IBD Drive Time: Jason Schairer, MD, on Extraintestinal Manifestations in IBD

Host Raymond Cross, MD, and guest Dr Jason Schairer discuss the varieties of extraintestinal manifestations that may be seen in patients with IBD, how to diagnose them and when to rely on colleagues in dermatology, ophthalmology, and rheumatology to help.

Raymond Cross, MD, is director of the IBD Center at Mercy Medical Center in Baltimore, Maryland, and professor of medicine at the University of Maryland. Jason Schairer, MD, is director of the Henry Ford Inflammatory Bowel Disease Center in Detroit, Michigan.
 

Welcome everyone to IBD Drive Time. I'm Raymond Cross from Mercy Medical Center in Baltimore, and I'm delighted to have my friend, Jason Schairer from Henry Ford in Detroit here to talk about extraintestinal manifestations in IBD. Jason, welcome to IBD drive time.

Dr Schairer:  I'm excited to be here. Thanks for having me on.

Dr Cross: Of course. Somany of our listeners can be trainees, advanced practice providers that are new to IBDs and new faculty. And just to get us started, when we think about extraintestinal manifestations in IBD, what are the classic ones that we were taught? And it seems like the list continues to expand. So what are the classic EIMs?

Dr Schairer: Yeah. So anyway, we're just going to call it EIMs. We can speed this along and work within the timeframes here because it's such a long acronym. But the classic ones are IBD spondyloarthritis, the rashes, and the ocular manifestations. Those are the ones that we have been hearing since we were in training. We can even break that down further and say that within the spondyloarthritises, we have the central versus peripheral, like the axial and peripheral. We have the rashes, pyroderma gangrenosum and erythema nodosum, and the ocular manifestations—uveitis, episcleritis, and scleritis—but those are the classic ones.

And there are so many more that affect all the various systems of the body because when we talk about IBD, we're talking about the immune system. So we often focus on the end result where the problems are, but the immune system can affect other organs. And I think most of the people in the audience understand that people with PSC, which affects the bile ducts, is common in people with IBD. And that's often associated as the extraintestinal

manifestation, but it's not in that classic list of what are the most common things we talk about, even though everybody knows PSC is associated with it. So we have lots of other organ systems that don't make the list but are associated with IBD.

Dr Cross: What about aphthous stomatitis? And I'm going to, I hate to ask double questions, but I'm going to ask you that. Oftentimes people can, people say with aphthous stomatitis, that that's consistent with Crohn's. So where do we classify aphthous stomatitis and is that particular Crohn's or can we see it in both?

Dr Schairer: Yeah, so this is one of the things that patients probably care about so much. And I think as a GI physician, I'm probably a little bit underequipped to handle it. It's very painful, it hurts, they can be present for weeks on end, it can affect how the patients eat, it can affect their weight. So this is a very painful, very front and center kind of symptom for a lot of our patients. And our data shows that it's associated both with ulcerative colitis and Crohn's disease. It's not one or the other. And I think that goes back into what we learned in training, which is ulcerative colitis is limited to the colon versus Crohn's. And all of these classification systems are absolutely true—except when they're not. So there's lots of parts of ulcerative colitis like terminal ileitis from washback ileitis and the aphthous stomatitis where we can have manifestations outside of the colon, but that doesn't make it Crohn's disease.

Dr Cross:    Yeah, I agree, Jason. I think it's obviously with both, but I think maybe where the confusion comes in, we talk about Crohn's can involve mouth to anus and people just take that that stomatitis is associated with Crohn's and it's really not true. Now, in fact, most of the EIMs to my understanding are more common in Crohn's and they are in ulcerative colitis, but you can see them in both. And of course, to make it more complicated, you can get orofacial Crohn's, which looks different than the classic aphthous stomatitis that we see.

Dr Schairer:  Yeah, there are so many things that go on above the neck that can be associated with IBD. So you're talking about Melkersson-Rosenthal syndrome, which is an orofacial granulomatosis that can present with swelling of like one side of the face, usually by the cheek or the jawline. And if that swelling gets to a certain point can actually affect, I believe, the trigeminal nerve—I'm not a neurologist, so someone can tell me I'm mistaken—and can cause a little pseudo paralysis that can hopefully come back with treatment. And other things can muddy the picture, so we're not sure what we're talking about. When we talk about aphthous stomatitis, I think we're talking about ulcers in the mouth. Where I come from, they're called canker sores, right? A lot of people get canker sores; they're not associated with IBD.

