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 Evan S. Dellon, MD, and Elizabeth T. Jensen, PhD, about a paper they published on predictors of patients receiving no medication for treatment of eosinophilic esophagitis.

Disclaimer: The information provided in this podcast is designed to support, not replace, the relationship 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:

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

[1:14] Holly introduces today's topic, predictors of not using medication for EoE, and today's guests, Dr. Evan Dellon and Dr. Elizabeth Jensen.

[1:29] Dr. Dellon is an Adjunct Professor of Epidemiology at the University of North Carolina School of Medicine in Chapel Hill. He is also the Director of the UNC Center for Esophageal Diseases and Swallowing.

[1:42] Dr. Dellon's main research interest is in the epidemiology, pathogenesis, diagnosis, treatment, and outcomes of eosinophilic esophagitis (EoE) and eosinophilic GI diseases (EGIDs).

[1:55] Dr. Jensen is a Professor of Epidemiology with a specific expertise in reproductive, perinatal, and pediatric epidemiology. She has appointments at both Wake Forest University School of Medicine and the University of North Carolina at Chapel Hill.

[2:07] Her research primarily focuses on etiologic factors in the development of pediatric immune-mediated chronic diseases, including understanding factors contributing to disparities in health outcomes.

[2:19] Both Dr. Dellon and Dr. Jensen also serve on the Steering Committee for EGID Partners Registry.

[2:24] Ryan thanks Dr. Dellon and Dr. Jensen for joining the podcast today.

[2:29] Dr. Dellon was the first guest on this podcast. It is wonderful to have him back for the 50th episode! Dr. Dellon is one of Ryan's GI specialists. Ryan recently went to North Carolina to get a scope with him.

[3:03] Dr. Dellon is an adult gastroenterologist at the University of North Carolina at Chapel Hill. He directs the Center for Esophageal Diseases and Swallowing. Clinically and research-wise, he is focused on EoE and other eosinophilic GI diseases.

[3:19] His research interests span the entire field, from epidemiology, diagnosis, biomarkers, risk factors, outcomes, and a lot of work, more recently, on treatments.

[3:33] Dr. Jensen has been on the podcast before, on Episode 27. Holly invites Dr. Jensen to tell the listeners more about herself and her work with eosinophilic diseases.

[3:46] Dr. Jensen has been working on eosinophilic gastrointestinal diseases for about 15 years. She started some of the early work around understanding possible risk factors for the development of disease.

[4:04] She has gone on to support lots of other research projects, including some with Dr. Dellon, where they're looking at gene-environment interactions in relation to developing EoE.

[4:15] She is also looking at reproductive factors as they relate to EoE, disparities in diagnosis, and more. It's been an exciting research trajectory, starting with what we knew very little about and building to an increasing understanding of why EoE develops.

[5:00] Dr. Dellon explains that EoE stands for eosinophilic esophagitis, a chronic allergic condition of the esophagus.

[5:08] You can think of EoE as asthma of the esophagus or eczema of the esophagus, although in general, people don't grow out of EoE, like they might grow out of eczema or asthma. When people have EoE, it is a long-term condition.

[5:24] Eosinophils are a type of white blood cell, specializing in allergy responses. Normally, they are not in the esophagus. When we see them there, we worry about an allergic process. When that happens, that's EoE.

[5:40] Over time, the inflammation seen in EoE and other allergic cell activity causes swelling and irritation in the esophagus. Early on, this often leads to a range of upper GI symptoms — including poor growth or failure to thrive in young children, abdominal pain, nausea, and symptoms that can mimic reflux.

[5:58] In older kids, symptoms are more about trouble swallowing. That's because the swelling that happens initially, over time, may turn into scar tissue. So the esophagus can narrow and cause swallowing symptoms like food impaction.

[6:16] Ryan speaks of living with EoE for decades and trying the full range of treatment options: food elimination, PPIs, steroids, and, more recently, biologics.

[6:36] Dr. Dellon says Ryan's history is a good overview of how EoE is treated. There are two general approaches to treating the underlying condition: using medicines and/or eliminating foods that we think may trigger EoE from the diet.

[6:57] For a lot of people, EoE is a food-triggered allergic condition.

[7:01] The other thing that has to happen in parallel is surveying for scar tissue in the esophagus. If that's present and people have trouble swallowing, sometimes stretching the esophagus is needed through esophageal dilation.

[7:14] There are three categories of medicines used for treatment. Proton pump inhibitors are reflux meds, but they also have an anti-allergy effect in the esophagus.

[7:29] Topical steroids are used to coat the esophagus and produce an anti-inflammatory effect. The FDA has approved a budesonide oral suspension for that.

[7:39] Biologics, which are generally systemic medications, often injectable, can target different allergic factors. Dupilumab is approved now, and there are other biologics that are being researched as potential treatments.

[7:51] Even though EoE is considered an allergic condition, we don't have a test to tell people what they are allergic to. If it's a food allergy, we do an empiric elimination diet because allergy tests aren't accurate enough to tell us what the EoE triggers are.

[8:10] People will eliminate foods that we know are the most common triggers, like milk protein, dairy, wheat, egg, soy, and other top allergens. You can create a diet like that and then have a response to the diet elimination.

[8:31] Dr. Jensen and Dr. Dellon recently published an abstract in the American Journal of Gastroenterology about people with EoE who are not taking any medicine for it. Dr. Jensen calls it a real-world data study, leveraging electronic health record patient data.

[8:51] It gives you an impression of what is actually happening, in terms of treatments for patients, as opposed to a randomized control trial, which is a fairly selected patient population. This is everybody who has been diagnosed, and then what happens with them.

[9:10] Because of that, it gives you a wide spectrum of patients. Some patients are going to be relatively asymptomatic. It may be that we arrived at their diagnosis while working them up for other potential diagnoses.

[9:28] Other patients are going to have rather significant impacts from the disease. We wanted to get an idea of what is actually happening out there with the full breadth of the patient population that is getting diagnosed with EoE.

[9:45] Dr. Jensen was not surprised to learn that there are patients who had no pharmacologic treatment.

[9:58] Some patients are relatively asymptomatic, and others are not interested in pursuing medications initially or are early in their disease process and still exploring dietary treatment options.

[10:28] Holly sees patients from infancy to geriatrics, and if they're not having symptoms, they wonder why bother treating it.

[10:42] Dr. Jensen says it's a point of debate on the implications of somebody who has the disease and goes untreated. What does that look like long-term? Are they going to develop more of that fibrostenotic pattern in their esophagus without treatment?

[11:07] This is a question we're still trying to answer. There is some suggestion that for some patients who don't manage their disease, we very well may be looking at a food impaction in the future.

[11:19] Dr. Dellon says we know overall for the population of EoE patients, but it's hard to know for a specific patient. We have a bunch of studies now that look at how long people have symptoms before they're diagnosed. There's a wide range.

[11:39] Some people get symptoms and get diagnosed right away. Others might have symptoms for 20 or 30 years that they ignore, or don't have access to healthcare, or the diagnosis is missed.

[11:51] What we see consistently is that people who may be diagnosed within a year or two may only have a 10 or 20% chance of having that stricture and scar tissue in the esophagus, whereas people who go 20 years, it might be 80% or more.

[12:06] It's not everybody who has EoE who might end up with that scar tissue, but certainly, it's suggested that it's a large majority.

[12:16] That's before diagnosis. We have data that shows that after diagnosis, if people go a long time without treatment or without being seen in care, they also have an increasing rate of developing strictures.

[12:29] In general, the idea is yes, you should treat EoE, because on average, people are going to develop scar tissue and more symptoms. For the patient in front of you with EoE but no symptoms, what are the chances it's going to get worse? You don't know.

[13:04] There are two caveats with that. The first is what we mean by symptoms. Kids may have vomiting and growth problems. Adults can eat carefully, avoiding foods that hang up in the esophagus, like breads and overcooked meats, sticky rice, and other foods.

[13:24] Adults can eat slowly, drink a lot of liquid, and not perceive they have symptoms. When someone tells Dr. Dellon they don't have symptoms, he will quiz them about that. He'll even ask about swallowing pills.

[13:40] Often, you can pick up symptoms that maybe the person didn't even realize they were having. In that case, that can give you some impetus to treat.

[13:48] If there really are no symptoms, Dr. Dellon thinks we're at a point where we don't really know what to do.

[13:54] Dr. Dellon just saw a patient who had a lot of eosinophils in their small bowel with absolutely no GI symptoms. He said, "I can't diagnose you with eosinophilic enteritis, but you may develop symptoms." People like that, he will monitor in the clinic.

[14:14] Dr. Dellon will discuss it with them each time they come back for a clinic visit.

[14:19] Holly is a speech pathologist, but also sees people for feeding and swallowing. The local gastroenterologist refers patients who choose not to treat their EoE to her. Holly teaches them things they should be looking out for.

[14:39] If your pills get stuck or if you're downing 18 ounces during a mealtime, maybe it's time to treat it. People don't see these coping mechanisms they use that are impacting their quality of life. They've normalized it.

[15:30] Dr. Dellon says, of these people who aren't treated, there's probably a subset who appropriately are being observed and don't have a medicine treatment or are on a diet elimination.

[15:43] There's also probably a subset who are inappropriately not on treatment. It especially can happen with students who were under good control with their pediatric provider, but moved away to college and didn't transfer to adult care.

[16:08] They ultimately come back with a lot of symptoms that have progressed over six to eight years.

[16:18] Ryan meets newly diagnosed adult patients at APFED's conferences, who say they have no symptoms, but chicken gets caught in their throat. They got diagnosed when they went to the ER with a food impaction.

[16:38] Ryan says you have to wonder at what point that starts to get reflected in patient charts. Are those cases documented where someone is untreated and now has EoE?

[16:49] Ryan asks in the study, "What is the target EGID Cohort and why was it selected to study EoE? What sort of patients were captured as part of that data set?"

[16:58] Dr. Jensen said they identified patients with the ICD-10 code for a diagnosis of EoE. Then they looked to see if there was evidence of symptoms or complications in relation to EoE. This was hard; some of these are relatively non-specific symptoms.

[17:23] These patients may have been seeking care and may have been experiencing some symptoms that may or may not have made it into the chart. That's one of the challenges with real-world data analyses.

[17:38] Dr. Jensen says they are using data that was collected for documenting clinical care and for billing for clinical care, not for research, so it comes with some caveats when doing research with this data.

[18:08] Research using electronic health records gives a real-world perspective on patients who are seeking care or have a diagnosis of EoE, as opposed to a study trying to enroll a patient population that potentially isn't representative of the breadth of individuals living with EoE.

[18:39] Dr. Dellon says another advantage of real-world data is the number of patients. The largest randomized controlled trials in EoE might have 400 patients, and they are incredibly expensive to do.

[18:52] A study of electronic health records (EHR) is reporting on the analysis of just under 1,000. The cohort, combined from three different centers, has more than 1,400 people, a more representative, larger population.

[19:16] Dr. Dellon says when you read the results, understand the limitations and strengths of a study of health records, to help contextualize the information.

[19:41] Dr. Dellon says it's always easier to recognize the typical presentations. Materials about EoE and studies he has done that led to medicine approvals have focused on trouble swallowing. That can be relatively easily measured.

[20:01] Patients often come to receive care with a food impaction, which can be impactful on life, and somewhat public, if in a restaurant or at work. Typical symptoms are also the ones that get you diagnosed and may be easier to treat.

[20:26] Dr. Dellon wonders if maybe people don't treat some of the atypical symptoms because it's not appreciated that they can be related to EoE.

[20:42] Holly was diagnosed as an adult. Ryan was diagnosed as a toddler. Holly asks what are some of the challenges people face in getting an EoE diagnosis.

[20:56] Dr. Jensen says symptoms can sometimes be fairly non-specific. There's some ongoing work by the CEGIR Consortium trying to understand what happens when patients come into the emergency department with a food bolus impaction.

[21:28] Dr. Jensen explains that we see there's quite a bit of variation in how that gets managed, and if they get a biopsy. You have to have a biopsy of the esophagus to get a diagnosis of EoE.

[21:45] If you think about the steps that need to happen to get a diagnosis of EoE, that can present barriers for some groups to ultimately get that diagnosis.

[21:56] There's also been some literature around a potential assumption about which patients are more likely to be at risk. Some of that is still ongoing. We know that EoE occurs more commonly in males in roughly a two-to-one ratio. Not exclusively in males, obviously, but a little more often in males.

[22:20] We don't know anything about other groups of patients that may be at higher risk. That's ongoing work that we're still trying to understand. That in itself can also be a barrier when there are assumptions about who is or isn't likely to have EoE.

[23:02] Dr. Dellon says that in adolescents and adults, the typical symptoms are trouble swallowing and food sticking, which have many causes besides EoE, some of which are more common.

[23:18] In that population, heartburn is common. Patients may report terrible reflux that, on questioning, sounds more like trouble swallowing than GERD. Sometimes, with EoE, you may have reflux that doesn't improve. Is it EoE, reflux, or both?

[24:05] Some people will have chest discomfort. There are some reports of worsening symptoms with exercise, which brings up cardiac questions that have to be ruled out first.

[24:19] Dr. Dellon mentions some more atypical symptoms. An adult having pain in the upper abdomen could have EoE. In children, the symptoms could be anything in the GI tract. Some women might have atypical symptoms with less trouble swallowing.

[24:58] Some racial minorities may have those kinds of symptoms, as well. If you're not thinking of the condition, it's hard to make the diagnosis.

[25:08] Dr. Jensen notes that there are different cultural norms around expressing symptoms and dietary patterns, which may make it difficult to parse out a diagnosis.

[25:27] Ryan cites a past episode where access to a GI specialist played a role in diagnosing patients with EoE. Do white males have more EoE, or are their concerns just listened to more seriously?

[25:57] Ryan's parents were told when he was two that he was throwing up for attention. He believes that these days, he'd have a much easier time convincing a doctor to listen to him. From speaking to physicians, Ryan believes access is a wide issue in the field.

[26:23] Dr. Dellon tells of working with researchers at Mayo in Arizona and the Children's Hospital of Phoenix. They have a large population of Hispanic children with EoE, much larger than has been reported elsewhere. They're working on characterizing that.

[26:49] Dr. Dellon describes an experience with a visiting trainee from Mexico City, where there was not a lot of EoE reported. The trainee went back and looked at the biopsies there, and it turned out they were not performing biopsies on patients with dysphagia in Mexico City.

[27:13] When he looked at the patients who ended up getting biopsies, they found EoE in 10% of patients. That's similar to what's reported out of centers in the developed world. As people are thinking about it more, we will see more detection of it.

[27:30] Dr. Dellon believes those kinds of papers will be out in the next couple of months, to a year.

[27:36] Holly has had licensure in Arizona for about 11 years. She has had nine referrals recently of children with EoE from Arizona. Normally, it's been one or two that she met at a conference.

[28:00] Ryan asks about the research on patients not having their EoE treated pharmacologically. Some treat it with food avoidance and dietary therapy. Ryan notes that he can't have applesauce, as it is a trigger for his EoE.

[28:54] Dr. Jensen says that's one of the challenges in using the EHR data. That kind of information is only available to the researchers through free text. That's a limitation of the study, assessing the use of dietary elimination approaches.

[29:11] Holly says some of her patients have things listed as allergies that are food sensitivities. Ryan says it's helpful for the patients to have their food sensitivities listed along with their food allergies, but it makes records more difficult to parse for research.

[30:14] Dr. Dellon says they identify EoE by billing code, but the codes are not always used accurately. Natural Language Processing can train a computer system to find important phrases. Their collaborators working on the real-world data are using it.

[30:59] Dr. Dellon hopes that this will be a future direction for this research to find anything in the text related to diet elimination.

[31:32] Dr. Jensen says that older patients were less likely to seek medication therapy. She says it's probably for a couple of reasons. First, older patients may have been living with the disease for a long time and have had compensatory mechanisms in place.

[32:03] The other reason may be senescence or burnout of the disease, long-term. Patients may be less symptomatic as they get older. That's a question that remains to be answered for EoE. It has been seen in some other disease processes.

[32:32] Dr. Dellon says there's not much data specifically looking at EoE in the older population. Dr. Dellon did work years ago with another doctor, and they found that older patients had a better response to some treatments, particularly topical steroids.

[32:54] It wasn't clear whether it was a milder aspect of the disease, easier to treat, or because they were older and more responsible, taking their medicines as prescribed, and having a better response rate. It's the flip side of work in the pediatric population.

[33:16] There is an increasingly aging population with EoE. Young EoE patients will someday be over 65. Dr. Dellon hopes there will be a cure by that point, but it's an expanding population now.

[33:38] Dr. Jensen says only a few sites are contributing data, so they hope to add additional sites to the study. For some of the less common outcomes, they need a pretty large patient sample to ask some of those kinds of questions.

[33:55] They will continue to follow up on some of the work that this abstract touched on and try to understand some of these issues more deeply.

[34:06] Dr. Dellon mentions other work within the cohort. Using Natural Language Processing, they are looking at characterizing endoscopy information and reporting it without a manual review of reports and codes. You can't get that from billing data.

