Overview and Recognition of EoE

Dr Jonathan Spergel (Children's Hospital of Philadelphia): First of all, we will start with some overview and recognition of EoE.

[00:19:28]

Case: Allen, a 15-Yr-Old Male

This is a typical patient with EoE. He is a 15-year-old male. Presents to urgent care with moderate chest pain, report difficulty swallowing food. The symptoms appeared 3 weeks ago but have gradually worsened over time. In talking to him, you realize he has had some symptoms in the past. His past medical history is just for mild asthma, just using an albuterol pill and no food or drug allergies. So, what is on your list of diagnoses and what are the things we think we need to worry about to ruling out?

[00:20:04]

Pathophysiology

Obviously, we were talking about EoE so that is one thing on this list, but you can think about other causes of food impactions whether it causes dysphasia or you can have narrowing of the esophagus, you can have a foreign body. These are all the things you occasionally you will need to rule out along those lines.

But when we think about EoE, it is no different than a lot of the other atopic diseases that we think about. We think about the same general mechanisms and risk factors. EoE you have the same environmental risk factors such as early antibiotics, formula feeding as an infant. We know food allergens are a major role. H. pylori is actually may be protective, so depending on the infection. Like other atopic diseases, you get activation of your immune system, whether it is eosinophils, mast cells, or T-cells. You get an impaired epithelial barrier.

Risk factors that exist. There is some high rate of ATP, there is some seasonal variation in the diagnosis of disease, and there is a special population which affects us a fair amount is called oral immunotherapy induced when someone is going on oral immunotherapy, they get EoE in a certain number of patients.

[00:21:23]

Pathophysiology

When we think of pathophysiology, and you can think about this in similar ways, you can change this slide for asthma or atopic dermatitis. You get this allergen through a disrupted barrier. You get the pure epithelial barrier dysfunction. These allergens come in and they activate our antigen presenting cells going through the alarmin, so IL-33, 25 and TSLP.

Induce our antigen presenting cells to induce IL-4 and IL-5. They induce Th2 cells. Th2 cells then secrete IL-4, 5 and 13, which makes the barrier leakier. These same cytokines then activate eosinophils and mast cells, which causes the symptoms that we see with EoE, which is the lamina propria fibrosis, some dysmotility. Again, that leaky epithelial layer. The allergens are typically in EoE food allergens. But occasionally you can also see some aeroallergens as well.

[00:22:28]

Epidemiology

EoE, like many other atopic diseases, has risen dramatically in the last 40 years. That graph is from 1989 to 2010 and it has gone up even more. Now if you think about EoE, probably we used to think as one in 2,000. Now it is almost one in 500 incidents. You can see it is anywhere from 5 to probably now 20 per 100,000. It is continuing to rise even faster than disease recognition, like all of our atopic diseases.

A lot of that is probably from the risk factors that we talked about in the past changes, C-sections, early antibiotics, changes in epithelial barrier dysfunction, which can be a whole separate lecture on why ATP is increasing.

[00:23:19]

Delay in Diagnosis of EoE

But one thing we do know with EoE is that there is a real delay, and the delay can range on medians of about 3 years. This delay often is longer as you get older. When we know poor delay, you are much more likely to get the complications from EoE, which are what we really want to avoid, which is the stricture formation, esophageal perforation and bleeding, which are rare things but do happen.

This slide here shows the delay. Delay is probably shorter in pediatrics because parents are hyper vigilant. But as you get older typically in the late teenage years and young adulthood is when you get that peak delay up to almost 5 years, up to 15 months in time.

[00:24:15]

Clinical Features

What do we know about EoE? It is 3 times more common in males than females. It affects all ages. The prevalence is about a quarter of the patients going under endoscopy for dysphasia is the most common cause of a bolus food impaction. Nowadays if you see someone with food impaction, it is probably EoE until proven otherwise.

The rates of ED visits have gone up about 10% each year for the last 10 years, so it is really risen pretty dramatically. There is a lot of patients out there. I think one of these things we are still seeing just at the tip of the iceberg.

