Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie: Welcome to UAB MedCast. I'm Melanie Cole. We have a panel today with Dr. Ame CaJacob, she's the Clinical Director of Pediatric Allergy and Immunology; and Dr. James Callaway, he's a gastroenterologist and an assistant professor, and they're both at UAB Medicine. They're here to highlight common causes and updated treatment options for eosinophilic esophagitis.

Doctors, thank you so much for joining us today. Dr. CaJacob, I'd like to start with you. Can you explain a little bit about EoE, the scope of the problem we're discussing here today? We had done a previous podcast on this. Tell us a little bit about what we're seeing in the trends, why we're updating this.

Dr. Ame CaJacob: So, the scope of EoE is getting more and more broad with time. So from studies, we know that both the prevalence and the incidence of eosinophilic esophagitis is increasing. And we're seeing this pattern in all of our other allergic diagnoses, right? So, that's why food allergy and everything else is so much more prevalent than it was in the past. And so, both on the pediatric side and the adult side, eosinophilic esophagitis, we're not only recognizing it more, but it's truly increasing.

So, I think on the pediatric side, it's about prevalence rates vary based on the study you're looking at. But in general, we think it's about 2% to say 6% of the population. They do think it is more prevalent than even things like inflammatory bowel disease and ulcerative colitis and Crohn's. And then if you have some specific symptoms like dysphagia or difficulty swallowing, then the chance of you finding eosinophils on your esophageal biopsies when you go to look and look into the microscope and start counting eosinophils, then your incidence of diagnosing EoE will increase with something specific like dysphagia.

Melanie: Dr. CaJacob, sticking with you for a second. As allergists and gastroenterologists are seeing more patients with EoE and you mentioned it's both on the increase and there is increased recognition, do you have any theories to what do you attribute this rise?

Dr. Ame CaJacob: Well, a couple things. Again, taking a big picture, a step back at our different atopic diseases, again that's atopic dermatitis or eczema, that's allergic rhinitis, it's asthma, it's eosinophilic esophagitis, right? And it's food allergy or anaphylaxis. So in general, we talk about things like the hygiene hypothesis. So, we're leading much cleaner lives than we did, you know, in the past when not many of us now are growing up on the farm, running around eating dirt. And because we're leading cleaner lives, then it's kind of shifting our immune system's tendency away from kind of a Th1 kind of pathway to a Th2 or allergic pathway. So, we're shifting from anti-inflammatory towards allergy. And so, we think, at least in part, that is the reason for the increase in all of our kind of allergic diagnoses.

There's other theories out there, certainly. And part of it is our diet and what we're eating, whether we delay introduction to food allergens, or whether we're changing bathing practices, all of this is intricately intertwined. And it's hard to have, say, food allergy without eczema. And eczema tends to be one of the primary things that can set off this whole cascade. And most eosinophilic esophagitis patients that we have are allergic or have some other allergic diagnosis, so they tend to run hand in hand. And I think that I'm sure Dr. Callaway's seeing this on the adult side as well.

Dr. James Callaway: Absolutely. I think the increase in just awareness of it is one of the big things. So, this probably existed before the early '90s when this was first described, but we have a much higher suspicion for this, and so we are finding it much more frequently now.

Melanie: And Dr. Callaway, since we are finding it more frequently, tell us a little bit about how the therapies have evolved over the years. What do you know now that you didn't know, say 10 years ago? And speak about some of those standard therapies that you're still using.

Dr. James Callaway: Sure. Well, the therapy for eosinophilic esophagitis typically revolves around a few different things. Elimination diets where we're actually trying to remove the allergen exposure by reducing that or eliminating that from the diet has been around and works. And in most patients, the difficult part with that is finding that particular food and identifying that properly. But elimination diet are things that work for a number of patients, if we can figure out the definite offending agent.

Other therapies that we talked about on our previous podcast were the use of proton pump inhibitors or also called PPIs and the use of swallowed kind of topical type steroids, trying to either decrease the inflammatory pathway or cascade or decrease overall inflammation.