[34:29] Similarly, they are trying to classify patient severity by the Index of Severity with EoE, and layer that on looking at treatments and outcomes based on disease severity. Those are a couple of other directions where this cohort is going.

[34:43] Holly mentions that this is one of many research projects Dr. Jensen and Dr. Dellon have collaborated on together. They also collaborate through EGID Partners. Holly asks them to share a little bit about that.

[34:53] Dr. Jensen says EGID Partners is an online registry where individuals, caregivers, and parents of children affected with EGIDs can join.

[35:07] EGID Partners also needs people who don't live with an EGID to join, as controls. That gives the ability to compare those who are experiencing an EGID relative to those who aren't.

[35:22] When you join EGID Partners, they provide you with a set of questionnaires to complete. Periodically, they push out a few more questionnaires.

[35:33] EGID Partners has provided some really great information about patient experience and answered questions that patients want to know about, like joint pain and symptoms outside the GI tract.

[36:04] To date, there are close to 900 participants in the registry from all over the world. As it continues to grow, it will give the ability to look at the patient experience in different geographical areas.

[36:26] Dr. Dellon says we try to have it be interactive, because it is a collaboration with patients. The Steering Committee works with APFED and other patient advocacy groups from around the world.

[36:41] The EGID Partners website shows general patient locations anonymously. It shows the breakdown of adults with the condition and caregivers of children with the condition, the symptom distribution, and the treatment distribution.

[37:03] As papers get published and abstracts are presented, EGID Partners puts them on the website. Once someone joins, they can suggest a research idea. Many of the studies they have done have come from patient suggestions.

[37:20] If there's an interesting idea for a survey, EGID Partners can push out a survey to everybody in the group and answer questions relatively quickly.

[37:57] Dr. Dellon says a paper came out recently about telehealth. EoE care, in particular, is a good model for telehealth because it can expand access for patients who don't have providers in their area.

[38:22] EoE is a condition where care involves a lot of discussion but not a lot of need for physical exams and direct contact, so telehealth can make things very efficient.

[38:52] EGID Partners surveyed patients about telehealth. They thought it was efficient and saved time, and they had the same kind of interactions as in person. In general, in-state insurance covered it. Patients were happy to do those kinds of visits again.

[39:27] Holly says Dr. Furuta, herself, and others were published in the Gastroenterology journal in 2019 about starting to do telehealth because patients coming to the Children's Hospital of Colorado from out of state had no local access to feeding therapy.

[39:50] Holly went to the board, and they allowed her to get licensure in different states. She started with some of the most impacted patients in Texas and Florida in 2011 and 2012. They collected data. They published in 2019 about telehealth's positive impact.

[40:13] When 2020 rolled around, Holly had trained a bunch of people on how to do feeding therapy via telehealth. You have to do all kinds of things, like make yourself disappear, to keep the kids engaged and in their chairs!

[40:25] Now it is Holly's primary practice. She has licenses in nine states. She sees people all over the country. With her diagnosis, her physicians at Mass General have telehealth licensure in Maine. She gets to do telehealth with them instead of driving two hours.

[40:53] Dr. Jensen tells of two of the things they hope to do at EGID Partners. One is trying to understand more about reproductive health for patients with an EGID diagnosis. Only a few studies have looked at this question, and with very small samples.

[41:15] As more people register for EGID Partners, Dr. Jensen is hoping to be able to ask some questions related to reproductive health outcomes.

[41:27] The second goal is a survey suggested by the Student Advisory Committee, asking questions related to the burden of disease specific to the teen population.

[41:48] This diagnosis can hit that population particularly hard, at a time when they are trying to build and sustain friendships and are transitioning to adult care and moving away from home. This patient population has a unique perspective we wanted to hear.

[42:11] Dr. Jensen and Dr. Dellon work on all kinds of other projects, too.

[42:22] Dr. Dellon says they have done a lot of work on the early-life factors that may predispose to EoE. They are working on a large epidemiologic study to get some insight into early-life factors, including factors that can be measured in baby teeth.

[42:42] That's outside of EGID Partners. It's been ongoing, and they're getting close, maybe over the next couple of years, to having some results.

[43:03] Ryan says all of those projects sound so interesting. We need to have you guys back to dive into those results when you have something finalized.

[43:15] For our listeners who want to learn more about eosinophilic disorders, we encourage you to visit apfed.org and check out the links in the show notes below.

[43:22] If you're looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.

[43:31] 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.

[43:41] Ryan thanks Dr. Dellon and Dr. Jensen for joining us today. This was a fantastic conversation. Holly also thanks APFED's Education Partners GSK, Sanofi, Regeneron, and Takeda for supporting this episode.

Mentioned in This Episode:

Evan S. Dellon, MD, MPH, Academic Gastroenterologist, University of North Carolina School of Medicine

Elizabeth T. Jensen, MPH, PhD, Epidemiologist,

Wake Forest University School of Medicine,

University of North Carolina at Chapel Hill

Predictors of Patients Receiving No Medication for Treatment of Eosinophilic Esophagitis in the United States: Data from the TARGET-EGIDS Cohort

Episode 15: Access to Specialty Care for Eosinophilic Esophagitis (EoE)

APFED on YouTube, Twitter, Facebook, Pinterest, Instagram

Real Talk: Eosinophilic Diseases Podcast

apfed.org/specialist

apfed.org/connections

apfed.org/research/clinical-trials

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

Tweetables:

"I've been working on eosinophilic gastrointestinal diseases for about 15 years. I started some of the early work around understanding possible risk factors for the development of disease. I've gone on to support lots of other research projects." — Elizabeth T. Jensen, MPH, PhD

"You can think of EoE as asthma of the esophagus or eczema of the esophagus, although in general, people don't grow out of EoE, like they might grow out of eczema or asthma. When people have it, it really is a long-term condition." — Evan S. Dellon, MD, MPH

"There are two general approaches to treating the underlying condition, … using medicines and/or eliminating foods from the diet that we think may trigger EoE. I should say, for a lot of people, EoE is a food-triggered allergic condition." — Evan S. Dellon, MD, MPH

"I didn't find it that surprising [that there are patients who had no treatment]. Some patients are relatively asymptomatic, and others are not interested in pursuing medications initially or are … still exploring dietary treatment options." — Elizabeth T. Jensen, MPH, PhD

"We have a bunch of studies now that look at how long people have symptoms before they're diagnosed. There's a wide range. Some people get symptoms and are diagnosed right away. Other people might have symptoms for 20 or 30 years." — Evan S. Dellon, MD, MPH

"EGID Partners is an online registry where individuals, caregivers, and parents of children affected with EGIDs can join. EGID Partners also needs people who don't live with an EGID to join, as controls." — Elizabeth T. Jensen, MPH, PhD

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. Andrew Lee, Vice President, Clinical Research at Uniquity Bio, about Thymic Stromal Lymphopoietin (TSLP) and eosinophilic esophagitis (EOE).

Disclaimer: The information provided in this podcast is designed to support, not replace, the relationship 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.

[1:13] Holly introduces today's topic, Thymic Stromal Lymphopoietin (TSLP) and eosinophilic esophagitis (EOE), and today's guest, Dr. Andrew Lee, Vice President, Clinical Research at Uniquity Bio.

[1:36] Dr. Lee has nearly 20 years of experience in the clinical development of new vaccines, biologics, and drugs. Holly welcomes Dr. Lee.

[1:52] Dr. Lee trained in internal medicine and infectious diseases.

[1:58] Dr. Lee has been fascinated by the immune system and how it can protect people against infections, what happens when immunity is damaged, as in HIV and AIDS, and how to apply that knowledge to boost immunity with vaccines to prevent infections.

[2:16] Dr. Lee led the clinical development for a pediatric combination vaccine for infants and toddlers. It is approved in the U.S. and the EU.

[2:29] Dr. Lee led the Phase 3 Program for a monoclonal antibody to prevent RSV, a serious infection in infants. That antibody was approved in June 2025 for use in the U.S.

[2:44] In his current company, Dr. Lee leads research into approaches to counteract an overactive immune system. They're looking at anti-inflammatory approaches to diseases like asthma, EoE, and COPD.

[2:58] Dr. Lee directs the ongoing Phase 2 studies that they are running in those areas.

[3:28] Dr. Lee sees drug development as a chance to apply cutting-edge research to benefit people. He trained at Bellevue Hospital in New York City in the 1990s.

[3:40] When Dr. Lee started as an intern, there were dedicated ICU wards for AIDS patients because many of the sickest patients were dying of AIDS and its complications.

[3:52] Before the end of Dr. Lee's residency, they shut down those wards because the patients were on anti-retroviral medications and were doing so well that they were treated as outpatients. They didn't need dedicated ICUs for AIDS patients anymore.

[4:09] For Dr. Lee, that was a powerful example of how pharmaceutical research and drug regimen can impact patients' lives for the better by following the science. That's what drove Dr. Lee to go in the direction of research.

[4:48] Dr. Lee explains Thymic Stromal Lymphopoietin (TSLP). TSLP serves as an alarm signal for Type 2 or TH2 inflammation, a branch of the immune responses responsible for allergic responses and also immunity against parasites.

[5:17] When the cells that line the GI tract and the cells that line the airways in our lungs receive an insult or an injury, they get a danger signal, then they make TSLP.

[5:28] This signal activates other immune cells, like eosinophils and dendritic cells, which make other inflammatory signals or cytokines like IL-4, IL-13, and IL-5.

[5:47] That cascade leads to inflammation, which is designed to protect the body in response to the danger signal, but in some diseases, when there's continued exposure to allergens or irritants, that inflammation goes from being protective to being harmful.

[6:15] That continued inflammation, over the years, can lead to things like the thickened esophagus with EoE, or lungs that are less pliant and less able to expand, in respiratory diseases.

[6:48] Dr. Lee says he thinks of TSLP as being a master switch for this branch of immune responses. If you turn on TSLP, that turns on a lot of steps that lead to generating an allergic type of response.

[7:06] It's also the same type of immune response that can fight off parasite infections. It's the first step in a cascade of other steps generating that type of immune response.

[7:30] Dr. Lee says people have natural genetic variation in the genes that incur TSLP.

[7:38] Observational studies have found that some people with genetic variations that lead to higher levels of TSLP in their bodies had an increased risk for allergic inflammatory diseases like EoE, atopic dermatitis, and asthma.

[8:13] Studies like the one just mentioned point to TSLP being important for increased risk of developing atopic types of diseases like EoE and others. There's been some work done in the laboratory that shows that TSLP is important for activating eosinophils.

[8:38] There's accumulating evidence that TSLP activation leads to eosinophil activation, other immune cells, or white blood cells getting activated.

[9:07] Like a cascade, those cells turn on T-cells and B-cells, which are like vector cells. They lead to direct responses to fight off infections, in case that's the signal that leads to the turning on TSLP.

[9:48] Ryan refers to a paper published in the American Journal of Gastroenterology exploring the role of TSLP in an experimental mouse model of eosinophilic esophagitis. Ryan asks what the researchers were aiming to find.

[10:00] Dr. Lee says the researchers were looking at the genetic studies we talked about, the observational studies that are beginning to link more TSLP with more risk for EoE and those types of diseases.

[10:12] The other type of evidence that's accumulating is from in vitro (in glass) experiments or test tube experiments, where you take a couple of cells that you think are relevant to what's going on.

[10:28] For example, you could get some esophageal cells and a couple of immune cells, and put TSLP into the mix, and you see that TSLP leads to activation of those immune cells and that leads to some effects on the esophageal cells.

[10:42] Those are nice studies, but they're very simplified compared to what you can do in the body. These researchers were interested in extending those initial observations from other studies, but working in the more realistic situation of a mouse model.

[11:00] You have the whole body of the mouse being involved. You can explore what TSLP is doing and model a disease that closely mimics what's happening with EoE in humans.

[12:23] They recreated the situation of what seems to be happening in EoE in people. We haven't identified it specifically, but there's some sort of food allergen in patients with EoE that the immune system is set off by.

[12:55] What researchers are observing in this paper is that in these mice that were treated with oxazolone, there is inflammation in the esophagus, an increase in TSLP levels, and eosinophils going into the esophageal tissues.

[13:15] Dr. Lee says, that's one of the main ways we diagnose EoE; we take a biopsy of the esophagus and count how many eosinophils there are. Researchers saw similar findings. The eosinophil count in the esophageal tissues went way up in these mice.

[13:34] Researchers also saw other findings in these mice that are very similar to EoE in humans, such as the esophageal cells lining the esophagus proliferating. They even saw that new blood vessels were being created in that tissue that's getting inflamed.

[14:00] Dr. Lee thinks it's a very nice paper because it shows that correlation: Increase TSLP and you see these eosinophils going to the esophagus, and these changes that are very reminiscent of what we see in people with EoE.

[14:51] In this paper, the mice made the TSLP, and researchers were able to measure the TSLP in the esophageal tissue. The researchers didn't introduce TSLP into the mice. The mice made the TSLP in response to being repeatedly exposed to oxazolone.

[15:20] That's key to the importance of the laboratory work. The fact that the TSLP is made by the mice is important. It makes it a very realistic model for what we're seeing in people.

[15:41] In science, we like to see correlation. The researchers showed a nice correlation.

[15:46] When TSLP went up in these mice, and the mice were making more TSLP on their own, at the same time, they saw all these changes in the esophagus that look a lot like what EoE looks like in people.

[16:01] They saw the eosinophils coming into the esophagus. They saw the inflammation go up in the esophagus. What Dr. Lee liked about this paper is that they continued the story.

[16:15] The researchers took something that decreases TSLP levels, an antibody that binds to and blocks TSLP, and when they did that, they saw the TSLP levels come down to half the peak level.

[16:35] Then they saw improvement in the inflammation in the esophagus. They saw that the amount of eosinophils decreased, and the multiplication of the esophageal cells went down. The number of new blood vessels went down after the TSLP was reduced.

[16:53] Dr. Lee says, you see correlation. The second part is evidence for causation. When you take TSLP away, things get better. That gives us a lot of confidence that this is a real finding. It's not just observational. There is causation evidence here.

[18:26] Ryan asks if cutting TSLP also help reduce other immune response cells. Dr. Lee says TSLP is the master regulator for this Type 2 inflammation. It definitely touches and influences other cells besides eosinophils.

[18:44] TSLP affects dendritic cells, which are an important type of immune cell, like a coordinating cell that instructs other cells within the immune system what to do. In this paper, they looked at a lot of other effects of TSLP on the tissues of the body.

[19:10] Dr. Lee says, There's a lot of research on TSLP, and one of the reasons we're excited about the promise of TSLP is that it's so far upstream; so much of the beginning, that it's affecting other cells.

[19:29] Its effects could be quite broad. If we're able to successfully block TSLP, we could block a lot of different effects.

[19:40] One treatment for EoE is dupilumab, which blocks IL-4 and IL-13 specifically, and that works well, but TSLP has the potential to have an even greater effect than blocking IL-4 and IL-13, since it is one step before turning on IL-4 and IL-13.

[20:14] That's one of the reasons researchers are excited about the promise of blocking TSLP. There are studies ongoing of TSLP blockers in people with EoE.

[20:34] Ryan asks if there are negative repercussions from blocking TSLP. Dr. Lee says in this study and in people, we are not completely blocking TSLP by any means. There will still be residual TSLP activated, even with very potent drugs.

[21:01] In the study, they block TSLP about 50%‒60%. TSLP is involved in immunity against parasites. In studies with people, they make sure not to include anybody who has an active parasitic infection. A person under treatment should not be in a study.

[21:27] Dr. Lee says we haven't seen any problems with parasitic infections becoming more severe, but that is a theoretical possibility, so for that reason, in studies with TSLP blockers, we generally exclude patients with known parasitic infections.

[22:17] What excited Dr. Lee in this paper was that they showed that when you block TSLP in the mice, then you get real effects in their tissues. Eosinophils went away. The thickening of the basal layers in the esophagus got much better.

[22:38] That kind of real effect reflected in the tissue is super exciting to see. That gives us more confidence that this could work in people, since we're seeing it in a realistic whole-body model in the mice.

[23:12] Dr. Lee says there are ongoing clinical studies on TSLP blockers for EoE. His company is studying an antibody that blocks TSLP in eczema, COPD, and EoE. One of the exciting things about immunology is that it affects many different parts of the body.

[23:42] EoE is associated with other immune-type disorders. There's a high percentage of patients with EoE who have other diseases. EoE coexists with asthma, atopic dermatitis, and chronic rhinitis.

[24:09] It's exciting that if you figure out something that's promising for one disease that TSLP affects, it could have very broad-ranging implications for a variety of diseases.

[24:22] Ryan shares his experience of his doctor talking to him about a TSLP blocker, tezepelumab, as a potential option when it's out of clinical trials. It would target something a little higher up the chain and help with some of his remaining symptoms.

[24:59] Ryan is excited to hear that this research is so encouraging and how it could potentially help treat EoE, asthma, and other conditions, all at once.

