Diarrhea, Chronic
Basics
Description
- Chronic diarrhea refers to a sustained change in stool consistency, characterized by loose stools (consistency between types 5 and 7 on the Bristol stool chart), and an increase in frequency of defecation (typically >3 loose stools per day) for >4 weeks (1),(2).
- Etiologies include osmotic, secretory, malabsorptive, inflammatory, infectious, and hypermotility (2).
Epidemiology
Incidence
Difficult to estimate as definitions vary
Prevalence
Varies by etiology; worldwide prevalence is ~3–20% (2). U.S. prevalence is ~6.6%.
Etiology and Pathophysiology
Disturbances in luminal water and electrolytes cause increased water volume in the stool.
- Osmotic (fecal osmotic gap >100 mOsm/kg) (3); resolves with fasting (2); less voluminous than secretory diarrhea
- Carbohydrate malabsorption: disaccharides (e.g., lactose), monosaccharides (e.g., fructose), and polyols (sugar substitutes); Mg, citrates, phosphate, and sulfate ingestion
- Secretory (fecal osmotic gap <50 mOsm/kg) (1),(4); does not resolve with fasting (2); characterized by watery stools that persist at night and during fasting
- Alcoholism, stimulant laxative ingestion; bacterial enterotoxins (i.e., cholera); postcholecystectomy/ileal resection <100 cm: Excessive intestinal bile salts cause choleretic diarrhea.
- 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
- Fatty diarrhea: characterized by bulky, foul-smelling stools
- Hepatobiliary disorders, cystic fibrosis (CF), chronic pancreatitis, diabetes mellitus
- Malabsorptive (1),(4): characterized by higher than average stool volumes
- Celiac disease, Whipple disease; tropical sprue, giardiasis, amyloidosis
- Chronic mesenteric ischemia, lymphatic obstruction (e.g., heart failure, lymphoma)
- Short bowel syndrome: Ileal resection of >100 cm leads to insufficient bile salts.
- Small intestinal bacterial overgrowth (SIBO); pancreatic exocrine insufficiency
- Inflammatory (1),(4): characterized by loose liquid stool with occasional blood
- Inflammatory bowel disease (IBD)—ulcerative colitis; Crohn disease
- Microscopic colitis; diverticulitis; vasculitis; radiation enterocolitis
- Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis, salmonella
- Neoplasms: colon cancer, lymphoma
- Hypermotility (normal fecal osmotic gap; 50 to 100 mOsm/kg) (1)
- Drugs (1),(4): confirmed by resolution of symptoms following withdrawal of medication
- NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents, excessive laxative use (factitious diarrhea)
- 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)
Genetics
Risk Factors
- Osmotic
- Excess ingestion of nonabsorbable carbohydrates (i.e., artificial sweeteners); magnesium-containing antacids (3)
- Excess ingestion poorly absorbed ions (phosphate, sulfate, magnesium) (1)
- Lactose intolerance, celiac disease
- Medications (i.e., citrates, phosphates, sulfates, magnesium-containing laxatives, sugar alcohols)
- Secretory (1)
- Postsurgical: 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, antibiotics, calcitonin) (3)
- Malabsorptive
- CF; chronic alcohol abuse, celiac disease
- Chronic pancreatitis/pancreatic insufficiency (fat malabsorption); medications (e.g., orlistat, acarbose, aminoglycosides, thyroid supplements)
- Inflammatory
- IBD, NSAID use, antibiotics, radiation; HIV/AIDS, colorectal cancer, invasive infection (tuberculosis, Yersinia)
- Pseudomembranous colitis (C. difficile)
- Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan), radiation
- Immunosuppressant therapy
- Hypermotility
- Psychosocial stress, preceding infection
- Stimulant medications (i.e., macrolides, metoclopramide, senna, bisacodyl [Dulcolax]) (3)
- Genetic predisposition
ALERT
Diabetes mellitus and cholecystectomy can cause secretory and osmotic diarrhea.
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: allergies to latex, banana, avocado, kiwi, and walnut (1)
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Citation
Domino, Frank J., et al., editors. "Diarrhea, Chronic." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688737/1.1/Diarrhea_Chronic.
Diarrhea, Chronic. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688737/1.1/Diarrhea_Chronic. Accessed December 3, 2024.
Diarrhea, Chronic. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688737/1.1/Diarrhea_Chronic
Diarrhea, Chronic [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 December 03]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688737/1.1/Diarrhea_Chronic.
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