Shiva: My name is Shiva Mozaffarian and I’m here today with gastroenterologist Dr. Lisa Malter to discuss inflammatory bowel disease from what it is to how IBD relates to psoriasis. Dr. Malter is a Professor in the Department of Medicine at NYU Langone Health, Grossman School of Medicine where she specializes in the diagnosis, treatment, and care of people with IBD which includes Crohn’s Disease and Ulcerative Colitis. Dr. Malter is also the Director of Education for the Inflammatory Bowel Disease Center leading efforts to provide education to patients like you and the general public, as well as, the Director of the Inflammatory Bowel Disease Program at Bellevue Hospital Center. She has written numerous publications addressing immunomodulatory agents for IBD which includes TNF inhibitors, IL-12/23 inhibitors, JAK inhibitors, and methotrexate – all of which are used to treat psoriasis and psoriatic arthritis.

Welcome Dr. Malter and thank you so much for joining Psound Bytes™ today. We know inflammatory bowel disease refers to conditions characterized by inflammation in the gastrointestinal tract. Can you define what is the gastrointestinal tract and what are the most common diseases that impact the GI tract?

Dr. Malter: Thank you for the question and thank you for having me today. The typical in terms of the gastrointestinal tract and the most common diseases we have ulcerative colitis which impacts the large intestine and we have Crohn's disease which can really affect anywhere from the mouth to the anus and in between and it's classically termed a skip lesion. So you have areas that are normal in the intestines and then it skips and you have areas that they're abnormal affected by the disease process.

Shiva: So you mentioned ulcerative colitis and Crohn’s disease. What are the typical symptoms for those diseases and when should someone seek help from a gastroenterologist? 

Dr. Malter:  So we'll start with ulcerative colitis because it's a little bit more straightforward. Ulcerative colitis involves inflammation always involving the rectum, which is the very bottom of the colon right before it exits out of your body and ascends or moves up in the large intestine, and so some people will have just inflammation in the rectum at the very bottom, and that's called ulcerative proctitis. And then there are a subset of patients who will have inflammation that goes above the rectum into the colon and that's when you get ulcerative colitis. And because the inflammation is affecting the very bottom of the colon and inflammation in the intestines leads to some breakdown in the tissue lining of the colon, you always get bleeding. So anybody who has ulcerative colitis is going to have some rectal bleeding. That's super common. There are other reasons for rectal bleeding. So if you have rectal bleeding, the assumption does not have to be that there's ulcerative colitis going on, but you do need to see a gastroenterologist to figure out why. But ulcerative colitis always has rectal bleeding. The other common symptom with ulcerative colitis is diarrhea. So the large intestine or the colon’s primary role is to absorb water as your stool passes through the colon, so that when your poop comes out, your stool comes out, it's solid, not liquid. When there's inflammation in the wall of the colon lining, it's unable to absorb properly and that's part of why you get diarrhea. So diarrhea and bleeding are the two most common symptoms with ulcerative colitis. In contrast, Crohn's disease, like I said, is much more complicated and you would suspect this because I shared with you that can affect the entire gastrointestinal tract from the mouth all the way down. I'm gonna go through some of the most common symptoms and that's when the intestinal tract is involved, including the very bottom of the small intestine, which is called the ilium and the large intestine, because that's the most common site of Crohn's disease. And in that case, patients can have abdominal pain. They can have diarrhea, but they don't have to. They can have bleeding, but they don't have to. They may have weight loss. They may have intolerance to food or get a stomach ache, and avoid food. They can also have things like just anemia or a low blood count, including due to loss of iron from even a small amount of bleeding. So patient may not report any bleeding, but they're actually losing like a microscopic amount of blood when they go to the bathroom, and eventually that catches up with the patient and they'll be very fatigued because they've been losing blood. It can also present with sores around the outside of the behind with Crohn's disease and sores inside the mouth as well. And I would make sure that if you're having any of these symptoms or you have any questions, you get an appointment to see a gastroenterologist.

Shiva: Given what you’ve just said, what is the prevalence of ulcerative colitis and Crohn’s disease in the U.S.? Is there an age range for when diagnosis occurs usually? 

