1. 1
    Current Diagnosis


    • Duration and frequency

    •   Presence of fever/blood

    •   Food/medication intake

    •   Travel history

    Physical Examination

    •   Gastrointestinal examination

    •   Hydration status

    •   Digital rectal examination

    •   Other systems: endocrine, ophthalmologic, skin


    •   Fecal occult blood testing

    •   Stool for ova/parasites, C. difficile and other bacteria

    •   Stool antigen for cryptosporidium, giardia

    •   Fecal electrolytes (Na, K, Osm)

    •   Fecal leukocytes

    •   Erythrocyte sedimentation rate (ESR)

    •   Complete blood count (CBC)

    • Other: iron panel (celiac sprue), TSH (hyperthyroidism), liver function tests (LFTs)

    •   Colonoscopy with biopsy

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  2. 2
    Current Therapy

    • Supportive care and rehydration, if necessary

    • Trial of discontinuation of possible offending medication/food (lactose, gluten, sorbitol)

    • Dietary modification with increased fiber intake (dietary or supplementation)

    •   Specific therapy as directed by culture and susceptibilities or biopsy

    •   Empiric therapy trial with antibiotics

    • Empiric trial of probiotics1  (limited evidence of efficacy in healthy adults with chronic diarrhea)

    1 Not FDA approved for this indication.

    Chronic diarrhea has traditionally been defined based on consistency, volume, and frequency of stools. However, recent studies have found that there is considerable variability in definition when using these markers. Therefore, the American Gastroenterological Association has released a consensus statement suggesting that chronic diarrhea should be defined as a decrease in fecal consistency lasting for 4 or more weeks.

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  3. 3

    Chronic diarrhea is a common cause of mortality in developing countries as well as the second leading cause of overall mortality in children 1 to 59 months old. The prevalence in the general population in developed nations and economic impact of chronic diarrhea has not been well established. This could be related to the variable nature of the studies that have been performed with regard to definition, population characteristics, and overall study design. Rough estimates based on this limited information suggest that chronic diarrhea can affect up to 5% of the population and can cost up to $350,000,000 annually from work loss alone.

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  4. 4
    Classification Based on Pathophysiology

    Elucidating the exact cause of chronic diarrhea can be very challenging, as there are several hundred conditions that can be related. It is often separated into three basic categories, including watery, fatty (malabsorption), and inflammatory (with blood and pus); however, these should not be strictly adhered to as there is often considerable overlap between the categories. Watery diarrhea can be further subdivided into osmotic, secretory, drug-induced, and functional types. Osmotic diarrhea is related to water retention; secretory diarrhea is due to reduced absorption of water; drug- induced is as stated in its name; and functional diarrhea is due to hypermotility of the gut.

    Watery Diarrhea

    Watery diarrhea can be subdivided into four categories, including osmotic, secretory, drug-induced, and functional types. Fecal osmotic gap can be calculated, which will help guide further workup and diagnosis. An elevated osmotic gap (> 125 mOsm/kg) is suggestive of possible osmotic causes, such as lactose intolerance. A normal osmotic gap can be associated with irritable bowel syndrome or may be indicative of a further workup for possible celiac disease. A decreased osmotic gap (< 50 mOsm/kg) points toward secretory causes, including infectious (ova, parasite, bacteria, giardia), endocrine (hyperthyroidism), autoimmune (Addison’s), neoplastic (pheochromocytoma), and anatomic defect.

    Fatty/Malabsorptive Diarrhea

    Malabsorptive diarrhea is, as the name implies, secondary to impaired absorption along the gut. This can be due to structural abnormalities (gastric bypass, short bowel syndrome, celiac sprue, pancreatic insufficiency) or structural abnormalities related to vascular compromise (mesenteric ischemia). Impaired absorption can also occur secondary to infections such as Tropheryma whipplei (Whipple’s disease), Giardia, small bowel bacterial overgrowth, and tropical sprue. Medications such as aminoglycoside antibiotics, orlistat (Alli, Xenical), thyroid supplementation, acarbose (Precose), and ticlopidine (Ticlid) can also cause malabsorptive diarrhea.

    Inflammatory Diarrhea

    Inflammation leading to diarrhea is often due to autoimmune, infectious, or neoplastic processes or radiation exposure. Autoimmune processes are felt to play a large role in inflammatory bowel disease (IBD), which often manifests as Crohn’s disease or ulcerative colitis.

    Infections such as Clostridium difficile, Mycobacterium tuberculosis, Yersinia, cytomegalovirus, herpes simplex virus, amebiasis, and Strongyloides can lead to a diarrhea with associated inflammation of the bowel. Colon cancer (villous adenocarcinoma) and lymphoma can also cause inflammatory diarrhea.

