Diarrhea, Chronic

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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 stool form is the most important defining factor; frequent defecation with normal consistency is termed pseudodiarrhea (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 luminal water and electrolyte balance within the intestine.

  • 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) (2,3)
    • 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
    • Adrenal insufficiency
    • Noninvasive infection: giardiasis, cryptosporidiosis
    • Microscopic colitis (lymphocytic or collagenous)
    • Protein-losing enteropathy
    • Idiopathic secretory diarrhea
  • Malabsorption (2,3)
    • Celiac disease
    • Whipple disease
    • Giardiasis
    • Chronic mesenteric ischemia
    • Lymphatic obstruction
    • 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 (2,3)
    • Ulcerative colitis; Crohn disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Vasculitis; radiation enterocolitis
    • Eosinophilic enterocolitis
    • Invasive or inflammatory infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
  • Hypermotility (normal fecal osmotic gap) (1,2)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
  • Drugs (2,3)
    • Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, SSRIs, β-blockers
    • Factitious diarrhea: excessive laxative use
  • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, Aloe vera
  • Infectious (2)
    • Bacterial: C. difficile, Mycobacterium avium intracellulare
    • Viral: cytomegalovirus
    • Parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. 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 (4).
  • Inflammatory bowel disease (IBD) is polygenic (5).
  • CF is caused by a mutation in the CF transmembrane conductance regulator (CFTR), resulting in abnormal exocrine gland secretions.

Risk Factors

  • Osmotic
    • Excess 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
    • 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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