All right. My phone says 1215, so I'll get started. Thank you all for being here. I'm Daryl Pardee from the Mayo Clinic in Rochester. Talking to my friend in the front row here that he said you must be happy to be in San Diego, being from Minnesota. It's the same temperature in Minneapolis right now that it is in San Diego, so still happy to be here. So we're going to talk about chronic diarrhea. If I can get the mouse to work. Here are my disclosures. And I really don't want to give a lecture for an hour. I'm sure you don't want to listen to a lecture for an hour, so I would love for this to be interactive. So whether you want to go to the microphone or just raise your hand or just shout out, I like doing these because I always learn something from you about your practice and how you approach these problems. But the rough outline here is just to go over the challenge. Why is there a bunch of people sitting in a room hearing about chronic diarrhea when they're in San Diego over the lunch hour? Mostly going to focus on a rational approach to the differential diagnosis, which will then inform a judicious approach to testing to try to manage your patients in a cost-effective manner. So they appear to be frozen here, guys. There we go. All right. So chronic diarrhea obviously is a common problem. Most estimates are between 1% and 5% of the adult population in developed countries have chronic diarrhea. Some studies say as high as 10%. That seems excessive to me, although some days in clinic it seems like that's probably an underestimate. It leads to a significant cost, impact on quality of life, work, and social activities. The problem for us as providers is that the differential is enormous and the number of diagnostic tests grows by the day it seems, and many of those tests are expensive, sometimes difficult to interpret, and really for lots of these areas there's not a lot of high-quality research. So it's our collective experience that drives this rational approach to the condition. I thought it would be worth spending a minute to review that normal fluid homeostasis, which comes into play when we're evaluating patients with chronic diarrhea. So depending upon the diet, anywhere upwards of 10 liters a day are presented to the small bowel from the stomach. Of that, the vast majority is absorbed in the jejunum, most of the rest is absorbed in the ileum, and only about 1 to 1.5 liters is delivered to the colon. So that's why talking to your patients about the volume of diarrhea can be helpful in terms of narrowing your differential. If it's large volume, watery diarrhea, that speaks towards likely a small bowel problem, whereas if it's small volume with bleeding and tenesmus and mucus, that points towards a colon problem. And as you remember, the colon would absorb about 90% of the water delivered to it. So of that liter, roughly 100 milliliters of stool comes out in a normal day, maybe up to 200 in the normal population. But the arbitrary definition of diarrhea from a volume perspective is more than 200 or 250 milliliters. But the colon also has the capacity to increase its absorption up to a level. So when you're getting diarrhea, it means whatever is being presented to the colon, either is more than it can adapt and absorb, or the problem is in the colon itself, where that absorptive ability is now compromised. How many of you use the Bristol stool chart or something similar in your office? Yeah. I used to not, but I do a lot because I had too many examples where a patient was talking about diarrhea. I was thinking of one thing, they were talking about something else. So using the stool chart, we have pads of them in every of our exam rooms, really helps to make sure you're on the same page with your patient. So the definition of diarrhea, chronic, arbitrarily is more than four weeks. That's because in the U.S. and other developed countries, most acute diarrhea is done in a week or two. So lasting more than four weeks is clearly getting out of the realm of expected for an acute diarrhea. As I mentioned, if you're collecting stool and measuring it, it would be more than 200 or 250 grams or milliliters in a 24-hour period. Clinically, when you do population surveys, normal bowel function is anywhere from three per day to one every three days. So if you use those population norms, less than one every three days would be considered constipation, and more than three a day would be considered diarrhea. It could also be defined by the consistency of the stool, with more than three quarters being loose or mushy or watery. But remember, again, when I work on the hospital service with our residents, I tell them that most of GI problems are symptom-based. And what symptoms are is a word that a patient is using to describe something they're feeling or experiencing. And the way they use that word might be different than the way you use that word. So when you're seeing someone for diarrhea, maybe the first question is, what do you mean by diarrhea? And, as you know, some people use that term to mean urgency or incontinence, but they're really not having diarrhea. The workup and the differential will be quite different based on what the actual complaint is. Okay, so now this isn't meant for you to read. Hopefully you have it in your syllabus if you want to go back to it. But it's only meant to emphasize how broad the differential is, all the different things we have to think about when we're seeing a patient with diarrhea in the office. And I hope to give you a paradigm that helps you narrow down the differential for the given patient that you're seeing in front of you. So, as I mentioned, one of the challenges we have is what do we order when we're seeing a patient with diarrhea? We have blood tests and stool tests and x-rays and scopes and biopsies and now breath tests. And how do we make sense of all that? And how do we understand, you know, the operating characteristics, for example? We'll talk about that in a little bit when we talk about breath tests for SIBO. Do you know for the tests that if you use breath tests for SIBO in your lab, do you know what the operating characteristics are? At Mayo, they're not very good. Sensitivity and specificity is not very good. So you have to at least incorporate that in your mind to decide am I going to even order it in the first place? And then