The real classic finding of oral Crohn's disease would be what we call like these knife-like lesions that often present near where the buccal mucosa meets the jaw line itself. Those are very painful and when we see those we go yep, that's definitely Crohn's disease. But a few small aphthous ulcers on the buccal mucosa, by the lips, in the front, by the tongue, you know that can definitely be from a multitude of things from medication effects to oral hygiene to Crohn's and ulcerative colitis.

Dr Cross: Agreed. So the next question is classically, when you and I were in training, we were taught that there are some extraintestinal manifestations that correlate well with disease activity, so if you treat the disease underlying, the EIM gets better and others have a completely independent course. So is that true? And if true, which ones typically correlate with active disease?

Dr Schairer: So I think most things that we learned in medical school are absolutely true, except when they're not. And I think a classification like this, where we look at a downstream product, like do you have swelling in your joints or rash in your skin, and is that associated with IBD? The majority of the patients, I don't know if it's 80, 90, or more percent, typically fall into those categories. So we can say somebody with an axial arthropathy typically does not have active IBD. And someone with a peripheral arthropathy, depending on, you know, the old system of type 1, type 2 may or may not be associated with IBD activity. But these systems that we have in place don't account for the exceptions. So, for instance, as our ability to define things evolves, as our ability to look and assess what's going on in the human body changes with deeper endoscopy, CT enterography, or capsule endoscopy, we know that in people with axial arthropathies like ankylosing spondylitis who have IBD, about 60% of them can have subclinical inflammation in their GI tract.

So even though we've traditionally said not associated with disease activity, it starts to get a little bit muddy when we start thinking about those things. If I was to go through and just give you general terms, I would say for the arthritis, axial is typically not associated with disease activity and peripheral typically is, but there's exceptions to both of those. For rashes, I would say erythema nodosum is typically associated with active IBD and pyoderma is not. But in many of our experiences, if someone has pyoderma, I would always encourage you to think locally and systemically. So what's going on locally with the patient's symptoms? What's going on systemically in the body? And should I look? And I would encourage people to go look and find active IBD for pyoderma because there's a lot of times it can be active.

Dr Cross: So along the lines of things that we learned in training for the peripheral arthritis or peripheral spondyloarthropathy, in the GI world we typically classify this as type 1 and type 2. Can you explain that to the listeners and should we even be using those terms anymore?

Dr Schairer: Right, so we asked two questions again, and if you ask me the second question first, I think we get out of this one a little bit faster. So the first question is, what is type 1 versus type 2? And when we talk about these IBD spondyloarthritis, and we start classifying it axial versus peripheral, the peripheral was further subdivided into type 1, type 2, wherein type 1—and usually in these classifications, type 1 is the more common of the things that we find—type 1 affected like the larger peripheral weight-bearing joints. So think of like your shoulders, your hips, your knees, your elbows, things like that. And in type 1, it was typically associated with disease activity.  Now the good news is that this tended to be like a subacute process. So it usually lasts days to weeks, but you know, shouldn't be lasting a year at a time, and it was associated with this nonerosive joint damage. So this is what we learned in training.

And we contrast that with type 2, which is a more chronic process. This is present for months to years at a time. It often affects the smaller joints, like the hands, the feet, and it's often not associated with IBD disease activity, although even though it's nonerosive, because it's there for so long, can eventually lead to more damage of the joints. But as they've gone on rheumatology, just like in GI, they've done a better job of defining and found out that we don't have distinct entities of type 1, type 2. There's a lot of overlap between these things. And when you put in all the IBD spondyloarthritises, it becomes almost a spectrum where the type 1 and the type 2 merged together and the more severe disease affects both type 1 and type 2 patients versus the milder cases may only have type 1. So it's not typically used for diagnosis and it's not even used for treatment because a lot of our medications, as we have more and more options, treat all of these things, whether it be ankylosing spondylitis or peripheral arthropathy, you know, the anti -TNFs and the JAK inhibitors are used in rheumatology clinics around the world and are used in GI clinics around the world to treat similar conditions.

Dr Cross:    Yeah, I agree. I think that distinction that really just created and added more confusion than anything, and I think for the listeners, and hopefully you agree, is that you know when your patient complains of joint pain and or swelling if their symptoms are active and or they have obvious signs of inflammation whether that's they've had a recent colonoscopy or imaging or their biomarkers are abnormal, you know, typically we're going to adjust their treatment or change their treatment and if the joint symptoms get better, great. If they don't, either they're incompletely controlled and we're not aware of that or it may be truly independent or the residual may be independent of activity.

