Practical Tips for the Diagnosis and Management of Chronic Diarrhea

David A. Johnson, MD

Disclosures

March 10, 2010

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Introduction

Hello, I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Today I want to chat with you briefly about how you approach a patient with diarrhea. I'll restrict this discussion to the topic of chronic diarrhea, because acute diarrhea is a fairly voluminous discussion and we can perhaps discuss it in another encounter.

Let's just talk about the patient with chronic diarrhea -- and by chronic I mean a definition of over 2 weeks. I will give you an example of a patient whom I saw the other day. She is a 35-year-old woman who is somewhat overweight and who has been trying to lose weight for some time. She has had diarrhea for the last 3 months. It has been episodic. She has also reported that she is having increasing heartburn over the last few months (coincident with her weight gain) and she is taking some over-the-counter antacid medication for these symptoms which have been occurring several times per day.

So if this patient is before you, what are the questions that you would ask? How would you work up this patient? We will come back to this patient at the end. I will give you some thought processes that I would have as I approach a patient with chronic diarrhea.

Understanding Diarrhea

Let's begin with the idea of understanding diarrhea. I like to work with the KISS (keep it simple, stupid) principle, so my approach is pretty simple.

A couple of basic understandings to diarrhea are as follows: virtually all diarrhea relates to increased motility of the GI [gastrointestinal] tract; this is often the case with irritable bowel syndrome and with decreased absorption, which is what you would see with malabsorption or some type of infiltrative process. Other patients may have an inflammatory process, and that can be stimulated from IBD [inflammatory bowel disease] or even toxins that are stimulating the colon. There may also be a secretory process or an osmotic process that causes an outpouring of the fluid from the intestine, either by the osmotic forces or by the secretory forces generated, particularly by neuroendocrine-type disorders. So, if you categorize diarrhea into those 4 basic categories, you then step back and say, okay, let's take a few historical points and understand really what the responsibilities of the small intestine and large intestine are.

The small intestine (or the GI tract) is faced with approximately 9 liters of fluid a day, about 8 of which is absorbed by the small intestine. Think of the small intestine as a primary absorber, not only of fluids but also of nutrients. The colon's primary responsibility is really to be a sponge. This is what I tell patients when I talk to them about colonic disease. The colon's primary responsibility is for absorption of water. So, you don't get malabsorption from the colon. About a liter of stool is presented to the colon every day as it responds to a normal dietary intake, and about 99% of that is absorbed by the time it gets to the rectum, so the defecation process occurs as the stool moves through the colon.

Clinical Evaluation of Chronic Diarrhea

So that being said, let's review a couple of historical points. We'll go back to our patient.

I want to always know when the patient comes to me if this is a chronic or acute process. I use that as a short-term or long-term approach. Two weeks is my threshold. For today's discussion, we will say long term is diarrhea lasting over 2 weeks.

Then I want to know if the diarrhea is constant or episodic. Is this occasionally occurring, or is this every day that you have a bowel movement it is diarrhea?

I want to take the age of the patient into perspective. Age focuses it a little bit for me as to what the differentials are. I am more concerned about elderly patients presenting with diarrhea, and it is more ominous to see this, in particular when we talk about some of the cancers associated with diarrhea.

Then I want to know what the response is related to fasting because this is going to take me down a pipeline -- is it osmotic or secretory-type diarrhea. So one of the key questions that I want you to ask is, what happens if you don't eat; do you notice a change?

Another side step of that type of question is, does the diarrhea waken you from sleep? We talk about functional diseases, like irritable bowel syndrome, and almost never do you get that type of history (ie, nocturnal awakening and stooling). Sometimes people will have to get up and go to the bathroom at night. Very frequently that is the case for secretory diarrhea or inflammatory diarrhea, for example, a patient with colitis. This is very unusual for a patient with what we call functional diarrhea, such as an irritable bowel syndrome. So that becomes a key question for me.

What happens as it relates to dietary intake? So key questions here are, do you notice any particular provocative foods? Obviously a key one here would be lactose intolerance. We see this more commonly in patients who are in the Mexican or the Mediterranean basins or Far East, and in African Americans. We see this in Puerto Rican people. We see this in patients as they age. This is less common in the North American Caucasian population, but lactose intolerance does occur as a function of aging, too. So that would be a question, are there provocative food groups? Some patients may give you a history that gluten-type products make them worse. That may be hard to call out [from the patient's history], but celiac disease is a very common disease.

It is estimated that the prevalence of celiac disease in the United States and across the world is close to 1 in 133 patients. There are again more common types of populations, for example, the Mediterranean basin and some of the Northeast Nordic basins are very common disease pockets. You think about celiac disease in a patient with chronic diarrhea. This is not a diarrhea that typically goes away. It tends not to be episodic. Just as an aside, celiac disease doesn't always have to present with diarrhea. It may present as iron deficiency. We see it now sometimes in patients with elevated liver enzymes. If the patient presents with intussusception or perforation related to an acute abdomen, celiac disease is in the differential. Atypical celiac disease would be patients without diarrhea who present with malabsorption, vitamin deficiencies, or unusual gassy bloating discomfort. Recognize that the prevalence of celiac disease is very high, and it is a very easy disease to screen for. We will come back to that when we talk about diagnostic approaches.