[25:16] Dr. Lee says that being in these later-stage studies is super exciting. If these late-stage trials are successful, the next step is to apply for regulatory approval with the various agencies around the world.

[26:40] Dr. Lee shares one takeaway for listeners to remember. Think of TSLP as an alarm that turns on inflammation. He compares TSLP to turning on an alarm during a robbery. There are multiple steps designed to protect the bank and the money.

[27:20] To extend that analogy, with TSLP, once you turn it on, all these other steps are going to happen. Inflammation is designed to protect the body. It's a protective response. If there's an infection, it can clear the infection.

[27:38] If the infection persists, as in HIV, the immune response, which is protective and beneficial, eventually becomes damaging. It becomes dysfunctional. In EoE, if you continually eat the allergic food, the inflammation becomes damaging to the esophagus.

[28:27] Long-term inflammation leads to replacing the normal esophageal tissue with fibrotic tissue, and that's why the esophagus eventually gets hardened and less able to let the food go through.

[28:40] In respiratory diseases, the soft tissue of the lung gets replaced with thicker tissue, and the lung is not able to expand.

[28:54] Dr. Lee says he people to think about TSLP as this master alarm switch. We hope that if you could turn off that TSLP, you could then avoid a lot of the complications that we see with chronic inflammation in these conditions.

[29:14] We're hopeful that you could even take away the symptoms that you see in these diseases, make patients feel better, and with extended treatment, you could begin to reverse some of the damage resulting from inflammation.

[29:32] Ryan likes that analogy and how Dr. Lee has concisely explained these complicated concepts.

[29:51] Dr. Lee thanks Holly and Ryan and adds one more plea to listeners. Please consider getting involved with research. Clinical trials cannot be done without patients. We need patients to advance new treatments.

[30:27] Researchers like Dr. Lee spend a lot of time thinking about how to make the studies not only informative but also fair to patients who decide to become involved. It's a lot of work and a fair amount of time commitment.

[30:44] If you don't want to be in a study, you can help by being on a patient feedback panel and reviewing protocols and informed consents. Follow your interests. Think about getting involved with research, however you can.

[31:06] Ryan and Holly are very grateful for the community, with so many wonderful clinicians and researchers, and so many patients who are willing to volunteer their time and their data to help researchers find better solutions going forward.

[31:26] Ryan thanks Dr. Lee for coming on and putting out that call to action. It's a great reminder for listeners and the patients in the community to look for those opportunities. Chat with your physician. Go to APFED's website. There's a link to active clinical trials.

[31:47] For our listeners who want to learn more about eosinophilic disorders, we encourage you to visit apfed.org and check out the links in the show notes below.

[31:53] For those looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.

[32:01] 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.

[32:11] Ryan thanks Dr. Andrew Lee for joining us today. We learned a lot. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda for supporting this episode.

Mentioned in This Episode:

Andrew Lee, M.D., VP Clinical Research, Uniquity Bio

"A Mouse Model for Eosinophilic Esophagitis (EoE)" Current Protocols, Wiley Online Library

APFED on YouTube, Twitter, Facebook, Pinterest, Instagram

Real Talk: Eosinophilic Diseases Podcast

apfed.org/specialist

apfed.org/connections

apfed.org/research/clinical-trials

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:

"I see drug development as a chance to apply cutting-edge research to benefit people." — Andrew Lee, M.D.

"When the cells that line the GI tract and the cells that line the airways in our lungs receive an insult or an injury, they get a danger signal, then they make TSLP." — Andrew Lee, M.D.

"Observational studies have found that some people with genetic variations that lead to higher levels of TSLP in their bodies had an increased risk for allergic inflammatory diseases like EoE, atopic dermatitis, and asthma." — Andrew Lee, M.D.

"There's a lot of research on TSLP, and one of the reasons we're excited about the promise of TSLP is that it's so far upstream; so much of the beginning, that it's affecting other cells." — Andrew Lee, M.D.

"Please consider getting involved with research. We can't do these clinical trials without patients. We need patients to advance new treatments for patients." — Andrew Lee, M.D.

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 three high school students who made less invasive EoE diagnostics the focus of a science fair project.

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:

[:51] 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.

[1:08] Holly introduces today's guests, three high school students from Texas who made EoE diagnostics the focus of a science fair project: Leyna, Nhu, and Jaden.

[1:47] Leyna, Nhu, and Jaden are best friends. Nhu was diagnosed with EoE last summer. Leyna said Nhu told them it took a long time for the doctors to diagnose her because they thought it could be different conditions.

[2:07] Nhu told them about her appointments and her endoscopy procedures. She had to miss school sometimes. Leyna and Jaden were concerned for her.

[2:22] Leyna took AP Bio. Her teacher was a sponsor for the science fair. Leyna thought this would be a meaningful project for the three friends to learn more about Nhu's condition.

[2:45] Holly shares that she wasn't diagnosed until her 20s, but she was sick for much of her childhood.

[3:13] Ryan shares that he was diagnosed when he was two, after two years of his parents taking him to different doctors and undergoing different tests.

[3:31] Nhu says it was hard to find a specialist. They found one and had to wait six months for an appointment. It was a long time, suffering from the effects of EoE with constant symptoms, a lot of heartburn, and painful vomiting.

[4:00] Nhu was diagnosed with EoE in her sophomore year of high school. Her friends have seen her endure a lot, but she's strong. Nhu had to miss an orchestra concert where she had a big solo, because of her EoE.

[4:32] Doctors thought Nhu could have something different, like H. Pylori or cyclic vomiting syndrome. They didn't have clear answers, which was confusing and frustrating for her family.

[4:50] Holly talks about how difficult it was for her to get a diagnosis, and how she was told she was vomiting to get attention. She shared her reaction when diagnosed. She would like someone to do a research study about the pain tolerance of people with EoE.

[5:41] Leyna says junior year is the hardest year of high school. She doesn't know how Nhu survived physics and AP classes with EoE on top of it, and making up late work.

[6:14] Nhu takes a weekly injection. Her symptoms happen almost monthly. Sometimes she misses school for two weeks and has to catch up on work. Leyna and Jaden help her with her schoolwork.

[6:47] Ryan shared how he missed a third of his senior year in high school. He's now on an injectable biologic that has helped him a lot. That treatment option wasn't available when he was in high school. Having supportive friends to send him his schoolwork and keep him up-to-date was very helpful.

[7:11] Ryan explains the esophageal string test (EST). This is a tool that was developed to help monitor eosinophilic esophagitis (EoE). The test works by having the patient swallow a capsule about the size of a Tic Tac that has a string attached.

[7:25] The capsule dissolves in the stomach while the string stays in place in the esophagus. After about an hour, it's gently removed. Along the way, the string collects samples from the lining of the esophagus, which are reviewed, similarly to a biopsy.

[7:37] Holly adds that what makes the string test unique is that it doesn't require an endoscope, anesthesia, or recovery time, things that usually come with a traditional endoscopy and biopsy.

[7:46] It's now being used with patients as young as four years old. While some people might feel some minor discomfort, it's generally much easier for regular monitoring than an endoscopy.

[7:57] Holly explains that she was involved in testing the device and developing a swallowing protocol for it at Children's Hospital of Colorado. We will talk more about this later in the episode.

[8:06] Ryan adds, to learn more about the development of the string test, listen to episode 26 of this podcast.

[8:10] The string test is one of multiple, less-invasive monitoring tools for eosinophilic esophagitis. Others include the sponge test and unsedated trans-nasal endoscopy.

[8:19] To learn more about unsedated transnasal endoscopy, listen to episodes 19 and 20, where we talk to clinicians and patients about this method.

[8:27] During that episode, we talked to the developers of the EST.

[8:38] Jaden tells how he, Leyna, and Nhu brainstormed ideas and decided to base their project specifically on how to diagnose EoE in a less invasive way than endoscopies.

[9:12] Before this project, they were not familiar with the EST. Nhu says her only option for diagnosis was an endoscopy.

[9:21] Holly says it's still like that in Maine. She came from an area of the country where the EST was researched, and it's interesting to her that she doesn't have access to it now.

[9:37] What appealed to the group about the EST as an alternative to endoscopies is that it was so different. There are so many advanced technologies, and the EST is just a capsule taped to a string. It is simple but innovative.

[10:13] Real Talk: Eosinophilic Diseases had Drs. Robin Shandas and Steven Ackerman, who were instrumental in the development of the esophageal string test, as guests on episode 26 of this podcast. Ryan encourages listeners to check out that episode at apfed.org/podcasts.

[10:42] They searched for keywords and analyzed a variety of scholarly literature. They collected a lot of data from Dr. Ackerman's papers.

[11:10] They also reached out to gastroenterologists on social media. A hard thing about science fair projects is coming up with an experiment. They didn't know what they could do just with compiled research, but they had a great sponsor who helped along the way.

[11:56] Leyna says they trusted that the doctors they reached out to on social media were competent in their understanding of different diagnostic methods. She notes that different locations may have different resources and different biases.

[12:14] Leyna says they talked to doctors in the U.S. and from different countries, including India and Mexico. She commented that communities in Mexico might not have the same resources as communities in the U.S. or India. That might change their understanding of the EST.

[12:33] We might have different biases because we don't have the same technology to research and find the same things about the EST.

[13:12] Leyna says they reached out to doctors on social media, but didn't get responses from that many doctors. Reaching out to patients would be a good thing if they want to continue the project.

[14:00] Jaden says most of the data they found was from Dr. Ackerman, including a survey he did comparing the data of the EST and the biopsies.

[14:10] They found that the EST and the biopsies were relatively similar in terms of discovering the eosinophilic count and determining whether the EoE is active or inactive.

[15:30] They found differences between ESTs and biopsies in finding how much of a certain chemical is in the patient's cells.

[14:43] Leyna comments that one of the doctors they reached out to told them about the sponge test, another less invasive method. They didn't research the sponge test, but it sounded interesting.

[15:00] Ryan says there are a lot of cool new techniques that are being researched, like the transnasal endoscopy that goes in through the nose, the string test, and the sponge test.

[15:13] Leyna says the cool thing was hearing about all these methods. They had hypothesized that there are less invasive methods that may be better than endoscopies.

[15:27] They were not able to prove their hypothesis yet. They learned a lot of different things that could be beneficial.

[15:42] Holly points out that the transnasal endoscopy is not scary. It's also known as the unsedated endoscopy. Holly has done both the EST and the unsedated endoscopy, and they each have pluses and minuses.

[16:15] Nhu explains how the team would meet at one of their houses, usually Leyna's house. One day, they watched Interstellar together, and the "Eureka moment" scene motivated them.

[16:41] They helped each other whenever necessary. When the project board was due, they all went to Leyna's house to work on the project board. They worked together as a team.

[16:51] Jaden analyzed a lot of the data. Leyna reached out to professors. Nhu helped Jaden understand some terms. On the day they presented the project, Nhu was sick in the hospital, which made them sad. They included a photo of her on the project board.

[17:28] Holly says that although Nhu wasn't there, it may have helped people know how sick EoE can make you feel.

[18:28] Leyna says one of the doctors they reached through social media told them that endoscopies have lots of benefits. The biopsy samples give healthcare professionals a clear idea of how many eosinophils per high-powered field, a key indicator in diagnosing EoE.

[18:57] The diagnosis gives a baseline for starting treatment for the patient, monitoring how effective the treatment is. You can't count the number of eosinophils per high-powered field using the string test.

[19:11] The EST is a gelatin capsule attached to a long string that you swallow. It dissolves in the stomach. It's less expensive than an endoscopy.

[19:33] Holly says one of the big differences is that you can't diagnose EoE on a string test. It has to be diagnosed with an endoscopy.

[19:40] Leyna says they learned that from the doctors and medical students who reviewed their project board. You can't diagnose EoE with the EST, but you can monitor it.

[19:52] The string test doesn't provide a direct eosinophil count, but it reflects the level of inflammation in your esophagus, and it can measure the protein biomarkers. That correlates with the eosinophil count from a biopsy. It is good for monitoring EoE.

[20:12] Ryan says that's a great idea. In the show notes, there is a link to the diagnostic consensus guidelines. They specify that you need an endoscopy and 15 eosinophils per high-powered field to be diagnosed with EoE.

[20:28] The EST can monitor the progression of the disorder as you're trying new medicines or an elimination diet. If you need an endoscopy every three to six months, it can be taxing.

[20:49] Ryan comments on the cost. Going through anesthesia for an endoscopy is very expensive, and not everyone has the insurance to cover these diagnostic procedures. The EST is an option you can do in a doctor's office in just over an hour.

[21:16] Holly asks if Nhu has participated in a string test. Nhu has not, but she would love to do a string test if she had the chance. Whenever she sees her doctor, she brings up her condition, and what could be better for her, such as the string test.

[22:06] The science fair is a huge regional fair in Houston, called the Science and Engineering Fair of Houston (SEFH). This was their first year participating. They were regional qualifiers from their district. When they got there, everyone else had six-foot-tall printed boards. It was a shock to them.

[22:56] They hope to level up their board for next year's fair. It was cool and eye-opening to see all these student researchers and get feedback from the people who walked by their booth. They heard some interesting things to use in their next project.

[23:15] One medical student in attendance came by their project board and suggested that while the EST may not diagnose EoE, maybe it could be used as a screening tool [to help identify people who should follow up with a gastroenterologist for a diagnostic work-up]. Interestingly, this was a medical student, and she had recently scheduled an appointment with a gastroenterologist for an endoscopy to see if she has EoE.

[24:04] This student didn't seem to know much about EoE, but felt she was experiencing symptoms that might indicate EoE. She told them she had learned so much from their board. Ryan says it's great that the project was able to help this person.

[24:44] Jaden says that the students at their school didn't know much about EoE, but when they looked at the project board, they were shocked by how incredibly difficult it is to diagnose EoE and how the EST could change a lot of things as a screening method.

[25:11] Jaden says their science teacher came by to see their board and how they were doing. He liked how they included not only the research information but also the stories of why they chose their project and why they were passionate about it.

[25:34] The day of the project, Leyna and Jaden were sad that Nhu couldn't be there with them. Their sponsor, Leyna's biology teacher, was sick, but showed up at the fair to view their presentation. They raised awareness about EoE. People learned about it.

[25:54] When Nhu told Leyna about her EoE, Leyna had no idea what it was. She's glad their project brought the issue to the table. They emphasized that more research needs to be done. There is much we don't know about less invasive methods.

[26:23] Nhu has considered a career in medicine since she has been in many hospitals and talked to a lot of doctors. Jaden sees himself in the engineering field, but he enjoys researching like this and seeing things through a different perspective.

[27:05] Nhu learned a lot about herself with EoE. Leyna loves how much they learned from this project. She is interested in pursuing scientific research. She thinks it's cool that Ryan is a graduate student.

[27:24] Leyna just got back from a five-week summer research program. It was insightful. She doesn't see herself becoming a doctor, but possibly doing research and advocating for different conditions.

[27:43] When Ryan was in high school, with all his hospital time, he had an interest in medicine, then he took a turn into engineering. He enjoys research. He's passionate about engaging in patient advocacy work through APFED.

[28:10] Ryan is glad for Leyna, Nhu, and Jaden that they were able to engage with this research and do it as a group and as friends. He says it's fantastic to hear from the group about the whole process they went through.

[28:23] Holly asks, looking back on everything you guys learned and experienced in this project, what's one question or idea you would still like to explore if you had more time and resources?

[28:38] Nhu wants to research finding more ways to diagnose EoE. Testing for EoE and finding EoE are very interesting for her.

[28:53] Jaden thinks that if they had more time, they would try to create a model of the EST to show how it works. He would possibly try to improve upon the model or develop something new. Instead of just relying on the data we have, he would try to collect data.

[29:26] Leyna agrees. She would like to build a prototype, understand how the capsule works, and find out whether the string down the esophagus is uncomfortable.

[33:41] Ryan suggests there is a doctor who would let them try the string test so they could see how it feels. Holly tried the string test at a major children's hospital while it was being researched. She doesn't want to ask her patients to do something she hasn't done, since she has the diagnosis too.

[30:37] Ryan comments that he enjoyed hearing about the process of the project.

[30:51] Ryan gives a quick recap: The esophageal string test is a tool to help monitor EoE. It is not a tool to diagnose EoE. If you or a loved one has EoE or suspect that you might, ask your clinician about the string test to see if it's an option for you.

[31:03] Holly adds: School science fairs are one way to bring education about eosinophilic disorders to schools. We love hearing about community science fairs and school projects that teach others about these conditions.

[31:13] For those of you looking to learn more about eosinophilic esophagitis, we encourage you to visit apfed.org/EoE.

[31:23] For those looking to find specialists who treat EoE, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.

[31:30] Ryan thanks Leyna, Nhu, and Jaden for joining us today. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda for supporting this episode.

