Full Circle: An Immunologist’s Unexpected EoE Journey

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