The dietary intake is really key. Are there any unusual foods, unrefined foods, and/or unprocessed foods that make you think more about some type of infectious diarrhea?

I always ask about their water consumption. Where is their water coming from? If it is well water, you start to think about things like Giardia. Obviously, if they have a travel history in endemic parasitic areas or if they have been camping and drank water from streams, again you would think about things that might lead you to the differential of infection that may be more chronic.

It is very unusual for some of the standard bacterial diseases to cause chronic diarrhea. Now there are exceptions to that, for example, Aeromonas and Plesiomonas, but for the most part stool cultures in these patients are going to be very unrewarding because this is something that doesn't necessarily relate to chronic diarrhea. There are exceptions to the rule always.

Just as an aside here I will tell you that in patients who are hospitalized, one of the things that I chastise the residents very frequently for is ordering stool cultures for somebody who develops diarrhea in the hospital. It would be very unusual to ever see a value of a stool culture being positive, so it is a minus 10 if you are taking a board question.

Antibiotic exposure would obviously make sense. You would think about C difficile if they have been hospitalized or had exposure to patients or chemotherapeutic agents or something that might put them at risk.

A recent change in their medications would also be something that would make me think about looking at their medications, particularly with the elderly population and with some of the cardiac drugs, the statin drugs, the Parkinsonian drugs, and a lot of these drugs.

Patients may be taking some of the medications as elixirs. One of the things that you will really want to look at when they go to medication supplements is what this is being mixed with as a base. Sorbitol is very frequently used to add in particular things like potassium chloride. So if somebody is getting KCl [potassium chloride] elixir, it is very frequently added with sorbitol, which is obviously an osmotic-type sugar that would potentially cause diarrhea. So look at the medications very closely. Digoxin and those things are obviously associated with diarrheal syndromes. Always look at new medications or review the medication list as you are going through this.

Now I want to take a focused history as well to see whether there are any ways in which I can more appropriately focus my differential diagnosis and better direct my work-up.

Is there something that suggests malabsorption? Is there weight loss? Are there systemic findings of a vitamin deficiency, a true malabsorption, or a pancreatic insufficiency syndrome? What are the relative risks for that? Are they an alcoholic? Chronic diarrhea in an alcoholic makes you think of pancreatic insufficiency. In somebody who has diabetes or other systemic disease that may involve visceral motility, you should think about diabetic gut. You should also think about patients who may have bacterial overgrowth. We are starting to see this overlap now even in patients who we labeled with irritable bowel syndrome. Think about it in particular as you start to evaluate the bariatric surgery patients, because these patients may be more subjected to a stasis of the GI tract. These patients may have more of a gassiness component to their diarrhea. Think about bacterial overgrowth, because sometimes a short course of a broad-spectrum antibiotic (in particular, rifaximin) will be very helpful for these patients.

If you are looking at a patient who is elderly, think about patients who have overflow diarrhea. Their perception is that this is diarrhea, but they may have a fecal impaction and they may be even having diarrhea as an overflow impaction, so again we clearly need to keep this in mind. A digital exam may be helpful but it may be necessary to have a KUB [kidney-ureter-bladder x-ray] to help detect a fecal impaction above the rectum. I use a gastrograffin enema x-ray for cases in which this high fecal impaction still cannot be fully excluded. This test is helpful for both diagnosis as well as treatment, as the hyperosmolar contrast frequently induces a bowel movement.

Weight loss always triggers to me a whole differential diagnosis that drives me to a more rapid and more aggressive approach to evaluating these patients. So [keep it] very simple. Think about systemic features that are what I call alarm signs. Is there evidence of bleeding that will lead to a whole different approach? This is not a simple diarrhea; this is more of an inflammatory diarrhea. Think about problems that may have occurred by a change in their diet, a change in their weight, or a change in their medications. Ask about other supplements.

A key that might become pertinent to this 35-year-old woman I just talked to you about is: what else is the patient doing with their ancillary intake, that is, during the day, what else do they do? Remember, this patient was a little overweight. She had been having some reflux symptoms. Ask about over-the-counter medications. Ask about the use of over-the-counter dietetic types of sweeteners. What became very apparent in this patient was that she was using a dietetic candy on a regular basis because she was trying to avoid caloric intake. She was taking some dietetic candy, and these things very frequently, if not uniformly, have mannitol or sorbitol, which are not absorbed, so they induce an osmotic component to the stool. So this patient was at risk for osmotic diarrhea. Remember, she had heartburn, so she was also taking frequent doses of Mylanta. Magnesium-containing products for heartburn may actually cause more problems in that setting because this creates an osmotic diarrhea.

Diagnostic Approach to Chronic Diarrhea

What do you do for this patient? What is my drill down to how I approach patients?