Mentioned in This Episode:

Dr. Robin Shandas

Dr. Steven Ackerman

"Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference"

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:

"Nhu and Jaden are my best friends. Recently, Nhu was diagnosed with EoE. I remember her telling us about the long diagnosis process. It took the doctors quite a long time to diagnose her because they thought it could be different conditions." — Leyna

"I thought that this would be a meaningful project for us to learn more about Nhu's condition [of EoE]." — Leyna

"The students at our school didn't know much about EoE, but when they looked at the project board, they were shocked by how incredibly difficult it is to diagnose EoE." — Jaden

"One of the main benefits of the string test is that endoscopies can be quite expensive, especially the anesthesia. It could be beneficial for people who don't have the money for an endoscopy." — Nhu

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 Anna Henderson, MD, a pediatric gastroenterologist at Northern Light Health in Maine, about bone mineral density in EoE patients. They discuss a paper she co-authored on the subject.

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:

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

[1:17] Holly introduces today's topic, eosinophilic esophagitis (EoE), and bone density.

[1:22] Holly introduces today's guest, Dr. Anna Henderson, a pediatric gastroenterologist at Northern Light Health in Maine.

[1:29] During her pediatric and pediatric gastroenterology training at Cincinnati Children's Hospital, she took a special interest in eosinophilic esophagitis. In 2019, Dr. Henderson received APFED's NASPGHAN Outstanding EGID Abstract Award.

[1:45] Holly, a feeding therapist in Maine, has referred many patients to Dr. Henderson and is excited to have her on the show.

[2:29] Dr. Henderson is a wife and mother. She loves to swim and loves the outdoors. She practices general pediatric GI in Bangor, Maine, at a community-based academic center.

[2:52] Her patient population is the northern two-thirds of Maine. Dr. Henderson feels it is rewarding to bring her expertise from Cincinnati to a community that may not otherwise have access to specialized care.

[3:13] Dr. Henderson's interest in EoE grew as a GI fellow at Cincinnati Children's. Her research focused on biomarkers for disease response to dietary therapies and EoE's relationship to bone health.

[3:36] As a fellow, Dr. Henderson rotated through different specialized clinics. She saw there were many unanswered questions about the disease process, areas to improve treatment options, and quality of life for the patients suffering from these diseases.

[4:00] Dr. Henderson saw many patients going through endoscopies. She saw the social barriers for patients following strict diets. She saw a huge need in EoE and jumped on it.

[4:20] Ryan grew up with EoE. He remembers the struggles of constant scopes, different treatment options, and dietary therapy. Many people struggled to find what was best for them before there was a good approved treatment.

[4:38] As part of Ryan's journey, he learned he has osteoporosis. He was diagnosed at age 18 or 19. His DEXA scan had such a low Z-score that they thought the machine was broken. He was retested.

[5:12] Dr. Henderson explains that bone mineral density is a key measure of bone health and strength. Denser bones contain more minerals and are stronger. A low bone mineral density means weaker bones. Weaker bones increase the risk of fracture.

[5:36] DEXA scan stands for Dual Energy X-ray Absorptiometry scan. It's a type of X-ray that takes 10 to 30 minutes. A machine scans over their bones. Typically, we're most interested in the lumbar spine and hip bones.

[5:56] The results are standardized to the patient's height and weight, with 0 being the average. A negative number means weaker bones than average for that patient's height and weight. Anything positive means stronger bones for that patient's height and weight.

[6:34] A lot of things can affect a patient's bone mineral density: genetics, dietary history, calcium and Vitamin D intake, and medications, including steroid use. Prednisone is a big risk factor for bone disease.

[7:07] Other risk factors are medical and auto-immune conditions, like celiac disease, and age. Any patient will have their highest bone density in their 20s to 30s. Females typically have lower bone mineral density than males.

[7:26] The last factor is lifestyle. Patients who are more active and do weight-bearing exercises will have higher bone mineral density than patients who have more of a sedentary lifestyle.

[7:56] Ryan was told his bone mineral density issues were probably a side-effect of the long-term steroids he was on for his EoE. Ryan is now on benralizumab for eosinophilic asthma. He is off steroids.

[8:36] Dr. Henderson says the research is needed to find causes of bone mineral density loss besides glucocorticoids.

[8:45] EoE patients are on swallowed steroids, fluticasone, budesonide, etc. Other patients are on steroids for asthma, eczema, and allergic rhinitis. These may be intranasal steroids or topical steroids.

[9:01] Dr. Henderson says we wondered whether or not all of those steroids and those combined risks put the EoE population at risk for low bone mineral density. There's not a lot published in that area.

[9:14] We know that proton pump inhibitors can increase the risk of low bone mineral density. A lot of EoE patients are on proton pump inhibitors.

[9:23] That was where Dr. Henderson's interest started. She didn't have a great way to screen for bone mineral density issues or even know if it was a problem in her patients more than was expected in a typical patient population.

[9:57] Holly wasn't diagnosed with EoE until she was in her late 20s. She was undiagnosed but was given prednisone for her problems. Now she wonders if she should get a DEXA scan.

[10:15] Holly hopes the listeners will learn something and advocate for themselves or for their children.

[10:52] If a patient is concerned about their bone mineral density, talking to your PCP is a perfect place to start. They can discuss the risk factors and order a DEXA scan and interpret it, if needed.

[11:11] If osteoporosis is diagnosed, you should see an endocrinologist, specifically to discuss therapy, including medications called bisphosphonates.

[11:36] From an EoE perspective, patients can talk to their gastroenterologist about what bone mineral density risk factors may be and if multiple risk factors exist. Gastroenterologists are also more than capable of ordering DEXA scans and helping their patients along that journey.

[11:53] A DEXA scan is typically the way to measure bone mineral density. It's low radiation, it's easy, it's fast, and relatively inexpensive.

[12:10] It's also useful in following up over time in response to different interventions, whether or not that's stopping medications or starting medications.

[12:30] Dr. Henderson co-authored a paper in the Journal of Pediatric Gastroenterology and Nutrition, called "Prevalence and Predictors of Compromised Bone Mineral Density in Pediatric Eosinophilic Esophagitis." The study looked at potential variables.

[12:59] The researchers were looking at chronic systemic steroid use. They thought it was an issue in their patients, especially patients with multiple atopic diseases like asthma, eczema, and allergic rhinitis. That's where the study started.

[13:22] Over the years, proton pump inhibitors have become more ubiquitous, and more research has come out. The study tried to find out if this was an issue or not. There weren't any guidelines for following these patients, as it was a retrospective study.

[13:42] At the time, Dr. Henderson was at a large institution with a huge EoE population. She saw that she could do a study and gather a lot of information on a large population of patients. Studies like this are the start of figuring out the guidelines for the future.

[14:34] Dr. Henderson wanted to determine whether pediatric patients with EoE had a lower-than-expected bone mineral density, compared to their peers. [14:44] Then, if there were deficits, she wanted to determine where they were more pronounced. Were they more pronounced in certain subgroups of patients with EoE?

[14:59] Were they patients with an elemental diet? Patients with an elimination diet? Were they patients on steroids or PPIs? Were they patients with multiple atopic diseases? Is low bone mineral density just a manifestation of their disease processes?

[15:14] Do patients with active EoE have a greater propensity to have low bone mineral density? The study was diving into see what the potential risk factors are for this patient population.

[15:45] The study was a retrospective chart review. They looked at patients aged 3 to 21. You can't do a DEXA scan on a younger patient, and 21 is when people leave pediatrics.

[16:03] These were all patients who had the diagnosis of EoE and were seen at Cincinnati Children's in the period between 2014 and 2017. That period enabled full ability for chart review. Then they looked at the patients who had DEXA scans.

[16:20] They did a manual chart review of all of the patients and tried to tease out what the potential exposures were. They looked at demographics, age, sex, the age of the diagnosis of EoE, medications used, such as PPIs, and all different swallowed steroids.

[16:44] They got as complete a dietary history as they could: whether or not patients were on an elemental diet, whether that was a full elemental diet, whether they were on a five-food, six-food, or cow's milk elimination diet.

[16:58] They teased out as much as they could. One of the limitations of a retrospective chart review is that you can't get some of the details, compared to doing a prospective study. For example, they couldn't tease out the dosing or length of therapy, as they would have liked.

[17:19] They classified those exposures as whether or not the patient was ever exposed to those medications, whether or not they were taking them at the time of the DEXA scan, or if they had been exposed within the year before the DEXA scan.

[17:40] They also looked at whether the patients had other comorbid atopic disorders, to see if those played a role, as well.

[18:03] The study found that there was a slightly lower-than-expected bone mineral density in the patients. The score was -0.55, lower than average but not diagnostic of a low bone mineral density, which would be -2 or below.

[18:27] There were 23 patients with low bone mineral density scores of -2 or below. That was 8.6% of the study patients. Typically, only 2.5% of the population would have that score. It was hard to tease out the specific risk factors in a small population of 23.

[18:57] They looked at what the specific risk factors were that were associated with low bone mineral density, or bone mineral density in general.

[19:12] After moving from Colorado, Holly has transferred to a new care team, and doctors wanted her baseline Vitamin D and Calcium levels. No one had ever tested that on her before. Dr. Henderson says it's hard because there's nothing published on what to do.

[19:58] The biggest surprise in the study was that swallowed steroids, or even combined steroid exposure, didn't have any effect on bone mineral density. That was reassuring, in light of what is known about glucocorticoid use.

[20:16] The impact of PPI use was interesting. The study found that any lifetime use of PPIs did seem to decrease bone mineral density. It was difficult to tease out the dosing and the time that a patient was on PPIs.

[20:34] Dr. Henderson thinks that any lifetime use of PPIs is more of a representation of their cumulative use of PPIs. At the time of the study, from 2014 to 2017, PPIs were still very much first-line therapy for EoE; 97% of the study patients had taken PPIs at some time.

[21:02] There are so many more options now for therapy when a patient has a new diagnosis of EoE, especially with dupilumab now being an option.

[21:11] Dr. Henderson speaks of patients who started on PPIs and have stayed on them for years. This study allows her to question whether we need to continue patients on PPIs. When do we discuss weaning patients off PPIs, if appropriate?

[22:05] Ryan says these podcasts are a great opportunity for the community at large and also for the hosts. He just wrote himself a note to ask his endocrinologist about coming off PPIs.

[22:43] Dr. Henderson says that glucocorticoid use is a known risk factor for low bone mineral density and osteoporosis. In the asthma population, inhaled steroids can slightly decrease someone's growth potential while the patient is taking them.

[23:10] From those two facts, it was thought that swallowed steroids would have a similar effect. But since they're swallowed and not systemic, maybe things are different.

[23:23] It was reassuring to Dr. Henderson that what her study found was that the swallowed steroid didn't affect bone mineral density. There was one other study that found that swallowed steroids for EoE did not affect someone's height.

[23:51] Dr. Henderson clarifies that glucocorticoids include systemic steroids like prednisone and hydrocortisone.

[23:57] Based on Dr. Henderson's retrospective study, fluticasone as a swallowed steroid did not affect bone mineral density. It was hard to tease out the dosing, but the cumulative use did not seem to result in a deficit for bone mineral density.

[24:16] Holly shared that when she tells a family of a child she works with that the child's gastroenterologist will likely recommend steroids, she will now give them the two papers Dr. Henderson mentioned. There are different types of steroids. The average person doesn't know the difference.

[25:15] Dr. Henderson thinks that for patients who have multiple risk factors for low bone mineral density, it is reasonable to have a conversation about bone health with their gastroenterologist to see whether or not a DEXA scan would be worth it.

[25:56] If low bone mineral density is found, that needs to be followed up on.

[26:03] There are no great guidelines, but this study is a good start on what these potential risk factors are. We need some more prospective studies to look at these risk factors in more detail than Dr. Henderson's team teased out in this retrospective study.

[26:23] Dr. Henderson tells how important it is for patients to participate in prospective longitudinal studies for developing future guidelines.

[26:34] Holly points out that a lot of patients are on restrictive diets. It's important to think about the whole picture if you are starting a medication or an elimination, or a restricted diet. You have to think about the impact on your body, overall.

[27:11] People don't think of dietary therapy as medication, but it has risks and benefits involved, like a medication.

[27:50] Dr. Henderson says, in general, lifestyle management is the best strategy for managing bone health. Stay as active as you can with weight-bearing exercises and eating a well-balanced diet. If you are on a restrictive diet, make sure it's well-balanced.

[28:12] Dr. Henderson says a lot of our patients have feeding disorders, so they see feeding specialists like Holly. A balanced diet is hard when kids are very selective in their eating habits.

[29:10] Dr. Henderson says calcium and Vitamin D are the first steps in how we treat patients with low bone mineral density. A patient who is struggling with osteoporosis needs to discuss it with their endocrinologist for medications beyond supplementation.

[29:31] Ryan reminds listeners who are patients always to consult with their medical team. Don't go changing anything up just because of what we're talking about here. Ask your care team some good questions.

[29:47] Dr. Henderson would like families to be aware, first, that some patients with EoE will have bone mineral density loss, especially if they are on PPIs and restrictive diets. They should start having those discussions with their providers.

[30:04] Second, Dr. Henderson would like families to be reassured that swallowed steroids and combined steroid exposure didn't have an impact on bone mineral density. Everyone can take that away from today's chat.

[30:18] Lastly, Dr. Henderson gives another plug for patient participation in prospective studies, if they're presented with the opportunity. It's super important to be able to gather more information and make guidelines better for our patients.

[30:35] Holly thanks Dr. Henderson for coming on Real Talk — Eosinophilic Diseases and sharing her insights on bone mineral density, and supporting patients in Maine.

[30:57] Dr. Henderson will continue to focus on the clinical side. She loves doing outreach clinics in rural Maine. It's rewarding, getting to meet all of these patients and taking care of patients who would otherwise have to travel hours to see a provider.

[32:01] Ryan thinks the listeners got a lot out of this. For our listeners who would like to learn more about eosinophilic disorders, please visit APFED.org and check out the links in the show notes.

[32:11] If you're looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at APFED.org/specialist.

[32:19] 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.

[32:28] Ryan thanks Dr. Henderson for joining us today for this great conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, Sanofi, Regeneron, and Takeda for supporting this episode.

Mentioned in This Episode:

Anna Henderson, MD, a pediatric gastroenterologist at Northern Light Health in Maine

Cincinnati Children's

"Prevalence and Predictors of Compromised Bone Mineral Density in Pediatric Eosinophilic Esophagitis."

Journal of Pediatric Gastroenterology and Nutrition

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, Sanofi, Regeneron, and Takeda.

Tweetables:

"DEXA scan stands for dual-energy X-ray absorptiometry scan. It's a type of X-ray where a patient lies down for 10 to 30 minutes. A machine scans over their bones. Typically, we're most interested in the lumbar spine and hip bones." — Anna Henderson, MD

"We wondered whether or not all of those steroids and those combined risks even put our EoE population at risk for low bone mineral density. There's not a lot published in that area." — Anna Henderson, MD

"If a patient is worried [about their bone mineral density], their PCP is a perfect place to start for that. They're more than capable of discussing the risk factors specific for that patient, ordering a DEXA scan, and interpreting it if need be." — Anna Henderson, MD

"I think we need some more prospective studies to look at these risk factors in a little bit more detail than we were able to tease out in our retrospective review." — Anna Henderson, MD

"Just another plug for the participation in prospective studies, if you're presented with the opportunity. It's super important to be able to gather more information and to be able to make guidelines better for our patients about these risks." — Anna Henderson, MD

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 Bethany Doerfler, MS, RDN, a clinical research dietician specializing in lifestyle management of digestive diseases at Northwestern Medicine. Ryan and Holly discuss managing nutritional deficiencies in patients with non-EoE EGIDs and a study Bethany worked on.

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:

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

[1:17] Holly introduces today's topic, common nutritional deficiencies that affect those with eosinophilic gastrointestinal diseases that occur in the GI tract lower than the esophagus (non-EoE EGIDs).

[1:31] Holly introduces today's guest, Bethany Doerfler, a clinical research dietician specializing in lifestyle management of digestive diseases, including gastroesophageal reflux disease, motility disorders, and eosinophilic diseases.

[1:45] Bethany currently practices as part of a multi-disciplinary team in a digestive health institute at Northwestern Medicine.

[2:03] Bethany began working with this disorder almost 20 years ago. She worked with Dr. Gonsalves and Dr. Hirano at Northwestern. Dr. Gonsalves invited her to work with EoE patients. Bethany had not heard of EoE.

[2:59] Bethany says the lens that we've used to look at food as the trigger and also a therapeutic agent in the esophagus, we're looking at in non-EoE EGIDs as well; at the same time, trying to make sure that we're honoring the other parts of our patient's lives.

[3:27] Before Bethany started working in GI at Northwestern, she worked in the Wellness Institute, doing nutrition for patients at Northwestern. Bethany has a research background in epidemiology and she wanted to see better nutrition research in GI.

[3:56] Through a friend, Bethany connected with the Chief of GI at that point. Northwestern had never had a dietician working in GI.

[4:08] Bethany is pleased to see a trend in healthcare of thinking about the patient as a whole person, including diet, psychological wellness, physical health, exercise, sleep, and more. Bethany wanted to see more research on GI disorders.

[4:38] Bethany says that eosinophils in the esophagus indicate that something is irritating the tissues, such as reflux, food triggers, aeroallergens, and other things.