I think I spoke to dilation therapy as well, which doesn't actually treat any inflammation, but can help treat some of the strictures or narrowings in the esophagus that can develop over years of untreated inflammation, which again speaks to us trying to find this earlier and treating it earlier with a hopeful attempt at reducing some of the kind of more late stage complications, which include a very small esophagus or these narrowings where food can actually get stuck on. But honestly, the most important evolution, it's actually just in the last year, which is the introduction of a monoclonal antibody called dupilumab, which is a new drug that is FDA approved for the treatment of eosinophilic esophagitis and works on those kind of cytokine pathways and inflammatory pathways that Dr. CaJacob spoke of earlier.

Dr. Ame CaJacob: Yeah. And the monoclonal that Dr. Callaway's referencing, dupilumab, has been around for many years in the allergy realm for other diagnoses. And it's approved for other indications like atopic dermatitis down to six months of age right now. And we've known for a long time that kind of blocking that Th2 pathway and that IL-4, IL-5, IL-13, these are Th2 cytokines that we talk about that can lead a patient towards kind of allergic diseases and dupilumab, what it ends up blocking is the IL-4 receptor alpha subunit so that it ends up blocking both IL-13 and IL-4, because both of those cytokines end up attaching to this IL-4 receptor. So when you knock out IL-4 and IL-13, those are two of our big Th2 cytokines. And so, blocking that entire allergic pathway really tends to help patients both numbers-wise, when you go in and do their scopes and the biopsies and counting eosinophils per high powered field, it helps objectively, but it also helps subjectively in the symptoms. Now, symptoms are different at different ages. But in adults, that can be dysphagia, that sensation of foods are getting stuck, near-food impactions or true food impactions and potentially chest pain. And so, it really can help alleviate a spectrum of symptoms.

Melanie: Dr. CaJacob, as pediatric patients transition into adulthood and go through their teen years, how does therapy and treatment change as they become adults? Does this stay with them? Tell us a little bit about that.

Dr. Ame CaJacob: Yeah. Unfortunately, it is a chronic disease, just like other numbers of chronic diseases. And so, this does stick with the patient. And the symptoms and what they feel change over time, but the underlying presence of the disease does not. So in some form or fashion, I do try to counsel patients that this will require treatment in some form or fashion, like Dr. Callaway mentioned, whether that's diet elimination or whether that is topical steroid therapy that's coating the esophagus. And the treatment choice will likely change as research advances. And it's a lot easier, say, as a young child for a parent to strictly avoid something in their diet, right? Parents can have great control of what their toddler's getting fed at Daycare, for example. But in teenage years going into college age years and as an adult, diet elimination is very difficult because you know what good food tastes like. So, adherence to diet elimination as you progress from teenage into adult years is incredibly, incredibly difficult despite best efforts.

And one treatment option that Dr. Callaway mentioned, esophageal dilation, if he does find a stricture in the EGD, that tends to be more of kind of an adult treatment rather than a pediatric treatment. So as you transition first as a child and as a teenager, it's more of an inflammatory phenotype is what we're seeing. But then, as inflammation is longer standing and settles into the esophagus, you tend to transition to more of a fibrostenotic picture in the esophagus. So, dilation is something not often done in kids or even into the early teenage years because you haven't really had enough time typically for that stenosis to set in fibrosis. So, it truly is more on the pediatric side. Something we do as a last resort is dilate, but it's a much more useful tool in adults where, again, that fibrosis or stenosis is longer standing. And Dr. Callaway can dilate. There's some arrest of dilation, but it's quite rare to have complications of a dilation, and he can certainly speak better to that than I can. But it's something done much more on the adult side and can be a quick way to alleviate that feeling of food getting stuck. But again, it doesn't address the underlying inflammation. It's a quick fix to the problem and a Band-Aid on the issue, but it doesn't fix the underlying kind of inflammation that has been chronic and long-standing.

Dr. James Callaway: Oh, that's exactly right. It really is a combination approach. Again, if we can find motivated patients that are willing to undergo elimination diets and find the food and stick with it, then that works great. But at least my experience, especially here in Alabama, is that's not always possible. And so, we do end up using the anti-inflammatory therapies that we've described so far for this disease and these symptoms.

Melanie: Dr. Callaway, as you're telling us how treatment has evolved over the years, you represent two specialties. Tell us about your combined clinic. Why is it relevant? What are you seeing are the largest benefits for these patients?