how am I going to interpret it? How confident am I in interpreting an abnormal result if the specificity, for example, is not very good? So we'll go through all that. As I mentioned, I'd like this to be a case-based interactive discussion. So I'm going to present a case and I'm going to ask for input from the audience. And if we get through this and we still have time left, I have a few more cases at the end that we could go through to make some additional points. So Ms. Smith is a 55-year-old woman with chronic diarrhea. She's having four to six non-bloody bowel movements and has had so for the past six or more months. She has some abdominal cramps that are partially relieved by a bowel movement. So a pretty common consult in your office. So what's your initial approach? Okay, an X-ray. Okay, anything else? Stool analysis. Which part of the wound? Okay, medication list. Okay. So again, this is a diarrhea talk, but when I'm in the hospital with my residents, I say that I haven't admitted a GI problem that can't be medication related. Think about it, constipation, diarrhea, abdominal pain, bleeding, hepatitis, et cetera. So careful review of the medication list, and we'll come back to that. It's really essential for almost every patient we see. I'm curious about which part of the world she's from. You said developed versus underdeveloped. Yeah. I have a little problem with that definition. Yeah. So where is she from? Where has she visited? So in other words, I think what you're saying is we need more history. This really wouldn't be enough to decide what the next steps are. And think about it. You're narrowing your differential from the minute you say hello to your patient. And all those questions you ask, the observations you're making help you narrow your differential. Am I worried or not? Alarm symptoms or not? Am I going to do invasive testing or not? So we'll go through that. So we need more information. So what does she mean by diarrhea? So in addition to medication review, which the other critical thing is the dietary review. How many patients do we see with chronic diarrhea, especially if there's bloating, that there's an underlying malabsorption, right? Lactose intolerance we're all very familiar with. I think back, a case I saw a long time ago when I was first on staff, a gastroenterologist from a large, successful private practice had done some of his training at Mayo, had seen a bunch of his colleagues, had a whole bunch of tests, and they couldn't find out why is this guy having so much diarrhea. And I just took a history, and he was eating enormous amounts of high fructose corn syrup with the junk food he was eating on his busy clinical days. And when he was at home on the weekend eating more healthy food, his diarrhea went away. So there was a clue right in the history, and I didn't do any more testing. We had him address his diet, and his diarrhea went away. And then, of course, artificial sweeteners, and that will come up later. I'd like to emphasize the fact that true food allergies, IgE-mediated food allergies, are really not very common in adults. In fact, our allergy colleagues won't even really do testing for true food allergies in adults unless there's something else, like angioedema, or something that makes them think it's a true food allergy. It's really we're talking about intolerances. And even true lactose intolerance, fructose intolerance, artificial sweeteners, we all have a different threshold for what we tolerate, perhaps based on our brush border enzymes, perhaps based on our microbiome. That will allow us to take a certain amount. Even people with true lactose intolerance can usually tolerate some degree of dairy products. Okay, and then as our colleague in the back said, careful review of medication lists. Not only what's prescribed, but those health food supplements, over-the-counter things they're taking that could be causing diarrhea. At least 700 medications list diarrhea as a potential side effect. And if you find that in your history, the diagnostic tests are stopping the medication, and then you may be able to skip a whole bunch of expensive tests down the road. All right, so what else might we find in our history? So past histories, things like radiation therapy, right, radiation enteritis with malabsorption, weight loss, that can happen decades after they had the radiation. And, you know, depending upon the quality of your medical record, you may not even know they had radiation therapy. They may even forget it was so long ago, so you have to tease that out. Do they have diabetes? And maybe that's predisposing to SIBO or diabetic enteropathy, whatever that is, chronic diarrhea is from the diabetes itself. Do they have vasculopathy? And they have chronic malabsorption. One of my most difficult patients right now, a lady with mesenteric ischemia that doesn't have any options for revascularization. Another overlooked clue is history of constipation. They've been constipated all their life. Now they're having diarrhea. And we start treating them with loperamide, and it gets worse because they're impacted and they're having overflow diarrhea. Their physical examination can be extremely helpful if they have an impaction in their rectum. And do they have a psych history? Which, again, you don't want to necessarily jump to conclusions, but could increase the risk of functional or even a factitious disorder. You have to review the surgical history. Do they have an ileocecal resection for a bad appendicitis or Crohn's disease and they've lost their ileal break or the ileocecal valve? Maybe they have bacterial overgrowth because that valve is no longer preventing the back migration of bacteria from the colon to the small bowel. Of course, blind loops, which are not that common anymore, but can predispose to bacterial overgrowth. And then vagotomy, of course, can lead to all kinds of GI problems, including diarrhea. Family history, some things run in families, as you know, the obvious ones like IBD and celiac disease. But, you know, you never want to miss a case of multiple endocrine neoplasia or other family cancer syndrome, which are being increasingly recognized now that we have more sophisticated genetic testing. And then finally, social history. So someone mentioned travel. Are they immigrants? Have they spent a couple months in Southeast