[00:24:53]

EoE Association With Atopic Diseases

The other thing we noticed, especially for us as allergists, it is strongly associated with atopic disease. This is a study that David Hill did at our institution a couple of years ago, looking at a birth cohort. When they looked at the patients, if they were diagnosed with atopic dermatitis, they were about 3 times more likely to get EoE. We know AD is a risk factor for food allergies. As you can see here, this is about 2 times more likely if you had atopic derm to get food allergies.

One of the more striking ones is if you had regular food allergies, you are 9 times more likely to get EoE compared to the general population. Asthma, as you can see, was 2-fold and allergic rhinitis was just under 3-fold. Having any atopic disease makes you much more likely to have EoE, suggesting this common pathogenesis and genetic backgrounds in our patients.

[00:25:53]

Conditions Associated With Esophageal Eosinophilia

But esophageal eosinophilia is not just EoE. It is important when we see patients with esophageal eosinophilia to make sure we have the right diagnosis. This is the long laundry list of different things that can cause it. Some of the things are really common, like gastroesophageal reflux or GERD, and it is really hard to differentiate the 2 of them because the medicines can overlap and the symptoms completely can overlap.

But when you end up having eosinophils outside the esophagus, you now have a different disease, whether, typically, it is eosinophilic gastroenteritis, where the eosinophils move up and down the GI tract. When you have a lot of eosinophils in the blood, then you have hypereosinophilic syndrome. Here, interestingly, is typically not associated with high eosinophil counts in the blood while EoG or eosinophilic gastroenteritis is.

You can get obviously connective tissue disease, you can get Crohn's disease, so you do need to use your clinical hat and determine that, yes, this is the right disease. We will assume that we have the right disease in our patients as we discuss a little bit going down.

[00:27:07]

Signs and Symptoms Vary Based on Age

The other thing with EoE is the symptoms do vary with age. This is probably due to how long that inflammation is there. When you have a little inflammation, the inflammation is just starting. The infants will say it hurts to eat so they will present with feeding difficulty and food refusal and end up getting almost a failure to thrive and poor weight gain.

As they get a little bit older, that damage in the esophagus begins to occur, and they get more classical reflux symptoms such as regurgitation, vomiting, and true reflux. As they get older, they really begin to get more pain, such as abdominal pain and chest pain. Then your teenagers and adults present classically with dysphagia and food impaction. Now the esophagus has been so narrow and so tight, and over time food actually gets stuck.

Interestingly, as we get things, sometimes it takes a long time for patients to revert to normal because they have these symptoms and they have some learned behaviors that they have to unlearn, especially a lot of feeding difficulties we see with children.

[00:28:19]

Collecting a Thorough History: Review Eating Habits

The other thing that happens is, this occurs gradually, patients develop a fair amount of compensation mechanisms. The late Eiko Hirano developed this great tool called IMPACT that uses this pneumonic to help figure out. These things are such as taking extra water, cutting food up into small pieces, prolonged mealtimes, avoiding hard textures, chewing, not taking pills.

One of my favorite questions I ask patients is, do you drink a lot of water? Are you the last person leaving the table? When you eat, do you feel the food going down? Some of my teenagers, when I ask that question, they are like, "Of course, I always feel the food going down." They do not know that is not normal. These are the things that we can ask our patients in a pretty quick manner and begin to figure out whether our patients have these symptoms. It is really important to review these things, because we see this not only in our EoE patients that are asthmatics, but I saw someone a patient today in clinic and asthmatic.

He was like, oh, is not it normal to use albuterol 3 times a day? I always think I am supposed to cough and wheeze with exercise. I am like, no, that is not normal. That is poorly controlled disease. They do not know what normal is. So it is important to teach them what normal is over time.

[00:29:50]

Endoscopic Reference Score

The other thing we look at when we look at, and this is important, when we look at the clinical results, is looking at something called EREFS. EREFS is the esophageal endoscopic reference score. This is what it looks like. If you look at it and think of it, hey, how does this compare to atopic dermatitis? It looks pretty similar.

