label type 2.

 

[14:15] These type 2 cytokines are responsible for influencing B cells to make IgE. In the tissue in EoE, we find that there is a large amount of these type 2 cytokines present.

 

[14:37] This is quite relevant because dupilumab, the monoclonal antibody that has been approved to treat EoE, targets type 2 inflammation by blocking type 2 cytokines.

 

[16:04] Dr. Ruffner says one of the biggest challenges in the field of EoE is we don’t have a way to stratify who should get which treatment for EoE. Patients have to choose between diet and pharmacologic therapy.

 

[16:48] We don’t know enough about the inflammatory profiles to give any patient the specific guided information that one therapy would be better than another.

 

[17:11] Pediatric and adult patients are given the same treatment options. Some dosing, such as proton pump inhibitors and dupilumab, is weight-based so different doses are needed.

 

[17:36] Over time, people’s needs change. From early school age to when people leave home, they may have very different needs. They may do well on diet therapy when their diet is controlled by parents, but, on their own, that may not be the best option for them.

 

[18:20] Therapy may change over time to support each patient’s individual goals. It can be challenging because therapies are imperfect. Each therapy has a percentage probability of success. Not every therapy is guaranteed to work for every individual.

 

[19:01] There is some flexibility and possibility of switching between therapies to support people. Ryan shares one of his experiences in changing treatments.

 

[20:03] Some patients are stable on a therapy for a time but then see symptoms creep back up. Dr. Ruffner strongly suggests they talk to their care team for an endoscopy and biopsy to see if they need to switch therapy and if their diet has changed.

 

[21:31] In young children, Dr. Ruffner sees a much higher incidence of feeding refusal. The child may have a preferred food or a preferred texture like puree, long past when that would be appropriate for the age.

 

[22:41] It can be very difficult to move past this learned behavior even if remission is achieved through therapy. The child may need feeding therapy to help with that.

[22:59] Feeding behaviors in older individuals may be much more subtle. Talk about them with your care team. Needing water to eat, cutting food very small, and fearing to eat around people are common eating behaviors to discuss in older patients.

 

[23:53] These eating behaviors affect people’s well-being deeply because they affect how social they feel when they are around people. Ideally, you want to be around people and share in social times.

 

[24:16] Holly has used these eating behaviors herself and notices them in other people. When adults come to her for therapy, she asks how many times they refill their water when they eat, and if food ever gets stuck. They are surprised that those are symptoms.

 

[26:01] Dr. Ruffner says it’s important to recognize the difference in symptoms in diagnosing EoE. The main risk factor of EoE is fibrosis, over time. The thought is that early in EoE there is an inflammatory phenotype, but later, there is a fibrotic phenotype.

 

[26:51] The phenotype refers to the presentation or characteristic of disease. What is the appearance at endoscopy? What do we see in the biopsied tissue? Is there fibrosis or not?

 

[27:15] This is the crux of the paper: Is this on a spectrum, that the inflammation is driving the fibrosis, or are these two different things altogether? There is some evidence to suggest that the inflammation contributes to this fibrosis over time.

 

[27:40] One thing that is missing is following a group of patients from the start and having that evidence. There is mechanistic evidence from studies to show that inflammation can contribute to fibrosis. That was one of the discussions in the paper.

 

[28:29] In endoscopies, something that can be seen with fibrosis or fibrostenotic features is more of an appearance of rings and narrowing of the esophagus. A proportion of patients with strictures or narrowing need to have them dilated.

 

[29:11] For patients who have dilation, it can help with symptoms significantly. When pathologists look at the tissue with fibrosis, they can see changes in the protein structure. There is more collagen and other changes in the tissue, causing fibrosis.

 

[30:03] Some patients use adaptive eating behaviors to adapt to significant changes in their esophagus and go for many years without being diagnosed until they present with an impaction when food becomes stuck in their esophagus.

