A case of chronic diarrhea

Clinical pearls for frontline PCPs

A 65-year-old woman presents for evaluation of a 6-month history of chronic diarrhea. She has generally been healthy throughout her life.

The medical assistant (MA) checks her in and notes normal vital signs, including a weight of 180 lbs, which was essentially the same as her weight at her annual physical exam 9 months ago. Her only medication is levothyroxine 100 g daily and as-needed clobetasol ointment when her psoriasis flares up. She had a normal screening colonoscopy about 7 years ago. Her only surgeries include an appendectomy and a gastric bypass done about 30 years ago.

The MA summarizes the intake for the physician: “Doc, Mrs. Jones comes in reporting about a 6-month history of frequent watery stools — probably five to eight per day. She hasn’t traveled anywhere unusual in the past year. Her only meds are thyroid and a steroid ointment, though she doesn’t use the ointment very often. Her appetite is good, and she feels well otherwise. Her weight is about the same as it was at last year’s physical. She’s just sick of pooping all the time. She also has had accidents a few times per week, which have been very embarrassing.”

The physician enters the room and asks more questions. The patient appears nontoxic. Her vital signs are normal. She has not traveled anywhere in the past year. She describes her stool using the Bristol stool form scale as type 7 — watery with no solid pieces, and she reports having five to eight stools a day. No blood or melena has been noted. No specific foods seem to make it better or worse. She has tried cutting out lactose- and gluten-containing foods without significant change in bowel habits. She denies fevers, abdominal pain or abdominal bloating. Before the onset of her symptoms, she always had a normal bowel pattern. She has never been an alcohol drinker. She is a proud blood donor, giving over 2 gallons of blood over the past 2 decades. There is no family history of intestinal-related issues.

Her physical exam is normal, except for a few slightly raised small psoriatic plaques on both elbows. Abdominal exam is normal, and the rectal exam is notable only for perianal redness from the loose stools. No fistulae were noted. Stool was hemoccult negative.

“Mary, I’m not sure what’s causing your loose stools, but it sure seems annoying for you,” the physician says. “Let’s get some lab work to see if we can identify the likely cause.”

The physician orders screening labs including C-reactive protein (CRP), a comprehensive metabolic panel (CMP), fecal calprotectin, a complete blood count (CBC) and celiac disease testing.

The test results come back the next week:

• CRP: 0.5;
• CMP: normal except for a potassium of 3.2;
• Fecal calprotectin: 175 g/mg (elevated);
• CBC: normal without leukocytosis or anemia; and
• Celiac testing: normal IgA antibody (Ab) level, and the patient’s tissue transglutaminase Ab is 5 U/mL (< 4 U/mL is negative; 4 U/mL to 10 U/mL is weakly positive; and > 10 is positive).

The physician reviews the results and sends Mary a note through the patient portal:

“Mary, I don’t think that there is any evidence to suggest bleeding in the intestine. The celiac testing was negative. The complete blood count was normal, without evidence for anemia. The metabolic panel was notable only for a low potassium, which is likely related to the chronic diarrhea. We will treat that temporarily with potassium replacement. The stool test came back elevated, which is often due to inflammation of the inner lining of the colon. This could be due to either Crohn’s disease, ulcerative colitis or something called microscopic colitis. I am not sure which of the three main types of colitis is causing your diarrhea. I think that the next step is to have you meet with one of our gastroenterologist physicians for a colonoscopy. That will allow him or her to look at the inner lining of the colon to help us sort this out.”

Philip A. Bain

The GI physician finds two polyps on colonoscopy that come back as adenomas (possibly precancerous), and these are completely removed. The inner lining of the colon looks essentially normal, but the pathologist reports that three of the samples biopsied had significant inflammation cells (lymphocytes).

Back in the PCP’s office, the physician says, “Mary, the GI doctor found two polyps that were possibly precancerous though were not cancer and could not explain the loose stools. She biopsied the inner lining of the colon, even though it looked normal to her during the exam. The path reports came back showing significant microscopic inflammation. I think that your loose stools are due to a condition called microscopic colitis. Fortunately, this is treatable and I will give you two medications — one to slow the stools down (loperamide), and the other to treat the inflammation (budesonide). Although budesonide is a steroid like prednisone, it has the unique property of starting to work just before it gets to the colon, so the chance of it causing more problems like prednisone, including brittle bone disease, diabetes and other steroid-related side effects, is low.”