Dr Schairer: Yeah, I would add to that, you know, I think sometimes we get hung up in the clinic where we're sitting, going, okay, it's supposed to be a migratory, oligoarthropathy. How many joints is that? Is this too many joints? Is it symmetrical? It doesn't fit what I learned in the textbook. And you go, what we learned applies to most patients, but there's a lot of people that outlie both ends of the spectrum where maybe it's just one joint or maybe it's symmetrical because they have 8 or 10 joints and we don't want to not treat them because it doesn't fit into what we recognize. We have to expand what we understand the disease to be.

Dr Cross: I agree, and I think that in many situations when patients have persistent joint complaints or new joint complaints that sound inflammatory, and we're going to come back to that, I think doing some assessment for active disease, whether it is just the biomarkers or repeating a scope, because it can significantly impact your treatment plan, I think is completely reasonable.

Now coming back to joint EIMs, unfortunately, there's not, in many places, are not enough rheumatologists to go around. So, for the listeners, if you want to be a little depressed, it's one more thing you're going to have to handle. Most of us have to be, not card-carrying rheumatologists, but have to be comfortable managing at least entry-level inflammatory arthritis. So, when you're talking to a patient who has joint complaints, Jason, what questions are you asking them to try to determine if this is an inflammatory arthritis?

Dr Schairer: We're actually going to expand that just a little bit to all the EIMs, whether it be dermatology and recognizing lesions, whether it be ophthalmology. I'm not going to do a split -lamp examination in my clinic, but I think reasonable questions that we can ask patients about how do we approach this, because at the end of the day, my patients view me as just a butt doctor. I'm the doctor they see because they're colon’s bothering them, and I don't think that they inherently bring me their joint problems, their skin problems, or eye problems. So I do think there's value in the clinic to just take one minute out of a very tight visit and just ask about the joints, ask about the eyes.

The key features for the arthritis questions to differentiate an osteoarthritis, which is usually just from overuse over the years, and an inflammatory arthritis, is that with an osteoarthritis, resting the joint makes it feel better. So they usually wake up in the morning, they feel pretty good, they start moving around, maybe they walk around a few flights of stairs, their knees and hips start hurting, they sit down at the computer and start typing, their wrists and hands start hurting. So it's an overuse process, versus an inflammatory arthritis, which it seems almost like in my head, like we're lubricating the joints.

When I sit there for long periods of time, the immune system just causes the joints to get more and more inflamed. And then people wake up in the morning, their joints are swollen, they're painful, they're tender. And it's hard to move the joints. And the more they move around throughout the course of the day, after they've moved around for, you know, getting up, showered, had breakfast, got out the door, things start to get a little bit better. And then they sit down at the computer for a couple hours, they stand up and then the back pain comes back. So really that timing of when the inflammation is bothering them, if it's worse in the morning and gets better with use, that's more of an inflammatory process. And then on physical exam, something I'm not very good at myself, but we had plenty of rheumatology fellows come through our clinic and point out to me is that just looking at people's hands sometimes is enough. If you can just feel a joint, you don't have to do an in-depth examination. If you can just feel that the joints are warmer than the surrounding areas. If it looks swollen, there's a lot of people who have arthritis in their hands and fingers and they don't bring it to our attention. So if we just take that time while we're talking to them to look at their hands and fingers, notice that they're swelling a little bit, ask if you can touch them, they feel warm to the touch. That would be an inflammatory arthritis.

Dr Cross:    Yeah, and I agree with everything you said. The other things to point out are that patients can often have involvement of their tendon sheaths, so they can be swollen and tender, and it often represents like a psoriatic arthritis. You can occasionally see sausage digits or dactylitis, so I have had a few patients presenting like that in addition to having some warm and swollen joints.

So how do you, what's your approach to managing patients with inflammatory arthritis? Let's say that their underlying luminal disease is controlled on whatever agent they're on. How are you managing concurrent inflammatory arthritis?

Dr Schairer: So really 3 principles. Normally for EIMs when I talk, I always talk about local management of problems, systemic management problems, and my third one is going to be asking for help. So local for these arthritis, there's not a lot that we can really offer people other than just maybe warm compresses and physical therapy. It is described that one could send them for steroid injections of the joints. I don't find that is a mainstay of how we treat in our clinic, but systemically, when it comes to medications used to treat these IBD spondyloarthritises, it's often something that the rheumatologist already has faith in also. So, for instance, the 2 classes that I think we trust the most in GI and rheumatology would be the anti-TNFs and the JAK inhibitors. And they're both utilized by both fields. They are optimized by both fields. It's important to understand that they may have different doses. So for instance, we may use a higher dose of a JAK inhibitor for an IBD patient than we would for a rheumatoid arthritis patient. So we have to talk with our rheumatologist and negotiate what the right dose is for the patient that we're seeing. But that's kind of like an idealized world. And there's a lot of times where just getting any of the patients whose IBD EIMs are associated with disease activity under control, it helps, right?

