Description

• Chronic diarrhea refers to an increased frequency of loose stools (Bristol types 5 to 7) and >3 loose stools per day for >4 weeks (1),(2).
• Etiologies: osmotic, secretory, malabsorptive, inflammatory, infectious, and hypermotility (2)

Epidemiology

Etiology and Pathophysiology

Altered luminal water and electrolytes increases stool water volume.

• Osmotic (fecal osmotic gap >100 mOsm/kg) (3); resolves with fasting (2); less voluminous
  • Carbohydrate malabsorption: disaccharides, monosaccharides, and polyols; magnesium (Mg), citrates, phosphate, and sulfate ingestion
• Secretory (fecal osmotic gap <50 mOsm/kg) (1); persists with fasting (2) and overnight
  • Alcoholism, stimulant laxative ingestion; bacterial enterotoxins; 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
• Malabsorptive (1): increased stool volumes
  • Celiac disease, Whipple disease; tropical sprue, giardiasis, amyloidosis
  • Chronic mesenteric ischemia, lymphatic obstruction
  • Short bowel syndrome (>100 cm ileal resection)
  • Small intestinal bacterial overgrowth (SIBO); pancreatic exocrine insufficiency
• Inflammatory (1): liquid stool with occasional blood
  • Inflammatory bowel disease (IBD)—ulcerative colitis (UC); Crohn disease
  • Microscopic colitis; diverticulitis; vasculitis; radiation enterocolitis
  • Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus (CMV), tuberculosis, Salmonella
  • Neoplasms: colon cancer, lymphoma
• Hypermotility (fecal osmotic gap 50 to 100 mOsm/kg) (1)
  • Irritable bowel syndrome (IBS); functional diarrhea (IBS distinguished by pain) (2),(3)
• Drugs (1): resolved with drug cessation
  • NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents, excessive laxative use
  • Herbal: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, etc.
• Infectious
  • Bacterial: C. difficile, Mycobacterium avium intracellulare; viral: CMV; parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. histolytica, Strongyloides
• Food allergies (1)

Risk Factors

• Osmotic
  • Excess nonabsorbable carbohydrates (i.e., artificial sweeteners); Mg-containing antacids (3), or poorly absorbed ions (phosphate, sulfate, Mg) ⁽¹⁾
  • Lactose intolerance, celiac disease
  • Medications (i.e., citrates, phosphates, sulfates, Mg-containing laxatives, sugar alcohols)
• Secretory
  • Postsurgical: small bowel resection/ileal surgery, vagotomy, bile acid malabsorption; 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; medications (e.g., orlistat, acarbose, aminoglycosides, thyroid supplements)
• Inflammatory
  • IBD, NSAIDs use, antibiotics, radiation; HIV/AIDS, colorectal cancer, invasive infection (tuberculosis, Yersinia)
  • Pseudomembranous colitis (C. difficile)
  • Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan), radiation
  • Immunosuppressants
• Hypermotility
  • Psychosocial stress, preceding infection
  • Stimulant medications (i.e., macrolides, metoclopramide, senna, bisacodyl [Dulcolax]) (3)
• Genetic predisposition

General Prevention

Varies by etiology; treat the underlying cause.

Commonly Associated Conditions

• IBD: arthralgias, aphthous stomatitis, uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, perianal fistulas, rectal fissures, ankylosing spondylitis, and PSC
• Celiac disease: dermatitis herpetiformis, type 1 DM, and IgA deficiency
• Latex-food allergy syndrome: latex, banana, avocado, kiwi, and walnut allergies (1)