Asia or sub-Saharan Africa? That's going to completely change your differential diagnosis. Do they have risk factors for HIV, Giardia? So in Minnesota, we get a yearly report from the Department of Health with all kinds of infectious disease data for the state. And that includes some GI infection data. And anyone know what the leading risk factors are for Giardia infection? It's not well water. It's not camping. Having exposure to poop from children. So daycare workers are having kids at home with diapers because kids can carry Giardia in their stools. So in Minnesota, that's even more common than exposure to well water or camping. So careful history there can help you look for an epidemiological clue that would direct your testing specifically towards Giardia, maybe other infections. Another one that I find really interesting is intermittent diarrhea. So I have a lady that has bad diarrhea for a day or two, and then is normal for five to ten days, and then gets diarrhea again. I mean, to me, that's got to be exposure to something, whether it's a medication or a diet, but we haven't been able to figure that out. If it's less striking, diarrhea a couple days, diarrhea not a couple days, that's characteristic of a functional diarrheal disorder or IBS. Maybe they're taking a medication every once in a while, and that's causing diarrhea and they haven't identified the connection. For dietary intolerance, I don't know about you, but I don't remember what I had for lunch yesterday, and neither do our patients. So I find a dietary diary incredibly helpful. Every day write down breakfast, lunch, dinner, snacks, and then when you have symptoms, and then maybe we can go back and look at that and start to identify some triggers that maybe wouldn't otherwise be apparent. So a dietary diary. And then, of course, one of the first branch points in your thinking is, do they have alarm features or not? Bleeding, fever, severe abdominal pain, significant weight loss, are obviously going to direct you away from maybe empirical antidiarrheal therapy to more specific, even invasive testing. And then nocturnal stools, I put a question mark there. We've been taught that that's a distinguisher between organic and functional diarrhea. I think it is for the most part, but some people with functional diarrhea have a little bit of nocturnal stools, especially if they have some BPH and they're waking you up to go to the urinal to go pee, they might have a bowel movement, and that doesn't necessarily mean it's an organic problem. All right. So I alluded to this when I told you the anecdote about that gastroenterologist that I took care of a while ago, but bloating, inflatus, now nonspecific, right, pretty common in irritable bowel syndrome, but raises in my mind the suspicion for some malabsorption, whether it's fructose or lactose or just exposure to lots of artificial sweeteners. The bacteria are fermenting those sugars and they're producing gas, which the patient experiences as bloating or flatulence. Do they have frequent infections, which is going to make you think about some underlying immunocompromised, like HIV or CVID or others. I mentioned this earlier when I talked about fluid hemoeostasis, but small frequent bowel movements, tenesmus, mucus, bleeding, are going to suggest proctitis rather than something higher up. And, again, the issue of overflow diarrhea, especially in our immobile institutionalized patients. All right. So let's go back to our patient. She has no alarm features, hasn't lost any weight, hasn't traveled. She has a past history of depression, hypertension, and obesity. She takes citalopram and amlodipine for depression and hypertension, respectively. And she has no family history of any GI disorders. So now what are you thinking? Nothing? Yes. Okay. So stool testing, okay, that would be something to think about. We'll come back to that. I'm going to give you some physical exam. So when you're doing physical exam for chronic diarrhea, obviously the general stuff like looking for dehydration, signs of malnutrition, any abdominal findings, which are often not present, but then looking for specific clues, which are not common, but when you find one can be really gratifying. So, for example, looking at things like extraintestinal manifestations of IBD. Twenty-five-year-old with chronic diarrhea, and one of the findings I'm going to show you in a minute, you might hone right in on IBD as a potential diagnosis. I have pictures for all these. So rather than reading lists, I'm going to show you the pictures. So what's that? Erythema nodosum. So a young patient, not even a young patient, a patient with chronic diarrhea and erythema nodosum, you might be thinking right away about IBD. Pyoderma gangrenosum, same thing, IBD, what's that? That's scaly vesicles on the knees, maybe on the elbows. I think I heard psoriasis. This is more vesicular, so it's dermatitis herpetiformis, which is essentially celiac disease until proven otherwise. This is a little bit more rare now. This is urticaria pigmentosa. So as opposed to regular urticaria, this is pigmented, and that's a fairly suggestive sign for systemic mastocytosis. Dermatographism, also for mast cell disorders. Periorbital purpura and macroglossia is amyloidosis. I had a patient referred to me from a very smart friend, gastroenterologist, who had a guy with chronic diarrhea. He had done all the tests, couldn't find an answer. He just had that suspicion that it wasn't functional, maybe because the guy was losing weight. I saw him with one of our nurse practitioners, and she was presenting the case to me and went through all the diarrhea history and the tests he had. By the way, he's having a really hard time standing up because he's lightheaded, and even when they give him IV fluids, that doesn't go away. On physical exam, he's got bruises all over his arms and legs. I went to see the guy. This is not his picture, but he had this big tongue with the furrows along the side, and he had amyloidosis. Hard to diagnose unless you think about it. The diagnosis for amyloidosis, GI involvement, they don't have GI symptoms, is very common. We often think of fat pad aspirates to stain for the amyloid protein. GI tract biopsies usually have amyloid. Before you do another invasive test, fat pad aspirate, if they have GI biopsies, you can go back