You get some edema so vs swelling, you get the rings and exudate. Exudates are those scratch marks. You get furrows, esophageal cell damage and you actually get stricture. The rating score goes from 1 to 2 to 3, depending on the area. You typically grade for the worst area when they look at the esophagus, but some endoscopists will do a score for the upper and lower. But typically it is done for one whole grade for the entire esophagus.

Then there is a more elaborate histology measure. Instead of looking at just eosinophils per high power field, the magic number is 15. A normal esophagus has zero, so anything greater than 15 is considered normal. It looks at 8.

[00:31:00]

EoE-HSS

There is something called, EoE-HSS, eosinophilic esophagitis histology staging score, developed by Margaret Collins and her colleagues, a bunch of pathologists, and just looking at a few important things. A lot of them are very eosinophilic driven, such as eosinophilic inflammation, layering, those eosinophilic episodes. But other things are important, such as basal zone hyperplasia, dilated intercellular spaces, lamina propria fibrosis, which the only typically seen when you get deep biopsies, and you look at these different parameters.

Interestingly, I was at a meeting with Margaret Collins recently, and the pathologists are now using AI and they will be able to scan this and rate this very quickly from digital images. This may be something that we might be able to get very quickly now from all of our pathologists.

[00:31:59]

Diagnostic Algorithm for EoE

What is the diagnostic algorithm? Diagnostic algorithm is typically when you do a biopsy you need to look for that esophageal. You have to have those symptoms that this esophageal dysfunction that we talked about initially.

Ideally, when you get a biopsy, you want a biopsy of around 6. Not everyone does 6 but you at least need to do 4. You do those biopsies and you need greater than 15 eosinophils high-power field. Then you have to rule out those non EoE causes like we just talked about.

The most complicated one is GERD because the symptoms completely overlap. In the past we used to recommend putting patients on a PPI first. The issue is PPIs interestingly have an anti-inflammatory effect. They actually work on STAT6, so they actually have a true effect of blocking Th2 pathways. They are truly an anti-inflammatory, which makes it a little bit tricky sometimes to tell between GERD and EoE.

I tell patients I put you on, we will talk about a little later on. If you get better on a PPI. I do not care what you want to call the disease. I got you better on the over-the-counter medicine. That is fantastic. You have mild disease.

[00:32:22]

Posttest 1

Let us go back to our pretest question again. Allen now presents the ED with moderate chest pain and difficulty swallowing. Which of the following is part of the diagnostic criteria for EoE?

1. An endoscopy biopsy greater than 10;
2. Eosinophilia persisting after a trial of a high-dose PPI; or
3. Esophageal erosion seen on endoscopy; or
4. Symptoms of esophageal dysfunction.

We still did not get it right, unfortunately.

[00:34:20]

Posttest 1: Rationale

The answer is esophageal dysfunction. Endoscopy biopsies need to be greater than 15. Esophageal erosions are not part of the procedure. You cannot see them, but they are not part of the diagnostic criteria.

[00:34:38]

Things are Looking Up! Recent Advances in the Management of EoE

Things are looking up. We would say we have recent therapies and advances in the management of EoE with 2 recently approved drugs and some really key large clinical trials done out of the NIH consortium. We will go over what we have seen.

[00:34:56]

Management of EoE: An Historical Perspective

This is a management. The first case reported was published back in the 1970s. The first guidelines came back in the early 2000s. The first food diets were published back in 2006 by Amir Kagalwalla. The first AGA guidelines came out in 2007, updated guidelines were published in 2011. Back in 2018, we just talked about PPIs were recognized actually more as a treatment. The updated guidelines in 2020. Dupilumab got approved in 2022 in adults and 2024 in children. Budesonide got approved recently. There is a recent updated AGA guideline that just came out, which really is not that different than the last guidelines.

In the recent guidance, which is identical to the guidelines published in 2023 in the Annals as the yardstick. Those are the new guidelines.

Let us talk about different therapies.

[00:36:05]

Elimination Diets: Pros and Cons

First is elimination diets. Elimination diets work well. We have been shown to be effective in both retrospective and prospective studies. You do not need medications. You are really removing what causes it.