Dr. Malter: So it's a great question and we've been seeing the prevalence sort of stay stable to some degree, but we are seeing the incidence of the disease increase in populations that historically have not been affected by the disease. So this was really thought to be a disease of patients that were coming from more temperate climates, North America, northern Europe, and we really see an increase in disease in patients that are coming from other parts of the world, Hispanics, blacks, patients from Asia, Southeast Asia. And we oftentimes will see an increase in disease in patients that have moved from another country once they become assimilated here and start eating a more western diet. There are a few small studies that have shown that. There's a recent study looking at inflammatory bowel disease, and it's really like 1%, one in 100 have inflammatory bowel disease at this time. And in terms of the age range, the most common age range presentation is between 15 and 30 and then we have sort of a second peak of disease between ages 60 and 70. Not so dissimilar from psoriasis, but we can see this disease present in children and even babies.

Shiva: Are there any triggers that prompt the development of IBD?

Dr. Malter: The short answer is no, and patients always come in wanting to understand what they did or most commonly what they ate that caused their inflammatory bowel disease. Because you have to assume it's kind of human nature that if you're having bowel symptoms, something you put in your gastrointestinal track is responsible for it. We do know that environmental exposures are one component and that would include diet. But it's really again a perfect storm situation between a patient that has some immune dysregulation, some alterations in their microbiome, some environmental exposure with an underlying genetic predisposition for this disease process to kick off. So there isn't really a clear trigger. We do know that some patients will have an enteric infection. So some type of bowel infection, like a gastroenteritis, especially in patients who have travelled somewhere, they'll get like a foodborne illness and then it will trigger the start of their inflammatory bowel disease. We do know that there's an increased risk of enteric infection, bowel infections, when somebody has underlying inflammation. So it may not be the infection that triggered it. Might be that it just unmasks the underlying inflammation, but there isn't really a clear trigger that I can tell you. 

Shiva: So Dr. Malter, a lot of people are confused by IBD versus IBS or Irritable Bowel Syndrome. Can you explain what the difference is between these two diseases?

Dr. Malter: Yes. So I'm so happy you asked that question. It's such an important question. It comes up all the time like patients, but also like even other health care workers don't really understand the difference. And it's big and really important to know the difference and how we manage all of this. So inflammatory bowel disease, when we do diagnostic evaluations of patients, blood tests, stool tests, radiology studies, endoscopy, colonoscopy. We find something real, some inflammation that is going on that is responsible for the patient’s symptoms and presentation. In contrast, irritable bowel syndrome, IBS, is something that is called part of our DGBI Group of diseases, which are disorders of the gut brain access where patients really have a hypersensitivity to some stimulus in the bowl that's causing a set of symptoms. And when we do diagnostic testing, when we do the colonoscopy, when we send the blood work, we do the stool test, all those things are negative. So there's nothing that we're picking up on and we're really focused on symptom management with that condition as opposed to treating somebody with very significant immunomodulatory or immunosuppressive agents to get it under control. The important thing to be aware though in addition is that patients who have inflammatory bowel disease can also have irritable bowel syndrome. So there can be a subset of patients that in line with our treatment goals for inflammatory bowel disease, which includes making sure that the patient is not only feeling well but the bowel is healing. Once we assess for that bowel healing, when we pick a treatment strategy, the bowel can be healed, but the patient could still have diarrhea. The patient could still have belly pain, things like that. And once you know that your anti-inflammatory treatment is achieving the goal and the patient’s inflammatory bowel disease is controlled and they still have symptoms, then you need to pivot and focus on treating the underlying irritable bowel, which is also at play.

Shiva: So you mentioned diagnostic testing. How is the diagnosis of IBD made?

Dr. Malter: So I touched on this a little bit. The diagnosis of IBD is tough to make because there is not what we call a gold standard, meaning there's not a blood test, a stool test, a specific pathology finding that says this is inflammatory bowel disease. So it really takes a careful history -- understanding the patient’s symptoms, understanding patient’s medications, understanding the patient’s family history, weighing all of those factors. And then depending on the symptoms, doing a specific work up which may include blood work, paying attention to the blood count, looking for anemia, paying attention to inflammatory markers in the body, which there are some bloodstream based inflammatory markers that we can check. We can check nutritional levels, that iron levels, vitamin B12 levels, things like that. Vitamin D that may impact or result in altered levels in the setting of an inflammatory condition. We can check stool testing, looking for inflammation in inflammatory kind of byproducts in the stool. Usually we have to pivot to some type of endoscopic procedure, most commonly a colonoscopy with biopsies. Sometimes, depending on symptoms, age, we also will do an upper endoscopy. That's a test that looks in the upper gastrointestinal tract, the esophagus, the stomach, and the very top of the small intestine. There are a subset of patients that will have disease located in the small intestine that's not reachable by a standard endoscope or colonoscope and in those cases we would need to do additional testing in the form of radiology studies. We can do certain types of MRI’s and CAT scans that evaluate the small intestine. And sometimes we'll have to do one of those pill cameras for any of you who have heard of those where you basically swallow a pill that has a little camera in it and it takes lots of pictures in your small intestine and that can help us as well. So it can be a series of different tests. We have to review the results from the radiology studies. We have to review the results from the biopsies with our pathologist. And sometimes it's a slam dunk and it's very clear what's going on, and other times we kind of have to go hunting and let time tell if it's the disease because sometimes the disease is in its very early stages and we can't make a definitive diagnosis. There are also a number of disease mimics. Things like medication can cause disease mimics, other disease processes, things like that. And so we have to be really careful to make sure that we're not assuming it's inflammatory bowel disease based on our work up but actually in fact the patient has some type of infection that needs to be treated first or they don't have IBD at all, they just have an infection.

