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Diarrhea, Chronic

Diarrhea, Chronic is a topic covered in the 5-Minute Clinical Consult.

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  • An increase in frequency of defecation, urgency, or decrease in stool consistency (typically >3 loose stools per day) for >4 weeks (1,2)
    • Abnormal form is the most important defining factor; frequent defecation with normal consistency is termed pseudo-diarrhea (2).
  • Etiologies include osmotic, secretory, malabsorptive, inflammatory, infectious, and hypermotility.
  • Infectious causes of chronic diarrhea are uncommon in immunocompetent patients. Parasitic etiologies are more common than bacterial.


Varies by etiology, overall ~3–5% of the population in developed countries is affected (2).

Etiology and Pathophysiology

Chronic diarrhea is typically the result of disturbances in intestinal luminal water and electrolyte balance.

  • Osmotic (fecal osmotic gap >75 mOsm/kg) (2)
    • Carbohydrate malabsorption
      • Disaccharides including lactose
      • Monosaccharides including fructose
      • Polyols including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)— cannot be metabolized and create an osmotic gradient
    • Magnesium, phosphate, and sulfate overload
  • Secretory (fecal osmotic gap <50 mOsm/kg) (2)
    • Stimulant laxative ingestion
    • Postcholecystectomy
      • Excessive intestinal bile salts cause choleretic diarrhea; often resolves in 6 to 12 months
    • Ileal bile acid malabsorption
    • Ileal resection of <100 cm leads to choleretic diarrhea due to excessive colonic bile salts.
    • Disordered motility
      • Postvagotomy
      • Diabetic autonomic neuropathy
      • Hyperthyroidism
    • Neuroendocrine tumors
      • VIPoma
      • Gastrinoma
      • Somatostatinoma
      • Carcinoid syndrome
    • Metastatic medullary carcinoma of the thyroid
    • Systemic mastocytosis
    • Protein-losing enteropathy
  • Malabsorption (2)
    • Celiac disease
    • Whipple disease
    • Giardiasis
    • Short bowel syndrome
      • Ileal resection of >100 cm leads to insufficient bile salt concentrations in the duodenum for optimal fat absorption, leading to fat and fat-soluble vitamin malabsorption.
    • Small intestinal bacterial overgrowth
    • Pancreatic exocrine insufficiency (cystic fibrosis [CF], chronic pancreatitis)
    • Inadequate bile acid production/secretion
  • Inflammatory (2)
    • Ulcerative colitis
    • Crohn disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Vasculitis
    • Radiation enterocolitis
    • Eosinophilic enterocolitis
  • Hypermotility (normal fecal osmotic gap) (1,2)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
  • Drugs (2)
    • Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, SSRIs
    • Factitious diarrhea: excessive laxative use
  • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, aloe vera
  • Infectious (2)
    • Bacterial: Clostridium difficile, Mycobacterium avium intracellulare
    • Viral: cytomegalovirus
    • Parasitic: Giardia lamblia, Cryptosporidium, Isospora, Entamoeba histolytica
    • Helminthic: Strongyloides
  • Food allergies (2)
  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II antigen-presenting cells (3).
  • IBD is polygenic (4).
  • CF is caused by a mutation in the CF transmembrane conductance regulator (CFTR), resulting in abnormal exocrine gland secretions.

Risk Factors

  • Osmotic
    • Excessive ingestion of nonabsorbable carbohydrates
    • Lactose intolerance
    • Celiac disease
  • Secretory (2)
    • Postsurgical: extensive small bowel resection/ileal surgery, vagotomy, bile acid malabsorption
    • History of neuroendocrine disease
    • History of stimulant laxative abuse
    • Dysmotility syndromes
  • Malabsorptive
    • CF
    • Chronic alcohol abuse
    • Chronic pancreatitis/pancreatic insufficiency
    • Celiac disease
    • Medications (e.g., orlistat, acarbose)
  • Inflammatory
    • Inflammatory bowel disease (IBD)
    • NSAID use
    • Thoracoabdominal radiation
    • HIV/AIDS
    • Antibiotic use
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress
    • Preceding infection
  • Genetic predisposition

Diabetes mellitus and/or prior cholecystectomy both cause secretory and osmotic diarrhea.

General Prevention

Varies by etiology; treat the underlying cause.

Commonly Associated Conditions

  • Extraintestinal manifestations of IBD include arthralgias, aphthous stomatitis, uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, perianal fistulas, rectal fissures, ankylosing spondylitis, and primary sclerosing cholangitis.
  • Celiac disease is associated with dermatitis herpetiformis, type 1 diabetes, other autoimmune disorders and IgA deficiency.
  • Many patients with IBS have behavioral comorbidities.
  • Latex-food allergy syndrome: associated allergies to latex and banana, avocado, kiwi, and walnut (2)

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Stephens, Mark B., et al., editors. "Diarrhea, Chronic." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116185/all/Diarrhea__Chronic.
Diarrhea, Chronic. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116185/all/Diarrhea__Chronic. Accessed April 18, 2019.
Diarrhea, Chronic. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116185/all/Diarrhea__Chronic
Diarrhea, Chronic [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 18]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116185/all/Diarrhea__Chronic.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Diarrhea, Chronic ID - 116185 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116185/all/Diarrhea__Chronic PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -