So today we're going to talk about IBD and IBS. So many times, because it's very similar, the acronyms here, we want to make sure everyone understands the differences. So we're going to go through some of the pathophysiology and the differences between IBD and IBS. So IBD stands for inflammatory bowel disease, IBS stands for irritable bowel syndrome. You heard earlier in one of the talks how irritable bowel syndrome is very common and it's not because the person is irritable, their gut is irritable. And so in an inflammatory bowel disease, there's inflammation throughout the GI tract. So, so far we've heard about diseases of the esophagus, stomach, and the small intestine. I'm going to cover a few of the diseases in the large intestine and Dr. Parti is going to cover the other diseases in the large intestine after me. And then you'll hear a little bit more about liver, gallbladder, and pancreas as well. And so inflammatory bowel disease, what are the differences? So for one, Crohn's disease can affect anywhere from mouth to anus, and that's what that picture is showing. The ulcerative colitis only affects the large intestine or the colon. That's one of the major differences. So disease location, where is the disease located, is one way to think about one of the differences between Crohn's disease and ulcerative colitis. Another way we look at the differences is the involvement. So in this picture, you can see what a normal colon or small intestine ileum should look like. As you heard earlier today, it is a pipe. In Crohn's disease, we can get inflammation throughout the pipe. We can call it lots of different ways. We look at it, we can see cobblestone. We'll see some pictures of that as I show you endoscopy pictures. You can get fat wrapping outside the intestine or outside of the pipe. So a surgeon may see that if a patient is presenting with, as you heard about strictures just in our last talk, you can see fat wrapping. And you can also see transmural inflammation, so thickened inflammation through multiple layers of the intestinal wall. Ulcerative colitis predominantly is a mucosal inflammation just on the top layer. So what you can see in the picture is your pipe in Crohn's disease at times can get narrow or smaller versus in ulcerative colitis, it's rare that you see that narrowing from the inflammation. So we're going to go through each disease. Crohn's disease, first we're going to talk about how do patients present. So just you heard multiple different presentations of symptoms in diseases of small bowel. Crohn's disease can mimic. You see this list, abdominal pain, diarrhea, nausea, vomiting. Patients may complain of lumps or bumps or drainage on their bottom. That's what we mean by perianal disease. Patients may have fever, weight loss. In children, they may not grow. They're just not reaching their height. They're not gaining weight. And so that could be a presentation of Crohn's disease as well. So a lot of these symptoms mimic other GI conditions that patients may have. So as gastroenterologists and in the field, we really try to take a good history, learning more about what their symptoms are. And the pictures are showing you different complications that can occur. So usually Crohn's disease starts with inflammation, however, if left untreated, or sometimes patients may just present with a stenosis or a stricture. Dr. Callaway talked to us about what an obstruction can occur, and patients with Crohn's disease can get obstructions from these strictures, so narrowings in the pipe. So really remember the narrowing of the pipe. That's how I always explain a stricture to the patient. And just think about your kitchen pipes. Your kitchen pipe is nice and open, but over time, if something gets clogged, things get blocked, it can lead to this stenosis. We also see something called fistulas in Crohn's disease. Fistulas, as you see by this picture, are connections from one organ to another organ. So we can get fistulas or connections from the ilium to the colon. We can get fistulas from the ilium to the skin. You can get fistulas from ilium or colon to the bladder. You can get fistulas from ilium, colon, or to the vagina. So a lot of different types of connections that can occur in Crohn's disease. How do we make the diagnosis? As you've heard, and you're going to get to experience endoscopy later this afternoon, but we truly make the diagnosis combination from sometimes we use radiologic imaging, so CT scan. In the old days, we used to use small bowel follow-through, and that's what this first picture is. But now we're using more CT scan, MR enterography to help us with the diagnosis. We also use colonoscopy, and then we take biopsies. So we use a combination of our clinical history. We look at our labs, and then we'll look at radiology, endoscopy, and pathologic findings to make the diagnosis. In Crohn's disease, we learned in medical school there is a specific finding on the pathology called a granuloma, which is a collection of cells. You can see, I don't know if you can see this pretty well here, but you see this dark purple collection compared to the lighter pink, and that's the granuloma that they see on biopsy. We don't always see granulomas in everyone who has Crohn's disease. So goals of treatment, just like in EOE, which you'll hear later, is one of the first goals of any treatment is improving the quality of life of a patient. We have secondary targets of improving clinical and endoscopic remission, clinical meaning we want to look at, make sure their labs normalize, endoscopic remission, meaning those ulcers that you saw in that previous picture, that they disappeared, that we heal them with the medications. Another goal is to maintain that remission. And now in the IBD world, we are even thinking about histologic healing, so healing at a histologic level, at the pathology or microscopic level. We're