So, we all talked about the different parts of your intestinal tract. I'm going to focus on three things, IBD, IBS, and microscopic colitis, three main clinical disorders of large intestine. And believe me or not, we still get confused, not only in industry, but also in our staff, our primary care physicians sometimes get really confused between IBD and IBS. So when I was naming our center, whether it should be IBD Center or Crohn's and Colitis Center, one of the reasons when we had our naming convention was, well, we shouldn't call it IBD Center because a lot of referrals can come because many physicians may still get confused between IBD and IBS. So easy thing to remember, IBD is when you have symptoms, diarrhea, pain, and you do endoscopy and you see inflammation. So symptoms plus visible inflammation, IBD. When you have a patient who has symptoms like diarrhea and pain, and you do endoscopy, and you see inflammation only under the microscope, that's microscopic colitis. So diarrhea with inflammation that we see only under the microscope. And then if you have symptoms like diarrhea and some other symptoms like constipation, pain, and when you do endoscopy and everything is normal, that's IBS. That's a syndrome, irritable bowel syndrome. And IBD is inflammation, inflammatory bowel disease. So one is a disease where there's inflammation, and one is a syndrome where you don't have inflammation. So IBD is divided into two main categories, Crohn's disease and ulcerative colitis. There is a third category that's called indeterminate colitis. Sometimes you are unable to differentiate, but majority, it's categorized into two parts, Crohn's disease and ulcerative colitis. Ulcerative colitis, we all know by the name, it's ulcers in the colon, it's called colitis. Just like you get arthritis, you get pneumonitis, you get bursitis, meningitis. You can get inflammation in the colon, and that's why it's called colitis. So ulcerative colitis when you see inflammation in the colon. Crohn's disease is a tricky name. Does anyone know why it's called Crohn's disease? Why Crohn's disease is called Crohn? Raise your hand if you know. Okay, so it's actually named after a physician who, in the United States, for the first time presented some papers. It was in early 1930s from Mount Sinai. There were three physicians who presented paper. So Ginsburg, Oppenheimer, and Crohn. So Crohn's start with C, and so he got the credit to present it the first, became the first author, and ever since we started calling this as Crohn's disease. It has some other names also. Terminal ileitis, regional enteritis, because that's the most common site of inflammation is terminal ileum. But then we shied away from the word terminal ileitis because the word terminal was like it was a terminal illness. So anyhow, so that's how the name came from the Crohn's disease. So just imagine as we were discussing that your intestinal tract is like rings of onions. So inside, and then there are other layers. So in Crohn's disease, you get inflammation in all those layers of your intestinal tract. And in ulcerative colitis, most commonly you get inflammation on the innermost layer that is called mucosa. So it's mucosal inflammation in ulcerative colitis. And in Crohn's disease, you can get inflammation throughout all the layers. So you can get mucosal inflammation, submucosal inflammation, all the way to the outermost layer called cirrhosis. And then you also see a lot of fat that comes and kind of like wrap your intestine. It's called creeping fat, or the wrapping of the intestinal with your fat in the peritoneum. In Crohn's disease, you get symptoms. Now you can imagine that you have inflammation in this tube that is narrowing down because of the swelling. So because of that swelling, you will get pain because contents will not be able to move. You can get diarrhea. You can get nausea, vomiting. Crohn's disease can affect any part of your intestinal tract from mouth to anus. In ulcerative colitis, you only get, as the word says, colitis. You get inflammation in the colon. So when you have Crohn's disease of upper tract, your esophagus, you can get esophagitis. You get nausea. You get Crohn's disease of your stomach. You can get Crohn's disease of your small intestine. Although they are rare, most common site is terminal ileum, which is the very last part of your small intestine. So you get abdominal pain, diarrhea, nausea, vomiting. Since it also involves the anal area, you can get perianal disease. You can get fistulas. You can get fissures. And then you can also get fevers and weight loss because you are nutritionally depleted. There is a lot of inflammation going on. You may not be able to absorb nutrients. And then because you are producing a lot of inflammatory markers, the cytokines and proteins, they can cause fever also. The way we diagnose Crohn's disease may be the patient presenting to the emergency room and complaining of abdominal pain. And you go do some x-rays and find that there is a narrowing because the Crohn's disease is now presenting with a stricture. Or you do an endoscopy because the patient was presenting with some