So we know, for instance, that vedolizumab, people think of this as limited to receptors in the GI tract. But in the GEMINI study, about 40% of the patients had improvement in their arthritis. So there is value to treating the underlying IBD, even if we don't think the medication is going to the joints itself to have an effect.

Dr Cross: Yeah, and I think that, you know, one important question to ask patients is, are there symptoms affecting their quality of life? I have a number of people that I think have inflammatory joint pain and they have minimal stiffness and they go on their day and I don't think you have to create a problem when there's not one.

In someone who's already stable on therapy, you know, I like to use COX -2 inhibitors for symptomatic control. I think all of us are pretty comfortable with methotrexate. This doesn't have to be parenteral methotrexate. This can be oral, low-dose methotrexate, you escalate over time. And for the younger people out there that have a new sulfasalazine, sulfasalazine can be wonderful for inflammatory arthritis related to IBD and it can be an add-on to their current therapy. You don't have to use high doses. I typically start 500 milligrams a day and every week I double the dose until they're 2 grams twice a day but for whatever reason I found in arthritis a gram, a gram and a half often is enough and the reason I do the ramp up is you can get some GI-related distress with that. And if you do the ramp up, I found it's much better tolerated. So I don't know if I'm sure you've used sulfasalazine in your days, Jason.

Dr Schairer: Yeah, and then I'd love to hear your thoughts about this because we know that it works for peripheral spondylarthritises. We know that it works for axial. We don't have a lot of head-to-head versus various agents, but the anti-TNFs do appear to be about, you know, 3 times as effective compared to sulfazalazine head-to-head. But when your patients are on, for instance, a JAK inhibitor or an anti-TNF, do you add sulfazalazine? Do you find much additional mileage by adding that on?

Dr Cross: So for what I'm doing, those approaches, those 3 steps, for me, it's usually people that are already on drug that are already stable and their gut is controlled, so it's an anon. And I have had people on biologic therapies that I've added sulfasalazine and they've gotten relief. I don't know what the numbers are. And likewise with methotrexate, I've seen that patients can get better. Usually, if I'm going to switch their advanced therapy, whether it's a biologic or small molecule, often—and I'm not going to say I've never switched to a JAK or something like that—often that's where I'm going to get rheumatology's opinion first before doing a wholesale med change. But adding on to existing therapy, I feel very comfortable doing that before asking for rheumatologists, but switching to another advanced therapy is a little harder.

You've presented and done a lot on education for EIMs, and I think it's one of the best talks I've ever heard is your talk on EIMs, particularly dermatologic, and the influence of skin color because all of our textbooks growing up, Jason, were white patients showing erythema nodosum and pyoderma with white background of skin and that's what we learned and now there are patients who are more like the colors of Benetton, they're not all white and these lesions may look differently. So how does skin tone impact your ability to diagnose or recognize these dermatologic EIMs?

Dr Schairer:  Well, first off, thank you for the kind words. I'm actually very proud of that talk. It was put together with our dermatologist at Henry Ford, Holly Kerr. And it's like you described. We look at these lesions in the textbook, and then we look at our patient in the clinic and say, "Is this the same thing?" And we know that different humans have different pantones of skin so that when we talk about, for instance, with pyoderma gangrenosum having this pathognomonic violaceous border, you go that, again, is absolutely true, except when it's not. And so being able to recognize that with different pantones of skin that maybe the violaceous border looks like a hyperpigmentation, for instance, understanding that the raised red lesions of erythema nodosum may appear darker compared to its surrounding tissue or even it evolves into bruises and what that looks like helps us recognize what's going on and get these patients onto the right therapy faster. And this is so

important because like I mentioned earlier, my patients are going all around Michigan seeing urgent care, family practice, dermatologists because of the things that are going on in their skin. And they never think to come to the butt doctor about these things. So being able to recognize that there's something going on that I can help with, that there's, for instance, erythema nodosum, and this is associated with active IBD, and I need to get their Crohn's disease better controlled, we'll get the patient on the right path faster. So I think it's very valuable to learn from the people in our community of what this pathology looks like. I think it's important to share with each other. My slide deck includes people from Japan and Egypt and various places around the world that they graciously shared pictures of what their pathology looks like so that we can learn and recognize it when it comes into our clinic. And I think that's one of the next steps we're taking in medicine is expanding what we're able to recognize by incorporating all these different varieties into our textbooks.

