Great. And just as a reminder, please do continue to put your questions in the Q&A box at the bottom of your screen. And as we have those come in, I will just share a case. This is a 30-year-old with occasional solid food dysphagia. An endoscopy was performed, and here are the endoscopic photos on that initial endoscopy. Any comments briefly on that? I don't know if you're trying to trick us, but it looks like a slam-dunk case for eosinophilic esophagitis. They've got all the features. They've got edema, rings, furrows, exudate. I can't see a stricture, but there could be something in the EGJ or the inlet. But it looks like a classic EOE case. And the biopsies did confirm this with the mitosophagus having biopsies with over 100 eosinophils per high-power field and superficial microepsis. The feature is consistent with EOE and the distal esophagus with up to 73 eos per high-power field. Additional biopsies in the stomach and the duodenum were unremarkable. And so the diagnosis of EOE was confirmed. And for first-line therapy management, the patient was started on PPI, BID. And the dysphagia has resolved in entirety. There was some intermittent chest pain, which was unclear if it was related or not to this process. And the patient had been told to have an endoscopy to check for healing and agreed to that. A repeat endoscopy is shown here. Any comments compared to the previous? Clearly, the exudates have cleared. I still see, obviously, rings don't always resolve. They often improve but don't resolve with effective therapeutics. I still think there's edema and furrowing here. And that far view on the right, obviously, is under distended. But it looks like pronounced furrows. But I think some of that's just under distension. So my concern is that there does still seem to be persistent furrowing and edema. So there may still be some activity here, even though the patient's feeling better. Yes, and indeed, there was still some activity. There was just in the mid-esophagus only some lymphocytes. There wasn't actually increased eosinophils. But there was increased eosinophils in the distal esophagus at 30 for high power field. With that, we talked to the patient about the continued activity that's seen endoscopically, as well as the eos at 30 for high power field in some areas, which was patchy but sometimes can be seen after treatment effect. And the patient agreed to go on viscous budesonide. Denied again any dysphagia, so no dysphagia symptoms. We discussed another repeat endoscopy check for healing. There was a little bit of ambivalence just due to the idea of doing another endoscopy despite having no dysphagia. But then the chest pain became more persistent. And a cardiac workup was negative. The deductible for the year was met. And we went on to repeat the endoscopy. And the endoscopic photos were similar to the last one. But at this time, the mid-esophagus showed eos 100 per high power field or more at both the distal and mid-esophagus. Thoughts or next steps for this patient? So I'm sorry, I missed. What dose of budesonide did you use and what formulation? It was one milligram twice a day with two vials to be mixed in 10 packs of Splenda. So you know, the one thing I always check is make sure the patient's actually taking it. And that Splenda thing is difficult. It's an extra step for busy people to do. So adherence is always a concern, again, for twice daily dosing and a liquid thing that doesn't taste so great. So assuming that was the case, I mean, you had a better response with PPI therapy here, clearly, endoscopically, histologically. This is one of those cases where I might consider combo therapy. There's no data to support that. In fact, the data that was done in the budesonide trial, the phase three trial, did not show any additive benefit when you combine PPI with steroid. But the response to PPI was pretty dramatic here, endoscopically, histologically, symptomatically. So I might choose to just go back to your high dose PPI and maybe, you know, layer in just once daily steroid. If there's any problem with the patient taking it, I like fluticasone better than budesonide. And you know, the liquid prep here, because of the added step where they have to mix it with the Splenda, I actually use a lot of fluticasone powder. I don't use the spray as much as the powder, because I think the powder makes more sense to me as a delivery mechanism. So that's one thing I would consider. And another consideration would be you could discuss diet therapy. You could discuss depilimab. And you could, you know, the patient may want to just do PPI model therapy and then do dilation. But the chest pain should be addressed too. And I don't know the mechanism for that. There are patients who have, there's a syndrome called FIRE, F-I-R-E, which is an immediate response of the esophagus to food. That's almost an IgE response. It happens more commonly. We're describing it as EOE. And it seems to occur even independent of the EOE activity. It's like an IgE response to certain foods, which can be brought in. And then the other time I see chest pain are patients