During the rectal exam, the clinician should note if the patient is wearing a pad or diaper for fecal leakage, the presence of hemorrhoids, and the type of stool in the rectal vault (whether it is soft or hard and if any blood is noted). Furthermore, assessment of the anal sphincter tone at rest and with squeeze will characterize sphincter function. In those with a history of constipation, straining with bowel movements, a sense of incomplete evacuation and perhaps even a need for digital manipulation of the perianal region to facilitate a bowel movement, a detailed rectal examination can be helpful to include or exclude pelvic floor dysfunction, including palpation of the pelvic floor muscles for tenderness and spasticity, assessment of pelvic floor and sphincter relaxation, and assessment of perineal descent. However, physical exam findings are imperfect and a specific test of anorectal and pelvic floor function, such as an anorectal manometry with balloon expulsion, is recommended for confirmation.
The findings on history and physical exam discussed above should direct a common sense approach to diagnostic testing in patients with chronic diarrhea. When there is a clear relationship between the symptoms and intake of particular foods, such as sugar alcohols, lactose, or fructose, then a trial of food elimination and a symptom diary is recommended with no additional testing. Similarly, if a suspect medication or supplement can be stopped without the risk of adverse effects, this should be considered.
If celiac disease is suspected, prior to recommending a gluten-free diet, the diagnosis should be confirmed with celiac serologies and an esophagogastroduodenoscopy (EGD) with duodenal biopsies (Fig. 3). Empiric gluten restriction without histologic confirmation of celiac disease is not recommended. Self-directed gluten-free diets are seldom completely gluten free, and to avoid accidental ingestion through lesser known sources such as medications and spices, consultation with a knowledgeable dietitian is essential. Also, celiac disease can have serious clinical consequences, such as osteoporosis, infertility, anemia, and vitamin and mineral deficiencies, which must be screened for and treated if present.
Microscopic colitis has similar symptoms as IBS and the only way to distinguish these two is with colonic mucosal biopsies. However, IBS is much more common, and in patients with mild symptoms and a lack of alarm symptoms, such as fevers, bleeding, and significant weight loss, empiric treatment with antidiarrheals may be acceptable before pursuing colonoscopy. In others who have more severe symptoms, or if conservative therapy fails, further testing to rule out organic testing is indicated. In addition, an opportunity for age-appropriate colorectal cancer should not be missed even in the absence of alarm features. If a patient with chronic diarrhea undergoes colonoscopy, mucosal biopsies should be obtained to assess for microscopic colitis (Fig. 4) and other less common disorders such as eosinophilic colitis. If a patient has undergone appropriate colorectal screening with a recent colonoscopy, then a flexible sigmoidoscopy with biopsies from the left colon requires less preparation and is less costly while diagnosing up to 90% of microscopic colitis cases .
In most patients with chronic diarrhea, basic laboratory tests such as complete blood count and a comprehensive metabolic profile are reasonable first tests to exclude anemia, electrolyte disturbances, and a high leukocyte count. Additional blood tests can be considered depending on the differential diagnosis such as a thyroid stimulating hormone in a patient suspected to have hyperthyroidism.
If this initial workup is negative or when the clinical presentation fits a functional disorder such as IBS without alarm features, treatment can be initiated empirically before further testing. For example, in suspected functional diarrhea or diarrhea predominant IBS, an antidiarrheal such as loperamide can be helpful. In a patient suspected of having constipation with overflow diarrhea, a bowel regimen such as with regular use of polyethylene glycol can be considered, particularly after pelvic floor dysfunction has been excluded. In those who develop diarrhea after a cholecystectomy or ileal resection, an empiric trial with a bile acid binder is recommended. However, it is becoming increasingly recognized now that patients with other forms of chronic diarrhea may also have bile acid malabsorption. For example, bile acid diarrhea is thought to play a role in as many as one-third of patients with diarrhea predominant IBS [6▪]. If abdominal pain and diarrhea coexist, then neuromodulators such as tricyclic antidepressants can be used for their anticholinergic and thus constipating effects.