[4:58] Eosinophils do belong in the stomach, the small intestine, and the colon. The challenge for researchers has been, how many, where are they supposed to live, and what are they supposed to look like.

[5:10] There is eosinophilic gastritis, where eosinophils can infiltrate the stomach, causing a lot of inflammatory responses that make patients sick. We see that in all parts of the small intestine and less commonly, in the colon, as well.

[5:32] It's a good reminder for listeners that eosinophils are white blood cells. When they're in the tissues, they can swell things up and cause the body to have this inflammatory response in these lower GI tract organs.

[5:49] The symptoms patients can experience are vomiting, diarrhea, and abdominal pain, among other things.

[6:14] The nomenclature for this subset of eosinophil-associated diseases has changed and Bethany says to hang tight, there is lots of work underway to nail this down further in the next couple of months to a year.

[6:29] The last guidelines were published by a Delphi Consensus in 2022. The experts in the field got together and voted on the scientific accuracy of certain statements to develop cut points for how to grade.

[6:48] The experts are asking questions like: What counts as eosinophilic gastritis? What do we think are some of the symptoms and the clinical findings so that we all are looking at things through the same lens?

[7:02] To get to these consensus statements, there's a lot of discussion, agreement, and good collegial discussions about making sure that we're looking at this accurately.

[7:12] We're trying to give the right names to the right disorders and give clear diagnostic criteria, so that we're helping our patients get a diagnosis, and we're not labeling something incorrectly and sticking someone with an inaccurate diagnosis.

[7:36] The proper terminology is eosinophilic gastritis in the stomach, eosinophilic enteritis in the small intestine, eosinophilic colitis in the colon, and eosinophilic gastroenteritis where the stomach and the small bowel are involved.

[7:53] There's more to come on the clinical criteria of what makes that diagnosis but we're getting the names and the numbers right.

[8:03] Holly agrees that having the symptoms given a named diagnosis is important to patients, knowing that researchers are looking into their illness.

[9:00] Bethany notes that the diagnosis also means that there are opportunities for medical therapy, cut points for which medicines or therapies work or not, and billing codes. If we can't bill insurance companies, patients might not get certain services.

[9:28] Ryan tells how beneficial it was for him to have access to multi-disciplinary teams and see specialists he might not have seen without the proper diagnosis and just thought it was a GI issue. He was fortunate to see a dietician and start dietary therapy.

[9:53] Bethany says the dietician's priority is the patient's health and wellness.

[10:13] These disorders carry clinical non-gastrointestinal manifestations: fatigue, concern over what to eat, food access issues, family support, and other food allergies. These are important things for a dietician to consider.

[10:37] Are patients growing as they should? Do they feel like they have enough to eat? Do they feel excluded in social settings? There's a list of important things that we want to be looking at. That's why it's important to have a multi-disciplinary approach.

[11:07] First, Bethany wants to see that her patients are physically and nutritionally well. That's a priority if we're going to try to get rid of some of the food triggers that could be exacerbating the disease.

[11:20] Before Bethany takes anything out of someone's diet, she wants to make sure that they're getting enough of the good stuff to help them feel good and grow.

[11:29] From a diet therapy perspective, Bethany is trying to apply a food removal or substitution protocol to other spots outside the esophagus. They're seeing that some of the triggers are very similar, both in the stomach and small intestine.

[12:09] Dr. Gonsalves, Dr. Hirano, and Bethany did a study, The Elemental Study, where they wanted to uncover if food proteins carried the same trigger risk in the stomach and small intestine as they do in the esophagus.

[12:35] They put their patients on a hypoallergenic elemental formula for a period, followed up, and looked at their biopsies of the stomach and small intestine. Fifteen wonderful patients made it through the trial.

[12:56] One hundred percent of the patients achieved disease remission and felt better. There were some genetic alterations in the patients. Then they started the process of reintroducing foods over the year.

[13:15] That was not part of the original grant but was the team's clinical interest to see what it is that people are allergic to. Some of the common suspects: wheat, dairy, eggs, soy, and nuts, were found to be very common triggers for EoG and EoN, as well.

[13:47] The benefit of working with a dietician as part of your team is, first, we can remediate things the disease has caused nutritionally, and second, we can think about how diet can be a therapeutic tool to use with medications or instead of medication.

[14:15] If you want to use nutrition therapeutically, you don't have to stay there if it's not the right time to be taking things out of your diet. We have some good, safe, medical therapies. You can find your food triggers but you don't have to pick that lane forever.

[14:42] Holly and Ryan relate their experiences with traveling abroad and going on medical therapies when they can't stay on their diets.

[15:57] Bethany says low levels of vitamins and minerals in the blood can be caused by a disorder or an elimination diet. In the U.S., dairy is the biggest source of protein for young kids. It's also the biggest source of calcium and vitamin D.

[16:22] Dieticians often say, if we are going to use dietary therapy for EoE or non-EoE EGIDs, we have to think of this as a substitution diet. If we remove something, we have to replace it with something equally nutrient-dense.

[16:39] Bethany and her group look at serum values of Vitamin D, B12, and iron they assess for patients. For kids, instead of drawing blood, they piece together what they're taking against what they need and see if there are gaps to fill with food or supplements.

[17:32] In patients with non-EoE EGIDs, Bethany says we see the disease intersect with the food supply. When we take milk out, we're cutting the biggest source of calcium and Vitamin D. We have to replace calcium and Vitamin D.

[17:55] In the 1950s, a public health law allowed wheat to be enriched with folic acid and other B vitamins and iron. When we cut out wheat, our patients aren't getting enough iron or B vitamins. We have to replace those.

[18:16] For patients who have eosinophils in their stomach and small intestine, their absorption in the small bowel may be directly impacted.

[18:26] People can have low levels of protein in their blood, maybe because they're eating insufficient protein or maybe because the disease doesn't allow them to absorb protein sufficiently when there's swelling in the small intestine.

[18:44] There are other nutrients, like zinc, for people who have diarrhea, and magnesium if you can't eat a lot of whole grains and nuts, There are quite a few nutrients that Bethany is broadly looking at.

[18:54] Based on the absorption in the small intestine, patients' doctors need to look at their B12, folic acid, iron levels, and Vitamin D.

[19:12] Holly loves Bethany's terminology of replacing, not just eliminating, foods. She will use that terminology with her patients to make it feel more supportive for them.

[20:40] A lot of people want to get all their nutrients through their food. That's not always practical. Vitamin D is hard to get exclusively in your diet if you're not drinking milk or eating wild-caught fish. You have to rely on fortified foods or add supplements.

[21:15] One, we want to take a look at your diet and ask how are your calories. We want to make sure you're eating enough. Two, if we suspect there are some vitamin deficiencies, we check your blood or just empirically supplement you.

[21:36] Supplementation should be done carefully. There are some vitamins where you can get too much of a good thing. Vitamins stored in the fat need to be at levels sufficient for repletion, dictated by age and gender. Dieticians know what to recommend.

[22:19] For patients who have non-EoE EGIDs, some have tentative swallowing, so Bethany tries to do as many liquid or chewable safe options for supplements as possible.

[23:46] Holly works with patients who have feeding difficulty, so she appreciates the liquid and chewable supplements for easier swallowing and quicker absorption.

[24:08] Bethany mentions that some fortified oat, corn, and rice breakfast cereals are highly enriched with B vitamins and iron. Look at the labels. It can be a way to layer in more vitamins without purchasing a supplement.

[25:24] Holly doesn't think patients understand how valuable a good dietician can be. She had one patient with celiac who was taking a supplement with gluten in it! She reminds listeners to always consult your care team before making any changes to your treatment plan.

[25:59] Bethany's favorite thing to talk about is foods and where to find what. If listeners have questions, she is happy to post answers on the website.

[26:25] The American Academy of Pediatrics says a cup of vitamin-fortified juice a day is not too much sugar and is a good source of Vitamin C and other nutrients. The calcium and Vitamin D you get from a cup of fortified juice is very value-available.

[26:46] In the non-dairy drink world, some are nicely fortified and some are not. If you make your almond milk, you're missing out on the fortifications.

[27:11] Bethany likes some of the fortified juices and some of the enriched non-dairy milk options. Those are the best ways to get calcium and Vitamin D for people who need calories. Instead of water with meals, substitute an enriched drink with meals.

[27:33] Some people struggle with protein, probably because of their level of food restriction. The typical animal proteins are great. If you can do soy, a cup of soy milk has eight grams of protein. Soy is a complete protein that mimics animal proteins.

[28:04] Cook your cereal in soy milk. Use it as the base of a smoothie. This is before getting into protein powders. Try legume-based proteins, if you can handle legumes. Your supplements have to be personalized. That's the tricky part.

[28:30] If you have a lot of food allergies or intolerances, it may be worth talking to your gastroenterologist, allergist, or dietician about adding elemental formula as a supplement. Bethany uses it often with food allergy patients as a safe supplement.

[29:31] Bethany primarily treats adults but also young adults transitioning from the pediatric side into the adult world. Sometimes a feeding difficulty follows patients into adult treatment. We need everyone at the table to treat this immune-mediated disease.

[30:32] Patient advocacy groups like APFED have ways to help you find dieticians. Also, the Academy of Nutrition and Dietetics has "Find a Specialist" on their website. Eatright.org. Dieticians can do telehealth if you are not near one.

[31:45] If the practice that you're in doesn't have a dietician, you could gently suggest they have one join the practice, or consult with the practice. Patient advocacy is strong.

[33:12] Bethany talks about getting an appointment with a dietician. On the pediatric side, it has to do with the billing code. Ask your insurance if they cover medical nutrition therapy, Billing Code 97802, and for which diseases. Insurance may have stipulations.

[34:14] If medical nutrition therapy is not a covered benefit, ask the dietician if they can do a sliding scale. Holly says she has seen plans in several states where the patient can use the HSA or FSA card to pay for medical nutrition therapy.

[34:49] Bethany believes in the pediatric world, where growth and development are concerns, there's a little bit better coverage.

[34:59] On the adult side, if Bethany has other diagnoses, like high blood pressure, or diabetes, she is also billing for those because she makes sure what she recommends is also in line with what is good for their heart and wellness in general.

[35:55] Bethany was intrigued to learn food proteins do trigger disease activity for our patients in the stomach and small intestine, just as in the esophagus.

[36:20] In the Elemental Trial, they were surprised to learn people with non-EoE EGIDs had more allergies than expected. They were more likely to have more than just one or two. They were also more likely to have rare food allergies like legumes or grains.

[36:43] A patient may want to learn all their food triggers, but they may be a highly allergic person and it may not be worth trying to remove all their food triggers.

[37:06] Bethany wants to remind listeners that the diet approach should be a substitution diet. If you take things out, you've got to replace them with other plants.

[37:18] There's great crossover nutrition between fruits and vegetables. Seeds are great as a fill-in for nuts. There are plenty of other whole grains out there besides wheat. There are lots of good ways to get that nutritional balance into your diet.

[37:31] For anyone who's eliminating a food group, even if you're substituting it, it's a good idea to talk to your doctor about filling in with a good multivitamin, multimineral supplement.

[37:59] Bethany says it's fun working with colleagues to look for other ways to look at this nutrition lens for patients with Non-EoE EGIDs.

[38:14] They are looking at noninvasive ways to find eosinophils to go faster with helping people find their food triggers without having to scope them.

[38:28] Bethany is hoping with that research to be able to help people learn how they can cheat, like having pizza once a month if they are allergic to dairy. That's a question for your care team, but we don't have a great science-based way to answer that.

[38:53] As we study more noninvasive ways to get at eosinophilic activity, we can give patients a little bit more freedom and quality of life. That's what Bethany is working on next.

[39:58] Holly thanks Bethany Doerfler for joining us on Real Talk — Eosinophilic Diseases. For our listeners, to learn more about eosinophilic disorders, please visit APFED.org and check out the links in the show notes.

[40:11] If you're looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at APFED.org/specialist.

[40:21] 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.

[40:34] Holly thanks Bethany for joining us today. Holly also thanks APFED's Education Partners Bristol Myers Squibb, Sanofi, Regeneron, and Takeda for supporting this episode.

Mentioned in This Episode:

Bethany Doerfler, MS, RD, Clinical Research Dietician specializing in lifestyle management of digestive diseases at Northwestern Medicine

Dr. Nirmala Gonsalves

Dr. Ikuo Hirano (In Memoriam)

The Elemental Study, Gonsalves, Doerfler, Hirano

Academy of Nutrition and Dietetics

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, Sanofi, Regeneron, and Takeda.

Tweetables:

"The lens that we've used to look at food as the trigger and also a therapeutic agent in the esophagus, we're doing that in non-EoE EGIDs as well, and at the same time, trying to make sure that we're honoring the other parts of our patient's lives." — Bethany Doerfler, RD

"We are trying to give the right names to the right disorders and give clear diagnostic criteria so that we're helping our patients get a diagnosis, and we're not labeling something incorrectly and sticking someone with a diagnosis that isn't accurate." — Bethany Doerfler, RD

"The diagnosis also means that there are opportunities for medical therapy, cut points for which we decide if medicines or other therapies work or not, and billing codes. If we can't bill insurance companies, patients may not be privy to certain services." — Bethany Doerfler, RD

"Look at the [fortified cereal] labels. You'd be surprised how much they look like a multivitamin, not only for B vitamins but for iron. … It can be a fantastic way to layer in more vitamins without having to think about purchasing a supplement." — Bethany Doerfler, RD

"There's great crossover nutrition between fruits and vegetables. Seeds are great as a fill-in for nuts. There are plenty of other whole grains out there besides wheat. There are lots of good ways for us to get that nutritional balance into your diet." — Bethany Doerfler, RD

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

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. John Accarino, an allergist and immunologist at Massachusetts General Hospital and Mass General for Children, on the topic of immunology support for eosinophilic esophagitis (EoE). Dr. Accarino shares his experiences as a person living with food allergies, allergic asthma, peanut allergy, and eosinophilic esophagitis. He tells how his experiences help him in his work with patients. Dr. Accarino shares some education on a variety of allergy mechanisms and the treatments that mitigate them.

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, and Regeneron. Ryan introduces co-host Holly Knotowicz.

[1:14] Holly introduces today's topic, immunology support for eosinophilic esophagitis (EoE), and introduces today's guest, Dr. John Accarino, an allergist and immunologist at Massachusetts General Hospital. Holly welcomes Dr. Accarino to Real Talk.

[1:49] Holly notes that Dr. Accarino is her allergist and immunologist.

[2:03] Dr. Accarino works at Massachusetts General Hospital and Mass General for Children. Allergy and Immunology is a field where he can see pediatrics and adults. Originally trained in pediatrics, now Dr. Accarino sees patients of all ages.

[2:23] Dr. Accarino grew up with allergies. He has experienced food allergies since he was young, along with allergic asthma, and some eczema, which he grew out of. Later in life, he was diagnosed with eosinophilic esophagitis. He talks with his patients about his experiences.

[2:47] Dr. Accarino also does research on drug allergies in the context of certain drug interactions that involve eosinophils.

[3:06] When Holly was referred to Dr. Accarino, it was for multiple sclerosis (MS). He told her, "It looks like you have EoE. I have EoE." It was a huge relief to Holly not to have to explain EoE to her doctor.

[3:41] Some patients start to explain their EoE to Dr. Accarino, and he assures them he understands where they're coming from. Sometimes, he has to be careful not to think everyone has his symptoms, as there is a large spectrum of presentations.

[4:26] Dr. Accarino wasn't diagnosed with EoE until he was in his allergy fellowship, after he suspected it when he had a food impaction at a steakhouse at a graduation party from his pediatric residency. He tried to manage the EoE with lifestyle changes.

[5:39] Dr. Accarino didn't often go to see a doctor during residency, but he realized it was probably a good time to get an endoscopy.

[5:52] Holly shares how she was also diagnosed as a clinical fellow. She was subbing for someone on the GEDP team at Children's Hospital in Colorado. Listening to all the patients, she realized, "This sounds a little bit like me … What is going on?"

[6:23] Even with his medical background, it took Dr. Accarino some time to decide to get the endoscopy and biopsies. You or your doctor have to have a high level of suspicion to realize this isn't just reflux. Food doesn't get stuck in every person's throat.

[7:01] Thinking back, Dr. Accarino remembers an instance as a child when a dry muffin got stuck in his throat. He stayed calm and waited for it to pass. He thought it was normal.

[7:39] He drank a lot of water and chewed his food a lot. Those are markers of potential esophageal inflammation.

[8:20] Different groups have different management strategies for EoE. Dietary management, topical steroids, biologics. A subgroup of people with EoE are responsive to proton pump inhibitors (PPIs). Finding the best management strategy is a work in progress.

[8:53] With pediatric patients, the parents control the diet, and the children eat what is prepared. He notes that with adult patients, sometimes they let foods slip through.

[9:10] If you want to do a single-food elimination diet with dairy, there's a lot of dairy in the American diet. Dr. Accarino tried eliminating dairy and wheat, but he still had persistent eosinophils with dietary elimination.