diarrhea and bleeding and weight loss. And that's how you find some ulcers inside the intestinal tract. And then when you do biopsies, you will see inflammation. And the classic finding on inflammation is granuloma. Just like you know that in eosinophilic esophagitis, you have to have a certain number of eosinophils. In Crohn's disease, the classic finding was that, yeah, this is Crohn's disease is when you see granulomas. Unfortunately, granulomas are not seen in all biopsies. And it's rare. It's about 10% or even less. But you see chronic inflammation. You see a lot of damage that occurs where you have normal crypts and are damaged. You get some abscesses there. And lots of inflammatory cells, a lot of neutrophils are there, lymphocytes are there causing damage. So how do you treat? Well, the first thing is, why do you treat? So the patient asked, just like eosinophilic esophagitis, patient may ask you, why are you treating me? I just had that food bolus, the food that was impacted, and my physician removed it. You're telling me I have EOE. Why do I need a treatment? I don't feel like it's causing me a problem. And some patients do have symptoms. So the goal of the treatment is twofold. One, you are trying to control inflammation. You're trying to control symptoms. And second, you're trying to prevent complications. So what you're trying to do is achieving remission. So remission is clinical remission, meaning your symptoms are improved. And endoscopic remission, meaning your bowel is healing also. And then not only you are trying to achieve that and bring the patient under clinical remission, you want to maintain that remission also. So you tell the patients that, I would like to give you some treatment so that your symptoms are under control, your inflammation is under control, but then I would like to continue that therapy so that I can maintain that remission, so that your bowel keep healing and you have a good quality of life. So how do we treat Crohn's disease? Just ignore the first two medications. We typically don't use these medications in Crohn's disease. In acute flare, we start with some steroids, just like eosinophilic esophagitis. We give them some steroids, topical steroids. Similarly, in Crohn's disease, if you are having a flare, you are having active symptoms, you start them on some steroids. But it's only a bridge therapy. You go to a maintenance therapy that can be immune modulators, such as azathioprine or 6-mercaptopurine. And then you move on to biologic therapy, which is, you have now more than one biologic therapy. If I was giving this lecture about 10 years ago, I would just say biologic and everyone will say, ah, infliximab or anti-TNF therapy. Now we have more than one anti-TNF therapy. We have infliximab, we have biosimilars to infliximab. We have adalumimab, which is also known by the trade name of Humira. We have sertalizumab, also known as Symsia by trade name. And then we have anti-integrants, which are, so imagine your intestinal wall is kind of like a war zone, and lymphocytes are your soldiers. So they are coming and attacking your intestinal wall. So there are different ways you can control these soldiers not to cause damage. One is, you take away the bullets. So even if they are trying to fire your intestinal wall, the bullet will not cause damage. And that's how anti-TNF works. So anti-TNF block the TNF, which is a bullet, which is a protein that causes damage. Then you have anti-integrants. Anti-integrants block the entry of lymphocytes into the gut. So now you are blocking the soldiers that they cannot enter the war zone so they don't cause damage. So they're called anti-integrants. And one that we have available is called vediluzumab, or Intivio. And then we have interleukin-12 or 23. You can actually block the lymphocyte factory back at the headquarter. There's just no recruitment, nothing is coming. And that's when you block 12 and 23. So one that we have right now is Eustachinumab, or also known as Stelara. If medical therapy does not work, or if you have a very limited inflammation area, you can resort to surgery where you can just resect the bowel. Sometimes when you develop fistulas, perianal fistulas, which are abnormal openings through the rectum into your skin, then you may have to do certain surgeries to correct those fistulas. Sometimes you put a thread called seton. Sometimes you just repair that surgically. And if you develop any abscess, then you sometimes drain that abscess. Now imagine in Crohn's disease, when you get inflammation in all the different layers, those layers can get inflamed and thin out, and then they can have a little leakage. And when the leakage happens through your bowel, all the feces or the bacteria can go out and cause a little bit of collection of pus. And you'll be calling that abscess. And sometimes these patients develop abscess, and you have to drain them. You either put a drain, or you do the surgery, you open the abdomen, and drain that abscess. Shifting gear to ulcerative colitis, as I said that the name implies, it's the inflammation of the colon. Unlike Crohn's disease, which can involve any part of