The downsides, often it will take multiple biopsies. It can be hard to do. Often it can be very costly. You may need a specialized diet. Sometimes it is hard to do when you have various feeding difficulties.

[00:36:38]

Types of Elimination Diets

There are 4 basic diets that exist as well. There is elemental diet, elimination and allergen-testing based diets. No one really recommends allergen-testing diets right now, because the standard allergy testing whether IgE testing by blood or skin does not work as this is a non-IgE mediated disease. IgG4 testing, like in IgE-mediated disease just tells me what you are eating. Again, it is not useful at all.

There are some T-cell functional tests that exist that are more experimental. They are being worked on. Eventually that may come out. The 6-food elimination diet is really 8 food groups. It is milk, wheat, egg, soy, peanuts, tree nuts, fish and shellfish. Legumes is only done by the Europeans so you can get really like 50 foods, 4 foods or milkweed, egg, and soy. Two foods is just milk and wheat, and one is just milk. They all work.

[00:37:38]

Histologic Remission Rates Based on Dietary Intervention

We will go over in a minute how well each one works, which is what we see here. The elemental diet, whether you look in children or adults, works in about 90%. Six-food elimination diets, depending on what study you look at anywhere from 50s to 70s in the randomized prospective study, which is actually about 60%.

The 4-food elimination diet, it is again about the same as the other foods of shellfish, which is fish. Peanuts and tree nuts are pretty rare foods. That is why the 4 and 6 do not make much difference. The 2 foods, which are milk and wheat, and the 2 most common foods are about 40%, and one food also works about the same. Allergen-testing foods basically do not seem to add much. That is why we really do not recommend them anymore.

[00:38:31]

Histological Remission Rates With Elimination Diets

This was the 2 NIH studies, 1 vs 6 in adults and 1 vs 4 in pediatrics. As you can see, there is not much difference between the 2. For deep remission in the 1 vs 6 in adults, there were some differences, but overall there is really not much difference. When we do diets these days, we typically recommend just starting with baked milk, because it probably works just as well as doing the more extensive diet. It is a little easier to do.

[00:39:05]

Step-down vs Step-up Approach in EoE

There are 2 basic approaches these days, you can do step-up or step-down. The step-up was really pioneered by the European group, and the step-down was really done by Amir Kagalwalla.

Along those lines, you basically biopsy. If things are normal, you either add or subtract until things get better. You biopsy every 4 to 6 weeks to figure out what food works. Typically, we do one food. If that does not work, we go to 2 foods. After that, we rarely do food diets anymore just because patients are difficult. But you can work your way up to 4 foods. We do not do 6 foods because removing fish, shellfish, and tree nuts are not triggers. You have to think about other triggers for EoE, such as beef, chicken, and corn.

[00:39:56]

Following up With Allen, 15-Yr-Old

Let’s go back to our friend, Allen. Allen has a history. We realized this was going on for a long time. When we biopsy him, we had 30 and 100 eosinophils per high-power field with basal zone hyperplasia and lamina propria fibrosis. This is known EoE.

We told them to avoid milk, and one of the triggers follow up in 4 weeks. He notes some improvement, but he is still really symptomatic. We typically will make the wait. Patients wait 2 to 3 months before advancing, but if someone is really symptomatic and struggling, we will advance as soon as in 4 weeks.

What are the treatment options available now for Allen? They are the ones we talked about. There is budesonide, there are the biologics, and there is PPIs. How do you negotiate this with patients? This is the classic shared decision-making going in the pros and cons of each therapy. Let us go over them and help come up with the right answer.

[00:41:04]

Poll 2

After elimination diet and his biopsies showed 40 and 50, what treatment would you start first?

1. Omeprazole;
2. Budesonide oral suspension;
3. Dupilumab; or
4. Esophageal dilatation.

In a group hooked a mixture, which is probably all okay. I personally recommend using omeprazolefirst. Probably, someone gets better with over-the-counter medicine. I always think about this, if I can get better with a moisturizer and atopic dermatitis, Miles[?] will do that. That is typically what I will do. I start with omeprazole. You could start with the other 2. Typically, we would recommend dupilumab if someone had concurrent atopic dermatitis or asthma. I really stuck with oral viscous budesonide just because I would rather start with a non-steroidal agent, if I can.

