My name is Jennifer Lightdale, and this is Ilche Noneski. And we are going to give a talk that we've never done together before in tandem, but we're going to have fun doing it, okay? It's supposed to make it dynamic, right? We're going to call it Dueling Eos instead of Dueling Canos, so we'll see how that goes. And it's really a talk about eosinophilic esophagitis as a clinical diagnosis, and really we want to give a shout-out. There's a lot of excitement right now in EOE and Sanofi and Regeneron, not necessarily companies that have much to do with endoscopy until all of a sudden they need us to be doing endoscopies to understand that people out there have this condition. So they actually are also getting excited about endoscopy and have been part of funding this great course. So we really thank them for that. And we are going to start our talk. So the presentation is going to be divided up obviously into the definition of history, epidemiology, pathophys, and natural history, clinical presentation, and treatments, and we'll hit on all these major points. So we do have some disclosures. My disclosures are always a little funny. I actually did sit on an advisory board for Sanofi at one point, but the rest of them are about formulas. I'm an expert in infant formulas, which weirdly is related to EOE, and you have nothing to worry about. So let's start with the case. So we have a 21-year-old Caucasian male college student presented to the ED with sudden onset of inability to swallow water, even a saliva after he had some turkey at Thanksgiving. In the emergency room, his symptoms suddenly resolve. If you're fortunate as the on-call doctor to have that situation. And now he presents to the office for evaluation. He reports several years of occasional sense of an uncomfortable slow transit of food, solids more than liquids. This occurs in his chest area while he's eating. His past history is notable for asthma as a child and then seasonal rhinitis. No significant history of acid reflux symptoms. Medications include an over-the-counter antihistamine. Physical exam is normal. One of the possible causes of it is dysphagia. Of course, EOE is what we're talking about today, but of course, you want to be excellent clinicians with a differential diagnosis that's broad and expansive, and Schatzky-Ring is certainly on the list. A peptic stricture comes to mind. Motility disorder, obviously less common perhaps in younger patients, but something that you can overlook if you're not considering it, especially if they're talking about solids greater than liquids. We're taught that liquids are typically what we see with motility disorders, but you definitely want to think about that. And then all these other etiologies that don't seem to make sense in a clinical setting, in this particular clinical setting. So here's what we see on EGD. You'll see here you've got linear furrows. You've got some exudates. Here you've got some linear furrows. You've got significant edema, potentially some luminal narrowing in this area as well. All right. So when we think about EOE, you can try to make the diagnosis endoscopically, but it's really all about histology. And you're really going to see more than just that eosinophil count. So we're seeing superficial layering here, these tiny little eosinophilic abscesses. I don't know if you can use your... And spongiosis, epithelial hyperplasia for sure, degranulation, and then you will over time get fibrosis. And really, the definition of EOE is that it's a chronic immune-mediated food antigen disease that has to have the symptoms. It has to have pathology, so you've got to get biopsies in order to make the diagnosis. And then you are counting eosinophils. So we're looking for an eosinophil count of at least 15 eosinophils per high-powered field. So since EOE is isolated to the esophagus, and you do need to rule out other causes of eosinophilia, I'll just point out that isolated to the esophagus, you certainly can have other ejids. So you can have eosinophils in the stomach, in the small bowel, and of course the colon. So it's important to realize that EOE is a relatively new condition. There were case reports in the 70s and in the 80s, but it wasn't really until the 90s where we started to appreciate this condition as a distinct clinical entity. In fact, when I was a fellow, we were still attributing this to maybe some type of atypical manifestation of GERD. But it wasn't until 2007 that Glenn Farood and the colleagues created the first consensus guidelines. And over the time, these guidelines and consensus statements have been changed. And up until recently, just this last year, we have updated U.S. consensus statements through ASGE as well as guidelines through the British Society of Gastroenterology, and we'll touch base on all of those. I should say, in your folder is the ASGE statement on EOE. So EOE is certainly something we consider related to atopy, and it is, compared to other atopic conditions, it is certainly prevalent. But it is not as prevalent as asthma, seasonal allergies, and then also eosinophilic gastroenteritis. What you want to know is that if you have EOE, you're very likely to have one of these other highly prevalent conditions. So this is the history you're trying to take. Oh, you're having dysphagia? Do you have asthma? Do you have seasonal allergies? Okay, I'm thinking about EOE. Talking about epidemiology. Yeah, so, you know, we see, sorry, from the North Carolina group, a study published looking at the prevalence of EOE, and I'm sorry about the mouse, the pointer being. You see that it tends to peak in patients between, we'd say, 25 and 45. I've seen cases of EOE in 70-year-olds, although it's less likely. So this is a good slide that tells us a little bit about the range, and when you're looking at a database of millions of patients. Yes, and by the way, being pediatric, I will notice we have a lot of it in peds as well. So it's, I mean, it's certainly something we're thinking about. Okay. Sorry, continue. Go ahead. So these are some of the prevalence numbers, but again, it's, I think the point to get across is it certainly should be on your mind, particularly if you're dealing with food impaction. We also know it's a global condition, so you're seeing it across the world, and this is a study comparing Switzerland to Ohio in terms of adults versus pediatrics. So this is a bunch of studies showing the global presence of EOE, and of course, we always notice, okay, nobody's really describing it in Africa. That's probably because they aren't looking. So I think, again, the goal is to really recommend that people be aware of this. Anything else you want to say on global presence? What was your thought with this? Sorry. Yeah, no, so basically, globally, the prevalence is about 8 in 10,000, so it's not uncommon, and when we look at the tip of the iceberg, you know, there's a lot of variations in studies depending on the region, and so, again, just emphasizing that if you don't think about EOE in patients that are coming through, you potentially can miss it, and you really need to be higher on the differential, especially in younger patients. It is associated with a lot of other factors, so actually, it's not just food-triggered. It can be aeroallergens that trigger it, so this time of year with ragweed and whatnot, you can actually start to see people having more food impactions, of course, overlapping with summer barbecues and things like that. We certainly know it's food-allergen-triggered. H. pylori has been associated. A number of infections have been associated. Actually, patients undergoing allergy therapy, so getting allergy shots, are likely to have their EOE flare up, though they may not have realized they had it before. Sometimes I have EOE patients who are now going for allergy shots, and I sort of want to work with them on that, and then also, PPIs have been linked to induce certain IgE antibodies. Okay, so you're going to talk pathophys. So pathophys, even though the eosinophilic esophagitis is limited to just the esophagus, there's a complex interplay between the environment and the immune system, and so what we think happens is you get aeroallergens and food allergens that trigger a cascade of events that release a lot of pro-inflammatory mediators, illerleukin-5, you get E-attacks, and remember, these eosinophilic responses are meant to take care of helminthic infections, are meant to kill parasites, so you can imagine that over time, persistent inflammation that's happening in the submucosal layers can then start going into the deeper layers, leading to eosinophilic inflammation, lamina propria fibrosis, you can get dysmotility as it affects the muscles, and then, you know, the epithelial permeability, I think, is a, you know, underappreciated aspect of this. There's a lot that's happening when all those gap junctions and tight junctions that we learned about in, you know, in school become disrupted and allow certain hostile environments to occur. So why do we care? Well, you know, over time, you know, those fibroblasts get recruited, you get degranulation of eosinophils, and it leads to fibrostenotic conditions, and so this is an important slide because the longer we wait to make the diagnosis, the prevalence of fibrotic features goes from 47 percent if there's a diagnostic delay in two years up to 88 percent if we're waiting 20 years. We're not waiting 20 years, typically, but, you know, within that time frame, it's meant to, you know, for all of us to appreciate that this can happen, and every 10-year increase in age, the odds of developing a fibrostenotic phenotype more than double. I like that we're using the term fibrostenotic phenotype. It tends to remind us of Crohn's disease, and as we talk about, you know, disease modification, trying to prevent fibrosis is going to be key. And the same thing here. The longer the delay, the increased risk of prevalence strictures, and the risk of strictures tends to increase by 9 percent. So if you're having patients that say, hey, I don't want to do therapy. This isn't a — you're going to tell me this doesn't cause cancer. I'm just having some trouble swallowing. I'm fine now. You can bring up these types of statistics to add more strength to the argument that they should be on some kind of therapy. So I will tell you, in PEDS, we don't see the fibrostenosis, and actually, if you think about what Ilchi just showed in terms of younger kids don't have that fibrostenosis, but yes, by the time they're 20 and going off to college, that's when they're going to show up with the turkey, just like you're — and yes, whether you see them or I see them really depends on, frankly, which hospital they show up in. So we see plenty of college kids. But what's going on is it's really this concept of inflammation over time is leading to fibrosis. That is what explains the different symptoms in children versus adults. And again, there's a diagnostic delay. Some of that diagnostic delay is honestly that patients have adapted and the family themselves hasn't noticed what's going on. But if we can get ahead of it with anti-inflammatory, and then as you get to the fibrostenosis, if you can actually dilate, you can make a big difference for the patients. Okay. So in terms of these presentations by age, kids tend to present more, you know, poor eaters, so they just aren't eating very well. As you get into sort of school age, now they might be vomiting. These are kids who, you know, we told the families, oh, they shouldn't have GERD after a year of age, and that GERD is just not going away. We're trying to understand that. Sometimes there's abdominal pain, but really it's as you get into the teenagers, that's when they're starting to say there's dysphagia or food impaction. And I think that this is why we had sort of noticed really very early on that there seemed to be this bimodal presentation way