not there yet, but we are at endoscopic remission or healing those ulcers endoscopically. So I tell my patients, when we look at what are our goals of treatment, so if you tell a patient this is what we, this is our goal, it helps them understand why they may need to take a treatment, and it's improving their quality of life, but I say it's also important to improve your labs and then have endoscopic or radiologic healing. We have multiple different therapies. You've heard myself and Dr. Pardee and Dr. Calloway, you know, allude to the different therapies and how we have a whole slew of therapies, I mean, therapies we could talk about for hours, you know, learning about the nuances, about the treatments, when you use the treatments, I think. But for your purposes, it's good to know that we can, sometimes we do use antibiotics. We use aminosalicylates of diseases extremely mild and probably limited to the colon. Steroids we use as a bridge therapy to get patients to feel better. Just like in EOE, sometimes we use steroids to help, but now we have a new drug. So you guys will be learning about that along with you guys. We use immunomodulators, which are drugs that can suppress the immune system. And so we're tending to stay away from those more now that we have better targeted therapies with biologics and small molecules. So the most famous or most commonly used, or I guess I should say most commonly used, the oldest biologic that we have is infliximab, and now there's also biosimilars for that. We also have a group along with that are called anti-integrin. So that is a drug called Vitalizumab or Intivio. Anti-IL-1223 drugs, we have Eustekinumab, also known as Stelara, and a new one that just got approved last week, Rizikizumab, which is Skyrizi. And so really exciting time. The small molecules are the JAK inhibitors. JAK inhibitors are not approved for Crohn's disease, so we'll go through that when we talk about it for Crohn's disease, I mean for ulcerative colitis. Now it's also important to remember that surgery can be part of our management option. So I don't think of surgery as a failure. Many times people are like, oh, surgery was the last case scenario, so that's why we went to surgery. Many times patients do better if they have surgery and then get put on medications, especially if they have a stenosis or a stricture. Other surgeries that may be needed is if a patient has a fistula, specifically from their colon to their perianal area, they can have that fistula removed, or sometimes they get a specific little plastic or tube called a ceton placed in there so they don't get recurrent abscesses. And so at times, surgery is a necessary management option for Crohn's disease. Now ulcerative colitis, as I said, is limited to the colon, but it is also an inflammation, and usually it starts in the rectum and can progress up just up to the left side, so that would be proctosigmoiditis. Then it can go further up into the left side of the colon, including the rectum sigmoid and descending colon, or it can involve the entire colon where we call pancolitis. So disease location is really important also in ulcerative colitis. One thing to also always remember is in ulcerative colitis, the rectum is always involved. It is actually the hardest part to treat because that's where patients feel most their symptoms. So what are the symptoms of ulcerative colitis? Patients may complain of bloody diarrhea. They may complain of mucus or white stuff or pus in their bowel movements. Patients can have abdominal pain. On their labs, they may be anemic. They can have weight loss, fever, and tinesmus. So tinesmus is a fancy word for that sense of urgency. So specifically in how do we ask our patients that, we say, well, when you go to the bathroom, you feel this urge to go, but nothing comes out, or maybe some mucus comes out, or blood comes out, but you always have that sensation that you need to go, and that's really from all the inflammation, the ulcerations that are in the rectum. Diagnosis is also made by colonoscopy. These are two different types of pictures that we can see on endoscopy. The first one is showing pretty advanced disease with this white patch right here in the front is a very large ulcer, and then they have what's called pseudopolyps, so a lot of inflammation there. And here, this other picture is a very angry-looking colon where the mucosa is red. Friable means when we touch it with our instruments, it bleeds. And so we won't probably get to see that in the pigs today because our pigs are not alive, but we can see that, and then you don't see the typical blood vessel pattern. So you guys saw in earlier lectures, you saw what a normal colon looked like, and this, obviously, you've lost that vascular pattern. So treatment for ulcerative colitis, very similar to Crohn's in the sense that we have multiple different therapies. However, we think of it just like we do in Crohn's as we look at disease location, and then we look at disease severity. And so you want to determine if it's mild, moderate, or severe, and we make those determinations based on patients' clinical symptoms, their laboratory findings, as well as their endoscopic findings. So the last two pictures I showed you in the previous slide would be more moderate to severe disease. Why is that important? So if we see more moderate or severe disease, we are going to choose other medications. If we see milder disease, we'll typically use aminosalicylates. And so just like in Crohn's disease, we have aminosalicylates. We use steroids as bridge therapy to get someone well quickly. We may use immunomodulators, and now we're using more targeted therapies with the biologics of anti-TNFs, the anti-integrins, and anti-IL-23 drugs. And in ulcerative colitis, we also have a category of drugs called small molecules, and we have two separate categories. We have ozanamide, the