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)
  • Irritable bowel syndrome (IBS); functional diarrhea (Pain differentiates IBS from functional diarrhea.) (2),(3)
• 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

• 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)
  • 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

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)