and ask your pathologist to stain it with Congo Red, and you may have an answer there. A physical exam, usually normal as it was for Ms. Smith, but sometimes you find that clue that really helps you make a diagnosis. Her exam, other than being overweight, was unremarkable. Now we'll get into testing. I heard stool chemistries. I heard KUV, other tests we would do. We're gastroenterologists. I'm having a hard time hearing the audience. Fecal elastase, maybe. I don't know if you saw this article. It just appeared in the last couple of months in the Red Journal by Michael Camilleri, which I think is a very rational approach to diarrhea. It replaced the slide I used to have in this deck that talked about testing. I'd like to read through this with you. I really want to hear from you if your practice is different than this because I wouldn't do everything that Michael proposes here, but I think it's a pretty good construct. Start off with looking for those iatrogenic causes. Are they on a medication that's causing diarrhea? If so, you don't need to work down this algorithm. You need to try to stop that medication. If you can't find an iatrogenic cause, then you're looking for the alarm features. Bloody diarrhea equals colonoscopy and a stool pathogen panel. Infectious diarrhea is an uncommon cause for chronic diarrhea in developed countries, but I still usually do it just to make sure I'm not missing something. Fatty diarrhea, and we'll get into how a patient might present with fatty diarrhea on another slide. But then you're thinking about small bowel assessment for malabsorption. And I would probably put a CT scan here, too, looking for chronic pancreatitis. So it's either maldigestion or malabsorption if the patient's describing, frankly, greasy stools. If they have typical features of irritable bowel syndrome, then you can go to the green box, which I'll talk about in a minute. But you don't necessarily need a lot of invasive testing if they have the classic symptoms of IBS. And then functional diarrhea is essentially IBS without the abdominal pain, and a similar approach there. If they haven't already, then assess their diet. Make sure there's not a trigger there that's causing the diarrhea. And then the green box, I would say, is a very reasonable first line of testing. So things like CBC, right? So if they have a high white count, you're going to be thinking differently. If they have anemia, you're going to be thinking differently. If you see, for example, hypokalemia, that's suggesting a more significant diarrhea problem with electrolyte loss. Some assessment of inflammation, whether it be CRP or sed rate or fecal-kale protectin. I don't usually do all of those, but at least one of them. Some standard nutritional parameters like iron folate and B12. What are we looking for there? So malabsorption, number one. But what if you see low B12 and high folate? Does that give you a clue? Yeah, bacterial overgrowth. That can be a clue to SIBO, right? The bacteria consume the B12 and produce folate. So that can sometimes be a clue. Screening for celiac disease, it's common enough in the general population. It's even more common in people with chronic diarrhea. So at least a serologic screen for celiac disease. Michael said stool tests for fat. That's like a spot fecal fat. I don't generally do that because the operating characteristics aren't that great. And as you know, fecal fat excretion can vary markedly throughout the day and from day to day. So for me, if I want to test for fat malabsorption, I do the 48-hour stool because that eliminates the day-to-day variation. But you might do a spot stool test for fat, and you might notice that elastase is not in here. Our feeling about elastase, even though our lab offers it, is that it's not a very good test. It's sufficiently insensitive and nonspecific that we feel it causes more trouble than good. So most of us don't use fecal elastase. If we're worried about pancreatic insufficiency, we'll probably do an imaging study of the pancreas. And if we're really worried, that would be an endoscopic ultrasound, which gives you the best images of the pancreas. All right. So that's the basic routine laboratory test for someone with chronic diarrhea that doesn't have alarm features or other specific findings. Does anyone do anything differently? No? Unanimous and enthusiastic agreement. So then the results will direct your next steps. So low hemoglobin, low albumin, abnormal MCV, excess fat in the stools. That's not irritable bowel. That's not functional diarrhea. That requires additional testing, maybe colonoscopy with biopsies, maybe small bowel assessment. Low serum potassium, again, suggesting significant diarrhea. You don't lose enough potassium to be hypokalemic unless you have significant diarrhea. That might point you toward something like doing the stool chemistries to look for electrolyte abnormalities. And Michael says hormonal screen. So that would be like your 5-HIAA and maybe some of the other ones. But one of the key points I want to make to you is those things are rare. By far in our lab, abnormal tests in hormone levels are false positives, by far, because they're ordered indiscriminately. So if you have a hormonal diarrhea, you generally have a syndrome, some other symptoms from the hormones, generally high-volume, watery diarrhea. So those should be really the only patients that you're worried about a neuroendocrine tumor because they're just so rare. All right. So then if you don't find alarm features on your history or physical, the screening lab tests are all okay, you're less worried about something real serious, then you can do empiric antidiarrheal therapy and have a table on that coming up. So that's an empiric trial of loperamide or diphenoxylate. And if that works, then you're good. You can continue that for maintenance therapy and just monitor your patients to see if something changes that makes you think that maybe we are missing something. But if you look at the epidemiology, right, irritable bowel present in like three-quarters of the population or something like that. I'm kidding. But irritable bowel is so common. And other things, IBD, mastocytosis, whatever, uncommon. So if you've done a good job with your due diligence ruling out alarm features and concerning labs, you're going to be in a pretty good spot