[9:24] Dr. Accarino then tried PPIs. To know if you have PPI-responsive EoE, you might do twice-daily omeprazole at a significant dose. Have the endoscopy after a few weeks pass and see if the eosinophils are still present in the biopsy.

[9:59] Dr. Accarino did that recently and still has the eosinophils. He plans to talk to his gastroenterologist about considering dupilumab, but he feels that he can mitigate his subjective day-to-day experience of symptoms with dietary elimination and PPIs.

[10:24] If you still have the presence of eosinophils on biopsy, there's still inflammation happening. In the long term, you still have to worry about fibrosis and narrowing.

[10:34] The last treatment Dr. Accarino tried was as a research participant in a study for dissolvable fluticasone. He received either the medication or a placebo; he doesn't know which.

[11:01] To stay in the study, he had to journal and report his symptoms regularly. He didn't have enough symptoms to stay in the study. They were looking for a baseline to see how it changed with either the placebo or the medication.

[11:20] In research, you have to have a baseline to start, and then you want to see improvement, plus or minus. With EoE, it's difficult. You have the biopsy and eosinophils, but there's a large spectrum of symptoms that people may experience.

[12:40] Holly appreciates Dr. Accarino's unique perspective as a doctor with EoE who has experienced various treatments and diets. He understands the concerns of his patients.

[12:43] Dr. Accarino says even taking a twice-daily PPI or other medication is difficult for a lot of people, and that's the most simple of these therapies.

[13:06] Dr. Accarino wants to validate everyone's experience in terms of how difficult it is to treat this disorder, how it may present in different ways, and how there may be a delay in diagnosis.

[13:16] This isn't IgE-mediated immediate food allergy, where you eat a food and may have swelling within minutes; you may have flushing or hives. That's very clear. With EoE, it's a different mechanism; in many cases, there is a delay.

[14:37] Allergy, in general, is under the purview of clinical immunology. Dr. Accarino is allergic to peanuts and has an IgE-mediated immediate reaction to them. If he eats a peanut, he has symptoms within minutes. He could have anaphylaxis. As a result, he carries an epinephrine auto-injector.

[15:01] If Dr. Accarino has a skin test, it will be positive for peanut. He has IgE antibodies to peanuts. He also has oral allergy syndrome where the body mistakes certain fruits, vegetables, or nuts with certain tree pollens or grass pollens.

[15:23] Oral allergy syndrome is usually a lower-risk condition where it's a less-stable protein that once cooked might not produce any symptoms. If it's raw when you consume it, you may have oral itching, a bit of throat discomfort, or tongue itching.

[15:54] Your stomach acid breaks it down so it doesn't get into your bloodstream and you shouldn't have a systemic reaction.

[16:01] If Dr. Accarino eats a peanut, his stomach acid doesn't break down the high-risk, stable peanut protein, it gets into his bloodstream, and he can have a systemic anaphylactic reaction.

[16:20] Chronic EoE symptoms can present with something like a food impaction, or bad reflux or belly pain, and nausea. The reaction may not be immediate. It may be progressive over days or weeks.

[16:38] FIRE is an interesting condition that takes some time to narrow down. It's an immediate response of the esophagus, but we don't think it's histamine-mediated.

[16:56] We don't know, exactly, the mechanism but it's in people with eosinophilic esophagitis. They feel differently, and there would be different specific food triggers.

[17:11] It took some time to figure out what was going on. Dr. Accarino felt like he had a lump in his throat, then a lump in his chest, nausea, and belly pain. It felt like a slow progression of EoE symptoms, and it was from specific food triggers, in his case.

[17:30] In some of the FIRE literature, they looked at banana and avocado. For Dr. Accarino, it took a couple of exposures to protein bars and milk protein whey isolate, specific to protein bars he had multiple times, until he figured out that was the trigger.

[17:50] Another protein whey isolate that Dr. Accarino scooped as a powder and made into a shake also led to FIRE.

[17:55] It took that event for Dr. Accarino to figure out it wasn't just a flareup of EoE or reflux but some trigger that caused this response that wasn't anaphylaxis but may be due to the recruitment of eosinophils or some immediate process not well understood.

[18:18] FIRE is going to be very hard to research. How would we figure this out? Would we bring someone in and do an endoscopy immediately and see what happens? There's a lot of descriptive data and case series.

[18:32] Dr. Accarino has had experiences when he knew it wasn't an immediate anaphylactic reaction, oral allergy, or reflux. He asked what else it could be in the context of EoE. When he looked at different case series, that's the presentation he had.

[19:17] Dr. Accarino acknowledges that having personal experience with FIRE, oral allergies, and IgE-mediated allergies, on top of EoE, has influenced his work as a medical professional. He can share anecdotes with patients as he explains the available testing.

[19:39] Dr. Accarino says a lot of immunology and allergy is explaining the diagnostic tools and management strategies we have and what we think is going on.

[19:50] The immune system is infinitely complex, and a lot of the practice is making a digestible analogy, not just in the context of allergic conditions but also everything with the immune system. There are so many cells doing so many different things.

[20:04] Dr. Accarino explains false positives in testing. He has positive scratch tests for peanuts, cashews, and almonds, which shows he has IgE for each of them. He is allergic to peanuts, but he can eat cashews and almonds. Those are false positives.

[20:56] When a scratch test is negative for immediate food allergy, it's a powerful predictive tool. But you may get false positives. How positive is it? There might be room for more discussion.

[21:10] There may be more hesitation for people who do large panels of food testing without any history of reacting to any foods.

[21:31] Some people have EoE triggered by milk or wheat but have negative skin tests. That doesn't mean they aren't triggered by these foods. The skin test is an IgE histamine mast cell mechanism, not for eosinophils, which are other immune cells.

[21:58] We go down these steps of thinking about diagnostic triggers and eventually treatment for those immediate symptoms mentioned for EoE.

[22:09] Dr. Accarino doesn't expect FIRE to be responsive to epinephrine. He doesn't have to stabilize the mast cells. It's a chronic disease that's flaring up. You treat it with a chronic type of treatment.

[24:10] Dr. Accarino says that for a doctor, immunology is rewarding, interesting, and complex, but it's intimidating until you get your foothold and see patients and clinical experiences.

[25:14] A lot of medical students and residents are a little fearful of immunology. They might not think about it too much. Dr. Accarino loves to talk about it and think about it. He can't think of anything more complex in terms of systems within our body.

[25:37] Ryan comments on his experiences with IgE-mediated food allergies, some environmental allergies that he has no idea how they work, and EoE, which he believes he has a good grasp on.

[25:55] Ryan imagines that having a physician with a good understanding of the immune system and also personal experience would be helpful for a patient with multiple allergic conditions.

[26:13] Dr. Accarino sees a large overlap of seasonal or year-round environmental allergies and EoE. There are some studies that show that endoscopies on patients with EoE may change at different times of the year if they have underlying seasonal allergies.

[26:33] Some people who have food allergies also have EoE or other eosinophilic disorders. Some discussions with them may be about blood tests that detect eosinophils in the bloodstream versus biopsies of the esophagus, stomach, or colon.

[27:15] It's thinking about what tests are available, what they tell us, and how to use them to predict the next steps, things like dietary changes or for immediate food allergy, considering challenges versus full avoidance. Each test has its pluses and minuses.

[27:35] People like a clear test, and they like an easy fix, but sometimes there's a lot of nuanced conversation of shared decision-making and trying things in a supervised setting.

[27:57] Holly speaks as a patient of the investigative testing Dr. Acarino is doing with her immune system trying to figure it out along with her MS and EoE.

[28:14] Dr. Accarino says the words immune system, immunity, and inflammation are used a lot in talking about foods. Dr. Accarino uses the framework of the immune system trying to help you.

[28:42] Sometimes, instead of making helpful antibodies to things like vaccines or viruses, that give you protection, the immune system makes antibodies that attack a certain organ or your joints.

[29:02] Dr. Accarino thinks of treatments that suppress the immune system in certain ways. Some treatments cool down the populations of many different immune cells. Oral steroids and prednisone are used for many conditions for autoimmune flares.

[29:29] Oral steroids, in the long term, may lead to weight gain, bone density changes, and diabetes. The big push for many diseases is toward non-steroidal biologics to target specific cells that cause disease.

[29:59] For Crohn's disease, a specific monoclonal antibody is used to target TNF-alpha molecules and blocks that inflammation pathway.

[30:14] For EoE, dupilumab, a specifically designed antibody, blocks a specific receptor in a specific pathway so the immune system doesn't have to be shut down and the patient doesn't have the side effects of steroids. It's a targeted therapy.

[30:32] What you see in commercials for injectable medications are large, designed antibodies that, if you took them in a pill form, your stomach acid would break down and digest. So they are injections and infusions that go directly into the bloodstream.

[31:22] Medications that end in -mab are monoclonal antibodies. They are very large molecules that would not be stable in stomach acid.

[32:09] Dr. Accarino talks of eosinophil normal function and aberrant function. IgE-mediated reactions are usually related to mast cells, a type of immune cell that shouldn't be in the bloodstream.

[32:54] Dr. Accarino can do a CBC with differential to see the number of white blood cells and the number of red blood cells. The differential of white blood cells will include neutrophils, lymphocytes, and eosinophils. It shouldn't show mast cells.

[33:19] If you have mast cells in your bloodstream, that's mastocytosis, a different problem. Mast cells live in your skin, in your gut, and around your blood vessels. They're full of granules like histamine and tryptase.

[33:38] Dr. Accarino explains how mast cells release their contents and how he would treat the resulting swelling or itch with an antihistamine or epinephrine. Epinephrine treats systemic reactions and stabilizes the mast cells.

[34:16] Mast cells have many receptors and may be triggered by many things other than IgE. This is a conversation Dr. Accarino has with patients who have chronic hives unrelated to any foods.

[34:29] Some people get hives from non-steroidal anti-inflammatory drugs NSAIDs. Some get hives from vancomycin. Some get hives when the temperature changes, from tight clothing, or from IV contrast. It's not an IgE-mediated mechanism, but it's still mast cells being degranulated.

[35:45] Dr. Accarino says people see hives and they think allergy. But, like EoE, it doesn't involve histamine. There can be hives that aren't related to allergies. This can be idiopathic urticaria or spontaneous urticaria.

[36:04] Sometimes, when switching from a day shift to a night shift, hormonal changes will trigger hives. Sometimes, the stress of having a family member in the hospital will cause hives. An accumulation of triggers can lead to mast cell degranulation.

[36:38] There are many ways that allergy can have different mechanisms and treatments, with different cells involved. There are different molecules that cause symptoms and manifestations.

[36:50] Navigating that and understanding what might be going on can give people a sense of reassurance. The biggest fear is a life-threatening allergic reaction. People will read about fatal anaphylaxis and wonder if it will happen to them with their condition.

[37:16] Sometimes, thinking of the cells involved and the pathways may give a level of reassurance that this may not be the same thing that they read about.

[37:28] Ryan thanks Dr. Accarino for joining us today.

[37:37] Dr. Accarino says it was nice to reflect on things and to go through different scenarios and experiences he has gone through. It was nice to have the opportunity to share them with Ryan, Holly, and all the listeners.

[37:57] 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.

[38:06] 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.

[38:15] 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.

[38:25] Ryan thanks Dr. Accarino for joining us today for this fun conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.

Mentioned in This Episode:

Dr. John Accarino, MD, Allergist and Immunologist at Massachusetts General Hospital and Mass General for Children

Episode 034: Food-Induced Response and Eosinophilic Esophagitis

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, and Regeneron.

Tweetables:

"Allergy and immunology is a field where I can see pediatrics and adults. I was originally trained in pediatrics, but now I see all ages, from infants up until older adults." — Dr. John Accarino

"Part of the conversation sometimes is trying not to overly bias myself, where I say, 'Oh, this is my experience.' … Like many diseases, there's a large spectrum of presentations, … different symptoms that people have." — Dr. John Accarino

"We don't think [Food-Induced Response in Eosinophilic Esophagitis is] histamine-mediated. We don't know exactly the mechanism, but it's in people with eosinophilic esophagitis. They feel differently, and there would be different specific food triggers. It took some time to figure out that was going on." — Dr. John Accarino

"When a scratch test is negative for immediate food allergy, it's a very powerful predictive tool. But there are times that you may get false positives. How positive is it? There might be room for more discussion." — Dr. John Accarino

"There are a lot of ways that allergy can have different mechanisms and different treatments, with different cells involved." — Dr. John Accarino

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. Wayne Shreffler, Chief of Pediatric Allergy and Immunology and Co-Director of The Food Allergy Center at Massachusetts General Hospital. Dr. Shreffler is also an investigator at The Center for Immunology and Inflammatory Disease and The Food Allergy Science Initiative. His research is focused on understanding how adaptive immunity to dietary antigens is both naturally regulated and modulated by therapy in the context of food allergy. This interview covers the results of a research paper on The Intersection of Food Allergy and Eosinophilic Esophagitis, co-authored by Dr. Shreffler.

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:

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

[1:15] Holly introduces today's topic, the intersection of food allergy and eosinophilic esophagitis.

[1:26] Holly introduces today's guest, Dr. Wayne Shreffler, Chief of Pediatric Allergy and Immunology and Co-Director of The Food Allergy Center at Massachusetts General Hospital and an investigator at The Center for Immunology and Inflammatory Disease and The Food Allergy Science Initiative.

[1:43] Dr. Shreffler's research is focused on understanding how adaptive immunity to dietary antigens is both naturally regulated and modulated by therapy in the context of food allergy.

[1:54] Holly welcomes Dr. Shreffler to Real Talk. When Holly moved to Maine, she sent her patients to Dr. Shreffler at Mass General.

[2:25] Dr. Shreffler trained in New York on a Ph.D. track. He was interested in parasitic diseases and the Th2 immune response. Jane Curtis, a program director at Albert Einstein College of Medicine, encouraged him to consider MD/PhD programs. He did.

[3:31] Jane Curtis connected him to Hugh Sampson, who was working with others to help understand the clinical prevalence of food allergy and allergens.

[3:51] As a pediatric resident, Dr. Shreffler had seen the burden of allergic disease, caring for kids in the Bronx with asthma. His interest in Th2 immunity, the clear and compelling unmet clinical need, and the problem of food allergy guided his career.

[4:31] Dr. Shreffler's wife has food allergies and they were concerned for their children. Fortunately, neither of them developed food allergies.

[5:21] Dr. Shreffler thinks the food allergy field has a lot of people who gravitate toward it for personal reasons.

[5:53] Food allergy is an adverse response to food that is immune-mediated. There is still uncertainty about this but Dr. Shreffler believes that a large percentage of patients with EoE have some triggers that are food antigens.

[6:27] The broad definition of food allergy would include things like food protein-induced enterocolitis syndrome (FPIES).

[6:47] The way we use the term food allergy in the clinic, there are two forms: IgE-mediated allergies and non-IgE-mediated allergies, including EoE.

[7:40] Some patients have food-triggered eczema, some have FPIES.

[8:04] In 2024, Dr. Shreffler and Dr. Caitlin Burk released a paper that looked at the triggers of EoE, particularly the intersection of IgE-mediated food allergy and EoE.

[8:41] Dr. Caitlin Burk joined the group as they were publishing papers on IG food allergy and EoE. It was a moment where things unexpectedly came together.

[9:17] Adaptive immunity to food proteins comes from antibodies that cause milk allergy, egg allergy, peanut allergy, or multiple allergies. The IgE has specificity.

[9:40] T cells also are specific to proteins. They express a host of receptors that recognize almost anything the immune system might encounter. They have a long memory like B-cells.

[10:09] The overlap in these two threads of research was regarding a population of T cells that are important for mediating chronic inflammation at epithelial sites, including the gut.

[10:36] These T cells have been described in the airways in asthma, in the skin in eczema, and the GI tract. Researchers years ago had also described them as being associated with IgE food allergy. People with IgE food allergies avoid allergens.

[11:13] T cells, being associated with chronic allergic inflammation, now being associated with food allergies which are not having chronic exposures to the allergen, was interesting and surprising.

[11:30] Dr. Shreffler and his group found the T cell subset in patients who don't do well with Oral Immunotherapy (OIT) and patients who have EoE with immediate symptoms.

[12:01] Dr. Shreffler notes differences. There are immediate symptoms of IgE food allergy. There is a subset of patients with EoE who have immediate symptoms that are not fully understood. Maybe IgE plays a role there.

[12:28] There are different mechanisms for how symptoms are caused and so different ways of making a diagnosis. A food allergy with an IgE antibody can be measured through skin tests and blood tests. This can help identify which foods are the trigger.

[12:57] This common T cell subset that we see in EoE and food allergy, helps to explain why IgE alone is not always a very specific marker for identifying people who will have immediate reactions when they're exposed to the food.

[13:17] For patients who react at low levels, it's not just that they have more or better IgE but they also have an expansion of these T cells that are common between EoE and other chronic forms of allergy and IgE food allergy.

[13:41] There's a lot to learn that might be relevant for patients about this T cell subset.

[14:23] These T cells are a specific subset of the group of Th2 T cells, which are a subset of all CD4 T cells. Some CD4 T cells are important for responding to viruses and tumors. Others are important for responding to outside allergens.