[00:42:20]

Proton Pump Inhibitors

What about PPIs? PPIs have 2 roles. They are antisecretory and anti-inflammatory. As I mentioned before, they block STAT6. They are very safe, they are cheap, they are recommended by all the guidelines. The response rate is about 40% to 60%, which is pretty good. Long-term associated risks are interestingly listed here but honestly are probably not true.

In the large meta-analysis studies looking at long-term use, when they looked at PPIs on these large 10,000 cardiac things, the only thing that they really saw was some lower GI infections. Everything else is not really seen. The bone fractures and dentals were not seen at all, so they are probably not really major issues. Pediatric and GI complications are not true at all. I would disagree with that. I have never seen that along those lines, and asthma is not a risk factor. Anxiety again is not a risk factor with these drugs. I would disagree with those risk factors in this slide.

[00:43:36]

Topical Corticosteroids

What about topical steroids? Basically we have been using off-label use by doing mixing and the remission rates in about 40% to 60%, depending on how you do it. You can see esophageal candidiasis in about 5% to 10% of the patients. I tend to like budesonide more than fluticasone just because I think we can get it down better.

Eohilia, which is the FDA-approved one, was approved about a year ago. It is approved, interestingly, for only 12 weeks of therapy, which is really bizarre because it is a chronic drug. It is also approved at a dose much higher than we typically recommend. It is got a very strong recommendation in the guidelines but we know that it does get maintained for a long time. It does work well.

[00:44:33]

Oral Budesonide Improved Histologic and Symptom Response vs Placebo in Patients With EoE

I mean, if you look at the data from the oral viscous budesonide, which was this dose, which was the 2-mg dose, they had about a 50% response rate of greater than 6, which is considered the FDA gold standard, and about the same rate of improvement in dysphasia, which led to the approval. But they only got approved for a 12-week period of time.

I would have no concerns of using it longer, but typically we will start off basically with half that dose which is 2-mg once a day. Typically, in pediatrics we will do either half or a quarter of that dose, which we would have to make with off-label use.

[00:45:21]

Budesonide Oral Suspension: Safety and Tolerability

The safety and tolerability. As you can see here, decreased cortisol is seen in these patients. You do get some real issues higher than placebo. There are some real side effects in the patient cohort. You do need to do some monitoring comparatively. I do not worry too much about some of these, but the cortisol is seen in the studies. It is one thing to do monitoring patients.

[00:45:59]

Budesonide Orodispersible Tablet Maintained Remission for 48 Wk

This is with a dispersible tablet which is the tablet that is available in Europe. They had a higher response rate, interestingly, in a lower dose, which is probably just how the drug is delivered. You can see they have a pretty good response rate. You can see patients are maintained in the study up to a year that they really do not see relapses or patients have clinical symptoms in the placebo arm within 90 days. While the patients really had great response either with clinical or histological, about 75% in the European product.

[00:46:50]

Posttest 2

In posttest two now, Allen is set to receive budesonide oral suspension. The 12-week course would budesonide resulted in which of the following outcomes when studied compared to placebo?

1. Improvement histology but not symptoms, so not dysphasia;
2. No improvement in dysphagia or symptoms;
3. Improvement in symptoms but not histology; or
4. Improvement in histology and symptoms.

As you can see, you all got it right. Fantastic. It improves both symptoms and histology. Fantastic. Everyone got it right.

[00:47:37]

Dupilumab

What about dupilumab? Dupilumab got approved to treat EoE above the age of one. It blocks IL-4 receptor-alpha, so blocking IL-4, 13, is a weight-based dosing as you can see on the slide. So 15 to 30 gets 200; 30 to 40 gets 300, both of those every other week, and 40 kilograms gets 300 mg every week. This dosing regimen is about twice the dosing regimen that is used for atopic dermatitis and asthma.