Shiva: Probably the biggest question that comes up – what causes IBD to occur? You mentioned inflammation earlier. Is IBD related to the gut microbiome and how is IBD related to psoriasis – what’s the connection here?

Dr. Malter: So I think as I touched upon earlier, we don't really know what causes it. It’s what we call this kind of perfect storm. Genetics, the environment in your body, the environment outside, some potential dysregulation of your immune system. I can't really say what causes it to occur. It's just that again, perfect storm that allows it to develop when there is some off factors in a genetically predisposed person. In terms of the gut microbiome, it is definitely a piece of the puzzle. There are some bacteria that are upregulated and other bacteria that are downregulated in the gut that, especially with Crohn's disease, may be contributing to the inflammatory process. We're not really at a place where we know how to modulate or change that gut microbiome to impact inflammatory bowel disease but is an area of concern. There are some concerns that the dysregulated gut microbiome, especially in Crohn's disease, may lend itself to an environment that allows psoriasis to develop, and this could be due to some increased permeability of the gut lining that allows bacteria and or toxins to enter the bloodstream and reach the skin and create a setup for psoriasis. There also is some notion that some of the intestinal or gut microbiome is responsible for keeping balance in the skin or homeostasis, and that can happen via the cellular development pathways and that altered balance can also potentially create the setup for psoriasis to develop. 

Shiva: So now I’m curious, what treatments are used to treat IBD? Is it possible to reduce the inflammatory response associated with IBD?

Dr. Malter: So there's a lot of treatments available. They’re not perfect. I would say our best therapies, I usually quote to patients “roughly two out of three patients will respond to our best therapies”, which isn't always a great statistic to say and unfortunately we don't always know which therapy is going to work for which patient. Fortunately, especially in the past three to five years we've had a really significant increase in the types of mechanisms available to us. So we do have a lot of things available. We pay attention to how severe the disease is in this moment in time, which we would call disease activity, as well as, if the patient’s had disease for a long time, that's severity. So how much of an impact the disease has on their life overall? And we also want to pay attention to whether or not they've had any therapies in the past for this disease and how they responded to those in order to make a determination about what's the best therapy at this moment in time. But we use a lot of similar medications that are used in psoriasis. So the medications called TNF blockers or anti TNF agents we will use some other medications things like ustekinumab, risankizumab, upadacitinib, and tofacitinib, which can be used in some types of inflammatory bowel disease, as well as some types of psoriatic arthritis. If the disease is more mild, we can use some oral anti-inflammatory agents as well. So it just depends on how severe the disease is and where the disease is located in order to make a treatment decision. This is a really, really complicated topic and then inflammatory bowel disease world we don't have great studies that help us understand how to choose an agent, and many of the agents have not been studied head to head against one another. So we're really oftentimes in a bit of a no man's land and using not clinical trial based data to make our decision making about positioning agents in inflammatory bowel disease.

Shiva: Some of the medications you mentioned to treat IBD are also used to treat psoriasis and psoriatic arthritis. So my question here is how important is it to coordinate care between a gastroenterologist, a dermatologist or a rheumatologist?