[15:01] In an allergy or a parasite infection, Th2 T cells are important. There is a subset of T cells that is driven by repetitive and chronic exposure to the triggering protein, antigen, or allergen.

[15:47] Most antigens are proteins that trigger an immune response. An antigen that elicits an allergic response is an allergen.

[16:30] A food trigger is a protein antigen that is an allergen. In IgE, food allergies, milk, and eggs are prevalent triggers early in life. For reasons not well understood, a lot of people outgrow them. In older patients, peanut and tree nut allergies are prevalent.

[17:01] In EoE, milk is one of the most common dietary triggers into adulthood. Some patients with IgE allergy to milk can tolerate it if it's well cooked. Patients with EoE are less likely to be able to get away with regular and ongoing exposure to milk protein.

[17:54] Milk, eggs, and nuts are common triggers in both conditions. There can also be rare food allergy triggers. That's part of the early evidence that the adaptive immune response was likely to be involved. It can be so specific for some people to rare things.

[18:20] Hallmarks of something being immune-mediated are that it is reproducibly demonstrable as a trigger. It's going to be long-lived. It's going to be generally relatively small amounts. The immune system is good at detecting small exposures.

[19:07] EoE is tricky because there's not that clear and easy temporal association between an offending allergen exposure for most people and their symptoms. People don't associate the symptoms with the triggers.

[20:14] A history of having blood in the stools can be milk-allergen-driven and was associated with a diagnosis of EoE in those kids when they're older.

[20:26] There are a lot of commonalities in the allergens but it's not always obvious clinically.

[22:40] A challenge in diagnosing EoE is that providers have to be on guard against their biases. They have to give a patient good advice. In EoE there is no test to identify triggers, except rigorous introduction, elimination, reintroduction, and endoscopies.

[24:18] For some of Dr, Shreffler's patients, it becomes less important to know their dietary triggers. They gravitate toward an approved form of treatment that may, if successful, allow them to have a more normal diet because of effective medication.

[24:50] Dr. Shreffler thinks there are other triggers, including pollens. There is evidence of seasonality of active EoE in patients shown to have allergic sensitization to pollens. That's indirect evidence. If the body is making IgE, it's likely making other responses.

[25:32] There are questions about how large the population of patients is who have EoE that may be more intrinsically than extrinsically driven because of genetic variations.

[25:54] Dr. Shreffler believes that EoE in some patients is allergen-driven and in some patients EoE is food-driven. Food is a trigger for the majority of pediatric patients and a large percentage of adult patients but not necessarily the exclusive trigger.

[27:04] If a patient is motivated to learn what dietary triggers may be at play, Dr. Shreffler often makes assessments outside of pollen season for allergens to which the patient has demonstrated positivity.

[28:09] Looking at the epidemiology, both EoE and food allergy are atopic disorders. You see an increased prevalence of asthma, hay fever, eczema, and even allergic proctocolitis in infancy. You see an enrichment of one disorder to another.

[28:29] The overlap of food allergy to EoE is stronger than you might expect. About 30 to 40% of patients with EoE will also have IgE food allergy. A higher rate will have IgE positivity, whether or not that food is a trigger of immediate symptoms.

[28:48] Patients with food allergies are about four times more likely to have EoE than the general population. That's a stronger association than the risk of eczema or other atopic conditions to EoE.

[30:09] There are differences between IgE food allergy and EoE. The presence of IgE gives a useful tool for identifying the food trigger in food allergy, but not in EoE. Identifying rare triggers in EoE patients is done by clinical observation.

[31:46] Epinephrine and antihistamines are not useful in treating EoE. Blocking IgE with Omalizumab has not been effective in trials in treating EoE. PPIs, topical steroids, and dupilumab are helpful for many EoE patients.

[32:38] Dupilumab has been evaluated a bit in food allergy in combination with OIT, and there was no statistically significant benefit from dupilumab in food allergy.

[33:25] A group in Pennsylvania has been evaluating epicutaneous immunotherapy as a modality to treat EoE. It's also being evaluated for IgE food allergy. Dr. Shreffler thinks it's something to keep an eye on.

[33:40] The oral route for immunotherapy can drive EoE for patients. As they become less sensitive from an immediate reactivity viewpoint, a significant percentage of patients develop GI symptoms. This has also been observed with sublingual therapy.

[34:14] Iatrogenic EoE, caused by the treatment, may resolve on the cessation of the immunotherapy treatment.

[36:25] Dr. Shreffler says in some cases, the shared decision is a decision where he has a strong evidence-based opinion. In some cases, there's a lot more room for a range of clinical decisions that could be equally supported by what we know right now.

[36:57] We've said that EoE is a contraindication for OIT. There is a shift happening. Dr. Shreffler sits with families and has a conversation about restricting diet or trying chronic therapy and keeping an ad-lib diet.

[37:38] What about doing the same thing by treating the immediate-type food allergy with chronic allergen exposure and then ameliorating the effects of EoE if it emerges, with another therapy? A hundred providers would have a diversity of responses.

[38:19] When there is a history of EoE in a family, Dr. Shreffler advocates for getting a baseline scope. It becomes an important "ground zero."

[38:28] The goal is to have less invasive ways to monitor these conditions.

[39:32] Chronic inflammation, which is the hallmark of EoE, is well-targeted by therapies like PPIs and steroids. Steroids don't help with IgE-related food allergies. They're not effective at blocking the IgE-driven immediate response.

[41:13] Until recently, IgE food allergy has only been managed with avoidance. We have some other tools now. Xolair is not effective in EoE but is effective in two-thirds to three-quarters of patients with immediate-type food allergies for preventing anaphylaxis.

[41:45] Dr. Shreffler refers to an upcoming study on the effectiveness of Xolair in treating people with food allergies. Those who were able to tolerate a minimum amount were allowed to begin consuming allergen. We'll get insight into how those patients did.

[43:08] Food-induced immediate response of the esophagus (FIRE) is immediate discomfort with exposure to some allergens. Dr. Shreffler explains it. Data supports that these patients are experiencing an IgE-mediated but local response to those triggers.

[44:59] If FIRE is IgE-mediated, it may be that Xolair would help suppress it in these patients. It's worth looking at Xolair for this subset of EoE patients.

[45:20] Ryan invites any listeners who want to learn more about FIRE to check out episode #34 with Dr. Nirmala Gonsalvez.

[45:37] In the paper, Dr. Shreffler wrote about what he hopes will be the practical usefulness of the finding, the intersection between IgE food allergy and EoE.

[45:56] A subset of Th2 T cells express a protein called GPR15. It appears to be a marker for the subset of cells that are playing a role in the EoE.

[46:36] Caitlin Burk's work now is looking at their activation status in active disease and post-diet elimination and remission. She is developing a data set that is leading us toward the possibility of focusing on that cell subset and techniques to adopt in clinics.

[47:12] She is also working out more advanced techniques to look at the receptors. Dr. David Hill at CHOP is working on similar research. This research has the potential to lead to the development of better tests for EoE.

[47:44] Holly tells Dr. Shreffler this has been such an informative episode with so many tidbits of things to help patients advocate for themselves. Holly thanks him for sharing all of that.

[48:12] Dr. Shreffler is trying to see what can be utilized from their research to make non-invasive tests to identify food allergen triggers for patients so they don't have to go through so many endoscopies. He sees it as a huge unmet need.

[48:31] Ryan thanks Dr. Shreffler for joining us. 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.

[48:41] 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.

[48:50] 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.

[49:00] Ryan thanks Dr. Shreffler for joining us today for this interesting conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.

Mentioned in This Episode:

Dr. Wayne Shreffler, MD, Ph.D., Chief of Pediatric Allergy and Immunology and Co-Director of The Food Allergy Center at Massachusetts General Hospital

"Triggers for eosinophilic esophagitis (EoE): The intersection of food allergy and EoE"

Dr. Caitlin Burk

Dr. David A. Hill

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, and Regeneron.

Tweetables:

"This fascinating problem of food allergy: why does the immune system do that for some people — recognize what should be nutritive and innocuous sources of energy as an immunological trigger? " — Dr. Wayne Shreffler

"A food allergy; because there is this IgE antibody, we can do skin tests. We can measure that in the blood. It's a useful marker for helping to identify which foods are the trigger." — Dr. Wayne Shreffler

"EoE is tricky because there's not that clear and easy temporal association between an offending allergen exposure for most people and their symptoms. People don't associate the symptoms with the triggers." — Dr. Wayne Shreffler

"Everything is shared decision-making. In some cases, it's a shared decision where I have a strong evidence-based opinion. In some cases, there's a lot more room for a range of clinical decisions that could be equally justified." — Dr. Wayne Shreffler

"Steroids don't help with IgE-related food allergy. They're not effective at blocking that IgE-driven immediate response." — Dr. Wayne Shreffler

"I'm trying to see what we can utilize from our research to make non-invasive tests to identify food allergen triggers for patients so they don't have to go through so many endoscopies. I think that's a huge unmet need." — Dr. Wayne Shreffler

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. Margaret Collins, a professor of pathology at the University of Cincinnati and a staff pathologist at Cincinnati Children's Hospital Medical Center. Dr. Collins was a member of the task force that produced the Guidelines on Childhood EGIDs Beyond EoE. In this interview, Dr. Collins discusses the guidelines and how they were created and shares some of the results, including an algorithm for diagnosing non-EoE EGIDs. She shares why she specialized in EGIDs and what her hopes are for the future development of the guidelines.

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

[1:13] Holly introduces today's topic, guidelines for childhood eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE).

[1:27] Holly introduces today's guest, Dr. Margaret Collins, a professor of pathology at the University of Cincinnati and a staff pathologist at Cincinnati Children's Hospital Medical Center.

[1:38] Dr. Collins specializes in the pathology of pediatric gastrointestinal disease, especially EGIDs, and is a central pathology reviewer for the Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR), as well as a member of APFED's Health Sciences Advisory Council.

[2:11] As a pathologist, Dr. Collins examines biopsies microscopically. For EGIDs, she determines the peak count of eosinophils per high-power field, or reports the numbers of eosinophils in multiple high-power fields, and analyzes the tissue for additional abnormalities.

[2:33] Dr. Collins then issues a report that becomes part of the patient's medical record and is provided to the patient's doctor.

[2:41] The biopsies Dr. Collins examines may be the first biopsies for a diagnosis, or follow-up biopsies to determine response to therapy, or as part of ongoing monitoring to determine if inflammation has returned even if the patient has no symptoms.

[3:07] Dr. Collins was inspired to specialize in EGIDs after speaking with patients with EGIDs. She used to give tours of the pathology lab at Cincinnati Children's Hospital. She met affected children and their caregivers. Their courage and gratitude moved her.

[3:43] Ryan mentions the wonderful patients and their families in the APFED community. Holly says that as a patient, it's fascinating to meet a pathologist. Pathologists are generally behind the scenes.

[4:42] Dr. Collins specializes in GI pathology, including eosinophilic-related conditions in the GI tract. EoE, eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis.

[5:16] In January 2024, "Guidelines on Childhood EGIDs Beyond EoE" were published in the Journal of Pediatric Gastroenterology and Nutrition. Dr. Collins served on the task force that prepared the guidelines.

[5:35] Non-EoE EGIDs affect all sites of the GI tract except the esophagus. All sites of the GI tract except the esophagus normally have eosinophils in the mucosa, which complicates the diagnosis.

[6:03] Like EoE, the diagnosis of non-EoE EGIDs is made after known causes of tissue eosinophilia are excluded.

[6:28] Consensus guidelines help bring attention to best practices and encourage uniformity of practices.

[6:50] This is especially important for rare diseases and for centers that see fewer patients with rare diseases than the more specialized centers. Guidelines based on the best information available help these centers.

[8:03] The best distribution of guidelines is to publish them in the medical literature and sometimes in multiple journals to target audiences of allergists, gastroenterologists, and pathologists. Guidelines may be presented at national meetings to increase awareness.

[8:36] Several specialties are involved in the care of patients who have EGIDs. If patients or caregivers learn of published guidelines, they can also inform their providers.

[9:23] Insurance is a big issue for so many patients. Getting coverage for both diagnostic and treatment options can be complex.

[9:50] The guidelines may be helpful to insurance companies to accept that a certain drug is needed by a patient with a certain condition. However, if the sequence suggested in the guidelines is not followed, there may be difficulty getting coverage in the U.S.

[11:11] Patients can advocate for themselves with insurance companies by explaining that the order of testing is not important but getting the recommended tests done is important.

[11:55] The greatest challenge the task force faced was the lack of large clinical studies and quality research reports. We're making progress in this field but we're at the beginning. Dr. Collins is hopeful that progress will be made in the next two to three years.

[12:24] When there were knowledge gaps, the task force filled them in with their published research and their own experiences. It's always reassuring to have a well-conducted clinical study that verifies that your thinking is correct.

[13:29] How long did it take the task force to create these guidelines? Longer than they wanted it to take! The years they put into composing these guidelines were greater due to the interruption caused by the [COVID] pandemic. They all felt good when they finished.

[14:18] The guidelines were written by 26 authors from five continents. These are international guidelines.

[14:44] Dr. Collins highlights the pathology. The guidelines state that non-EoE EGIDs should be considered clinicopathologic diagnoses, as EoE is, meaning that biopsies from the affected site in the bowel must show excess eosinophils.

[15:10] The guidelines, for the first time, recommend threshold eosinophil values for a diagnosis in the parts of the GI tract other than the esophagus. For a diagnosis of EoE, a threshold value of greater than or equal to 15 eosinophils per high-power field.

[15:36] The guidelines now recommend that for a diagnosis of eosinophilic gastritis, a threshold value of greater than or equal to 30 eosinophils per high-power field is present.

[15:48] For a diagnosis of eosinophilic duodenitis, a threshold value of greater than or equal to 50 eosinophils per high-power field. For a diagnosis of eosinophilic ileitis, a threshold value of greater than or equal to 60 eosinophils per high-power field.

[16:03] For a diagnosis of eosinophilic colitis in the right colon, a threshold value of greater than or equal to 100 eosinophils per high-power field. For a diagnosis of eosinophilic colitis in the transverse and descending colon, a threshold value of greater than or equal to 80 eosinophils per high-power field.

[16:12] For a diagnosis in the rectosigmoid, a threshold of greater than or equal to 60 eosinophils per high-power field.

[16:18] These numbers may change over time. One or more thresholds will likely change as we gain more experience with these diseases. The pattern won't change.

[16:29] Several studies have shown that the normal pattern of eosinophil presence in the mucosa in the GI tract is that the number increases from the stomach to the right colon and then decreases throughout the colon to the rectosigmoid.

[17:40] When giving tours of the hospital, Dr. Collins found that people understood better when they knew the numbers and could see the slides of their biopsies.

[18:48] Dr. Collins found literature reviews that suggested that the GI mucosa was often normal in non-EoE EGIDs. She believes that in the next few years, as we publish more and gain more experience, we will realize that is not the case.

[19:14] There is already a method for scoring the mucosa in the stomach in eosinophilic gastritis (EoG) and there are abnormalities found in a majority of patients. We have to work on the rest of the GI tract.

[19:35] Dr. Collins was surprised that there's not very good information about the use of proton pump inhibitors (PPIs) in eosinophilic gastritis and eosinophilic duodenitis. There haven't been studies about that. We need to work on that, too.

[20:47] Dr. Collins isn't sure we can recognize misconceptions about non-EoE EGIDs at this point. It might be premature to label any belief as a misconception. We thought that eosinophils were responsible for all symptoms in EoE, but we know now that is not true.

[21:10] Dr. Collins thinks we need to wait a bit before we decide that we know for sure all about non-EoE EGIDs. Ryan is excited to learn what the research will show us next.

[21:44] Holly loved learning about the algorithm in the guidelines.

[22:01] Dr. Collins says this is the first effort to create uniformity in the way in which non-EoE EGIDs are diagnosed. This algorithm can change over time. It provides signposts for the diagnosis, based on the information we have currently.

[22:20] The diagnosis of non-EoE EGIDs should rest on symptoms and the detection of dense eosinophilic inflammation in the mucosa by biopsy and the absence of evidence of other diseases, such as parasitic and other diseases, that might cause dense eosinophilic inflammation in the GI tract.

[22:46] The algorithm suggests that the particular anatomic site or sites in the GI tract responsible for the symptoms should be determined, for example, eosinophilic gastritis or eosinophilic colitis.

[23:03] The algorithm also suggests that the involved part of the wall in the involved anatomic site should be identified.

[23:13] For example, if the symptoms are suggestive of mucosal disease, without deeper mural or wall involvement, the clinical investigation can proceed directly to endoscopy.

[23:26] However, if symptoms suggest partial or complete bowel obstruction, which is typical of deep muscular involvement, then imaging studies should be considered before proceeding to endoscopy, to confirm or refute that there is a bowel obstruction.

[23:47] If the obstruction is identified, a full-thickness biopsy of the bowel wall may be indicated, possibly requiring a non-endoscopic surgical procedure. If obstruction is not identified, then the investigation can proceed to endoscopy.

