Description

• 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.

Epidemiology

Incidence
Difficult to estimate as definitions vary

Prevalence
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)

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)
  • 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

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)