Thank you, Sarl. That was a great presentation. We got to learn not only about GERD, but also about other important causes of esophageal dysfunction. I think what it does is it shapes our discussion with patients about what potentially could be going on. We've got some questions we're going to start with, but I do have a question for you, Sarl, if you don't mind. I do not routinely do esophograms in patients with EOE. Can you give us a little bit of guidance in terms of how you use them pre- and post-treatment? So we generally use them pre-treatment to see how aggressive, like you alluded to earlier, we need to be with either dilation or the choice of medical therapy. I tend to not use them as much after therapy or dilation. On some occasions, when we find patients with steroid-responsive EOE, they still have dysphagia. That's when I will sometimes do an esophogram with a tablet to see, well, now that we have the eosinophils out of the esophagus, why are they still having dysphagia? That makes a lot of sense. Yeah, we typically reserve the esophograms for other causes of esophageal dysphagia that aren't explained by that, but I can imagine if you've got somebody with pretty advanced disease who perhaps waited a little longer to be seen, who shows up with a pretty narrow esophagus, when you're having discussions with them about treatment options, dilation may be something that needs to be offered, even if the patient's symptoms seem to be a little bit better with the treatment, maybe setting expectations that, hey, we're going to put you on some therapy, medical therapy, topical therapy, but it's likely you're going to need a dilation based on what we're seeing on the esophogram. Yeah, and just to follow up on that point, oftentimes these patients with EOE are hypervigilant. Is it due to a football's impaction that makes them now very scared? And they really feel a lot more. Esophogram with the tablet is oftentimes helpful to really show them, well, here's the esophogram, here's the tablet passing nicely through your esophagus, and you can ask them if they felt that versus if they didn't feel that. So I find it helpful in that cases too. That's a good point. So we'll go through some of these questions, or all of the questions actually, they're great questions. Please continue to contribute. The first one that came through was, can you put a patient back on PPI therapy for maintenance after treating with budesonide for eight weeks? I'd like to take a stab at that. So the data for combination therapy really isn't all that strong yet, but practically speaking, there's two schools of thought on whether you're putting patients, taking patients off PPIs, if that's the first line treatment. Going back to my silly example of a hostile environment where people are trying to invade, I think given the safety profile of PPI, and given how we know that this condition is chronic, and given that the side effect profile for steroids may not be as well tolerated, I tend to leave patients on PPI while I'm trying to escalate therapy to something like a topical steroid. Again, some schools of thought are you can't really tell one from the other, it'd be nice to see. So I would say it really depends on your patient's willingness to be on a chronic medication versus episodic treatment. My personal preference is to keep patients on PPI, given that I think it does augment the landscape and perhaps decreases the amount of penetration of food allergens into the esophagus. Do you want to take a stab at the second one, please? Yeah, sure. So did you ask if you wanted to or you wanted me to? I'm sorry. You. Okay. So why isn't food allergen testing done? It's kind of a coin toss. There's three different ways you can typically do this. You can do this with a skin prick testing, and they looked at adults with that and they found that it really didn't show a positive predictive value on that. You can do IgE testing looking for blood work that stimulates that, but again, not a strong correlation. There is some results with atopic patch testing where you might be able to get some negative predictive values from that. What that means basically is you go through the allergen testing and it's less likely that if you don't show up with atopic patch testing, being allergic to, let's say, shellfish, the chances of EOE being caused by shellfish goes down. The problem is the positive predictive value isn't very good, and so it's basically a coin toss. There is some instance with using allergy testing in patients that have other atopic diseases. We do know that EOE follows a seasonal variation, and we know that patients are sort of primed. Their immune system is primed, say, during the time where they might have outdoor allergens, and so it's not surprising that EOE may get worse in that scenario. If you've got a patient who's got multiple atopic conditions, getting formally tested is very reasonable in the sense that all of that can contribute to their being miserable throughout the year, and in particular during certain seasons where they have their various allergen triggers. Again, what the consensus is at this point is that you're really going to get better responses from food elimination trials followed by endoscopy, and we'll hear a little bit more about that later than you are by going and getting formally tested and then saying, well, I have an allergy to cow's milk or an allergy to dairy or gluten that hasn't panned out. I'll take the third question. If you have a patient have allegrate A or B esophagitis, they comply with dietary, lifestyle, and after two to three month therapy of PPI. Do you recommend that they also be on lifelong PPI or just class C or D primarily? A good question. It depends on their symptoms. I tend to—I'm not too concerned about grade A esophagitis. Grade B is likely somebody I will continue on PPI. Lifeline depends on if this is controlling their symptoms. You can consider a lower dose, but if you look at the guideline C and D, it's important to rule out Barrett's as it can be really hiding underneath that esophagitis. So, to answer the question, I would think yes, if they have grade B or greater esophagitis in symptoms, fair to put them on a dose that control their symptoms. Next question. Do you foresee any role of PCABS in the treatment of EOE? As far as I know, most of these studies are coming from erosive esophagitis. I'm not sure if you have anything to add to that. Yeah. So, PCABS