 

[30:46] This makes EoE a challenging disorder for many because it can be very difficult to diagnose. The journey to a diagnosis is very individual. As a group, adults are much more likely to have fibrosis, leading to dysphagia, strictures, or impaction.

 

[31:25] Statistically, across all patients, you see fibrosis more in adults than in children.

 

[32:42] In the paper, Th1 cells are mentioned. Th1 is an immune system term referring to a cell that produces interferon-gamma. Studies show there may be differences in interferon signaling in different age groups but it needs to be studied further.

 

[33:57] Dr. Ruffner’s team had looked at a small group and saw that interferon signaling seemed to be relatively similar between children and adults. Both CD4 and CD8 T cells (types of immune system cells) are potentially producing interferon in the esophagus.

 

[34:32] More study needs to be done around those immune system cells and their potential significance in EoE, if any.

 

[35:33] The paper suggests that EoE in children and adults is essentially a spectrum of the same disorder rather than distinct diseases.

 

[35:42] Aspects of immunology, responses to different treatments across children and adults, the similar responses to diet and different medications, and over time in the same individuals, indicate these are changes and complications over time.

 

[36:41] Dr. Ruffner suggests that medical researchers need to understand which patients are at the highest risk of complications and work to identify the best treatments to prevent those.

 

[37:14] Dr. Ruffner is thinking about the response to proton pump inhibitor therapy. One of the things she is looking at is whether or not proton pump inhibitors affect how eosinophils migrate into the tissue.

 

[37:33] They are finding that it seems that PPIs can decrease the degree of migration of eosinophils into the tissue. They are very interested in looking at that. Ryan says when Dr. Ruffner gets that paper published, she’ll have to come back on the show!

 

[38:06] Ryan thanks Dr. Ruffner. For our listeners who would like to learn more about eosinophilic disorders, including EoE, please visit APFED.org and check out the links in the show notes.

 

[38:15] If you’re looking to find a specialist who treats eosinophilic disorders, we encourage you to use APFED’s Specialist Finder at APFED.org/specialist.

 

[38:24] If you'd like to connect with others impacted by eosinophilic diseases, please join APFED’s online community on the Inspire Network at APFED.org/connections.

 

[38:33] Ryan thanks Dr. Ruffner for participating in the podcast episode. Holly also thanks APFED’s Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda for supporting this episode.

 

Mentioned in This Episode:

Dr. Melanie Ruffner, MD, PhD, Attending Physician with the Division of Allergy and Immunology and the Center for Pediatric Eosinophilic Disorders at Children’s Hospital of Philadelphia

“Pediatric and adult EoE: A spectrum or distinct diseases?” by Stanislaw J. Gabryszewski, Melanie A. Ruffner, and Jonathan M. Spergel

 

APFED on YouTube, Twitter, Facebook, Pinterest, Instagram

Real Talk: Eosinophilic Diseases Podcast

apfed.org/specialist

apfed.org/connections

 

Education Partners: This episode of APFED’s podcast is brought to you thanks to the support of Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda.

 

Tweetables:

 

“EoE is a chronic allergic condition that affects the esophagus. The esophagus carries food from the mouth to the stomach. In people with EoE, the immune system overreacts to food allergens and causes inflammation in the esophagus.” — Dr. Melanie Ruffner

 

“In EoE, there are no blood or allergy tests that make it easy to diagnose EoE without an endoscopy.” — Dr. Melanie Ruffner

 

“Is EoE on a spectrum, that the inflammation is driving the fibrosis, or are these two different things altogether? There is some evidence to suggest that the inflammation contributes to fibrosis over time.” — Dr. Melanie Ruffner

 

“When pathologists look at the tissue with fibrosis, they can see the changes in the protein structure.” — Dr. Melanie Ruffner

 

“There are some folks who have adapted their eating behavior quite significantly and may have quite a number of chronic changes in their esophagus that they have adapted around, and they go for many years without being diagnosed.” — Dr. Melanie Ruffner