We'll move over to Dr. Hirano for the final case, and I'll leave it to Iko how he wants to do it, and then we have to have – you guys are going to start your – the other session at 9.30, so let's proceed. You can turn up the lights a little bit in the room, and I'll do this quickly. I know we're – I want to be cognizant of the time and get you guys to the next session at 9.30, so you can rope me off the stage any time. So this is a 56-year-old woman with a history of atrial fibrillation, GERD, and this comes in with a complaint of dysphagia. Long-standing GERDs have been managed effectively with a PPI, but in spite of the management of her GERD, she's had progressive dysphagia over five years. Outside hospital endoscopy, it was considered non-diagnostic. She does have this history of mouth ulcerations, some lower extremity skin lesions, which were not clearly diagnosed. She had been diagnosed with a variety of things. They thought it was psoriasis and cellulitis, you know, some cutaneous yeast infections. Got some various empiric therapies, which were really not all that effective. So she underwent an upper endoscopy at Northwestern, and we saw lesions, which I'll show you in a minute, characteristic lesions. And biopsies were non-diagnostic, it just showed chronic inflammation, some granulation tissue, really not giving a specific diagnosis. So we're going to go to the video here and look at the initial endoscopy. This patient's been in our system for a little bit now, and I've done multiple endoscopies, and I always need to use XP, because there's a high-grade stricture here, which you'll see. So this is in the proximal esophagus, it's probably about 20 to 25 centimeters down, and you see this lesion here. So maybe I'll poll our panel. What do you think this—I mean, we have the title of the session, but can you describe what you're seeing here? You know, it's a classic look of lichen plantus, and I think that when you go through that lesion, it's going to just peel right off, in all likelihood, this glistening. The history is right, it's a female with some skin issues. We assume it's going to be lichen plantus because of the title of the session, but it's that glistening appearance, and as I said, I bet you that's just going to—it looks like an ulcer, but it's not, it's just going to peel right off. Yeah, it's interesting. You know, when I first started seeing these, I thought, you know, they almost look like an ulceration, but it's not an ulcer, it's actually just completely desquamated tissue, it's like a snake skin. It's very much like the appearance you see after you do RFA for Barrett's esophagus. So that will slough right off, and this is a very narrow opening, it's probably a couple of millimeters, and the scope is not going to easily get through that, but I want to show you what happened next. And as we play this, maybe the panel in the audience, you could say, actually, in the audience, how many of you have seen a case of esophageal lichen plantus? So probably about half the people. It's out there, and it goes underdiagnosed. People think it's EOE because you have these widely spaced rings a lot of times, but it's not EOE. It's misdiagnosed as EOE, as lymphocytic esophagitis, as idiopathic strictures, as reflux disease. So many of these patients are out there, and we'll talk about some of the clues endoscopically. Let me just advance here. So this is me pushing the scope, and exactly as Gary predicted, this was not set up. I didn't know what the case was exactly going to show, but basically, removing that snake skin from the esophagus here, very much like what you do with RFA for Barrett's. You can see this extends down through the entire esophagus, but interestingly, with these esophageal lichen plantus cases, it's often a proximal predominance. Many times when the stricture's there, it's a proximal predominance stricture. If you think about esophageal lesions and esophageal strictures, there's a small list of things that cause proximal strictures. Distal strictures, we're thinking about EOE and GERD. But the proximal esophagus, what are types of things that can give you a proximal esophageal stenosis? I just told you lichen plantus is definitely one. Other things on the list, pale esophagitis, radiation, head and neck radiation, caustic injury can give you panesophageal, but it could be proximal predominant. There's another one that's great for the boards. It's the IPMN, the intramural pseudodiverticulosis. That's another classic one for the board exam. I was going to say, one time I had an inlet patch that had a stricture proximally. Large inlet patch. Remember that inlet patches, most of them contain parietal cells that can secrete hydrochloric acid. You can get a peptic stricture in the upper esophagus. But usually with that, you'll see a large inlet patch, often circumferential, and it'll be a very annular, short stricture, not a long caliber stricture like this. Quite frankly, a lot of people with EOE, even in the absence of a narrow caliber esophagus distally, will have these very high proximal strictures that get missed, I think. This is the endoscopy after all that slough has been removed. Some people put this in the category of esophagitis superficialis desiccans, a sloughing membrane, which is not a specific diagnosis, it just tells you the appearance. But all that membrane's been removed now, and you can see that you can more adequately assess the esophagus at this point. So to our panel first, esophageal lycoplanus, we could poll the audience, what do you do with this? And I'll tell you, there is no guideline, there is no consensus on how to manage esophageal lycoplanus. You know, probably the best single article that came out was last year in the