that have food impactions. They get impactions and they get something stuck in their pain. And there are rare cases where you can actually have esophageal dysmotility in EOE, where there's muscular infiltration of the EOE, which Bonnie, you know, from the UT Southwestern group, now the Baylor group, has described. So there's a different possibility to account for the chest pain. Great. And can you comment a little bit on what you tell patients or even other providers about the need for sort of this concept of surveillance for EOE, or just to check after therapy, both in terms of when a change is made, or in terms of just in general, what you are counseling patients these days? Yeah, I think it's very important to repeat endoscopy. You know, I think patients are often used, as you mentioned, as shared decision making. And part of shared decision making is cost. And that has become very important to bring it up, because some patients are embarrassed to bring it up, that it can be $1,000 out of pocket for endoscopy. So I think that's an inconvenience and a time. But I think it's very important that you really don't rely purely on symptoms alone. And that's been shown in multiple studies now, that symptoms can be out of step or dyssynchronous, dissociated from the endoscopic stricture activity or the histologic activity. And that gets to these adaptive eating behaviors that patients have, all the ways they've adapted their eating, and avoiding steak, eating carefully, and chewing carefully, and drinking a lot of liquids, and all those things. They can mitigate symptoms and leave you undetected, but they can have a high-grade stricture developing or progressing under your eyes. So I consider any patient that comes into the ER with a food impaction that was under my care as a failure of my part. I mean, I should have been able to prevent that. And so I use the endoscopy. Now, the timing of that we can discuss amongst our expert panel here, and it varies. If they've got a stricture to begin with, I bring them back sooner. Sometimes it's three to six months, or sometimes even earlier, depending on the grade of the stricture. If it's really minimal symptoms, then you can bring them back at six months or a year. And the frequency at which you do that will depend on how they do at each time point. Every case is individualized. If the patient does well at a year, there's nothing to say you have to bring them back every year, that you might spread it out more. But it really depends on how their course has been. And I absolutely have patients who have been more difficult to control, and some who have been very easy to control. Great. Going to some questions from our group. Any specific testing prior to initiating dipilumab? There's nothing for dipilumab itself. There's no baseline testing for blood work. There's no renal or hepatic metabolism that's required. So there's no baseline testing required for using dipilumab used for eosinophilic esophagitis. Obviously, we're going to do a baseline endoscopy to characterize their disease. And how long do you keep patients on dipilumab? Unfortunately, for any EOE therapy, whether it's dipilumab, steroids, dietary therapy, or PPIs, we know that this is a chronic disease. So there's no cure right now. So anything you're starting, any therapeutic option you're starting has to be continued long term. So if it's dipilumab, you're going to be continuing that weekly dosing of dipilumab. You know, I tell my patients, is it forever? No. I don't think anything's forever. You know, if you asked me a year ago, we wouldn't have had dipilumab. So the field keeps evolving and changing. We're getting better techniques, better treatments, better understanding of the pathogenesis. There are absolutely ways that are being developed to better determine the food triggers for this disease and better understanding of the pathogenesis. So I think that it's not forever. It's until we, you know, refine our therapeutic approach. But for now, it's long-term therapy. It's not forever. And could you discuss how you prepare and dose the flipticazone powder for the EOE treatment? So I'll direct you to a series that was written by one of our fellows, now faculty, Leila Kia, KIA. You take the, not the mediodose inhaler, which obviously it delivers only the mist, but I always found it a little bit illogical to have patients gulping at air to get the flipticazone down. It does work, but it's just not very intuitive. So what you do is you take, this is all off-label, but you take the discus, the Flovent discus, flipticazone discus, and you open it. It's a clamshell. You open it, and nicely inside it are these foil-lined packets of flipticazone that's nicely aliquoted at 250 micrograms per little packet. And you just open the packets, peel back the foil, and drop it on your tongue. And it delivers flipticazone. You swallow the powder. It mimics what you do with the flipticazone tablets that's under pharma development right now, but I like that as a more intuitive approach to get the flipticazone powder to the esophagus. But again, the mediodose inhaler