are potassium competitive acid blockers for those who aren't familiar with the abbreviation and they've been recently approved in the United States for erosive esophagitis. There have been no studies that I'm aware of that have really kind of looked at PCABS specifically for EOE, but the premise behind it remains the same, right? If the acid in our stomach is refluxing into our esophagus, creating a hostile environment that is encouraging dilation of intracellular spaces, allowing all that stuff to come in, suppressing acid by other means would be a reasonable thing to do. I can't imagine we're ever going to see a head-to-head trial between the two, but it's possible that whatever the PCABS are doing mechanistically in suppressing acid may be better in terms of how they're affecting EOE. Time will tell on that. Next question. Many of my patients aren't sure if they have a true nickel allergy or are just hesitant to do a Bravo. Do you ever send for official allergy testing? What questions do you ask to a certain true allergy? That's a great question and I'm not sure we've gotten a good answer from the manufacturers of the Bravo about this nickel. I think if there's concern about the true allergy, I would certainly have not done that, but I would certainly send them for testing if that's an option. The beautiful thing about being virtual is I could look that up while Sara was talking, so I got familiarized that the prevalence of nickel allergy in Europe at least is anywhere from 8 to 19 percent, so it's not a small percentage and I think it becomes more of an issue with the orthopedic instruments and causing that. I think I've experienced it once or twice where patients will ask about it. My suspicion is that if the patient is asking you about a nickel allergy, that's the person you probably want to get tested because they potentially have had some exposure and something had provoked them, whether it was some type of jewelry or a piercing or some other type of metal that they had on their skin that caused the dermatitis. Next question is recommendation for PCAPs for esophagitis. It's a fairly new drug on the market. I certainly have not used it a lot. I've had some trouble getting it covered. The studies that I've done, I don't have memorized, but it's certainly an option to use for esophagitis. I've had some limited experience in patients who have had reflux esophagitis that have been refractory to traditional medical therapies. I've had some patients that probably have some refractory. They've been on dexlansoprazole, the long-acting, and they continue to have breakthrough symptoms and our suspicion is that they really do have significant GERD. I've got them on the PCAP and they seem to be doing better. This is, of course, anecdotal. And then as Saru mentioned, insurance does want you to jump through hoops and probably try three or four PPIs before they would be willing to cover that. Less problematic with Medicare than with some commercial insurances. Next question, prior to a heliotopical steroid dose with budesonide was one milligram. Are you continuing two milligrams BID dosages after 12 weeks or tapering to two milligrams or less? Saru, do you want to take that at all? Yeah, I haven't really prescribed with helium much. I think it's still something that's going to be decided either by insurance coverage or symptoms. I mean, if I think about just the other topical steroids, I generally start three milligrams BID. And then if they're in remission after eight to 12 weeks, I go to a bedtime dose that could be 1.5 milligrams in the form of the budesonide compound that they mix with honey. It all depends on what you're using, but try to go down to a bedtime dose if you can. I would agree with that. I think there's going to be some movement on that. What we did mention earlier, and it kind of begs to stress again, is that we do need to bring these patients back to see how they're doing and as convenient as it is for patients to take time off and the expense of going through that, the only way we're going to know whether any of these regimens work is, number one, the patient is committed to doing them, and number two, that they're willing to come in at the appropriate times and have surveillance endoscopies. Next question is, can you give guidance when to do pH impedance testing on or off PPI? If a patient can't come off of PPI for testing due to severe symptoms, is it worth doing the test? You know, in my practice, generally, if patients have ongoing symptoms despite the PPI, I would do the pH impedance study on the therapy to really get the correlation. Is there a symptom correlation what they feel? Is there acid in their esophagus? That's just what I do to really get a sense while they're on therapy to get a sense. You can certainly do it off of therapy. Going back to the previous question, if there's a concern for nickel allergy, generally done on therapy to evaluate response and really see what's going on over 24 hours in their esophagus. And not much more to add on that from our standpoint. We don't have impedance available in our community, so we do send some patients to some of the closer academic centers to get that done. With Bravo's, we do them, of course, off and on so that we can check the correlation of symptoms with the amount of potential increases in acid exposure once you stop the PPI and then go back on to the PPI. The question, are you stopping PPI for two weeks or longer to biopsy? Is that, Rosanne, a question for EOE? Regardless, it used to be when we were thinking about eosinophilic esophagitis, we would say the persistence of eosinophilia after GERD has been ruled out, but the new consensus statements and guidelines suggest you should be taking them whenever you're going in. Patients who are coming in with food boluses, for example, sometimes we just push the food bolus through and we don't take biopsies. We want to wait until they get on something. The guidelines, the British guidelines have said you take biopsies at the time of the index endoscopy. So regardless of their acid suppression, you know, if they're showing up with symptoms suggestive of EOE, endoscopic findings suggestive of EOE, and they've got a lot of eosinophilic infiltration, we work through that diagnosis of EOE and then we can, you know, go from there.

esophageal conditions

Eosinophilic Esophagitis

esophograms

combination therapy

potassium competitive acid blockers