[24:05] If there is abdominal distension, suggestive of fluid accumulation, consideration should be given to sampling the fluid, using a needle to pull some fluid out to determine if there are numerous eosinophils in the fluid that would indicate eosinophilic ascites, with the eosinophilic inflammation involving the outer lining of the bowel wall.

[24:41] The signposts are a little involved. They are a reasonable way to approach working up a diagnosis of non-EoE EGIDs.

[25:34] How is EoE ruled out before using this algorithm? It's sometimes difficult to distinguish symptoms that are relevant only to the esophagus and symptoms that are relevant only to the stomach.

[26:26] Someone with upper tract symptoms only will have an upper tract endoscopy, especially if that person has mucosal symptoms that seem to be relevant to the mucosa only. The best thing is to take biopsies of the esophagus, stomach, and duodenum to be sure where the eosinophil infiltrate is.

[27:06] If the person has lower tract involvement only, such as diarrhea and lower abdominal pain, and no upper tract symptoms, a transnasal endoscopy could be used to determine if there is EoE in addition to the non-EoE EGIDs. Each case is different.

[29:12] As a pathologist, Dr. Collins has seen the guidelines for treating eosinophilic conditions evolve. They've become more specific as our knowledge of the data concerning the disease has increased. PPIs are now considered a treatment for EoE.

[30:12] Dr. Collins says we need clinical trials testing therapies in children and adults with non-EoE EGIDs. We need to determine which patients have single-site disease and will only have single-site disease, and which patients may develop multi-site EGIDs.

[30:42] Those aspects will be addressed in the next version of CEGIR, if it's funded.

[30:49] Ryan tells Dr. Collins it's been fantastic having her on the show. This has been a good overview of non-EoE EGIDs and the new methods clinicians are looking into to help people get a better diagnosis and treatment.

[31:11] Dr. Collins says we don't have validated instruments yet to measure symptoms, evaluate the mucosa, and evaluate the biopsies under the microscopes. We need to create those validated tools to help us determine the significance of our findings.

[31:31] Some data strongly suggest that eosinophilic colitis is different from the rest of the EGIDs; certainly from the upper tract EGIDs. We need to move more deeply into what eosinophilic colitis actually is.

[32:05] For our listeners, feel free to check out the article we've been mentioning in the show notes. We'll include a link to it.

[32:11] For those of you who would like to learn more about eosinophilic disorders, please visit APFED.org and check out the links in the show notes.

[32:18] 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.

[32:27] 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.

[32:36] Ryan thanks Dr. Collins for joining us today for this great conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.

Mentioned in This Episode:

Margaret H. Collins, M.D., A.G.A.F., Director, Gastrointestinal Pathology

Division of Pathology ML 1035

Cincinnati Children's Hospital Medical Center

"Guidelines on Childhood EGIDs Beyond EoE," Journal of Pediatric Gastroenterology and Nutrition.

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, and Regeneron.

Tweetables:

"The best distribution of guidelines is accomplished by publishing them in the medical literature; sometimes in multiple journals to target audiences of allergists, gastroenterologists, and pathologists." — Dr. Margaret H. Collins

"Guidelines may be helpful to insurance companies to accept that a certain drug is needed by a patient with a certain condition." — Dr. Margaret H. Collins

"It's always reassuring to have a well-conducted clinical study that verifies that your thinking is correct." — Dr. Margaret H. Collins

"This is the first effort to create uniformity in the way in which non-EoE EGIDs are diagnosed. This algorithm can change over time. It provides signposts for the diagnosis, based on the information we have currently." — Dr. Margaret H. Collins

"We don't have validated instruments yet to measure symptoms [for non-EoE EGIDs], evaluate the mucosa, and evaluate the biopsies under the microscopes. We need to create those validated tools to help us determine the significance of our findings." — Dr. Margaret H. Collins

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 Jason Ingraham, an adult living with eosinophilic fasciitis (EF), and Dr. Catherine Sims, a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital. They discuss Jason's experiences living with EF and Dr. Sims's experience treating EF. They share Jason's journey to diagnosis and the importance of working with a group of specialists. They share tips on medication and physical therapy, how to communicate with your medical team, and manage your activity and mindset.

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:

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

[1:14] Holly introduces today's topic, eosinophilic fasciitis, with guests, Jason Ingraham and Dr. Catherine Sims.

[1:25] Jason is an adult living with eosinophilic fasciitis (EF). Dr. Sims is a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital.

[1:52] Dr. Sims explains what EF is. Patients may present with symptoms of large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do.

[2:42] EF, as with most eosinophilic disorders, doesn't follow the textbook. Some people will present with one symptom and some with multiple symptoms. There is a disconnect between how we diagnose conditions like EF and how patients present.

[3:01] There are major and minor criteria for the diagnosis. As in Jason's case, it takes time for the symptoms to present. Things develop over time. It took multiple specialists to diagnose Jason.

[3:38] Eosinophilic conditions are incredibly different from each other. When Dr. Sims sees a patient with high eosinophils, she thinks of three major buckets: infection, autoimmune diseases, and cancer.

[4:12] Patients will often see many different specialists. In Jason's case, they had done a skin biopsy that wasn't as helpful as they hoped. That led him to get a deep muscle biopsy to collect the lining of the muscle.

[4:47] Fasciitis is the inflammation of the muscle lining or fascia. A sample of the fascia can demonstrate under the microscope if there is a thickening, swelling, or inflammation of the lining of the muscle.

[5:24] Dr. Sims as a rheumatologist treats a number of rare diseases. Eosinophilic fasciitis is an ultra-rare disease.

[5:43] Jason had a local primary care doctor and a rheumatologist who both did a really good job and referred him to Dr. Sims. She had the benefit of their hard work to guide her next steps. Because EF is so rare, she has pitched Jason's case twice in rheumatology grand rounds sessions.

[6:18] During one of these sessions, Dr. Sims was advised to get the fascial biopsy that ultimately led to the diagnosis. She benefited from the intelligence and input of dozens of doctors.

[6:59] In the Fall of 2022, while hiking on vacation with his wife, Jason was extremely fatigued, and his forearms and lower legs swelled. His socks left deep impressions. It was difficult to reach his feet to put socks on. He spent a lot of time uncharacteristically resting.

[8:09] Jason's primary care doctor ran lots of blood tests. He thought it might be a tick bite. Jason started seeing specialists, having tests and hospital visits.

[8:57] Jason worked with a rheumatologist in Wilmington, an infectious disease doctor, and a hematologist/oncologist who reached out to a Duke expert. He also saw a pulmonologist and a dermatologist. He got the referral to Dr. Sims for March of 2023.

[9:57] The first diagnosis Jason received was after his first hospital stay in January of 2023, when he had bone marrow biopsies, CT scans, ultrasound, and other tests. He was deemed to have idiopathic hypereosinophilic syndrome (IHES).

[10:30] It was only a few weeks before his local rheumatologist said his panels were back and one tipped it from an IHES diagnosis to eosinophilic granulomatosis with polyangiitis (EGPA). He joined the Vasculitis Foundation and researched EGPA.

[11:03] Dr. Sims told Jason that EGPA was a working diagnosis but he didn't check all the boxes. There was the underlying thought that maybe it was something else. He had a second flare when he came off of prednisone in June of 2023.

[11:48] Dr. Sims scheduled Jason for a muscle biopsy while he was off steroids. That's how he got the diagnosis of eosinophilic fasciitis (EF). Jason says the disorder is hard for him to pronounce and he can barely spell the words.

[12:52] Jason's wife Michelle encouraged Jason to track his symptoms and medications and keep track of data. Going from specialist to specialist, the first thing he did was give the history.

[13:31] Jason found it helpful to create a spreadsheet of data with blood test results, meds, how he was feeling each day, his weight, and even notes about when he had difficulty putting his socks on. Jason is an advocate of owning your continuity of care as you see different doctors.

[14:42] Jason says the doctors at Duke talk very well between themselves.

[14:49] Jason likes to look back at that spreadsheet and see how far he's come, looking at the dosage he was on during and after flares and the dosage he's on now, or zero, on some of the medications. That's a little bit of a victory.

[15:16] Holly works at a private hospital without Epic or CareEverywhere so she gives physical notes to her patients to give to their doctors. She comments that a great PCP, like the one Jason had, can make all the difference in the world.

[16:18] Jason's PCP, Dr. Cosgrove, referred Jason to Duke for a second opinion. That was where he met Dr. Sims. He's glad to have both Dr. Sims and his PCP accessible.

[17:35] Jason says the number of questions you have with this type of thing is immense. When you look up EF, you find very little and the literature isn't easily digestible by patients. Being able to reach out to your doctors for a quick question is super helpful.

[17:56] Jason has been able to do telehealth follow-ups and not always have to travel or take off work, which has been extremely helpful. He has been at Duke a good handful of times for various things but remote follow-ups are helpful.

[18:52] Dr. Sims says people just don't know about EF as it is an ultra-rare diagnosis. Even physicians don't understand what causes it. It's lumped in with all other eosinophilic conditions but these disorders don't all present the same way.

[19:19] EoE doesn't look like EF, even though they're both driven by the same immune cells. Dr. Sims says the first need is educating providers and patients on what the diagnosis is; awareness in general when a patient is having this swelling of extremities.

[19:44] Dr. Sims says at his baseline, Jason is very active with multi-mile hikes. When Dr. Sims met him, he was off from the baseline of what he was able to do. Being aware of your baseline and changes from that is very informative for doctors.

[20:07] Dr. Sims talks about the patient being a liaison between multiple specialists. Bringing data to your subspecialist always helps facilitate care and come up with a bigger picture of what's happening.

[20:23] Jason first went to Dr. Sims with the diagnosis of EGPA. She said, let's treat the EGPA and see what happens but they kept an open mind. With ultra-rare diseases, sometimes it's difficult for patients not to have a label for their condition.

[20:45] Dr. Sims explains to her patients that sometimes we live in the discomfort of not having a label. She keeps an open mind and doesn't limit herself to just one diagnosis. She seeks feedback from providers who have seen this before and know what works.

[21:07] Just as Jason described, you will go through multiple diagnoses. Is this cancer? Is it a parasitic infection? Where did you travel? You will see many subspecialists. It's extremely anxiety-provoking.

[21:31] When Dr. Sims did her grand rounds, she gave a third of the presentation, and the other two thirds were presented by an infectious disease doctor and a hematologist. In these cases, you need more than one subspecialist to complete the workup.

[22:10] Dr. Sims says there are a lot of misconceptions that the patient will get the diagnosis right away and the right therapy and get better. There are multiple therapies, not just medications. There are lifestyle and work modifications; it's a gradual process.

[22:22] One of Dr. Sims's goals for Jason and Michelle is to get back to doing the things that they enjoy, tennis and hiking. That's a measurement of the quality of life that a patient has.

[22:34] Talking to your doctors about how you're feeling and how you're functioning is huge. It may be that this is your new normal, but it may also be that we can make adjustments to maximize your quality of life.

[23:00] There are misconceptions about the journey of diagnosis and treatment. Have a close relationship with your subspecialist. PCPs have a high burden of expectations. As a rheumatologist who treats rare diseases, it's helpful to take on a part of that burden.

[22:31] If you don't have good communication with your providers and they aren't listening to you, you can always go get another opinion. The provider relationship is life-long.

[23:43] It's important for your provider to take what's important to you into consideration when they make treatment decisions.

[25:00] As a rheumatologist, steroids are a first-line therapy for Dr. Sims. Their role is the quick control of inflammation. The goal is always to get you off of the steroids as soon as possible, in the safest way possible.

[25:17] When Jason came to Dr. Sims, he was on mepolizumab for the working diagnosis of EGPA. Mepolizumab is one of the primary therapies for EGPA. They talked about not making treatment changes as they were navigating what was happening.

[25:40] They didn't want to make a change of medication and then have that be mistaken for disease activity. They didn't want too many variables moving at once.

[25:47] Typically, the first-line therapy is steroids, meant to help with the swelling, pain, and tightness that patients will get lining their muscles and give them a bit more functionality and decreased pain.

[26:00] Long-term, Dr. Sims gives immunosuppressant medication. She prescribed methotrexate for Jason. In EF, the immune system is overly activated, attacking the lining of the muscles and causing the symptoms.

[26:51] If you suppress the immune system activity, that leads to decreased inflammation and symptoms in the patient. Steroid use, over a few months, is detrimental, with low bone density, weight gain, high blood pressure, and diabetes.

[27:14] Dr. Sims starts with prednisone and folds in medications like mycophenolate or methotrexate.

[27:19] Mepolizumab is an interleukin 5 blocker. Interleukin 5 is part of the immune system and is necessary for eosinophils to grow, function, and multiply. The goal of using mepolizumab is to lower the eosinophils that are contributing to the disease symptoms.

[27:48] Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer. We know how to manage those.

[28:08] If there is no response, we may add something like mepolizumab. As Jason was already on mepolizumab, Dr. Sims added methotrexate.

[28:20] IVIG, an infusion of immunoglobulin, has also been used as a quick way to control inflammation. It is used in other autoimmune diseases like myositis, which is inflammation of the muscle itself.

[29:08] With untreated eosinophilic fasciitis, the lining of the muscle may continue to be inflamed and can lead to fibrosis, damage that cannot be reversed. The patient can become very disabled. Contracture is one result of this.

[30:16] Jason says when he tried a new medication, he monitored if it was a good fit and if the side effects were less impactful than the underlying disease. Dr. Sims adjusted his dosages or tried to get off certain medicines as needed.

[30:59] After his muscle biopsy from his left calf, it took about a month to get back to walking easily. He was already in physical therapy, going many times for a variety of things. He had back pain, potentially related to his EF. His physical therapist was great.

[31:56] The stretches alternated between upper and lower body. Jason bought tools to do the stretches at home. When he's not feeling as well, he goes back to some of those same stretches. When he was on steroids, he took long walks to strengthen his bones.

[32:39] Jason started making phone calls to supportive family and friends on his walks and started listening to podcasts related to his condition or medications. Getting back to tennis and hiking is important to Jason. He's happy to be out there.

[33:20] Jason was open with his employer about his condition. Some of the weekly meds can make him not feel well. His employer gives him some flexibility. He has good days that far outnumber the bad days. He doesn't have to think about EF too much now.

[34:33] It's nothing like when he was in a flare, especially when he was in a flare before being diagnosed. What gets him through a bad day is giving himself some grace and understanding while he waits for his meds to catch up. He rests more than he wants to.

[35:33] Low-impact exercises like walking help Jason. He's trying to find a support network that gets EF. That led him to APFED, to find anyone experiencing something like what he was. He saw a conference that included a session on EF.

[36:09] Jason signed up for the conference and there he met Ryan's mother who has EF. They were each the first person the other had met with EF. They decided to connect after the conference. They talked on the phone for about an hour.

[36:39] She told Jason how she got into APFED and talked a lot about her son who had eosinophilic diseases. Soon after, Jason talked to Ryan as a primer for this podcast.

[38:15] Having a community to relate to, even if it's one person, is massive. It can make you feel less isolated.

[38:42] Holly says it's hard having a chronic illness. She thanks both Jason and Dr. Sims for sharing so much information and their journey and she asks for last words.

[38:58] Dr. Sims believes finding a community is critical. She interviews a lot of patients for research and isolation is a frequent theme. Even the doctor doesn't know what it's like to live with the condition you live with daily. As Jason said, give yourself grace.

[39:33] Dr. Sims tells her patients that they're different from the general population because they have to spend so much time and energy managing their condition that they can't do x, y, or z today, and that is OK. She says to stay motivated and positive.

[40:12] Find what works for you. Walking is good for your physical and mental health. Have the goal of getting back to what makes you happy. Take initiative and find non-medication ways to recuperate. You have control over ways you can feel better.

[40:43] Connect with others and share your story, like Jason did today. It may make someone's journey a little easier and make them feel less alone. Utilize your condition for good, for a bigger purpose.

[41:04] Jason had wished he could meet someone who could tell him what EF would be like over the years. He says to stay positive and find out what you have control over. Jason believes the future is bright for being able to do many things for a long time.

[42:26] For our listeners who would like to learn more about eosinophilic fasciitis, please visit APFED.org and check out the links in the shownotes.

[42:33] If you're looking to find a specialist who treats eosinophilic disorders, like Dr. Sims, you can use APFED's Specialist Finder at APFED.org/specialist.

[42:43] 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/.

[42:55] Ryan thanks Jason and Dr. Sims for joining us for this excellent conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.

Mentioned in This Episode:

Dr. Catherine Sims, rheumatologist

Duke University Hospital

Durham VA Medical Center

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, and Regeneron.

Tweetables:

"EF patients may present with large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do." — Dr. Catherine Sims

"Steroids are … first-line therapy. Their role is the quick control of inflammation. The goal is always to get you off steroids as soon as possible, in the safest way possible." — Dr. Catherine Sims

"Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer." — Dr. Catherine Sims

"Stay positive and find out what you have control over. The future is bright for being able to do many things for a long time." — Jason Ingraham