works. It's been shown in multiple studies it works, but I just, I like the powder as an alternative to the mediodose inhaler. And another question, would increasing the dose of PPI or giving it longer than eight weeks before checking make sense? It's a great question. There is a dose response. That was nicely shown in a study from Spain where they started off with double dose twice daily, then they went to double dose once daily, and then single dose. And they showed that there was a loss of response every time they stepped down on the dosing. So there is some rationale, particularly for a patient like yours where there was a, you know, looked like a pretty good response, and I forgot the dosing you used up front, that you might consider trying a little bit higher dose. But it's a consideration, especially when you see that initial almost there but not complete response to using a higher dose. But clearly if it's not, if that doesn't work, you know, you got to switch therapies. And any endoscopic findings that would prevent you from proceeding with dilation in patients with EOE? The things that would make you pause before dilating? Not really. I mean, maybe if you saw, I mean, ulcerations or erosions are very typical for EOE. They do occur. Sometimes they can happen from pills. There are patients with concomitant herpes viral infections. But if you see ulceration, I would think, well, there's something else going on here. And I probably wouldn't dilate. I would biopsy looking for viral, looking for a pill esophagitis, looking for concomitant erosive esophagitis before dilating. But if it looks just like, if it's just a high-grade stricture in EOE, you know, I've dilated patients with four to five millimeter strictures. So the severity of the stricture doesn't dissuade me from dilation. It's just, if there's something atypical that you're seeing that's not included in EREFs, some other feature that's not part of that, then, you know, maybe think about maybe there's something else going on. I don't know if others on the panel have anything to add there. Any endoscopic finding that might dissuade you from dilating? Yeah, no, I think any of those additional findings, like significant viability, inflammation, anything that makes you question the diagnosis. And I often find that it is, I might do a dilation, but I might be more ginger the first time and be a little bit more and willing to go a couple more stages when the inflammation is completely under control. Then, any insight into potential use of calcium channel blockers for eosinophil esophagitis with respect to eosinophil migration being tied to calcium-gated mechanisms? Yeah, I should let you address that. I mean, it's too specular, Ron, to Susan and Adair Chang observation. I don't know if they're pursuing a trial on that or if others on the call. I have never used it, but it is conceptual, has a conceptual therapeutic role, but I have not seen it used in any kind of clinical experience. Has anyone else on the panel used a calcium channel blocker? I have not used it for that specific purpose, but in regards to some questions about whether eosinophils or mast cells have created effects in neurotoxic effects in the muscle, we've used it for esophageal dysmotility, but not for that specific purpose. It's worth mentioning that, I mean, there are some very interesting reports from Japan, particularly of this muscular variant. Sometimes their mucosa is clear, sometimes it's not, but it's a muscular variant of eosinophilic esophagitis, just like we've seen with eosinophilic gastritis and enteritis, where the muscle muscularis propia gets infiltrated. And those patients can respond very nicely to systemic steroids, so I tend to use systemic steroids there. Yeah, and we have tried to use systemic steroids and do have a trial for that, but it'll be interesting to see how we can further investigate the muscular effects of eosinophilic esophagitis, and that is something of interest. Question about the goal. So do you think that one needs to decrease the eosinophils to below 12 for fear of development of esophageal strictures in the future, or what are your thresholds? I'm going to quickly answer that, and I think Madhav has his hand up for a while. But in terms of the threshold, I think most of us in practice are using 15, trying to drive the EO count under 15. The more normal it gets, normal is zero, so the closer it gets to normal, the better. The FDA has weighed in, and they used that threshold of six or fewer eos per power field, and that was a bit arbitrary. I think it was done to distinguish that diagnostic threshold of 15. If it went from 15 to 14, it doesn't look as significant as going from 15 to 6. But in practice, I think we're just trying to get the EO to under that diagnostic threshold, but certainly the closer to normal, the better. But I don't think you have to necessarily shoot for 6 or 12, so it's a little bit arbitrary. You know, this is when exactly when I use the endoscopy. So if that endoscopy normalizes, I don't really care about 15 or 20 eosinophils, to be honest with you. If