Red Journal by Joel Richter, which was really, I think, the best comprehensive summary. Treatment is really a challenge. I mean, I do try topical steroids. The success is variable to not especially good. I'll often involve my dermatologist. I know Dave Katska will use systemic therapy. I don't know about you, Iko, I don't have the guts to do that. But I mean, I think that's kind of my shopping list here, or sometimes just intermittent dilations. But it's a real challenge in terms of finding, because we just don't know the right way to treat it. And do you just repeat endoscopies based on symptoms, or are you looking for any response to treatment endoscopically? Well, this also has supremal potential also, so I do survey these patients over time. Anyone in the audience have any pearls or experience with how to manage this? We're all waiting to hear from you with the answer. I don't have any, you know, huge insights here, but it is something I'm seeing more and more of in my practice. And these patients, I'll tell you, they're hard to manage. When they get these high-caliber, you know, severe strictures, they're much harder to manage than eosinophilic esophagitis patients. So as Gary mentioned, this review by Joel Richter's group in Florida is really one of the best. It has a lot of pearls in it, and I just summarized some of the important information here. It's an autoimmune disease, like implanted chronic disease, and interestingly, a lot of patients with this do not have the cutaneous involvement. We always say, oh, you have to have a diagnosis by your dermatologist. But 40 percent in some series only had esophageal involvement. They might eventually, years later down the road, get cutaneous involvement, but many of them do not have that. The other important thing to always ask patients about is oral involvement. That is something that is not listed on their past medical history, and you know who diagnoses it the most? Dentists. Dentists, because they're inspecting the oral cavity, they'll say, oh, my dentist told me I have lichen plantus. And if not, you know, they'll tell you they have these painful sores in their mouth that look very different than herpes sores, and they're usually around the gum line, the tongue and on the sides of the cheek, the buccal mucosa. So you open the mouth, and you'll see the characteristic lesion, and I'll show you some examples of that. I think it's good for GI doctors to recognize it, again, because many times the esophagus is the predominant organ involved. And that gets to Gary's point. These patients are difficult to manage because nobody wants them, to be honest with you. Dermatologists don't like this either, because often they don't have the cutaneous. They say, why am I, why are you sending this to me? They don't have any skin involvement. They don't have vulva involvement. They don't have, you know, why should I manage this? This is your disease. This is an esophageal disease. So they throw it back to us to manage these patients. So you will absolutely see patients and be kind of left with how to manage them. Typical onset, usually it's an older person's disease, and interestingly, the majority of patients that get the esophageal involvement in most series are women. In this male clinic series, 90% were women, but there's a small number of patients that can be male as well. So this is some of the oral manifestations. Again, good to see these images, because once you see it, then you get pattern recognition. You can see the gum line affected, these little white spots. That's why dentists, when they're doing their dental cleaning, they'll notice these lesions. That line right here, right along the incisors right here, I think there's some trauma that happens when you bite down, and it causes some more prevalent lesions right where the teeth hit the buccal mucosa. There's also the cutaneous involvement and nail bed involvement, so I think it's good to see. This is all from Joel Richter's review. And, you know, I showed you the video, but this also shows some of the other lesions. It can look like a ringed esophagus. It can look like an EOE-type appearance, except you don't typically get the furrows and extra that you do with EOE. You get the desk formation, the desiccans appearance, and these high-grade, often proximal predominant structures. And once you, on roof, get rid of that slough, then you can see the denuded epithelium underneath that. So these are characteristic appearances. Now, unfortunately, the biopsies, we all are taught on our, you know, your boarded review, look for the civet body, look for the civet body. That's the, you know, the necrotizing epithelial cell. But it turns out that's found in less than 25% of cases. So you could ask your pathologist to look for it, but don't be surprised when they tell you, I don't see it. And they'll just say there's some lymphocytic infiltration. And it's often non-diagnostic. So pathology, we rely on it to give us a diagnosis, but many times the pathologic diagnosis is not there. So it really comes down to a clinical diagnosis. Many patients, whether you see the oral, the cutaneous lesions, whether you have the character — I think those endoscopic appearance with that sloughing membrane like that and these superficial erosions is very characteristic. Proximal predominant strictures, those are all the clues. And you can make an empiric diagnosis without having patho-pneumonic pathology. Now this is, again, I don't expect you to read this. This is the summary from Joel's article just a year ago, summarizing the state of the art of the therapeutic options for lichen planus of the esophagus. These are all very small series. The largest series are using swallowed topical corticosteroids, much