your intestine, and it can be a skip lesion, you can have inflammation in the rectum, and then the next area of inflammation could be in your small bowel. And then the next area of inflammation could be in your stomach. So you can skip the lesions. Or you can have inflammation in your large intestine, where it can cause inflammation in the ascending colon, and then the next area of inflammation can be in descending colon. It's called skip lesions. In ulcerative colitis, the inflammation starts from rectum, and then it just moves up. So if you have inflammation only of the rectum, then it's called ulcerative proctitis. When you have inflammation that involves the sigmoid colon and the rectum, you will call it ulcerative proctosigmoiditis. And when the inflammation goes above, you call left side colitis, and then once it moves into the transverse colon, you call it pancolitis, and then it can involve the entire colon. Very rarely, it can also spill a little bit into the small bowel. That's called terminal ileitis, or some kind of a backwash ileitis that can happen in ulcerative colitis. But that's the extent of its going. It doesn't go all the way in your small bowel. And that's why we learned about capsule endoscopy, that sometimes you're not sure whether this is Crohn's disease, whether this inflammation is just confined to the large intestine. Could that be a Crohn's disease, where you have inflammation entire colon, but now you also have inflammation in different areas of small intestine? And when you are trying to make that determination, sometimes you resort to capsule endoscopy, and these patients do undergo capsule endoscopy evaluation and see if they have inflammation in small bowel. It doesn't make a big difference in terms of treatment, but when it comes to surgery, whether they are undergoing surgery for ulcerative colitis or Crohn's disease, whether they need to be on a medication after surgery, it makes a difference. So sometimes you pause and say, well, is this really ulcerative colitis, or could there be a Crohn's disease? Just like Crohn's disease, ulcerative colitis also presents with diarrhea, pain, since it starts with the rectum. So one of the very common symptoms of ulcerative colitis is urgency, rectal urgency. So these patients complain of going to the bathroom frequently, and bleeding, bloody diarrhea is also very common. So bloody diarrhea, mucus in the stool, abdominal pain, anemia, weight loss, fever, tenesmus, all of these are common symptoms of ulcerative colitis. And when you do colonoscopy, you can see inflammation. This is, on the left side, is severe inflammation. It's probably involving more than just mucosal layer, but you can see ulcers there, and here you can see this is all ulcer. This is not normal. This may be normal right here. So this is normal. This is abnormal. So you can differentiate. This is all ulcer. Same here. This is a milder form, where you can see that there's a lot of redness here. You don't see the normal pink, shiny mucosa with blood vessels. So all that is lost, and now you're seeing inflammation. Similarly, in ulcerative colitis, you start therapies. Typically, you start, if you are in a flare, you start with steroids, but you can also give aminosalicylates, which is the newer version of sulfasalazine. You may have heard of sulfasalazine, and rheumatologists use sulfasalazine for joint pains. We were using sulfasalazine for a long, long time. Then we refined it. We took the sulfa out. Then we produced a compound called aminosalicylate. We've been using aminosalicylates for ulcerative colitis for a long time. Aminosalicylates work on the mucosal surface. So that's why we use in ulcerative colitis, and that's why we don't use in Crohn's disease, because as I just mentioned, Crohn's disease causes inflammation in deeper layers of your intestine also. So aminosalicylates will not work on those deeper layers. If that doesn't work, you go up, immune modulators, Imuran, mercaptopurine. Same thing, biologics. Almost all the biologics that we use for Crohn's disease are also now used in ulcerative colitis Recently, we have developed a new class called small molecule. So small molecules are different than biologics. Biologics are like your MABS, right? So small molecules, there are two types right now that are available for ulcerative colitis. One is called JAK inhibitors, like tofacitinib and opetacitinib. The other class is called ozanimod, which is your ziposia. It blocks these soldiers coming from the lymph nodes. So even they can't leave the lymph nodes, all these lymphocytes get blocked there. So they don't even come all the way to the intestinal. So that's how ozanimod work. The other two ones, the JAK inhibitors, tofacitinib and opetacitinib, they actually goes into your lymphocytes. They go into the DNA and ask your DNA to stop making these inflammatory proteins. So that's how they work. If medical therapy doesn't work, then they undergo surgery. Even if they have only limited ulcerative colitis, such as they are just rectum and sigmoid colon is involved, and you are unable to control that inflammation. Unlike Crohn's disease, where