S1P molecule, and then we have JAK inhibitors. So we have two JAK inhibitors. We have tofacitinib, also known as Zeljanz, and then upacitinib, which is a drug that got approved earlier this year, also known as Rinvoke. And so we're learning how to position all these therapies and using them as well. So that could be a whole other two-hour talk. So I just wanted to introduce the drugs, the names, and how we choose. So choosing is based on disease location, disease severity. So there's a third inflammatory condition of the colon called microscopic colitis. And in microscopic colitis, patients typically present with chronic watery diarrhea. They may have weight loss. They may have malabsorption. We heard about malabsorption from Dr. Callaway. And then in these patients, we'll do a workup. We'll check their stool studies, rule out infections, and then we do a colonoscopy. And what's interesting and what's the difference between this disease compared to Crohn's and ulcerative colitis is when you do a colonoscopy, their colon looks normal, as like in this picture. However, when we take biopsies, we see evidence of inflammation on the biopsy specimen. And that's how we make that diagnosis. Treatment, there are two types of microscopic colitis. We have collagenous colitis and lymphocytic colitis. And as you can see on the slide is in collagenous colitis at the top of the mucosa or the biopsy specimen, you'll see this collagen band. It's this pink band that's right up here at the top. And then in lymphocytic colitis, you'll see more of a collection of lymphocytes. So how we treat this disease, as I said, we make the diagnosis by doing a colonoscopy. And you can see this is several pictures of a normal-looking colon. And we take biopsies and on biopsies, we will see the evidence of inflammation. Treatments do include antidiarrheals, aminosalicylates. At times, we may use budesonide, which is a milder steroid with limited systemic side effects and patients tolerate that well. At times, we may also use in severe or refractory cases. We will use immunomodulators or targeted biologic therapy as well. So those are the major inflammatory conditions of the colon. So Crohn's disease, ulcerative colitis, and microscopic colitis. Now what about irritable bowel syndrome? Irritable bowel syndrome is a chronic condition of the lower GI tract. It can also affect sometimes the upper GI tract as well, but we're going to keep it very simple. So hallmark symptoms, abdominal pain, discomfort. Patients may have constipation. Patients may have diarrhea. So you're hearing recurrent similar symptoms in a lot of the GI conditions that we treat. But the hallmark symptom is that patients may have severe abdominal pain or bloating. Once they have a bowel movement, those symptoms improve with defecation. So that's one of the things that we may be asking our patients when we are taking our history. IBS is very common, or some form of IBS is very common. In the United States, it can affect up to 15% of the population. It is more common in women in the United States. Now interestingly enough, in India, where my family is from, IBS is more common in men compared to women. So it's very interesting to see the same disease but different variations in different races and ethnic populations. So there are three subtypes that we talk about with IBS. We have IBSD, which is the diarrhea variant. So patients will say, at times they say, oh, some days I have constipation, some days I have diarrhea. When we're teasing out the history, they may say, oh, actually I have diarrhea five days out of the week, and only one or two days a week I have constipation. And so we see more of that of the bowel pattern. Now IBSC, constipation variant, is the opposite. They have more constipation, less diarrhea. And then those who are 50-50 are IBSM, or mixed diarrhea and constipation. So the true definition of IBS is abdominal pain or discomfort with at least two or three of the following features, relieved with defecation, onset is associated with a change in frequency of stool, onset is associated with a change in the form of stool. And so this is actually based on a group called, this is considered the Rome criteria. So a group of IBS experts get together in Rome every few years and go over definitions, treatment options, and management. And so that's how they came up with this. What are the causes? So we talked about in Crohn's and ulcerative colitis that it is an inflammation. It is an autoimmune disease. Irritable bowel syndrome, it's what we call a multifactorial. It's not just one thing that can cause it. So it's a combination of altered gut mobility. So either some people, their GI tract moves very fast, or some people, their GI tract moves very slow. So if it moves very fast, they'll have diarrhea. If it moves very slow, they could have constipation. So just as you heard earlier in the morning, some people have an iron stomach, some people don't, right? So that's that visceral hypersensitivity. So some people feel certain things more compared to the person next to them. They may have an imbalance in gut neurotransmitters or hormones and an imbalance in their gut bacteria. So we're learning more and more about the GI gut microbiome and learning how that affects us in different disease states. There's also, as many of you have probably heard, the mind-gut connection. So that's where the psychosocial factors come in is that we share a lot of... The GI tract shares a lot of the same receptors, specifically the serotonin receptors that are in our brain also go to our gut. So we say our GI tract is our second brain. And so there's a lot of that. If you think about that sensation or that saying, I have butterflies in my stomach, people get that when they're really nervous or when they have to go up and perform. They may go puke or they may go have diarrhea. And that's that mind-gut