that you had to think. So you had really kids presenting early, and then you had the 30-year-olds that you saw before. And these were some of the early stuff. We do know that men tend to have this more than women, or boys more than girls. It tends to present. By the time you actually have that fibrous stenosis, that's when you're going to present. There's often that atopic history. It does tend to happen in white patients. And there can be very strong family histories. And these days, yes, I'm getting family histories of EOE, so, you know, I'll be there, and it'll take – it's amazing. It can take 20 minutes of the visit before somebody mentions, oh, yeah, dad has EOE. Okay, thanks. So, you know, it's really – I think we're starting to get now people with EOE having children. The typical pediatric patient has persistent reflux. They might have all those other symptoms. But, you know, even if I want to probe more, I can sort of say, hey, are they the last kid at the table? Yes. Does this – a kid is chewing very carefully, cuts their food into small pieces, gagging, food refusal. And I'll ask – I actually can elicit this. I'll say, can you feel food? And a seven-year-old can tell me, can you feel food go from your mouth to your stomach? Do you feel it slide down your esophagus? And they say yes. I'm like, okay, that's a problem. So, you know, I think really asking some of these questions can make a difference for people. There's more data out there on the, you know, again, these different kids, whether infants and toddlers, the grade school, or the adolescents. But I think a lot of it, which this is a little too small to look at, there's coping behaviors that the families have come up with. And frankly, if you think about friends you have, and we're probably surrounded by people who are cutting their food into very small pieces and are truly afraid of food getting stuck. And it's like starting to say, huh, maybe that's something you could do something about. All right, findings on endoscopy. So there is now this standard approach to grading what you see that involves using a score called ERIFs, which stands for edema rings, exudates, furrows, and strictures. And I think Ilche pointed many of these out before. But you certainly can see any of these alone, or you can see them in isolation. And I think one of the most classic findings, honestly, is the ringed-looking esophagus. It's sort of fascinating. You can really see that on an upper GI too. You can also see certainly proximal or any strictures at all. And you can see narrow-caliber esophagi if you are dealing with something that's quite swollen or inflamed. All right. So, oh, so this is yours still? Is it mine still? So we do see all of the same features in EOE. We rarely see the stenosis. But really, you can have all the same features as you do in adults. So they just don't have that fibrous stenosis yet, but they've got everything else going on. So another reference, just so you have it. These are the eREFS grading system. I will say that probation, for example, if you're using that, has this built in. You may have already used it as you're characterizing the EOE. So you can see that there are varying degrees of inflammation. And I just want to point out, it's important for you to use this to allow you to gauge response to therapy once you put the patients on whatever treatment they're going to be on. Another one, just to give you some examples of how varying it can be depending on severity. And then there's a score here that you can use. We won't spend too much time. You can put the score together and go from there. And I mentioned before we move on. So what's really funny about this score, eREFS, is this can, again, stand for the rings, exudate, furrows, et cetera. Or it also can stand for EOE endoscopic reference score. So you'll see both. I don't know why they can't standardize that. But anyway, you'll see different papers using it different ways. The other thing I'll say just from a QI standpoint is anything like this, the more it can be posted up in a unit, the more everybody's gonna grade the same way. So really encouraging your unit to put these up on the wall can make a big difference. So treatment options for EOE, there's a five-pronged approach that we'll cover. And that includes dietary therapy, PPI therapy, topical steroids, dilation, and the use of a biologic dopilomab being the one in particular. The goals of therapy, of course, elimination of symptoms. We want all of our patients to feel good. We want to reduce mucosal inflammation. Going back to the previous slides, we want to control the amount of inflammation happening at the mucosal level. We want to correct the disease consequences, namely fibrostatic presentations and food impactions and preventing complications. So there's been a lot of talk about what's our right endpoint for treatment. And I think for a very long time, we've been aware that treating to symptoms, which is resolution of dysphagia without the need to avoid food based on texture, actually probably is just the tip of the iceberg. It's pretty clear that patients can feel clinically better with many things we try for them, but they will still have eosinophils on their biopsy. So one question has been whether the EOE should be, whether our treat to target goal is histopathology or endoscopy. And at this point, they have come up with, I think in 2020, they sort of said, look, we want all three. So you're looking for resolution of symptoms, resolution of the eosinophilic inflammation to less than five to 15. And then you also want to feel like the endoscopy looks better. So that ARIF score got better and there's no stricture. So diameter's greater than 15 millimeters. I don't remember who's doing this. So, you know, in terms of initial choice of EOE therapy, you certainly want to think about efficacy of the medications. This has to be shared decision-making. There's a lot of choice to be made here. Some of this you can recommend it and the family's not going to do it and won't particularly talk about diet, but then these days there are medications. People may not want medicines. You do want to think about the disease severity. If this is somebody who's repeatedly presenting to your ER in the middle of the night with their turkey, you probably would like them to do something and it's really important to engage with the patient and get them to understand that. Unfortunately, insurance is a big story for us. So understanding what the insurance will cover and even some of the seemingly very cheap medications like using the swallowed topical steroids can be difficult to get insurance coverage for. There are dietary resources you have to think about, but really it's a shared decision-making that's going to guide your treatment decisions. The options for clinical management are the same in children and adults. So I won't spend time on that, but there is one big difference. So treating children always involves discussions with parents. So I certainly have had the child ready to do one thing and the parent is just on a different page. And so this was a little paper that talked about you have to do a family meeting if the kid's old enough and you're really trying to decide what direction you're gonna go into. Okay, elimination diets. Yeah, so this is from a paper that's coming out by Saru Myberg, who's a nurse practitioner at Mayo Clinic. He and I are publishing this for nurse practitioner use at a conference. But essentially what we are able to do is show you the typical six food, and we'll come back to elimination diets, but typical six food elimination diet include fish, nuts, eggs, soy, wheat, and dairy. And then there are modifications that you can use to help patients along. As we'll see, dietary modification can be a challenging thing to do. I had a dairy farmer who had eosinophilic esophagitis and I offered him a choice of getting dairy out of his life and he kind of looked at me and said, I'll take whatever medical therapy you have to offer. And this is a great slide about kind of what the dietary landscape is these days. So one of the sort of, I think, turning points for EOE was really recognizing that a complete elemental diet where you basically take somebody and put them onto an amino acid based formula actually solves the problem. You'll have elimination of the eosinophils, so 92% deep remission, meaning you can't find eosinophils in the tissue, everything's cleared up. This is not easy to do, so we certainly can still do it. Sometimes we're using a nasogastric tube. It is difficult to tolerate this diet and it certainly doesn't taste good. So I don't know how many people have tried an amino acid based formula, but not tasty. The six food elimination diet gets you pretty good. It gets you to 72% sustained deep remission. So that's really taking out all of those foods and getting you to a pretty good level of all of those foods and is a tough diet to do, but if you do it well, it gets you pretty good. What's really interesting is moving into easier diets, if you will, in terms of elimination. So you can take out milk and wheat, and that's been shown to have a 40% deep remission rate. And then there's the four foods, which is milk, wheat, eggs, and nuts gets you 60% deep remission. Basically, you've got something here about the British Society guidelines. When you start to get into these elimination diets, it's really important to bring in a registered dietitian. You're definitely gonna be working with micro and macronutrient deficiency. So you definitely wanna, don't do this alone and explain to the family that you'd want them to see a dietitian. I think one of the most interesting things that came out of DDW, I wanna say now three years ago, was all the work around one food diet, and the one food is milk. So this is the elemental diet data that's in kids and adults. You can see an amino acid-based diet really leads to remission of the disease. Six food is 74 and 70%. And then one food, just taking out milk alone, even for your dairy farmer, would get you to 65% remission. So it's quite effective, actually, to take out just milk, and that has increasingly become my practice. I really just focus on milk for patients. And so this has been written up. This was in gastroenterology. This is, I can't remember where this is, another one from, now I'm gonna get confused, another gastroenterology paper. Okay, I'll let you move to PPI. So the question's always been, what's the impact or PPI therapy for GERD? And initially, when the diagnosis of EOE was still a little bit confusing, is EOE a manifestation of GERD? What is the complex interplay between acid reflux and eosinophilic infiltration? Stu Speckler and his colleagues published a nice sort of discussion or thought paper on what's the complex interaction at the level of the cellular level. But one of the things that I wanted to demonstrate was Corinne Blanchard and Mark Rothenberg at Cincinnati did a whole genome-wide study on children looking at EOE compared to GERD, and they found there was different gene expressions, and particularly with eotaxin-3. And so it is a different condition, even though PPIs are used to treat eosinophils, eosinophilic esophagitis, it is a distinct clinical entity in terms of how it's expressed at the gene level. But there is a condition that we think of as PPI-responsive eosinophilia, so we understand there's a complex interplay, and that was the slide I was meant to show you. Now, as far as PPI therapy for EOE, this is my typical first line when patients are refusing dietary modifications. The meta-analysis looked at PPI monotherapy and found a 40% histologic response, a 60% clinical improvement. Patients do pretty well. I have two partners that have EOE, and both of them are using their PPIs as their choice. We have been called for food impactions on them, and we grumble just like every other time, but we show up. The 2022 British Society Guidelines describe that failing PPI trial is no longer needed to rule out EOE diagnosis. So it used to be the diagnosis of EOE was the persistence of greater than 15 eosinophils after an eight-week trial of VID-PPI. That's no longer needed, so you might see that maybe on a board test. I don't know. Hopefully, it'll end up in the right place. For a more accurate diagnosis, what the BSG guidelines are saying is you stop PPI for three weeks, and then you do your endoscopy. Obviously, patients will have superimposed GERD. Stopping patients on their PPI can be a miserable scenario, so you'll have to think about perhaps some alternative acid suppression regimens like an H2 blocker. What we do, based on BSG guidelines, is you put them on VID for eight to 12 weeks. You repeat the EGD on therapy, take biopsies, of course. If there's histologic remission achieved on PPI, you can continue that, and when it's achieved, you can get pretty good results. I mean, this is when you can get that, and so oftentimes, these patients will continue on it. Unfortunately, just like any other chronic condition, whether it's seasonal allergies or EOE, if you stop it, you get symptom recurrence after 12 months in about 90% of patients, and everybody gets histologic recurrence at some point. Corticosteroid therapy. Swallow-through ticosone, of course, is the option, the easiest available, right? Just the steroid inhaler that we use for our asthma patients, for example. 62% histologic remission. Oral viscous budesonide, we think, tends to probably cover more surface area. You're expecting the swallow-through ticosone to get to the right, to cover the entire esophagus. We know that the viscous budesonide probably works better. That's my choice for our EOE patients, and there's a newer formulation, an oral dispersible formulation, and studies have shown to give anywhere from 58% to 84% remission at the 6- and 12-week mark, and up to about 50% over a longer period of time, usually in a year. I think this is only in Europe. Oh, in Europe, right, yes, in Europe. So, unfortunately, yes, the oral viscous budesonide is literally, you have to home-make it, so still in the U.S. We don't really have a good way of getting it from the pharmacy. Do you have a question? Ah. We have a compounding pharmacy that does that, but the insurance can sometimes be a little bit particular about paying for that. What's your thought on that? Yeah, I tend to use maple syrup, and I open the splenule and mix it with five mLs of maple syrup, and that seems to stick, and it's a lot better, in my mind, than the Splenda we were using for a long time. It always grossed me out, and now really grosses me out. But I think some of you may know there was an FDA trial that finished and seemed very promising in terms of this now being a compound that would stick to the esophagus, and for unclear reasons, it didn't get approved, so anyway, so what we've got there is the orodispersible budesonide is available in Europe, but not here, so. All right. Yeah, go. Yeah, so patients will worry about long-term steroids. Obviously, they hear corticosteroids. They think prednisone. Obviously, prednisone is riddled with long-term complications, but we do know in about 12 to 22% of patients that they can get candida from the various topical corticosteroid formulation. Usually, it's a minor symptom, and the corticosteroid can likely be continued while you're also providing treatment for the candida. Adrenal insufficiency, we think about with long-term prednisone use, for example. It's pretty low risk from a clinical standpoint, no real clinical impact. There might be a serologic impact, but there's still limited data on that. The BSG recommendations do recommend checking cortisol and bone marrow density in children and adolescents who are on long-term topical corticosteroid therapy. All right. So, just adding quickly to what I will tell you about what I do with steroid therapy, at least, is I sometimes am using it in an as-needed basis. So, the kids who are more symptomatic in the spring and the fall with their seasonal allergies, that might be when we go on it, then we'll come off it for the winter. So, you can sort of, the nice thing is you can do that. It's topical, and it's like hydrocortisone on a rash is the way I explain it to the families. So, the big game changer is starting to work with the biologics, and this had been sort of a frustrating situation. I think there had been a lot of hope on different treatment targets, but the one that's really seems to be working and got FDA approval last May, so it's been a little bit less than a year now, or, sorry, a little bit more than a year now, is anti-IL-4-R-alpha, or dupilumab, and basically, it's an IL-4-receptor alpha monoclonal antibody. It's inhibiting signaling of both IL-4 and IL-13. It is out there and approved for multiple atopic conditions, so you're seeing a lot of ads on TV for eczema, for, I mean, basically for many other conditions, not just EOE, but it's been approved now for patients greater than six years of age for dermatitis, and then also as an add-on in asthma, and then also in adults as add-on for chronic rhinosinitis with nasal polyposis, so I think all of that made it easier to get the approval when it seemed to really make a difference for EOE, and it does seem to make a difference with EOEs. It's a biologic that really can help, and this was the randomized controlled trial that basically was well done and helped to get the approval. I'm trying to think what else I want to say because it's hard for me to see this for some reason. I mean, basically, guys, what you're seeing is against placebo, it really reduces eosinophil count, and I think there's a really promising sensation about this. I don't know how many of you out there have prescribed this yet for your patients. Anybody? Yes, I'm seeing some nodding yeses, and I'm seeing some nodding nos. Okay. I'm just curious. Can I see hands? Who's prescribed? Yeah. Okay. So right now, I'm going to say about 10 percent, not even, of the group has done this, but let's see back in a year and see where you guys are, so it's really ... Okay. So there are hopefully other biologic treatment options that are coming for EOE, and again, this is really moving into the biologic world, so very similarly to inflammatory bowel disease, this seems to be the way to go to really try to target inflammation and keep it under control, and so you'll see these coming through, ideally, over the next couple of years, so many of them in phase three already, and again, they're going after the various pathophysiology targets, and you can see they've got a lot of different targets to go after. It is interesting when this is ... I'm going to try this. No. Oops. Oops. I was going to show you eotaxin. Can everyone see eotaxin? It's pretty far down the pathway, so a lot of the initial work had been on eotaxin three, and it just didn't pan out. It's very interesting. It's obviously a complex condition, so there's more to it than going that targeted. Okay, dilation. Take over. Yes. Show of hands, how many of the fellows have used bougie dilation, savory dilations? Is that something that ... Raise them up. Okay, okay, so still prominent. I've had some colleagues that weren't really trained with it. I think it has its benefits in certain kinds of situations, particularly if you have transesophageal luminal narrowing. But as you know, there's two different approaches that we can take. We can take a savory or bougie dilation or a through-the-scope balloon dilation. Certainly in this particular example, we're using it for something at the GE junction. But when it comes to EOE, either approach is acceptable, and it's 95 percent effective in improving symptoms. And so when you're talking with your patients about all the treatment regimens, I can get you 95 percent better, you know, tomorrow when I schedule you for your upper. That usually, you know, is something that they're excited about. As you'll see a little bit later, we want patients to be on treatment first, medical treatment, some other type of treatment, non-endoscopic treatment, before we decide to dilate. Now you're always concerned about perforations. You know, you see how friable the mucosa is when you biopsy these EOE patients. You're scared. But what's reassuring, and you can tell patients and their families, is that that rate of perforation is really, really small. And compared to peptic stricture, this was reassuring to me, compared to peptic stricture, there really isn't that much of a difference. Now when you dilate these patients, and if you look back after a savory dilation, the esophagus looks angry. And you'll see some pictures of that here. I mean, we're talking about a pretty significant rent, and we see that in about 9 percent of patients. And I just had a patient that I dilated. He was back from college, and he had called up saying that he had had some significant chest discomfort. I thought I'd perfed him. Of course, we always worry about that. The good news is that those symptoms responded with just some dietary modifications and some Tylenol. Nothing more involved than that. So best to reserve, as I mentioned, until you've tried medical therapy. I tell patients, we want to soften the mucosa. We want to let that medicine marinate a little bit in the esophagus and see if we can get the medication to work and to decrease the amount of inflammation. We can get about a year out of this, maybe a little bit more in patients. And so that's encouraging. And the goal is a luminal diameter of 16 millimeters at the least. And again, we know that it doesn't address the underlying disease. But when you're talking with your patients, you have to say, hey, I'm going to stretch you. You're going to feel better after a year. But we still have to get back to modifying the disease. The consensus statement? You can... Yeah. So the ASG consensus statement that, again, you have in your packets is really to take esophageal biopsies at that first EGD. And that's even if it's during a food bolus impactions. I know it's hard. It's middle of the night. But go ahead and get the biopsies. You're going to help the patient help yourself. And the other thing is to do it even if you don't think you're seeing any signs of EOE endoscopically. So really recognizing that it can be patchy, but it also just can be hard to figure out, especially with a food impaction happening. We also want to get stomach and duodenal biopsies at the index EGD because you can have more of an EGD. So if it's not just isolated to the esophagus, you have to think a little differently about the condition. And actually, I can tell you, I'm not... I think there's still data that we need on how some of these biologics are going to work for EGDs beyond EOE. The number you want to get with biopsies is six. And this number and this coming out actually changed my own practice a couple years ago because I was getting 2-distal, 2-mid. Now I'm getting 2-distal, 2-mid, 2-proximal, which sort of slows me down. But I am doing that. And the goal here is really to understand where the disease is and also increase your sensitivity specificity. And if you get the six biopsies, the feeling is the sensitivity has gone up to 100%. So the other thing the ASGE wants you to do is try to use that ARIF score. Probation has it. As we mentioned, it's easy to include. It's going to help you because it's going to guide your treatment response. So really understanding what that ARIF score was going in will help you know how to compare going out and, frankly, at follow-up endoscopies for this person's lifetime. It's still not being commonly utilized in practice. So again, from a do it better than we do it, just train yourself now to use these standardized scores. And then do do follow-up EGDs with biopsies. It's really the only way to know. And