Dr. James Callaway: Sure. So, I guess as a gastroenterologist, primarily, I guess difficulty swallowing is what comes to my clinic by far the most. These patients may have symptoms of regurgitation, chest pain, as Dr. CaJacob mentioned, sometimes food avoidances; food impaction, which is the most dreaded of the, I guess, complications that patients had where food physically gets stuck in the esophagus and may require endoscopic removal. All of those things are big quality of life issues. We eat at least three times per day. We swallow 600 plus times per day. And so, swallowing is something that we're all very used to doing. And so when that's dysfunctional, when patients are having problems with that, it's a big quality of life issue. And so, it typically will lead to those symptoms of esophageal dysfunction that I described. It requires them to come to either our clinic or the allergy clinics or the ENT clinics actually with complaints of food sticking in their throat. And so, kind of all of us are used to, at least now that we more easily recognize this particular entity, we are looking for this earlier on and trying to treat it early on to try to prevent these kind of late stage complications and honestly really improve our patient's quality of life. Because if you can swallow and all of a sudden can't swallow, that is definitely a problem.

One thing that's interesting to note is that patient's ability to adapt, which is I guess one comment I want to make that speaks to the importance of the comments that Dr. CaJacob made about the chronicity of this disease. It really doesn't go away. And oftentimes patients start feeling better and they start swallowing better, so they feel like they don't need their medicines anymore and they may be lost to followup. And so, it's really important for physicians and practitioners to keep track of these patients because we really don't want to lose control of, hopefully, the improved inflammation that we get with therapy. Because if left untreated, they can really start to have some of these endoscopic problems that require us to do dilations and disimpaction of the esophagus. And that's really what we're trying to avoid here, because that's just not very fun.

Dr. Ame CaJacob: And one of the other things where I feel like we will work together to take care of these patients is, as Dr. Callaway mentioned, you know, a food trigger is oftentimes in many patients, it's 90 plus percent of patients, food elimination if you truly stick to it can work. But that's not always the case. Some patients can eliminate all the food in the world and all the food groups and they're still having trouble. So, on my side of things, I help to not only try to by history identify what food trigger may be a problem, but I also have other tools at my disposal that Dr. Callaway doesn't have. So, skin testing and trying to take a look at the bigger picture as well. So, a number of patients with EoE can be triggered by environmental allergens. I mean, we don't really think about it as such, but we're breathing in these pollens and dander all day long, we're swallowing part of that. And so, environmental allergies truly can be a trigger for EoE symptoms. And we do find that, say, new EoE diagnoses, the majority of them are made in the spring and fall in the peak of the pollen season. So, there's variability to this too. So from my standpoint, it's helping to control the environmental allergy burden and maybe identifying or helping to treat other allergic comorbid conditions like asthma, right? A lot of these patients can have a chronic cough, which, as you can imagine, if you've got EoE and/or reflux, that you can have material reflux up to the throat and patients can keep a chronic cough because of just refluxed food material. But maybe that chronic cough is actually asthma, right? Which a number of these patients have asthma and have attributed their cough for years to reflux and EoE symptoms, but maybe they truly have asthma. So, we'll screen for asthma and help to treat that and, otherwise, just making sure that they're not having other more severe food reactions that can arise and maybe even require, say, an epinephrine autoinjector.

Dr. James Callaway: Yeah, totally agree. I think every single EoE patient that I see at a minimum deserves at least an allergy referral to screen for these other atopic type things, because it's at least 80 plus percent of patients have something else that maybe was either not really recognized or have a history of and just not well managed. So, it's a good team approach.

Dr. Ame CaJacob: You know, the one thing I really wish was that our skin testing did tie in better to diet elimination. We all wish it was as simple as you come to me, I test you to a panel of foods and, "Aha, this is positive and that's your trigger for EoE." But unfortunately, it just does not work like that. And usually, kind of the clinical history and story that the patient tells me about different food groups that tend to flare their symptoms, that's more telling than any skin testing or blood allergy testing I have. I mean, it's just not otherwise indicated. Food testing, unless they're having, again, that immediate severe food reaction that needs an EpiPen, then our skin testing and blood testing is really just of little utility unfortunately.

Melanie: Thank you both so much. Such an informative episode this was. Thank you for sharing your expertise on EoE. For other providers and for more information, you can visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.