[00:48:10]

Dupilumab LIBERTY EoE TREET: Histologic Remission

This is the pivotal trial for the adults called the LIBERTY trial. This is looking at histology remission at 24 weeks and at 52 weeks. In the weekly, you can see there is about a 60% of the patients had improvement in the symptom and with histology in that first panel. This was maintained up to 52 weeks as patients got shifted from placebo into the active arm, it had about the same rate. It really worked well along those lines.

[00:48:48]

Dupilumab LIBERTY EoE TREET: Dysphagia Symptoms

Interestingly, when you looked at symptoms, only the weekly had the improvement in symptoms. The 2 weeks did not. That is why the weekly dose got that improvement in symptoms.

This is looking at the symptoms here. As you can see the weekly, the dark blue ones, let me see if I can use that. The dark blue ones here and here are the weekly, as you can see, had good control of the symptoms, while every 2 weeks, which is this one was the same as placebo. That is why the weekly was improved and it was maintained up to Week 52.

All right. I will show you how to get rid of those.

[00:49:32]

Dupilumab LIBERTY EoE TREET: Safety

As you can look at this AEs, the biggest issue with dupilumab is injection site reactions, which is seen in many patients. Everyone complains. The big trick is to take the drug out 24 to 48 hours in advance. Compared to placebo, besides the injection site reactions, not much difference along the lines. A little more of the serious AEs, but they were not considered related to the drug.

[00:50:17]

Dupilumab EoE KIDS: Efficacy and Safety

This is the KIDS study, which, interestingly, had a similar set of response rate of about 60% looking at less than 52 weeks. Looking at low dose and high dose, high dose was slightly better. Again, looking at your safety profile, injection site reactions are the bigger one that you see, but placebo group actually had a fair amount. There was more COVID-19 in the active group, probably not due to immunosuppression, but it was listed there.

There is a separate study that shows that COVID-19 actually responds well to dupilumab. It was probably not related but it is what was seen in that study. I would just watch for viral infections. It was not seen in our asthma studies or atopic derm studies.

[00:51:11]

Proposed Treatment Algorithm for EoE

This is a potential algorithm and we think about how to treat it. This is from our guidelines. When you get diagnosed with EoE, typically you can do any of them, whether it is a PPI, a topical steroid, or elimination diet. Typically, once things they get better.

If things do not respond and we modify and we think about other things. We think about going with dupilumab for patients who are severe, who have lots of concurrent other diseases, we typically will start with what we build up going from 1-food, 2-food, 4-food, and 6-foods, as you can see.

When things get better, we can lower diet or broaden diet along those lines. Some occasionally will do combinations of diet plus corticosteroids and diet plus dupilumab. Dilatation is not a therapy. It is really off to the side, and it is used for patients who have strictures. A lot of patients, if you have a stricture, all these therapies probably will improve the stricture but may take months to years.

Dilatation is a quick fix to help patients feel better. But they need to be on some maintenance therapy no different than we do for asthma or atopic dermatitis as you put patients on these foods over time.

[00:52:41]

Therapeutic Pyramid for EoE

When we think about this, it is like a pyramid, we have monotherapies, which is a similar thing. We can switch things out, we can combine things and we can use biologics at the top. We also can use elementals at the top. We rarely do it along those lines, but we do it occasionally for all patients fair because it does probably have the highest success rate of up to the mid 90% approach. We typically step-up, but you could use step-down therapy as well depending on. This is the shared decision-making looking at how severe a patient is and how quickly they want to get better.

[00:53:21]

Maintenance Therapy and Monitoring

When we think about it, again, this is a chronic disease, so you do need the therapy. We really look for improvement in 3 areas. So, no major symptoms, no near-normal histology, whether it is less than 15 or less than 6. I think that is debatable. I personally like less than 6 but I think you have to do it as shared decision-making. You want your endoscopy to look normal. That is our EREFS, looking at over the fixture of edema, rings, exudate, furrows and strictures. You want them to be looking as normal as possible.

When we think about therapies, what we start with, you have to look at all the things. We thought about approval of drugs, what is available, what is patient preferences. Typically, we do biopsies every 12 weeks. For dupilumab, we tend to do it longer. You do 3 to 4 months, and we look at symptoms and we reevaluate. We will alternate therapies and we reduce our increase over time.