patients will feel better. Almost anything you do for them, they're going to feel better. But you're trying to avoid them having complications down the line. So again, going for dilation, you can consider that for any patient with EOE, regardless of luminal stenosis. The idea is you dilate to disrupt the mucosa and target diameter. I put 54. French, that should be 48. Sorry about the math. The balloon or bougie is based on what your endoscopic preference is. Again, I tend to use a bougie dilation when I'm dealing with what looks like diffusely narrow esophagus. If there's a dominant ring, I probably would focus on the balloon. When you have fibrostenosing EOE, of course, you want to dilate, but you want medical therapy. And then if you have enough clinical suspicion, you can dilate empirically in a normal caliber esophagus. Yeah. There's two questions from the virtual audience. Is there a role for injection of steroids during dilation? And how much do you dilate up to? So how do you decide what size you're going to start dilating with and how far up do you go? And is there a role for injecting steroids at the time of dilation? There's no role for injecting steroids. I mean, this is a chronic, chronic condition. So you're really not going to help yourself in any way doing that or help the patient. In turn, they do talk about be prepared for multiple dilation sessions. I think it's aiming for 5 to 10 at most every session. So it usually takes two or three to really get the patient up to the 15, if they're severely strictured and presented with their food infection. You can consider it much like a peptic stricture. You can kind of gauge what the diameter is and increase sequentially that way. You're just having to treat it because it's a different disease process, but pretty much the same. So this is a—anything else as far as questions there? No? OK, great. So this is an algorithm that Saurav Myberg, my colleague, uses when he sees patients up at Mayo Clinic. It's there for your reference. We're not going to go over all of that. But to help establish a diagnosis, of course, you do EGD with biopsies. You then move to PPI BID for two months. If there's no response, you can use topical steroids for eight weeks. Food elimination diet, of course, is an option. You know, I typically continue a PPI because I think it does have disease-modifying capabilities. I think it does. I always tell my patients, if I'm living in a bad neighborhood and people are trying to break into my house and I leave the windows open, I mean, they're going to get in a little more often. So if I'm thinking about what acid reflux potentially is doing to bathe the esophagus and increasing mucosal permeability, I think that it would be a reasonable thing to do, perhaps at a lower dose while you're trying other things. And then consider dilation, of course, after medical therapy. And then, of course, in patients who have not responded, dupilumab can be an option. All right. All right. So our conclusions are that eosinophilic esophagitis is a chronic immune-mediated inflammatory condition of the esophagus that affects males more commonly than females and generally will present in your 30s. The pathophysiology is probably related to genetics, allergies, and other environmental factors. And there are some common clinical presentations. You just have to be looking for them. Dysphagia, food impaction in adults, and then reflux, vomiting, abdominal pain, failure to thrive in children, more feeding disorders in kids. Increase of fibrosis over time is our concern. And that can occur with longer duration of disease, so earlier diagnosis and treatment is important. All right. So some questions that we're going to do. EOE is more common, less common, or as common as IBD? I don't have any buttons for you to push, but… How many people think it's more common than IBD? Less? About the same? Okay. So a mixed picture. It all depends on the study. It all depends on the region, right? But what I wanted to emphasize is IBD is rising at incredible rates, right? So it's probably 100% increase in IBD in the last 10 years, and it's a global problem. And when you think about your clinic, if you're seeing general GI, if you're seeing patients with Crohn's, ask yourself, am I seeing the same amount of EOE patients? Because in certain settings, I should be, right? So patients are coming in with these types of symptoms, you've got to realize that it's pretty common. True or false, EOE is the most common cause for food bolus presentation to the emergency department. True? It's true. Right, right, of course. And children with EOE are most commonly going to present with dysphagia, chest pain, food allergies, or failure to gain weight? Okay. Yes. Yes. They don't usually come in. They just don't have the fibrostenosis, so they're not going to come in necessarily with full-on dysphagia or signs of strictures. Okay. And then adolescents and adults with EOE most commonly present with dysphagia, chest pain, food allergies, or failure to gain weight? Easy. We don't want to make this hard. We tried. It's 6 o'clock. It's time for dinner. It's 6 o'clock. All right. So the answers are there, but we want to go over it. So the diagnosis of EOE is made when patients have greater than 15 EOs per high-file period after failing PPI therapy for eight weeks. That's true for now, but again, the new guidelines suggest that because of significant overlap between GERD and EOE, the best thing to do would be to discontinue the PPIs before you do your uppers so that you can get a clean assessment of what the eosinophilic landscape is. It may not be as practical as I mentioned, but it's certainly reasonable to try. Treatment for EOE includes food elimination, acid suppression, topical corticosteroids, endoscopic dilation, biologic therapy, or all of the above. Okay. Your boards are going to be about this easy, guys. Just don't even go to the course in D.C. What's it called? The Steinberg course. Don't even go there. I'll take questions. It's about this easy. I think we're almost there. All right. True or false? Up to 60% of treated EOE patients achieve long-term remission, greater than six months. That's false. A Swiss study looked at patients who were treated who stopped treatment. 