that it's probably irritable bowel or functional diarrhea. If that doesn't work, though, okay, you're not done. You're trying loperamide. You're trying diphenoxylate. They're no better. Okay. You probably missed something. Or at least you want to make sure you didn't miss something. So then you might go back and do one of those other tests in the green boxes. And then your subsequent steps will depend on the results of those tests. And you can see on the lower left there he's telling us how he interprets stool chemistries. And I have another slide on that. So I'm going to skip through that. Michael is a motility expert, as you probably know. So he uses gut transit studies in his algorithm. I don't think I've ever ordered that test for my patients because I'm not sure we have a specific treatment for rapid transit other than what we would do for diarrhea. But here, when we get to this point, that's when I'll think about doing that 48-hour stool. That does a couple things that I'll outline in the next slide. So I do think that's a really important test as we work down the algorithm. All right. So how do stool tests help me classify diarrhea? Number one, you know, you have that patient that you're wondering how bad the diarrhea really is. If they have normal stool output, they don't have diarrhea, at least not when that was being collected. So you have to be careful if they're taking antidiarrheals or whatever that they're not taking it while you're doing the test to see how much diarrhea they have. But if that's not the case and they have less than 200 grams of stool, then they don't have diarrhea. They may have urgency. They may have what's called pseudo-diarrhea, which we'll talk about in a minute. But at least you can reassure them, look, your stool output is actually normal. So maybe I'm not going to hammer you with antidiarrheals because you don't have diarrhea. Maybe we'll use a sensory medication like a TCA. If they have more than 200 grams or 250 grams of stool, that's abnormal. If they have a normal gap, that is secretory. If they have an abnormal gap, that's osmotic. And the way you calculate that, you'll remember this. 290 minus 2 times the sodium plus potassium. And that should be less than 50. More than 100 is abnormal. 50 to 100 is kind of an indeterminate zone. And why do we use 290 as opposed to the measured osmolarity? Because if the stool sits around in the container, the bacteria will continue fermenting the carbohydrates and will raise the osmolarity. If the measured osmolarity is only helpful, what if it's really low? Like you do your stool, you measure sodium potassium, and you measure the osmol, and it's 150. Bless you. That's not physiologically possible. So that strongly suggests they're putting water or dilute urine in their collection to make it look like they have diarrhea. So a very low osmolarity is helpful. Very high doesn't help. That means it's probably been fermenting, and it's just not interpretable. We now have a way to directly measure bile acids in the stool. We're looking at both the distribution of primary to secondary as well as the absolute number or amount of, excuse me, bile acids. Michael's done a lot of pioneering work here. We have normal ranges for both of those. And that would be a way to test for bile acid malabsorption. So if I'm going to do a 48-hour stool to measure volume and fat, I'm going to do bile acid assessment at the same time. And then, of course, doing fecal calprotectin, fecal lactoferrin, fecal WBC is a way to measure for inflammation, so that if you hadn't already done a colonoscopy, if those are abnormal, you're going to do a colonoscopy looking for IBD. All right. So, again, if the stool test is normal, the stool, sorry, weight is normal, that's really helpful information. They don't really have diarrhea. So hyperdefecation means they're going to the bathroom more than three times a day, but it's not diarrheal. And you might have picked that up at the beginning if you used the Bristol Stool Scale. Say I'm going four or five times a day, but it's Bristol 4. Okay, that's not diarrhea. Let's look at a different differential diagnosis for that. They might have intermittent diarrhea, right? Doesn't this happen all the time? You do the test and it's normal. They say, yeah, but I wasn't having diarrhea that day. So then you need to figure out what that means. Maybe, again, they're not talking about diarrhea. They're talking about incontinence. The amount of stool is normal, but they're leaking and they're calling diarrhea. Yes, sir? Stool phenolphthalein. Stool phenolphthalein. So that's a laxative that used to be available. It was associated with cancer, so it's not available very much anymore. And our lab doesn't test for phenolphthalein anymore. Anyone know what tests you can do on the stool if you're thinking about laxative abuse? Sorry, I'm having trouble. I'm still not hearing you, but you can check for sulfate. You can check for phosphate, right? So some of the osmotic laxatives have a sulfate or a phosphate, and you can measure that in stools. Okay. Secretory diarrhea, as you know, generally high volume, persists with fasting, but you really have to fast for 24 to 48 hours to really see a difference. So that's not as reliable clinically as maybe we were taught. Microscopic colitis, relatively common cause of secretory diarrhea. Biolase and malabsorption. Stimulant laxatives. So these ones you're not going to pick up on stool chemistries because they're not osmotic, but you have to then think about history. I had an old guy that had diarrhea, and I said, do you take any over-the-counter supplements? He goes, yeah, I take a few. I said, what are they? He goes, I don't remember. I said, bring them in when we have our follow-up visit. He brought in a suitcase that had all these bottles in it of all these supplements and things he was doing to make him stay young, and many of them have a little bit of aloe, a little bit of cascara, a little bit of whatever. When you add them all up, he was taking a lot of laxatives and didn't even know it. And then, again, rarely neuroendocrine tumors for secretory diarrhea. Osmotic, avoids with fasting or avoiding the osmol that was causing it in the first place. Generally lower volume. Generally not nocturnal, although if they're eating that thing before they go to bed, it