Once things are better, we will often rebiopsy if there is change in symptoms or every 2 to 3 years to make sure things are better. There will be alternate ways to follow patients’ esophagus. There is no blood marker right now, but there will be some not less invasive ways to measure the esophagus, whether it is something called transnasal endoscopy or esophageal string test, or the cytosponge, or other ways to get esophageal tissue to monitor patients in the future.

[00:54:57]

Biologics Currently Being Investigated for Use in Patients With EoE

What is down the pipeline? A couple of things down the pipeline. There is tezepelumab and cendakimab. Tezepelumab, as we know, is approved for asthma, and it is in a phase III trial, which is actively recruiting. Cendakimab has actually finished the trial. Their results have been reported out in abstract, which shows some improvement in symptoms and biopsies as well.

Last I heard, they were probably going to submit to the FDA. There are other IL-13 inhibitors called barzolvolimab, and there is an S1P receptor antagonist. There are some other ones. There is another swallowed fluticasone product. There are other longer-acting biologics being looked at in the treatment of the disease to look at for EoE.

[00:55:57]

Following up With Allen, 16 Yr Old

Let us go back to our original patient. Allen has returned to clinic after 18 months and his biopsies really are unchanged. He still has symptoms. He has now failed both dietary therapy and a PPI. He wants to know about what else? What questions would you ask at his stage at this point? Basically, we would talk about what his symptom are? How often is he getting food impactions? Does he have other atopic diseases? What things would you think about the therapies talking about? Do you want to do daily medication or a weekly medication? Do you want a solution like a pill or do you want a shot?

Once these are done, we will need another endoscopy. You have to talk about these patients all these things. This is the classic shared decision-making.

[00:56:57]

No Longer Home Alone: Strategies for Improving EoE Care

What do we think about the strategies for long-term improving care.

[00:57:02]

Challenges for Shared Decision-making in EoE

This is the classic shared decision-making regarding diet and medical therapy. Talking about side effects, financial considerations, the idea of endoscopy, talking about dietary substitutions. Some patients do not want to do anything vacations. They want to take the true cause. Then you need to say, hey, you are taking milk out, what can you supplement it? It is talking to the family. You need to know that this is a long-term disease and that you will be needing to follow them chronically over time.

[00:57:35]

Shared Decision-making: SHARE Approach (AHRQ)

This is the classic thing that we think about with our patients is this shared decision-making. This is this great approach done by the AHRQ, is you talk to your patients, you seek their participation. You help them explore the options, assess the patient's values and preferences, and reach a decision and help them evaluate. You help guide them.

You can give your opinions, give what you think the pluses and minuses, but you do it by working with them along the lines of true shared decision-making. This is true for every disease. You will get much better compliance and buy in from the patients.

[00:58:18]

Multidisciplinary Healthcare Team

The thing is, this is truly a multidisciplinary disease. This is a disease that really gets seen by allergists. This is an allergic disease of the GI tract. As an allergist immunologist, a lot of our patients we talked about earlier really are much more prone to like it. We have to ask these questions and we will have ways to monitor our patients in the future. But it is a GI disease, and the other things that we have to think about, whether they need a dilatation or we think or worry about other causes of it because they can have concurrent reflux, or could they have Crohn's. We need our gastroenterologists to help monitor those things.

If they do diet, we have to work about dietician therapies. Along these lines, if they end up in the ER, we will need a pathologist to read slides. Often these patients end up in ENT, because they are getting food stuck. We need all of our partners, whether it is our pharmacists, our advanced practitioners, a speech pathologist, because they have the feeding difficulties to work with them, because they have learned poor eating behaviors. You need a good occupational therapist. You will need all these groups to help you partner with them to get our patients better.

[00:59:40]

Team-Based Approach for EoE Management

This is truly the team approach to EoE management:

• Providing education;
• Talking about the expectations;
• Having a good way to ensure follow up;
• Work with a transition from going from pediatric to adult; and
• Talking about different options and training on administration of therapies.