82% of the Swiss study had relapse within six months of stopping a corticosteroid, and only 2% of patients were able to discontinue therapy altogether. So you'll see these patients in follow-up. Maybe you've done an upper endoscopy on them. Their EOs went from 35 to 5. They feel great. Maybe they got dilated. And so now they're having this question about, do I really need to be on this medicine? And the answer is yes, because if we don't, within about a year, you're going to have some type of recurrence. And eventually, you're going to start to have symptoms again. All right. All right. We did pretty good. We did. I think we did. We did really well, didn't we? Are you guys all OK? Everyone still awake? OK. Thank you. Yes. Some questions. For the patients that you've had on dupilumab, how long do they stay on it? Can you have a drug holiday, like with IBD? Are you trying to treat to a target, and then do you continue it forever? Yeah. So first off, we only have been treating them now for the past 15 months. So I don't know how long we'll keep them on it. But I will tell you, first, I was saying that for many of my patients, the drug was approved basically while we were at DDW last year. And I got home from DDW, made a couple of phone calls, had five patients scoped, and had five patients on it by July. So it was really, I was quite excited. And the families were so relieved that there was something out there. In pediatrics, we deal a lot with Crohn's disease and ulcerative colitis. And we've become quite facile, I think, with biologics. And it's really, I'm so relieved that there's now a medicine. So I'm sort of taking that approach. The treating to target, without a doubt, is we're at histologic remission. I mean, I'm really looking for histologic remission. And right now, I'm going to continue them on it until the insurance company tells me I can't. But they seem to be doing well on it. It does have a really favorable side effect profile. That's one of the reasons it's become so, well, it's approved, really, for eczema down to, I think we had age six here. But I'm pretty sure it even goes lower than that for some of the pediatric conditions. So I mean, it's really a drug that we're feeling quite safe about, as safe as you can. And I think right now, that's probably for the foreseeable future, that they'll stay on it, like any biologic. Yeah? In terms of first line versus second line, how are you choosing first line to pill him up? I don't think, at the moment, it is first line for me, still. So it is interesting. The PPI responsiveness is not to be understated. The number of kids who have 100 EOs per high-powered field, I put them on PPI, and they literally melt away. It's easily 10%. 1 in 10, easily, that happens with. If not more, I don't remember the numbers that are technically published. And that is why I do think PPI has a role for most patients. And like I said, I really have become a fan of the single-food diet. So I really have gone after milk, and that really has worked for many patients. So I think those two things, plus using the corticosteroids when we need them, I think you can actually, for many patients, make them feel better. But there are some that you just can't. So this is where it comes in. If you think about it, before you need to go to the pill lab, there are effective therapies, right? So there's a lot of conversation about, is PPI going to work? Am I comfortable being on a long-term? If it's not working, can I manage with corticosteroids and dietary? You have dietary elimination. It's an option. It's not always practical. But I certainly think if it were me, I'd rather exhaust those options first before potentially being on a biologic therapy if I didn't need it. I guess the follow-up to that is, if the patient presents with fibrous stenosis, and the trials for the pill lab haven't been on fibrous stenosing disease, so is there hope that this is the first line in that population? Is that going to be studied? Because I'm not sure PPI and diet reverse fibrous stenosis. At that point, you're just doing dilations. So a dilation certainly does, and so I always think about that being the reset button. But if you're able to control the eosinophil count, that should be your surrogate marker for inflammation. So if I go from 100 eos to 5 eos on PPI, at some point, I will hit the reset button with the dilation. There's not enough studies looking at patients on these types of therapies long term. Great study. Do you use dupilumab as monotherapy in your practice, or do you combine it with PPIs or steroids, or with the six-food elimination, like as a little bit of everything? I still haven't prescribed dupilumab in my patients, so I'm going to defer to Dr. Iqbal. No, actually, so I think I'm trying to think of the kids I've had on it. Many of them were ready. They either had already stopped, they had just had enough. I definitely have the teenagers that have just had enough, and they just don't want to take medicines anymore. Or the families, actually, there's so much negative press at the moment around PPI that that's also, I think, has definitely percolated down to patients, and they are worried about long-term being on PPI. So they would prefer to be on the dupilumab, and that has been for the most, I think almost all of them, it's this monotherapy. If I'm giving PPI at this point, it's because they have GERD symptoms on top of their EOE, but not for the EOE. Thank you, everybody. We'll be available for questions afterwards.

eosinophilic esophagitis

early diagnosis

fibrosis

treatment options

endoscopy

biologic therapy

multidisciplinary approach

EOE treatment