    Clinical Manifestations History

    Thorough investigation of a patient complaining of ongoing diarrhea- like features should always include a detailed medical history. A clear understanding of the patient’s symptoms is vital: not all complaints may truly be defined as diarrhea but may rather be symptoms related to an interplay between fecal incontinence and stool impaction. A detailed history of travel, food intake, and medication use is essential. This can help direct the early workup and diagnostic testing. Stool frequency, volume, and consistency can aid in categorization; however, they are no longer what define the condition, as noted above.

    Physical Examination

    The physical examination is very important to the workup and diagnosis of chronic diarrhea. Ophthalmologic findings such as episcleritis or exophthalmia can be related to IBD; skin findings such as dermatitis herpetiformis can be related to celiac sprue (seen in 15– 25% of patients with celiac disease). Prominent lymphadenopathy and weight loss can be suggestive of possible infection or malignancy. A thorough abdominal examination should include the evaluation of bowel sounds (hypermotility), skin for scars (surgical cause of diarrhea), tenderness (infection/inflammation), and masses (neoplasia) and should be followed by a digital rectal examination with fecal occult blood testing. Anoscopy can also be employed to detect for ulcerations or fecal impaction, given that seepage around impacted stools can create a picture similar to diarrhea.

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  5. 5
    Testing for Diagnosis

    Serum testing for chronic diarrhea should include a complete blood count (CBC), serum electrolytes, liver function tests, serum albumin, thyroid-stimulating hormone, and erythrocyte sedimentation rate. An iron panel should be performed if indicated based on the results of the CBC. Serum anti-tissue transglutaminase antibody testing may be helpful if symptoms are suggestive of celiac sprue. Stool evaluation may include fecal occult blood testing, fecal leukocytes, stool ova and parasites, stool culture (including Salmonella, Shigella, and Campylobacter), and stool antigen for Giardia. Stool testing for Cryptosporidium should be considered, especially in the immunocompromised. Stool pH and electrolytes may be helpful, especially when the patient is lactose intolerant. Stool testing for C. difficile should be performed if the patient has recently used antibiotics or been hospitalized. If medication abuse is suspected as a possible cause, a stool laxative screen (i.e., stool phenolphthalein test) may be warranted. Diagnostic testing may include a colonoscopy with biopsy.

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  6. 6

    The exact cause of chronic diarrhea can prove elusive, and treatment trials may be warranted. Specific treatment depends on the specific diagnosis. If there is concern of possible bacterial or protozoa infection, an empiric trial of vancomycin (Vancocin), ciprofloxacin (Cipro), or metronidazole (Flagyl) may be warranted. If there is concern for possible medication (Table 1) or food relation to diarrhea, a trial of discontinuation of offending substance/food may be reasonable. The effectiveness of probiotics1 looks favorable; however, large intervention studies and epidemiologic investigations of long- term probiotic effects on healthy adults are largely missing. At this time, probiotics have been found efficacious in treatment of acute diarrhea, prevention of antibiotic-associated diarrhea, and prevention of traveler’s diarrhea. Dietary modification continues to be an important starting point for treatment with increased intake in bulk forming agents such as fiber. Treatment of specific disorders such as Crohn’s disease and ulcerative colitis are discussed in other chapters.

    Table 1

    Medications Commonly Associated with Diarrhea


    Data from Schiller LR, Sellin JH. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th Edition, Philadelphia, 2010, Elsevier; and Soriano M, Vaziri H. Clinical Gastroenterology, Diarrhea: Diagnostic and Therapeutic Advances, New York, 2010, Humana Press,  Springer.

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  7. 7

    De Vrese M., Marteau P.R. Probiotics and prebiotics: Effects on diarrhea. J Nutr. 2007;137:8035–8115.

    Everhart J.E., ed. Digestive Disease in the United States: Epidemiology and impact. Washington, DC: National Institutes of Health; 1994 NIH Publication No. 94-1447.

    Fine K.D., Schiller L.R. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology.


    Juckett G., Trivedi R. Evaluation of chronic diarrhea. Am Fam Physician. 2011;84:1119–1126.

    Rodrigo L. Celiac disease. World J Gastroenterol. 2006;12:6585– 6593.

    Soriano M., Vaziri H. Clinical Gastroenterology, Diarrhea: Diagnostic and Therapeutic Advances. New York: Humana Press, Springer; 2010.

    Thomas P.D., Forbes A., Green J., et al. Guidelines for the investigation of chronic diarrhea, 2nd edition. Gut.

    2003;52(Suppl. 5):v1–v15.

    Whitehead W.E., Borrud L., Goode P.S., et al. Fecal incontinence in U.S. adults: Epidemiology and risk factor. Gastroenterology. 2009;137:512–517 e2.

    World Health Organization. Children: Reducing mortality, Fact Sheet #178, Available at (accessed October 17, 2013).

    1  Not FDA approved for this  indication.

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