sure could cause nocturnal stools. Carbohydrate malabsorption is a big one here. Again, go back to that really careful dietary history. Taking osmotic laxatives. And again, sometimes they don't know it, right? They're using a lot of magnesium-containing antacids for their heartburn, and it's enough to give them diarrhea. So ask about that. And then SIBO. SIBO is interesting. It can cause osmotic or secretory or sometimes both. But that would be on the differential if you do stool chemistries and you have an osmotic diarrhea. And then, finally, steatorrhea. So for those of you who have experienced steatorrhea, hopefully not your own but your patient's, there's a distinct odor, there's a distinct appearance, greasy, oily. Stool that floats on the water is not a reliable sign of steatorrhea. It could just be air in the stool. But oil that floats on the water or oil that goes down the side of the bowl after they flush would be a pretty good indicator of steatorrhea. And then I break that down into two big buckets that I alluded to earlier. Malabsorption, which is a small bowel problem. They're not absorbing the fat. Either most typically small bowel mucosal disease like celiac disease or extensive Crohn's disease, or lymphatic obstruction where they might be absorbing it through the mucosa but it has nowhere to go because it's obstructed. Or the other big bucket would be maldigestion. Almost always that's pancreatic insufficiency. It can be caused by SIBO. And then remember your patient with bile acid malabsorption. The treatment is bile acid sequestrance. It doesn't improve absorption. It just prevents them from irritating the colon. Bile acids are very potent laxative in the colon. But some people are just on the border of not just bile acid malabsorption but bile acid deficiency. So your liver, our liver, increases production of bile acids commensurate with the loss. But it has a limit. And if a patient's losing more than the liver can produce, either because of bad bile acid malabsorption or because you gave them a binder that's now taking even more of it into the toilet, they become bile acid deficient. And as you know, bile acids help you digest your fat. So sometimes you give someone a bile acid sequestrant and they're worse. it's because you've tipped them over from bile acid diarrhea to steatorrhea. So that's a really important clue to what might be going on for your patient. And then inflammatory diarrhea, typically blood, abdominal pain, fever, tenesmus if the rectum's involved. We most typically think of IBD, which is good because that's a common cause of inflammatory diarrhea, but could be chronic ischemia. Infectious colitis is uncommon, especially in people that aren't immigrants or travelers to some other part of the country or other part of the world where these things are more endemic. And then rarer things like eosinophilic colitis, GVHD. Increasingly, any of you seeing checkpoint inhibitor colitis in your practice? These drugs, thank goodness, are being used for lots of different cancers, keeping people alive, but causing a lot of side effects, including in the GI tract. So again, usually that wouldn't be a surprise to you, but review the medication list, should tell you they're on one of the checkpoint inhibitors. And even some of the newer chemotherapies beyond checkpoint inhibitors have a significant rate of diarrhea. So we're seeing more of that as they get more and more novel anti-cancer drugs. All right, now a couple more important points. So this also is relevant for Ms. Smith, our patient. Don't miss an opportunity for colon cancer screening. So even if they don't really have alarm features, maybe you don't need a colonoscopy because of their diarrhea specifically, but I think she was 56. Take an opportunity to do a screening colonoscopy. You'll rule out microscopic colitis, IBD, but also make sure she doesn't have any polyps or cancer. So EGD with duodenal biopsy, if you're worried about malabsorption or have other concern for celiac disease like a family history or dermatitis or pediformis. How many of you do small bowel aspirates in your practice for evaluation of SIBO? A couple. Yeah, we do it too. We sometimes look in the mirror when we do it and wonder why we do it. Just because you know the gold standard is jejunal cultures, right? That's where we have the greater than 100,000 colony forming units. I don't know about your practice. We don't do jejunal aspirates. We do duodenal aspirates. So how do you interpret that? Is it still 100,000 or is it 50,000 or 10,000? We don't really know. How many times you see a fellow doing an EGD or maybe a staff and the ordering doctor wanted aspirates and there's no fluid there, so they push on the water button until there's enough water there to aspirate it out. Not gonna help the operating characteristics of that test. But anyway, so if you do it, just know there's certain caveats with interpreting it. What's the, do you have another way to diagnose SIBO in your practice? Hydrogen breath test. Did I hear breath test? Hydrogen breath test. Again, so look at the operating characteristics that your lab uses. We do it too, but there's a lot of false positive, false negative. I think the best test is a history. And I will often say, have you had antibiotics for a UTI or a sinus infection or ear infection, whatever? And it's striking how often someone will say, yeah, you know, I had a sinusitis. I took Augmentin and my diarrhea went away. Probably SIBO, right? Or a darn coincidence. But that, to me, if I had that history, I'm gonna go right back to another prescription of antibiotics. And if they get better again, I've made a diagnosis of SIBO. All right, so CT scan or endoscopic ultrasound, I don't have a primary role for evaluating chronic diarrhea unless you're worried about alarm features, weight loss, something to make you think you might have chronic pancreatitis or the rare patient with a neuroendocrine tumor. If, in your mind, Crohn's disease is on the diagnosis and you're gonna do cross-sectional imaging, I just ask that you do an enterography, right? You get everything else you get with a plain scan, but you get better pictures of the small bowel. So that will help you look for Crohn's disease as well. Hydrogen breath test we just talked about. So the hydrogen breath test for SIBO we just talked about. Also, there's hydrogen breath tests for the carbohydrate malabsorption that are similarly poor to the breath test for SIBO. We have debates about once or twice a year whether we should even offer these tests in our lab because of the operating characteristics. So again, rarely serum hormones, 5-HAA, gastrin, VIP, shouldn't be part of your standard hot buttons for diarrhea workup. I say never IBD serologies. They're not meant to be diagnostic. They're meant to help you, if you have someone with indeterminate IBD, to help you say is there more evidence for Crohn's or more evidence for UC. They're just not good enough to be a screening test for the general population with chronic diarrhea. All right, let's now shift. We go to 1.15 or 1 o'clock? 