Diarrhea, Chronic



  • 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 (1).
  • Etiologies include osmotic, secretory, malabsorptive, inflammatory, infectious, and hypermotility (2).
  • Infectious causes of chronic diarrhea are uncommon in immunocompetent patients.


Difficult to estimate as definitions vary

Varies by etiology; worldwide prevalence is ~20% (2). U.S. prevalence is ~6.6%.

Etiology and Pathophysiology

Disturbances in luminal water and electrolyte balance cause increased water volume in the stool.

  • Osmotic (fecal osmotic gap >100 mOsm/kg) (3); resolves with a fasting trial (2)
    • Carbohydrate malabsorption: disaccharides (e.g., lactose), monosaccharides (e.g., fructose), and polyols (common sugar substitutes); Mg, phosphate, and sulfate ingestion
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1),(4); does not resolve with a fasting trial (2)
    • Alcoholism, stimulant laxative ingestion; bacterial enterotoxins (i.e., cholera); postcholecystectomy/ileal resection <100 cm; excessive intestinal bile salts cause choleretic diarrhea; resolves in 6 to 12 months
    • Disordered motility: postvagotomy, autonomic neuropathy
      • Hyperthyroidism
    • Neuroendocrine tumors: VIPoma; Carcinoid syndrome, gastrinoma, somatostatinoma
    • Metastatic medullary thyroid cancer; adrenal insufficiency
    • Noninvasive infection: giardiasis, cryptosporidiosis
    • Microscopic colitis; protein-losing enteropathy
  • Malabsorptive (1),(4)
    • Celiac disease, Whipple disease; tropical sprue, giardiasis
    • Chronic mesenteric ischemia, lymphatic obstruction
    • Short bowel syndrome: Ileal resection of >100 cm leads to insufficient small bowel bile salts.
    • Small intestinal bacterial overgrowth (SIBO); pancreatic exocrine insufficiency
  • Inflammatory (1),(4)
    • Inflammatory bowel disease (IBD)—ulcerative colitis; Crohn disease
    • Microscopic colitis; diverticulitis; vasculitis; radiation enterocolitis
    • Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
    • Neoplasms: colon cancer, lymphoma
  • Hypermotility (normal fecal osmotic gap; 50 to 100 mOsm/kg) (1)
    • Irritable bowel syndrome (IBS); functional diarrhea: pain differentiates IBS from functional diarrhea (2),(3).
  • Drugs (1),(4)
    • Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, newer gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents
      • Drug-induced diarrhea is confirmed by the resolution of symptoms with medication discontinuation.
    • Factitious diarrhea: excessive laxative use
  • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, etc.
  • Infectious (1)
    • Bacterial: C. difficile, M. avium intracellulare; Viral: cytomegalovirus; Parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. histolytica, Strongyloides
  • Food allergies (1)


  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes (3).
  • IBD is polygenic. First-degree relative of IBD patients have 10-fold increased risk (3).
  • CF transmembrane conductance regulator (CFTR) mutation contributes in CF.

Risk Factors

  • Osmotic
    • Excess ingestion of nonabsorbable carbohydrates (i.e., artificial sweeteners); magnesium-containing antacids (3)
    • Lactose intolerance, celiac disease
  • Secretory (1)
    • Postsurgical: extensive small bowel resection/ileal surgery, vagotomy, bile acid malabsorption; history of neuroendocrine disease or stimulant laxative abuse; dysmotility syndromes
    • Medications (i.e., NSAIDs, caffeine, metformin, colchicine, carbamazepine) (3)
  • Malabsorptive
    • CF; chronic alcohol abuse, celiac disease
    • Chronic pancreatitis/pancreatic insufficiency (fat malabsorption); medications (e.g., orlistat, acarbose)
  • Inflammatory
    • IBD, NSAID use, radiation; HIV/AIDS
    • Antibiotic use (commonly clindamycin, amoxicillin, ampicillin, cephalosporins)
    • Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan)
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress, preceding infection
    • Stimulant medications (i.e., macrolides, metoclopramide, senna) (3)
  • Genetic predisposition
Diabetes mellitus and cholecystectomy can 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 PSC.
  • Celiac disease is associated with dermatitis herpetiformis, T1DM, and IgA deficiency.
  • Latex-food allergy syndrome: associated allergies to latex and banana, avocado, kiwi, and walnut (1)

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