you can just take that part out and join the rest together, in ulcerative colitis, you undergo total colectomy, total procto colectomy. So you get your rectum out, your colon out, and either you live with ileostomy, with a bag, or you connect everything together and form a J pouch, where you actually join your small intestine back to the anal canal. Shifting gear to microscopic colitis, as I said, this is where patients are having symptoms and microscopic inflammation. Typically, it involves middle-aged females. They are commonly presenting to your practice with watery diarrhea, chronic watery diarrhea. They're explaining that they are having six or seven watery bowel movement, no blood. And when you do endoscopy, a colonoscopy, everything looks normal. And many times, I see patients who are coming with a diarrhea, let's say a 67-year-old female coming and saying, I'm having this watery diarrhea. And I go through the different possibilities, and one possibility is that, let's do a colonoscopy to see why you're still having diarrhea. And the patient would say, well, I just had my colonoscopy two years ago, and it was a screening colonoscopy. Everything was fine. I didn't even have a polyp. And my physician said, I'm good for 10 years, or I may not even need another colonoscopy. So I have to explain to those patients that, yes, your colon may look normal, but we have to do biopsies to find out if there is a microscopic level of inflammation that is causing microscopic colitis. And this is what you see. You either see collagen, and if you see a thickness, you can see here, I'll point out right up here, there's a collagen band. You see this? This is a collagen band. You don't see that in lymphocyte, like, you don't see it here, so you can appreciate this collagen band. So if it is more than 10 micrometer, I think that's the depth of this. So if you see a significant collagen band, it's called collagenous colitis. And if you see lots of lymphocytes, so lots of these cells here causing damage microscopically, it's called lymphocytic colitis. So microscopic colitis comes in two different flavors, either collagenous colitis, or it comes as lymphocytic colitis. And you do biopsies to confirm that diagnosis. The treatment is, typically, you start with some topical steroids, like budecinide or Entercor. There are other treatments, such as sometimes you use antidiarrheals, bismuth, cholestyramine, to help control those symptoms. In very rare cases, sometimes you have to use off-label therapy with some biologics also. IBS, as we talked about, it's a very prevalent disorder or syndrome. Majority of our clinical practice and prior practice, if you are not specialty-focused, you see a lot of IBS patients. We see a lot of IBS patients in our practice. It's a chronic condition with abdominal pain, change in bowel habits, 15% of US population is affected by IBS. Women are two times more likely to have IBS symptoms or IBS than men. There are different types of IBS. Some patients complain of abdominal pain and diarrhea. Others complain of abdominal pain and constipation. And some have mixed pattern, where they will say, I have days when I get really constipated, and then I have days when I get really, I started having loose stools or diarrhea. Abdominal pain, there is a definition of abdominal pain. It's not like all abdominal pain. So abdominal pain, usually what happens is that you have to have two out of these three features. One, that, oh, I'm having abdominal pain, but every time I go to the bathroom, I feel better. After having a bowel movement, my pain gets better. That's a very typical symptom of IBS. Sometimes they come and say that, well, I have this abdominal pain, but I'm also seeing and noticing a change in the frequency of my stool. I didn't used to go that often or that less, but now this is happening, along with this abdominal pain. Or I'm noticing that my stool consistency has changed now. So any of two of these things, along with the pain, would define your IBS syndrome. Why do we get IBS? IBD is the inflammation, where you get these lymphocytes causing damage. We still don't know why people get IBD. They're a mixture of different things, genetics, immune system problem, environmental factors. Similarly, in IBS, there's not one pathway, just like, okay, well, this is why you get IBS. There are psychosocial factors, stress, anxiety, depression plays a very important role. There is a very strong brain-gut axis. I give this example to all patients. Just like when you see a delicious food and your mouth start watering, or sometimes you see a very nasty thing and you feel like you need to puke. So your brain is telling your intestinal tract to behave. When you are in panic, your anal sphincter get tight, or you get constipated, or you feel like you need to go to the bathroom. So there is some gut-brain axis that works. And under stressful condition, it can go abnormal. Sometimes it can get short-circuiting. So there could be an imbalance of gut neurotransmitters also. So there are now a lot of working theories that how your gut microbiome, or how your gut microbes influence these gut neurotransmitters