For patients with ongoing diarrhea without a diagnosis despite the above testing, particularly those with severe symptoms or diarrhea that does not respond to empiric antidiarrheal therapy, additional testing is necessary. At this point in the evaluation, it may be helpful to perform stool testing. In those with travel history to or recent immigration from endemic areas such as Asia and sub-Saharan Africa, a 3-day stool ova and parasite collection can help rule out pathology such as hookworm . Evaluation with a 48–72 h stool collection while consuming a high-fat diet characterizes stool volume, is helpful in assessing for pseudodiarrhea, and for determining the presence of steatorrhea (pancreatic insufficiency, SIBO, and small bowel mucosal disease). Assessing stool electrolytes can broadly categorize the diarrhea into secretory (osmotic gap <50 mmol/kg) and osmotic (osmotic gap >75 mOsm/kg, e.g., osmotic laxatives, fructose, or lactose malabsorption) mechanisms. Assessing stool leukocytes and blood can determine the presence of inflammatory diarrhea, although clinical features, such as frank blood, significant abdominal pain, or fever are usually present and such testing is not always needed. Assessing stool pH can give an indication of carbohydrate malabsorption (pH < 5.5), as can specific breath testing (e.g., hydrogen breath testing for lactose intolerance), although a careful history is often sufficient in these cases.
Carcinoid tumor is an uncommon cause of chronic diarrhea and indiscriminant testing with urinary 5-hydroxyindoleacetic acid has a very low yield. However, this yield is higher in patients who have flushing, hepatomegaly and/or a cardiac murmur. Pancreatic function testing such as via secretin stimulation test, although specific, is not readily available. If steatorrhea is suspected and small bowel mucosal disease has been ruled out with a normal small bowel biopsy, then evaluation of the pancreas to exclude malignancy or chronic pancreatitis is indicated with dedicated pancreatic imaging such as a thin cut abdominal computed tomography scan with attention to the pancreas or endoscopic ultrasound. If steatorrhea is confirmed and serious pancreatic pathology is excluded, then a trial of pancreatic enzymes is reasonable, although this must be done properly to provide useful clinical information. Additionally, in those where Crohn's disease (inflammatory diarrhea, weight loss, and abdominal pain) is in the differential diagnosis, cross-sectional imaging to evaluate small bowel such as a computed tomography or MRI enterography is indicated.
Since currently, testing for bile acid malabsorption is not readily available in most centers in the United States, an empiric trial of bile acid binding resins such as cholestyramine is reasonable, particularly in patients whose diarrhea started after loss of ileal function via disease or surgery or after a cholecystectomy. In patients with a relevant history, such as scleroderma, strictures or surgically altered anatomy, hydrogen breath tests for SIBO may be helpful. However, the sensitivity and specificity of this test is highly variable [8–10][8–10][8–10], such that some practitioners use an empiric antibiotic trial based on strong suspicion and careful assessment of the risks and benefits involved. Alternatively, one can consider a duodenal aspirate for bacterial cultures to assess for SIBO, particularly if an upper gastrointestinal endoscopy will be performed to exclude other causes.
Visual clues on EGD that can be helpful, include furrowing and scalloping (celiac disease), ulcers (Crohn's disease or NSAID enteropathy), and white punctuate marks (lymphangiectasia). However, these findings are insensitive and nonspecific, and even if an EGD is endoscopically negative, duodenal biopsies should be obtained to rule out small bowel pathology such as celiac sprue, and less common entities, such as giardiasis, eosinophilic gastroenteritis, tropical sprue, and Whipple's disease. Particularly for celiac disease, multiple duodenal biopsies (>6) from the duodenum, including the duodenal bulb as well as the second and third parts of the duodenum, should be obtained . Similarly, even a normal appearing colon should be biopsied in patients with chronic diarrhea to assess for microscopic colitis. A colonoscopy with biopsies can provide a histological diagnosis in approximately one-third of chronic diarrhea cases . Obtaining biopsies from a normal appearing terminal ileum is not recommended since they are unlikely to be helpful [13,14][13,14].
Finally, hormone secreting tumors as a cause of chronic diarrhea are often considered but rarely found. There are a large number of potential tests that can be done to assess for these disorders, but the tests are expensive, and when performed indiscriminately will lead to unnecessary expense and an unacceptably high false positive rate.
Chronic diarrhea can be quite distressing to patients, and achieving an early diagnosis and effective treatment plan is paramount. Clues are often provided in the symptomatology and physical examination which should not be overlooked. These features may promote a logical, efficient, and cost-effective approach to ordering tests and procedures, and ultimately to treatments that improve patient well-being and quality of life.
We would like to thank Thomas C. Smryk, MD and Carilyn N. Wieland, MD for providing figures for this review.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
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Keywords:Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
chronic diarrhea; evaluation; management