Thank you, Amitav, for the introduction, and I'm just going to talk about a case of refractory eosinophilic esophagitis, and the discussion will be basically focused about how do we recognize these cases of refractory EOE and how do we manage these cases in clinical practice. So these are my disclosures. So I'll be presenting a very typical case that we see in our practice. So this is a 30-year-old male with a past medical history of intermittent dysphagia, probably going on for about five years, and the point of entry into our medical system was through an ER visit, which is not quite uncommon, with a food impaction. And this was at an outside facility, and he subsequently presented to the GI clinic. And during my interview with the patient, he denies any past medical history of GERD symptoms, any seasonal allergies, any reported food intolerances as well. So at the time of his ER visit, he was placed on omeprazole 40 milligrams twice daily, and he actually completed treatment for 10 weeks prior to seeing us in endoscopy with us, and then he did mention compliance to the medication at the time of the interview. So although these endoscopy findings were not what we saw during the ER visit, this was the first EGD that he had with us. This picture is of the proximal esophagus, and this one is of the distal esophagus. Now unfortunately, this patient, we could not get into the distal esophagus with the regular EGD scope because of stenosis, so we had to switch our scopes to a pediatric scope as well. Now, you can see that the patient has some edema of the mucosal lining, he has circumferential folds, he has a few white plaques, not really any furrows on endoscopic exam. So we basically described the mucosal changes as having ringed esophagus, some white plaques, which is the exudates in the ERF score, and circumferential folds, congestion, stenosis, and tight circumferential folds. Now during our endoscopy, we did notice the intrinsic stenosis about 25 centimeters from the entry point. This was measured about 7 millimeters in diameter, lasting for about 5 centimeters. So we dilated, through the scope, esophageal dilator with a 5.5 CRP balloon, started at around 6 millimeters and went on up to 10 millimeters for dilation. Now we did take biopsies at that time, and biopsies showed about 35 EOs on high power field in the distal esophagus, and in the mid esophagus, about 25 EO snowfields per high power field. Now subsequently, this patient came to our clinic, and the plan was to start him on budesonide 1 milligrams twice daily for about 8 weeks, and then we repeated an endoscopy, and these are the findings of his endoscopy about 3 months later, after 8-week treatment. And these are images after dilation, but if you closely observe, there's not much edema on the esophageal wall, again, it's hard to appreciate the white plaques. We do still continue to see some circumferential folds, and so forth. So the pathology of the biopsy came back as about having 100 EO snowfields per high power field in the distal esophagus, and about 50 EO snowfields in the mid esophagus, so it was indeed worse than what it was a few months ago, before he was started on budesonide. Now, then we got this patient back into clinic to discuss with the patient how he was doing clinically, right? Okay, I see the endoscopy findings probably better than what it was before, pathology not a good sign, but how was the patient doing? So he does report improvement in his dysphagia symptoms, which I'm not surprised about, because of the dilation, and the second question that was critical for this patient was to find out if he was compliant with the budesonide treatment, and he reports compliance to budesonide treatment for about eight weeks. So the discussion for the panel today would be trying to kind of put together some questions as to how do we manage, how do we first recognize these patients in clinical practice? I mean, when do we start considering that we are dealing with a case of refractory EOE, and what are other points that we need to check with the patient before we kind of move on to the next set of therapies, and are there any clinical phenotypes, meaning clinical risk factors that we can get from his or her history to kind of know that these patients might be the ones we are dealing with in terms of refractory EOE, and what are the options for continued testing, because these patients will need repeated testing to kind of see if our treatments are working, would that be repeated EGDs, or do we have any other non-invasive office-based testing, and we did touch on stricture dilation, and also like to kind of talk about newer therapies and how are we able to actually use them right now in clinical practice, or when do we expect these kind of newer therapies to become mainstream. So I would leave it up to the panel. So the first question would be, when do we consider a diagnosis of refractory EOE? Who wants to start off? David. I'm sure you just shaved the plate. Thanks, Amitabh. What is refractory? All right. Thank you, Amitabh, and thanks, Shivanti, for the great case presentation. So I don't think there's any clear definition for what is refractory. To me, refractory is when you've really used every medical option you can, short of just dilation as the only therapy. So that begs the question, what can you do here that is not? So the first question I would ask, Shivanti, is can you tell me exactly how this patient is taking the budesonide, how they're mixing it, what they're mixing it with, what time of day they take it, those type of details, if possible, please. Sure. That's an important point because we are dealing with, is this patient actually truly refractory EOE or not? So the patient was given a milligram of budesonide that he uses with applesauce, thickens it, and is divided into two doses. And he takes it in the morning, swallows it. And the instructions were given that he shouldn't be eating or drinking anything for 30 minutes after he takes the budesonide. So that was his mode of treatment or taking the medication. All right. Thank you. So that's my first concern because applesauce being a rather granular substance, one question would be, are you getting full homogeneous mixing of the budesonide in something like applesauce as opposed to honey or maple syrup or something