that can then influence how your brain interact back with your intestinal tract. Motility problems can happen. Sometimes we see IBS after an episode of infection. So there are theories about how these, it's called post-infectious IBS. So you got an infection, you got salmonella infection, and ever since I got that infection, doc, I just felt like my symptoms never went back to normal. So that's a common scenario. Visceral hypersensitivity, sometimes patients have, they become very sensitive to a stimulus, whether it's a mechanical stimulus or a chemical stimulus that a normal person, if they are consuming and your gut is expanding, or you are having a little bit of bloating, we can tolerate that. But these patients with IBS, even a little bit of distention, a little bit of stimulus exacerbate their symptoms, and they perceive these symptoms more than a normal, healthy person. So how do we diagnose these? There's no definitive diagnostic findings or markers. Like IBD, you see that we saw an x-ray, we saw imaging, endoscopy showing your markers of inflammation are high. You may be anemic. Your calprotectin in the stool may be high. Your C-reactive protein in the blood may be high. In IBS, you don't have those markers. You don't have those diagnostic tools. It's a clinical diagnosis. Sometimes you rule out all those things, and then you come to the conclusion of IBS, or you have classic symptoms of IBS. The key thing is to rule out alarming symptoms that may want you to do other investigations. Older patients presenting with these symptoms, if you have weight loss associated with it, if you are anemic, or you are complaining of blood. So any time a patient come in telling me that I'm having abdominal pain with diarrhea, and I ask them about if they are experiencing weight loss, if they're having bleeding, or if I look at their labs and they're anemic, that may alert me like, hey, I need to rule out other things, such as IBD, or inflammation in the gut, or malignancy, or something else, or an ulcer. How do we treat IBS? Very complicated. We actually sometimes dread taking care of these patients, because it's hard to take care of these patients, and it's very complicated. That's where the concept of holistic medicine, that's where you have to treat the patient as a whole, and that's where I call, and when I teach my students, that medicine is not just science. There's art to it, and that's how you treat your IBS patients. So you talk to them about lifestyle modifications, you ask them about their diet, sometimes you ask them to take fiber, sometimes you ask them not to take fiber, dietary modification, there is a diet these days that we commonly prescribe to our IBS patients called low FODMAP diet, where it's a less fermentable diet, so it has less fermentation, psychological evaluation to address their stress, anxiety, symptom-specific treatment, we give them antidiarrheal if their diarrhea is a main symptom, if constipation is a main symptom, we give them laxatives, antispasmodics, anxiolytics, antidepressants sometimes work, sometimes these antidepressants are given not only to help with their depression and anxiety, but also they actually have some neuromodulatory role where they actually calm down the nerves that are coming to their intestinal tract and help them feel better in terms of their gastrointestinal symptoms also. There are some specific drugs that we are using also in IBS, if they are having diarrhea, there is a drug that is now approved called eloxidiline, that's Viberzi is the trade name, we use it for IBS diarrhea, not on all the patients, there are some contraindications, you have to be careful using this drug, then there are some other drugs that we're using in constipation, predominant IBS, such as linectalide, Linzes is a trade name, and IBS, which is libipristone, which is ametiza, alternative therapy, we talk about hypnotherapy, stress management, developing coping skills, abdominal breathing exercises, so it's a combination of everything to help find relief for these IBS patients, and interestingly, all these three things can overlap also, IBD patients, about 30% of IBD patients can have IBS, for many reasons, the stress of having IBD, the change in the gut microbiome, so that can lead to a lot of these patients to have IBS, similarly, we learned about celiac, so sometimes you can see that celiac patients come to you, say I'm doing gluten-free diet, and I'm still having diarrhea, you find out that they have microscopic colitis, so there's a lot of overlap between lots of diseases, that's where an astute clinician would say, okay, well let me just look and make sure that they are not suffering from other things, and you probably will learn tomorrow, and I'll share that with you, IBD patient, now there's a discovery through some literature, and that there is an association between eosinophilic esophagitis and IBD also, so some IBD patients actually have, the prevalence of eosinophilic esophagitis is more in IBD patients. So I think that concludes my talk, so thank you for your attention.

IBD

IBS

microscopic colitis

inflammation

endoscopy

treatment options