1.15? Okay. All right. So the question was about the test for sucrase isomaltase deficiency. I don't use it in my practice. I'm not aware if some of my colleagues do or not. Anyone else using it regularly? Pretty rare. Did I see a hand over here? No, just someone with a phone. All right. Yes. Yeah, capsule endoscopy. Anyone using that for chronic diarrhea? Hard to get it approved. Probably for good reason. I think it's a reasonable test if you're worried about an enteropathy. Not all celiac disease is in the proximal small bowel. Certainly Crohn's disease. In our practice, maybe because of our radiologists, we did some research a number of years ago looking at capsule versus CT enterography for obscure bleeding and Crohn's disease. And the CT enterography was better than the capsule. So we tend to do CT enterographies, but I know not everyone has the same radiology access that we do, and capsule would be another reasonable test. But think about what you're looking for. CT or MR enterography. CT or MR enterography. And again, in our practice, we have some MR radiologists that specialize in that, and they're pretty good. So when we look at the yield of the two, they're equivalent, but that'll be dependent on the expertise in your institution. Some have good MRI radiologists, not so good CT and vice versa. MRI's more expensive, takes longer. Most of the time it's the closed magnet, so people with claustrophobia have a hard time with that. I have a guy that has a shoulder problem, so he has a real hard time getting his arms out of the way for an MRI. CT is more readily available, less interpreter dependent, and a little bit of radiation, yeah. So we think about radiation for our young patients. Our radiologists, including our medical physicists, tell us that our cells are less sensitive to radiation as we get older. Anyone know what the cutoff is for being old for that question? 35. Welcome to the club. But the point is that, so first of all, this notion of diagnostic ionizing radiation, HERM, that comes from extrapolation of estimated exposure at Hiroshima and Nagasaki. So depending on how far you were from ground zero, you got a certain exposure. Then they looked at cancer risk based on distance from ground zero. And then they say, well, if you had a one time exposure from a nuclear weapon, or you have a little bit of exposure from a CT scan over time, that must be the same, right? I don't know, is it? So our medical physicists will argue that that's not even a fair comparison. But the other thing, now who wants to risk a cancer in one of our patients? So for a younger patient, especially someone, I think, like a Crohn's patient that's gonna need repeated imaging, definitely would favor MRI. Older patient, maybe a one time CT scan, I'm not really worried about it. Partly because our radiologists have been really good at innovating, and the radiation exposure for CT over the years has gone incredibly low. It's like just a little bit more than a chest X-ray now. It's incredible. So the risk become, if there's any risk at all, becomes less. But when we looked at our, I'll be with you just a second, when we looked at our Olmstead County population with IBD, about 25% of our Crohn's patients had enough radiation exposure that we were worried about it. And based on a very conservative reason to worry that I just mentioned. So again, for those patients with abscesses or fistulas or bad disease activity where I'm gonna be doing a lot of surveillance radiologically, I really would favor MRI. Or now we have ultrasound. And I bet if I asked you to raise your hand, a lot of you are using more ultrasound in your IBD practice for good reason. Where did you go? There you are. One non-invasive test you use for pancreatic function. That's a hard one. Yeah, so the question was, if I heard you correctly, for everyone else who may not have heard you, non-invasive testing for pancreatic function. It ain't easy. We are now looking at bringing back, bless you, a test of direct pancreatic function. So an endoscopic procedure with pancreatic juice collection. So sort of a modification of the secretin stimulation test. But really, to be honest, our approach to pancreatic insufficiency, whether it's chronic pancreatitis or not, is largely image-based and stool test-based. So cross-sectional imaging or EUS, looking for features of chronic pancreatitis. And then do you have steatorrhea? So if you have those, then we don't worry about fecal elastase or any of the other testing. I realize we could probably have a debate about that for an hour, and even our pancreas experts have a debate about it. But the point of the matter is, we don't really have a great non-invasive test for pancreatic insufficiency. Okay. Yeah, so again, I'm sorry, I'm having a hard time hearing up here, but I think you said the role of colonoscopy in someone that we think otherwise says irritable bowel. Absolutely don't miss a chance to do a screening colonoscopy. Remember that, right? Something's going on. Okay, well no, that would, I might not do a colonoscopy just for polyp surveillance or polyp screening in a 25-year-old. But I'm gonna be thinking about IBD. And so for those screening blood tests, I'll do a CRP and maybe a fecal calprotectin. And if either one of those is abnormal, if they have a low albumin, if they have a low hemoglobin, I'm gonna go to a colonoscopy and look for Crohn's disease. Blood slam dunk. Even if you see a hemorrhoid, someone's bleeding, I would do a colonoscopy, make sure you're not missing a cancer. Scary what's going on with the epidemiology of colon cancer. And