Dr. Malter: That's a fantastic question. So I can't underscore the importance of a multidisciplinary team for the care of patients with these diseases and in inflammatory bowel disease, it's really a head to toe condition with the extra intestinal manifestations as well as side effects from our medications. And we need a humongous team that goes beyond the rheumatologist and the dermatologist oftentimes. But I would say rheumatology and dermatology are the two specialties that I collaborate most frequently with. We want to talk about our disease process that we're taking care of and when we want to coordinate decision making regarding the therapies that we choose with the goal of using either the same agent to treat both conditions or targeting two inflammatory pathways potentially with two different agents, one from the gastroenterologist and one from the other clinician. We also want to be monitoring for side effects together and we want to be thinking about if we're going to use an agent, if it has an impact on the other disease state. We want to have a clear discussion about the choice to do so and make sure the patient’s informed of the risks and benefits as well. 

Shiva: So once someone has IBD and they’re following a treatment regiment, are there any further preventative steps that can be taken to minimize impact of IBD?

Dr. Malter:  Absolutely. So as I mentioned, head to toe disease. Not only from the extra intestinal manifestations of the disease, but also from side effects, from medications, and in a comprehensive IBD center, we will be taking care of risk for cancer. So of course we have a risk of colon cancer in inflammatory bowel disease, but some of our medications and the disease itself may put some patients at risk for Melanoma or skin cancers. There can be increased risk of cervical cancer for women pending certain exposure to certain agents. We pay attention and beyond cancer risk to getting vaccine histories and making sure patients are vaccinated to all the things that they should be vaccinated for. Especially you’re thinking about, medications that potentially suppress the immune system and put patients at risk for certain specific infections. So we're taking care of that. We're paying attention to bone health, especially in our patients that have had exposure to steroids in the past. We pay attention to mental health because we know that there's an increased risk of anxiety and depression seen with inflammatory bowel disease. We're paying attention to nutrition. Those are the primary areas. We do have actually a couple of publications, one that I've co-authored that addresses healthcare maintenance and preventative care and inflammatory bowel disease. So it's very much a part of our care process and a colleague of mine has deemed the concept of the medical home for IBD because there's so much different care that we need to provide these patients. And oftentimes, because these patients are diagnosed early, they don't have a primary care doctor. And so the gastroenterologist ends up almost becoming that default primary care doctor.

Shiva: And are there any updates you can share on research developments for inflammatory bowel disease? Do you think a cure is possible for ulcerative colitis and Crohn’s disease?

Dr. Malter: I think we're a bit aways from a cure because we need to get really to the root of understanding the interplay between the various factors that I've talked about a few times earlier in the podcast. I do think we're making headway in these different spaces, but we are not quite there yet. I think the biggest updates are really with regard to our treatment armamentarium right now because we have novel mechanisms being added. And the biggest question remains about how to position those agents. But these are two sort of different storylines that need to evolve in order for us to get there in terms of treatment choices, but also in terms of underlying mechanism of disease. And I suspect we'll have more agents before we'll really have any more understanding of the underlying processes. Nobody wants to have inflammatory bowel disease, but it's really an exciting time to be taking care of inflammatory bowel disease because we have so much more to offer our patients than we did even just a few years ago.

Shiva: Yeah, I mean just like psoriasis where a number of new agents have come out in the last few years.

Dr. Malter: Yep, exactly.

Shiva: Dr. Malter, thank you so much for being here with us today. I know we’re almost at time here but just one last question, do you have any final comments you would like to share with our listeners about IBD?

Dr. Malter: I would just really like to encourage anybody who is suffering with any gastrointestinal complaints, has any family history, and if there is an underlying history of psoriasis to just get seen by a gastroenterologist because inflammatory bowel disease is a chronic progressive disease, especially Crohns, and the sooner we can diagnose and treat the better off you'll be. If we let the disease fester, it can sometimes be really hard and we're sometimes forced to use surgery as our first line therapy and we don't really want to have to do that in most circumstances. And so the sooner you can get seen, the better in order to really try and have a chance of getting the disease under control and not having it run your life. Our goal is for patients to be able to, similar to psoriasis and psoriatic arthritis, be comfortable, not be running to a bathroom, be able to work, go to school, take care of their family, et cetera. And if you have inflammatory bowel disease and it's not adequately treated, those goals cannot be achieved. So we really just want to encourage not letting it fester so that we have the opportunity to get a handle on it. 

Shiva: Thank you Dr. Malter for being here today and for increasing our knowledge about inflammatory bowel disease and what the connection could be with psoriatic disease. For our listeners, if you would like more information about comorbidities or diseases associated with psoriatic disease, contact our Patient Navigation Center at (800) 723-9166 or email education@psoriasis.org. This episode is brought to you with support from Bristol Myers Squibb.