like that? I don't know the answer to that. It may work quite well. My other tip that I use for patients, I agree, I have them take them in the morning and then don't eat or drink afterwards. So I usually have them take the budesonide after breakfast because this way they're not hungry or thirsty. And then the second dose I have them take right before they lie down to go to sleep. And the reason I do that is because when they lie down and stop swallowing and go to sleep, the dwell time of the budesonide is going to be a lot longer. So fine-tuning the budesonide, I think, would be the first step in a patient life. The second possibility is we will sometimes go up to three milligrams twice a day. We haven't published on that, at least in our experience, sometimes for the really refractory patients that will start with that or the treatment-resistant patients, or we suspect. So that might be something. And then there's the question of if you combine PPIs with steroids, is that more efficacious? And there's some data back and forth, particularly if there may be some component of reflux that's not being treated, we'll be able to get some of these patients into remission as well. And then, of course, there's diet therapy. So this patient has not tried that, it sounds like. So we can certainly go that route as well. So this is clearly a difficult patient to treat, but I think there are a lot of options before we call this patient truly refractory. But obviously, I'd love to hear what Shivani, Felice, Phil, and others say. Thank you. Yes. Nicely put, Dr. Kaczka, I agree, especially with a young patient, you want to make sure that they're compliant, they're taking it right. And the fact that I saw you had some endoscopic, the endoscopic findings looked improved, and the stricture looks improved. And the fact that his EOs are going the wrong way, one would consider if he does have an underlying allergic component, and the diet triggers that could be in play, and what his peripheral eosinophil count is, and if that has a contribution in addition to everything else that's going on. Philip, Felice, when do you send these patients for diet? Do you do it right at the beginning? Do you wait and see if they respond? What would you have done? You're muted. Felice, you're muted. You're muted. Thank you. Thank you. Just augmenting what others have said in terms of the young male patient and taking medication, this patient's not used to taking medication, especially two times a day medication, especially medication that they actually have to prepare. I've never really done it in applesauce. I mean, I am definitely more of a fan of like the honey, that type of coating. But I can tell you when they have to do work to take medicine, it's very hard in terms of compliance. Diet, you know, it's kind of come back and forth. You know, we used to send much more frequently for evaluation for even allergy testing initially. And now, you know, do big panels of allergy testing, you know, blood and, you know, the tape test, allergy testing, you know, all of that. And now we're doing a little bit less. And I think it's so much easier because we've limited how many foods that we will take off at this point in time. So we're doing it a little bit earlier, I would say, just because the dietary component is so much easier to incorporate than what it used to be. You know, in terms of what Dr. Katz had shown, that long, ongoing, frequent, repetitive endoscopies afterwards are you making an impact and stuff like that, that's kind of gone by the wayside. So I'd say we're incorporating it because it's just easier if the initial treatment doesn't help, we'll pull that into play. So Felice, would you say that you would start with a two-food elimination in terms of making it easy for the patient along with some kind of a steroid treatment as well? Well, I think, was your patient on PPIs? I couldn't tell that. Were they, were they not? He was on PPIs prior to the first endoscopy, yeah. Okay, fine. So, I mean, we're, in general, we're starting with PPIs as an upfront, I mean, that's kind of one of our first starting points. And then, you know, it was hard for me to definitely say whether or not the strictures improved or whether or not there was one, you know, culprit stricture, because I think, of course, he got better because there was a dilation. So that wasn't surprising to me at all that his symptom improved. And we were just hoping that the EOs were going to get better. And then, so the fact that he got better symptomatically, I wasn't holding an enormous amount of weight that the EOs were going to improve. I just said, you dilated him. So if he didn't get better with the procedure, then the dilation wasn't good enough, right? So I kind of put that away in my mind as to whether or not that was a sign that he was going to be, you know, doing well with our medical management. So I think if he's still symptomatic, in spite of a good dilation, you need to add something on at that point in time. And I don't mind it being one or the other. What I don't like doing is putting more than one thing at one time. I mean, the reality is, it's a long disease from a long time since childhood, right? And so if you now put on steroids and do dietary and PPI, you don't know which one I think is being impactful. And so I like to do a little bit more of a Socratic kind of method in this and adding one thing at a time and then assessing whether or not that was an impactful move. Philip, can I ask you, what dilators do you use? When do you use your Bougie? When do you use balloons in someone like this? Um, I'm a, I'm a, I'm a Bougie Savory guy. Um, I prefer them unless there's a clear focal stricture. Um, if I do use balloons, I've used the technique that, uh, the Chapel Hill guys have, uh, have described occasionally, but I feel pretty comfortable in, uh, in going direct to the stricture. So for this person who was described as a lead point stricture, I would have agreed with the balloons. If I had to do this young man again, I would probably use Savory's, um, and I'd have a low threshold for using fluoroscopy, even though it's probably not necessary, but I definitely use a guide wire, um, to do my dilatation.

refractory eosinophilic esophagitis

clinical practice

biopsies

eosinophils

treatment options