connection getting activated. Now, for some people, it's overly active and it causes them symptoms of IBS. So very complex syndrome and disease, but this is how... Why is it important to know what are the causes? This is how we figure out what therapies and what to target for treatment and management options. The diagnosis, it's more of a diagnosis of exclusion. There's no specific finding that will say, hey, this is what you have. So number one, when we are looking at patients, we want to make sure we've ruled out other diseases. You've heard similar symptoms and other diseases of the small intestine and colon. So if someone is over the age of 50, if they have weight loss, if they're anemic, or if they're bleeding, that's not IBS. That we have to look for another cause. So it's patients who may have diarrhea, constipation, but they should not be anemic, they should not be losing weight, and they should not have blood in their stools if it's irritable bowel syndrome. Now treatment is quite complicated. So we always think about treatment as when we look at causes. So this slide is just a summary slide of different options that we may use for treatment. So many times we'll try lifestyle modifications. So if a patient is constipated, we will try to have them increase their fiber, their hydration. We make dietary modifications. So even if with IBS diarrhea, variant fiber helps remove the water and give patients more form stool. For patients who are high stress, high anxiety, or have depression, we may have them undergo psychological or psychiatric evaluation and therapies. Now we do target treatments where we want to go more symptom specific. So for those who have diarrhea, antidiarrheals. For those who have constipation, laxatives. There are now more specific receptor drugs. So targeted therapies, just like in Crohn's and colitis, we have targeted therapies. We also have targeted therapies based on different receptors in the GI tract where they can target for IBSD versus IBSC. And then a lot of complementary alternative therapies. I work out, I live and practice in California, so that is a very big thing. So I would say a lot of patients with irritable bowel syndrome are seeking alternative therapies. So it's very good for us to know what are they doing, where they're working, acupuncture, hypnotherapy. There's a lot of good data with hypnotherapy, stress management, and integrative medications. Integrative medical approaches. So we are looking at that. Another one that's not on this list is looking at the gut microbiome. And so we target, we have antibiotics that sometimes we may use as well. And that's where dietary modifications can help as well. So these are all very complicated diseases. So hopefully this was a quick dip in the pool for IBD and IBS. And I'm happy to take questions. How often are you finding Crohn's outside of like the intestines? Like you find in the stomach, the esophagus? So esophageal and upper GI Crohn's is probably about 5% to 10% of patients with Crohn's disease but you have to look for it because the biopsy, you have to have that clinical suspicion and look and communicate with your pathologist because sometimes they can just say it's, you know, chronic inflammation and you don't put that together. But usually when you look at it from an epidemiology standpoint, about 5% to 10% of people with Crohn's have upper GI involvement. Great question. So that most likely people are referring to irritable bowel syndrome. So in that category, I have a spastic colon. So when we talked about, if you look, let me pull up that one slide, all right, whoops, right here, where we talk about the different causes, that visceral hypersensitivity, that's what patients are, people are referring to when they say they have a spastic colon. They feel it. They feel the contractions going through. Gastroenteritis is used a lot. Where does that fit in? So gastroenteritis, by definition, means you can have an inflammation anywhere in your GI tract. The most common cause of gastroenteritis are usually infections, usually viral or bacterial. Differentiating factor between ulcerative colitis and Crohn's is just location. Can ulcerative colitis progress into Crohn's and if it can, like what will be that, what will cause that? Sure. So sometimes patients come to us and they'll say, oh, I was diagnosed with ulcerative colitis. And really, it may have been that they could have had Crohn's disease, it just wasn't investigated. So at times, you can miss it if you don't do an upper endoscopy in EGD or if you don't look at their small intestines. So it's really looking at disease location and then if they have more mucosal inflammation, so inflammation just on the surface layer versus transmural. So at times, you know, and then we also have to remember Crohn's disease, about one-third of patients only have involvement of their colon. So it looks like ulcerative colitis too. So it's really looking at how they're responding to therapies, picking up nuances. And in 10 to 15% of cases, it's very difficult to sometimes make that distinguishing factor. On that subject, because that's great, that like is the worry of every gastroenterologist that treats IBD, ulcerative colitis and Crohn's, is there anything pathologically that might distinguish the two? So great question. So as we said, in Crohn's disease, about 25% of patients may have findings of granulomas on their biopsy. So that can help us figure it out. We have a blood test that we don't use all the time, but they're what we call antibody markers that help us distinguish between Crohn's disease and ulcerative colitis. There's a lot more work now in genetic markers as well. And so those are some of the laboratory ways that we also look. Okay. Thanks, everybody. Thanks for the questions.

inflammatory bowel disease

irritable bowel syndrome

IBD

IBS

Crohn's disease

ulcerative colitis