I went from a highly inflamed endoscopic appearance to a normalization, I don't rest all my treatment decisions based on a single high power field from the entire esophagus that represents one probably ten thousandths of the surface area of the esophagus to make a clinical decision. I'll put a lot more weight onto the endoscopic appearance. Madan? No, thank you. I really loved the discussion. It was pretty good. One question from my side, and you know, kind of similar to IBD world, where now so many therapies are there. What about the positioning of the currently available options? Like, do you put one over the other in terms of preference, in terms of discussion with the patient? I mean, dietary part is there, then PPI is there, medications in terms of steroids are there, but we don't like steroids in the long run. So any comment about the positioning? Yeah, thanks. And I'm sorry that I did gloss over that slide. I think it's in my slide deck that will be circulated. No, no, no. But it's the whole shared decision making. So I almost always start with PPI therapy. Safe, easy, when it works, it works beautifully. But the caveat is that it doesn't work in most patients. You know, in our experience, about 30% of patients respond. The series up to 40% respond. So again, it's so easy to start with two months of high-dose PPI therapy once daily is what I start with. And after that, you know, I do have patients, they don't want to try any medication. They want to go with diet. And for those diet-centric individuals, you know, we all have them in our clinics. They want to do gluten-free for anything. And so if they're really great, I mean, if they're willing to go through the endoscopies it takes to do it, try the dietary therapy. And for patients who don't want to give up milk, cheese, ice cream, and all their favorite foods, then you can talk about medical therapy, which, you know, is follow topical steroids. And now I think, you know, dupilumab is another medical option for our patients. Thank you. And then there is a question that ties back a little bit into our conversation from the first session in regards to like, and playing this maybe a little bit more thinking on or elaboration on the tacrolimus in terms of mentioning the levels and looking at the dose. Do we have to check levels? Dr. Richter's paper did not mention the levels. And is it part of the practice? What dose do you start with or how quickly do you titrate up? Yeah, I do follow Joel's regimen. I have been checking laboratory testing, both at baseline and during therapy, and I do have, I do follow levels. What I've done is I've adapted what he wrote, and I do talk, I spoke to our dermatologists who use it a lot more often than we do. But one troubling thing is that I have a hard time finding a dermatologist that wants to manage this unless they've got cutaneous involvement or obvious oral or, you know, perineal involvement. They don't see the outcome to follow, so they rely on the GI doctor to manage it. So it's been frustrating for me as a gastroenterologist to have to titrate the medications, but I have had to do that. And do you ever use fully covered stents in these patients with particularly long refractory strictures? Let me let Dana talk about that, as she mentioned it in her talk about using stents for benign strictures. Yeah, I think that is an option. You know, there are some issues with stent placement, you know, such as causing ulceration, perforation. In that setting, you obviously would want to put in a covered stent because you want to eventually take it out, so there's those issues of, you know, migration. So, but I think it is an option and one that you would have to discuss with the patient. I think it also depends on the location of the stricture. So, you know, if you have a distal esophageal stricture and your stent is going to traverse the GE junction, you know, you're going to have to be concerned about free reflux. You know, it's obviously not a great therapy for proximal stricture. So, you know, I think it may have a role, but probably overall has a limited role because we're generally able to achieve, you know, satisfactory lumen diameter with dilation and steroid injection. Great. You know, that's been my experience as well. It follows the literature where I've tried it on several patients, both with lichen planus and EOE, and technically it's successful, but the durability is very limited. It's been maybe less than 25% of patients. Once you take that stent out, the stricture tends to go back again, but I have had some success. I mean, probably less than 25% patients get a durable response where I was dilating them almost every month, and they've been able to go now for several months between dilation. So, you know, when all else fails, I think you're, you know, certainly do not, surgery is a horrible treatment option for benign strictures. So, if you can do anything short of surgery, I think there may be a role for stenting. Thank you.

30-year-old patient

solid food dysphagia

eosinophilic esophagitis

endoscopy

proton pump inhibitor therapy

biopsies