luckily there's some smart people trying to figure out what the heck's going on, microplastics or something else, but something is changing the epidemiology of cancer. So I would say don't miss a chance to do colon cancer screening. And if we go back to that algorithm, if you try loperamide and they're no better, next step is colonoscopy. Was there another hand? Yes. What's the role of thyroid and TSA? Yeah. When I was a resident and we were doing morning report, whenever we get pimped on the differential, I would always say thyroid disorder. And I was right most of the time. So I don't know about you, it's been a long time since I've seen someone with diarrhea because of hyperthyroidism, but it's such a common disease, it's so easy to test for. So that algorithm had TSH as part of the basic lab testing. You should also check for C. diff. There are people who come with chronic C. diff for months and years. I wonder about that. Does C. diff cause chronic diarrhea? Probably, probably. But usually it's an acute diarrhea. But for whatever reason, the patient may have hung around at home hoping it would go away. So yeah, stool testing for pathogens I think is very reasonable. Certainly the more acute it is, the more I'm gonna test for pathogens. If there's any blood, I'm testing for pathogens. If you get a patient with a diarrhea, and that is the C. diff, and you repeat the clinic for three days, maybe the stool for C. diff comes indeterminate, and the diarrhea persists for three days. So if they test positive for C. diff. Initially they got great, and then a few weeks later, having recurrent diarrhea, the stool for C. diff is indeterminate. And what do you mean by indeterminate? When we send a stool, the lab will tell you stool for C. diff is indeterminate. Okay. So the problem with C. diff testing, it's a multi-step process, right? And we'll talk about that in a minute. But the first step is to think before you do anything. And what I mean by that is we get into issues of specificity, sensitivity, when the tests are used indiscriminately. So someone, I covered the C. diff clinic at Mayo, and now more than half the patients we see don't have C. diff. They have something else and a positive test, because the test was ordered inappropriately. But what you describe, a person with diarrhea, if they have risk factors for C. diff, even better. But diarrhea, no other cause, obvious, positive C. diff test, they respond to vancomycin or fideximycin, that's C. diff. That's a solid clinical diagnosis for C. diff. And again, assuming the third point is true, that they got better on treatment. Then if it comes back, it would be appropriate to test for C. diff, indeterminate. So probably what that means is your lab is doing a multi-step test. So they do a test called GDH, which is a protein secreted by all clostridia, whether they're toxigenic or not. If it's negative, it's a pretty good test to exclude C. diff. But they often do that together with either a PCR or a toxin assay. And indeterminate is when one's positive and the other's negative. So the recommendation there is then to adjudicate that. Like if it's a GDH positive, toxin negative, you adjudicate it with a PCR. And then whatever the PCR is, that's a tiebreaker. But as you know, as a clinician, it's our responsibility to interpret the results. Tests are not 100% one way or the other. So in that case, even if the C. diff test was indeterminate, they had C. diff before, pretty clear. They responded to treatment. Now the diarrhea's back, I would treat them again. Where we get into real trouble is that same patient, but they don't get better with treatment. Then what is that? Is that resistance C. diff or is that C. diff carriage and their diarrhea's due to something else? And that's a difficult situation to work through. I see other hands. All right. So it's about 108. Maybe we'll wrap up, Ms. Smith, and then we'll be done. So in your, hopefully you have these slides. These are the recommended dose ranges for the various treatments we use to treat diarrhea. Obviously a lot of individualization based on your patient, their comorbidities, what other drugs they're on. So as you recommended, we did a careful history with Ms. Smith before we took out her ordering pad. And her diarrhea started a little bit after she started citalopram. It's one of those drugs that's notorious for causing diarrhea. Someone mentioned metformin in the back. There's some real common offenders. And it got even worse when she decided to be healthy and go sugar-free everything because of her obesity. So we stopped her citalopram, switched to nortriptyline for her depression, which is also a constipating drug, and had her stop the artificial sweeteners and her diarrhea went away. So it was a case where we could tease out the differential really just based on a careful history and we avoided any testing. So I just put a slide in here for elixadiline. Are you guys using that much in your practice? Yeah. Pretty good drug for diarrhea. Not the cheapest drug you'll ever use. That standard dose is 100 milligrams twice a day. Sometimes I'll start with 75, or certainly if they're having side effects that aren't too terrible, I'll go down to 75. Excuse me. And remember, there's some pretty specific pancreatic obiliary and other contraindications to using it. So be careful. If you're using it, make sure they don't have one of these contraindications. So in summary, chronic diarrhea is common, has a very broad differential, and an enormous menu of diagnostic tests. That's our responsibility to think through. Careful history, medication review, dietary review, and a good physical exam is mandatory. Can be very rewarding for you and your patients. And then stool testing can narrow the differential quite a bit because each of those categories based on stool testing has its own differential. So that 48-hour stool with stool chemistries can be very helpful. And ultimately direct a cost-effective evaluation. So with that, it's 110. I don't think we'll get into any of the extra cases I had. Maybe we'll stop there so you have time to get to your session. And hang around if you have questions. Thank you very much.

chronic diarrhea

diagnosis approach

cost-effective management

Mayo Clinic

Dr. Daryl Pardee

diagnostic challenges

stool testing

alarm symptoms

empirical treatment