Dr Cross:    Jason, that was great. Before I get to the last couple questions, I just want to remind the listeners that we are sponsored by the AIBD network. You can find us on Apple Podcasts and on Spotify. I also want to remind the listeners that our last AIBD regional of 2025 will be in Cleveland October 11th through October 12th, and of course the national meeting is in Orlando. It's held December 8th to December 10th, but we do also have some premeetings ahead of December 8th as well, so look for those.

So Jason, EIMs, when you're selecting an advanced therapy, do you consider them when you're picking a therapy?

Dr Schairer: So the right answer here is yes, but I think you and I practice similarly where we probably don't get a whole lot of treatment naive patients coming into our clinic, right? So, I think in a treatment naive patient going, "Okay, this person has not just active ulcerative colitis or Crohn's, but also this EIM," then I think working with the ophthalmologist, the dermatologist, the rheumatologist, negotiating for one medication that would treat both conditions, optimizing what's the appropriate dosethat would treat both their condition and my condition because that's not always the same, I think that's appropriate.

And for instance, like the IBD, spondyloarthritis, you know, yeah, the anti-TNFs and the JAKs are great first value. But like you, I'm sure, I see a lot of patients who’ve already been on an anti-TNF and they've already been on ustekinumab or vedolizumab, and we have to pick something. So I do want to emphasize that for a lot of these conditions, even though the medications are newer and we may not have as much data or we don't have 20 years of experience with them, a lot of them are showing value in treating these conditions for our patients. So the most important thing is controlling the IBD, working with our team to pick a medication we think is going to be helpful for both. But yeah, in a perfect world where my patients have never been on anything and they come in with an arthritis and I can use a JAK inhibitor or they've never been on anything and they come in and they have uveitis and I can negotiate, you know, what's the topical medication and systemic, I do have favorites, but I don't think we always get the pick in 2025.

Dr Cross: It gets very confusing when we talk about disease severity and disease activity, but when we talk about disease severity, we're trying to prognosticate what a patient's risk for severe disease, meaning multiple resections in Crohn's, difficult to control, disabling disease or high risk for colectomy in UC, or if they've had disease for a long time just looking back and saying they've had severe disease. Do you think that patients with EIMs have a more severe disease? Are you more likely to start those patients on an advanced therapy early?

Dr Schairer: So, yes and yes, but with a caveat to the first one. So, we know, for instance,

with ulcerative colitis that if you have an extraintestinal manifestation, you're more likely to go for a colectomy. So definitely, yes, they are associated with severity of disease and worse prognosis. But then you have to ask, well, what does that really mean? Because we're always talking about the downstream effects of this, what does it do to the colon or the eyes, etc. And the process is this person's immune system is overactive. And it's now at this point started to attack multiple organ systems, it might be incorporating multiple pathways for how it's overactive. So at a certain point, we're just saying is more difficult treat to treat disease associated with worse outcomes? And you go, yeah, that's definitely a possibility. But yes, if I see EIMs, we know they're more likely to have second EIMs. If you see EIMs, we know we're more likely to have bad outcomes. And I would advocate for, I wouldn't even say aggressive therapy, I would just say getting people into remission by whatever means is necessary. I don't think that changes my end strategy with that process.

Dr Cross:    Yeah, it's well said. And we’ve got to quit using that word aggressive because it makes people think dangerous and advanced therapies are not dangerous and we shouldn't be hesitating to use them. In fact, we should be using them more freely. So that's a great point.

All right, this is what the listeners actually listen for Jason, the fun fact. So tell us something fun about you that they may not know or I may not know.

Dr Schairer:  Okay, so I had the pleasure of hanging out with you a couple of weekends ago. You came to Detroit. Hopefully we showed you a good time and showed you some nice areas of town. I absolutely love living in Michigan. And so not that next day, but a few days later, we found ourselves up in the thumb. So again, for any of your listeners who were not from or around Michigan, you just hold it your right hand, you look at your palm, you say, yep, the thumb, that's where Jason was.

And I went with my kids and I went with my sister and her kids. And that weekend we went e-foiling, which is like a surfboard attached to a hydrofoil that goes over the water, not through the water. And it is a very serene, magical, fun experience, or so the videos would have me believe. I spent most of my time star fishing off the side into the water, but for the minute I was up, it was pretty cool to do with the family. So that was my fun, cool thing, was going e -foiling in the thumb of Michigan.

Dr Cross:    You were the first IBD Drive Time, I guess, that e-foiled or at least that admitted to e-foiling, so you're unique. All right, Jason, this has been great, very informative, as always. Thanks for hosting me a couple of weeks ago in Detroit, I had a great time, and we hope you have you back soon on IBD Drive Time.

Dr Schairer:  Thank you my friend, it's been great.