like for eosinophilic esophagitis. The largest series came from the Mayo Clinic. They reported that, you know, most of their patients could be managed with steroid, topical steroid therapy. They use high doses of liquid steroid, up to 3 milligrams. So it's a higher dose than what we're using for eosinophilic esophagitis. And they reported this high response rate, but I should note that in their series of patients that got treated with swallowed topical steroids, a lot of them underwent esophageal dilation. So did the improvement happen from the dilation or did it happen from the steroid? And a lot of them were also on concomitant immunosuppression. So I don't know if it's purely a steroid benefit. I've had Gary's experience. I have not been overwhelmed with the response to swallowed topical steroids. For EOE, it works great. For lichen planus, it's definitely, I'd say the minority of my patients achieve a significant response to swallowed topical steroids. I always try it because it's safe, it's easy, but usually they need more potent immunosuppression to get there. So if you've got esophageal involvement, they usually need more potent immunosuppression. You can see what the things that have been tried, cyclosporine, tacrolimus, rituxan has been tried, TNF inhibitors have been tried. So a variety of different agents, all small, uncontrolled series have reported the response. In Joel's series, which he used systemic tacrolimus, and that was not in any of the reported literature. It's just his own experience of treating dozens of patients with esophageal lichen planus. And he found that it was effective for most patients, and that I think the most important thing is that in his experience, it reduced the need for repeated dilation. These patients with the high-grade structures, these are patients that I sometimes bring back two or three times a year when they get down to like this patient needing a transnasal scope every time. It's hard to dilate them up to a successful diameter. These are patients I don't shoot for that 15 to 16 diameter. Sometimes I'm happy with a 12 to 14 millimeter, because you just can't get them very high. Just tears the esophagus every time, and you go back a few months later, it's back down to a small diameter again. So I haven't had a tremendous success. So now, you know, since Joel's experience, I've been trying tacro now. I can't get my dermatologist to see these patients unless they've got cutaneous. So I'm prescribing tacrolimus now. I've tried hydroxychloroquine, Plaquenil, very safe. Get an eye exam and try it, but I have not found it to be effective. It's safer, I think, than tacro, but I have not had my own experience has not been successful with hydroxychloroquine. This is the Mayo Clinic series, and this is their, they had different categories of response. This is their swallow topical steroid experience. They said they had these complete responders. You can see on the far left, that doesn't look that bad on the far left. Before, there's like one little excoriation here, so I'm not sure that's a dramatic example of a response. And here, they said a partial response, and here, there's no response. And again, they said that 60-plus percent of patients had a response endoscopically to swallow topical steroids. I think it may just help clean up the mucosa, but not deal with the stricture formation. The other important complication to keep in mind, unlike a plant, is cancer. So this is another esophageal disease that predisposes patients to squamous cell cancer, and maybe some of our panel has seen dealing with cancer in these patients, just like with epidermal metaplasia. The Mayo Clinic had the largest series of this, 132 patients with a 6 percent prevalence of squamous cell cancer in that series, and no clear risk factors were identified. This was a scary patient from Joel's paper. Had regular endoscopies, and for a stricture, it's getting dilated. Six months after dilation, they show the picture before, which is A and B, and then after, six months later, came back for another dilation, had a squamous cell cancer. So that's a little bit scary, where there was no identifiable mucosal lesion, and yet developed a cancer within six months. So I think that's a little concerning. There are no recommendations for how often to survey these patients. I think my patients are coming in usually twice a year to get dilations, but as you can tell in this example here, you don't always see lesions. I don't know if there's any other experience people have had, either in the audience or on our panel. I have somebody, actually, who I shared with Dave Katska, who was on Rituxan, and I've been following for over a decade, and had, just on routine surveillance biopsies, had high-grade dysplasia, and then we ended up doing a chromoendoscopy and EMR, and it ended up being high-grade dysplasia. Had pretty high-grade stenosis, came back three months later, was dilated at the first, and then again, but actually had significant improvement in the inflammation with the intralesional steroids. Yeah. There's anecdotal, and then it is on the list here for tritamcinolone-kenolade injections. The problem, as you know, is that these are often extensive lesions, so it's not just the focal area. You'd have to be injecting up and down the esophagus, and that's a lot of steroid injections. If they have a dominant structure, I think it makes sense to try that, but... We should let these guys go to the... Yes. Thank you. All right. For our in-person audience, you have a 10-minute break, and for the virtual audience, please stay tuned, because there will be some live demonstrations starting shortly.

Dr. Hirano

esophageal lichen planus

dysphagia

GERD

treatment options