The office nurse calls Mary about a month after starting the two medications, and Mary reports that she was somewhat better — her stools were less watery and had decreased to one to four per day. The loperamide made her life more manageable, and she was no longer having “accidents,” fortunately. At the 3-month follow-up office visit, she was markedly improved, having one to two semiformed bowel movements per day. The physician keeps her on the budesonide for 3 more months and then stops it. At her annual physical exam visit, she reports that her diarrhea has not returned.

Lessons learned:

1. Chronic diarrhea is a relatively common disorder in an ambulatory primary care practice. Diarrhea is typically defined as more than three stools in a 24-hour period. Acute diarrhea is defined as less than 4 weeks (usually less than 2 weeks), whereas chronic diarrhea is more than 4 weeks in duration. Acute diarrhea is usually caused by an infection in the intestines.
2. There are many causes of chronic diarrhea and generally have to be separated by whether the patient lives in a resource-rich or resource-poor country, because the causes are significantly different between the two. In resource-rich countries, irritable bowel syndrome (IBS) is a very common cause of diarrhea and is nearly always associated with crampy abdominal pain. Using the Rome criteria for IBS can be useful in deciding whether IBS is the culprit. Lactose intolerance is common, especially among certain demographic groups. For example, up to 85% to 90% of Asian Americans have lactose intolerance. Celiac disease is somewhat common, affecting at least 1% of the U.S. population, although many more have gluten intolerance without frank celiac disease.
3. Using the Bristol stool form scale can help the patient more accurately describe their stool.
4. Symptoms that can occur with the loose stools include abdominal pain, nausea and vomiting, fever, weight loss, bloating, rectal urgency, blood or mucus in the stool, and fecal incontinence. These can help narrow down the cause. Stool characteristics that can be useful in diagnosis include bloody stools, fatty/greasy stools or dark melenic stools.
5. Alarming symptoms that would prompt more urgent evaluation include weight loss, unstable vital signs including fever, tachycardia, and/or hypotension, age older than 50 years, severe abdominal pain and/or bloody stools. Diarrhea that occurs at night and disturbs sleep is also another red flag.
6. Various conditions can occur in association with certain causes of chronic diarrhea, including autoimmune disorders like hyperthyroidism, rheumatoid arthritis, psoriasis and dermatitis herpetiformis associated with celiac disease.
7. The initial step in evaluating a patient is to take a good history — noting the precise description of the stool, frequency, occurrence at night, risk factors, comorbid conditions, recent infections, recent travel, HIV or another immune-compromising condition and what medications the patient is taking. Physical exam is usually normal.
8. Lab testing involving the “5 Cs” — CRP, CBC, CMP, celiac testing and fecal calprotectin — can narrow the possibilities down considerably. If these are not helpful in nailing down a definitive diagnosis, a colonoscopy is usually warranted. In general, stool cultures are not helpful except if there is a high pretest probability based on the history for Giardia.
9. Fecal calprotectin is a better test to screen for inflammatory bowel disease than fecal leukocytes.
10. Once the diagnosis has been made, management usually involves symptomatic treatment like loperamide, psyllium, bismuth subsalicylate and/or cholestyramine, as well as disease-specific treatments such as budesonide for most causes of inflammatory bowel disease, which include Crohn’s disease, ulcerative colitis and microscopic colitis.
11. Microscopic colitis is a relatively uncommon disorder causing chronic diarrhea often seen in older patients and in women. The mucosal lining typically looks grossly normal and is diagnosed by finding either collagen and/or elastase (collagenous colitis) or excessive leukocytes (microscopic colitis) on biopsy. It is not known exactly what causes microscopic colitis, but it is generally thought that genetic factors and autoimmune responses play a role. Certain medications that affect the inner lining of the colon and smoking increase the risk for microscopic colitis. Whereas other inflammatory conditions like Crohn’s disease and ulcerative colitis increase the risk for developing colon cancer, microscopic colitis does not.

References:

• Burgers K, et al. Am Fam Physician. 2020;101(8):472-480.
• Descoteaux-Friday GJ, Shrimanker I. Chronic Diarrhea. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544337/. Accessed Sept. 11, 2024.
• Hempel KA, Sharma AV. Collagenous and Lymphocytic Colitis. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541100/. Accessed Sept. 11, 2024.
• Tome J, et al. Mayo Clin Proc. 2021;doi:10.1016/j.mayocp.2021.03.022.