Well, I go for my best guess as to what is causal. If I am thinking osmotic diarrhea I talk to them about things like lactose deficiency. I talk to them about their medications. In this case the patient was taking medications which may create a diarrhea.

What would I do as a diagnostic work-up?

I would start first with simple things. I would start with a good history because this is going to steer you very quickly into a differential that will drive you, because I think you can get way overextended on the diarrhea work-up.

I would start with a basic metabolic panel. I want to see if this patient is hypokalemic or has some nutritional evidence of anemia by CBC [complete blood count], microcytosis or something that would drive macrocytosis, a B12 deficiency. We think about small bowel disease, iron deficiency, the same. Again you think about patients who have evidence of overt bleeding. You would think about early intervention with an endoscopic procedure and that would most frequently involve colonoscopy.

Stool studies are pretty cheap and easy. I start with a stool fecal leukocyte test. If I suspect a secretory diarrhea, I will do stool electrolytes. What does that mean? I order a stool sodium and a stool potassium. What do you do with that? You take the stool sodium plus the stool potassium, multiply by 2, and then subtract it from 290, the estimated stool osmolarity. This number is what is called the osmotic gap. Patients who have osmotic diarrhea, for example, those with lactose deficiency or some patients that have occult use -- in this patient's case sorbitol- or magnesium-containing products, those patients would have a high osmotic load. Take their osmotic gap, that is, 290 - 2 (Na + K); if it is greater than 50, this makes you think more about osmotic diarrhea. The pearl here is that if the diarrhea is due to an osmotic cause, the osmotic gap is almost always over 100.

Secretory diarrhea drives you toward the much more rare types of diarrhea. You are thinking about things like Zollinger-Ellison syndrome, gastrinomas, and other neuroendocrine tumors (carcinoid tumors). These are very unusual, so it is not very cost-effective to profile all of these patients with chronic diarrhea and you are starting to look at global work-up. I would again focus those for secretory diarrhea if it is truly defined.

You may find a patient who has bile salt diarrhea, and this is something that is frequent in a patient after a cholecystectomy. Bile salt dumping in those patients may respond very nicely to a bile salt binding agent like Welchol or one of the cholestyramine-type products. In the patient who provides a good historical association to diarrhea onset after having a cholecystectomy, I wouldn't do much more initially than to try them empirically on a bile salt binding-type therapy. You would extend your work-up subsequently if the patient did not quickly respond in a week or two.

So my diagnostic work-up would include a CBC with differential, a comprehensive metabolic profile looking for some evidence of malabsorption from the albumin, and renal insufficiency. Changes suggestive of electrolyte disturbances would skew me toward a lot more aggressive work-up. I would include stool studies, ova and parasites, fecal leukocytes, and, if you think warranted, stool electrolytes and a qualitative fecal fat. Qualitative fecal fat will be helpful if it is positive. You just order a qualitative fecal fat on a random stool specimen. If it is negative, it doesn't rule out significant steatorrhea, because basically you have to challenge them with a diet containing 100 g/day of fat before you can actually evaluate that patient adequately. If, however, the qualitative fecal fat is positive, it just means they are dumping a lot of fat into their stool, which again may steer you toward more evaluation for malabsorption. Certainly it will steer you toward the definition of either small bowel or pancreatic malabsorption, and those work-ups would be appropriate as you define that.

I would consider the possibility of celiac disease in the patient. Don't miss this one. This is a pretty common diagnosis as reportedly approximately 1% of the population has the gene for celiac disease. If you are thinking about celiac disease, there is a serologic profile to look at the antigliadin antibodies and the tissue transglutaminase. This is something in the endomysial antibody. The pearl here is that if you order a celiac profile, make sure you get the IgA (immunoglobulin A). About 3%-5% of patients are IgA deficient, and, if they are IgA deficient, their celiac profile will be erroneous and it will not be positive. About 10% of patients who are IgA deficient will actually have celiac disease. So make sure you order an IgA in your celiac evaluation.

We are seeing a lot of patients with bacterial overgrowth -- think about the [patients who have undergone] GI bypass, obese patients, patients who have had previous GI surgery, perhaps the diabetic patients and patients with scleroderma.

Microscopic colitis is something I think almost any time I have a chronic diarrhea that I can't really define; if the patient has not had a recent colonoscopy, I will push that patient toward a colonoscopy. Ask your gastroenterologist, and make sure they do biopsies appropriately for that.

Conclusion

If we come back to our patient, I would say that we have a 35-year-old [woman] who is a little bit overweight and who has a little bit of heartburn. In taking a good history, we know this patient was taking some mints on a regular basis to try not to overeat and these [mints] had sorbitol. She is also taking magnesium-containing products for her heartburn. This is a simple solution to this patient without a whole lot of diagnostic testing. Again, the key is the keep it simple, stupid, or KISS, principle. Make it easy. Take a good history. Direct your work-up appropriately.

Hopefully I have given you some practical tips for your next patient with chronic diarrhea. I am Dr. David Johnson. Thanks for listening. I look forward to our continued interactions in the series GI Common Concerns -- Computer Consult.

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