[01:00:03]

Transitions in Care

The last thing we will talk about is transition in care. This is going from pediatrics to adults. This is true not at any age. As a pediatric person, it is hard to get patients to transition over. They do not want to switch. It is tricky. Along those lines, the people who get pushed over earlier or diagnosed later are less likely to do it. Patients on chronic therapy, parents do not want to transition them. You really want to transition them in that young adult college age group, and you really want to start those conversations probably when they begin to hit adolescence.

[01:00:55]

Challenges in Transition of Care

There is a lot of barriers that exist. Patients are non-adherent as teenagers. They are not independent from their parents, so they do not show up. Many places do not have a formal transition program. Well, luckily over at CHOP at Penn, that we do, but that is not many places do. That really helps.

Transition readiness is not assessed, even at a place like us who have multi-transition programs. You have to find the doctors to communicate over looking at all the histories and knowing that EoE does have intermittent symptoms. That is tricky for many patients.

[01:01:39]

6 Core Elements for Adolescent Transition of Care

When we think about this, it is like the 6 core elements of this transition is beginning to tell families that, hey, when you become that 18 to 21, we are going to transfer you over, identifying those questions, and have them teach that. There is some various checklists that you can assess the skills. You do that as young teenagers. Begin to work on, hey, this is your plan, this is what you will be doing, transferring them over in that college age group, whether you do it at 18 or 21, I think it really varies on you as an individual. Both are okay as you wean things over. And make sure that they transition over, find an adult partner for both pediatric and adult allergy. For allergy, it is a little bit easier because many of us are trained to do adult in pediatrics, so we just need to transition them over just for an adult gastroenterologist. This is an important thing to think about as we transition our patients over.

[01:02:48]

Posttest 3

Last post-test question. How often do you engage in shared decision-making with patient and caring to optimize outcomes for patients with EoE?

1. Never;
2. Rarely;
3. Sometimes;
4. Frequently; and
5. Always.

We like that. Most people do it always, which is fantastic. It is probably the best way to do it, but not only for EoE, for any disease. Frequently, it is probably fine. I am glad no one has never or rarely.

[01:03:38]

Question and Answer Session

We will now go with question and answers. There are a couple of questions about therapies and treatments, so we will talk about them.

The first question is, if a patient receives histologic and symptom remission with the PPI, do you try to wean them off at some point or continue indefinitely?

Typically, we will actually try to wean them off. EoE is a chronic disease. But sometimes they may have reflux. It is really hard to tell the difference to be honest because reflux can cause esophageal eosinophilia as well, usually not as high. We will leave them on for about 1 to 2 years. This is probably true for any therapy.

After 1 to 2 years, we will try to wean them down or if they are on diet add foods in, and then we will try to say, hey, you are doing well. We have had a few patients and the answer is probably less than 5% that will be able to wean off any medicine, whether it is diet or steroids. They have been asymptomatic in normal histology for several years, so it is a rare thing to do.

But we typically will try to wean them off. But most patients if you are a PPI responder, interestingly, over time many of them begin to fail at PPI. It looks like you begin to become, some people, what we call low metabolizer and high metabolizer. After chronic use, some patients will switch over and lose that response rate. We will monitor them but most patients cannot stay on PPIs, will end up failing. But there is a few patients we continue on. PPIs, I am not worried about side effects.

The other question is what to do about kids with budesonide, whether it is kids or adults? Once we get them better, whether we typically will biopsy them after 3 to 4 months, so 12 to 16 weeks, if things are fine, we will reduce the dose. If they are on 1-mg, we will go down to a half. If they are on 2, we will go down to 1. We will typically cut the dose in half. If things are fine, we will check them 4 to 6 months later and change the doses accordingly.

It is a chronic disease like asthma. We need to keep people on them chronically. There are a few patients with really mild disease that maybe you can do intermittently like during the pollen season. They are just pollen driven. But we also have some patients like in asthma, that we need to bump up the meds during bad times of the year, whether after pollen seasons along those lines we try to switch as well.

We also will do the same thing with dupilumab. If patients are on dupilumab, if they are on weekly, if they are doing great after 6 months to a year, we will try to decrease to every 2 weeks. We will move up and down as they need to with the therapy.