Description

• Chronic diarrhea is defined as an increase in frequency of defecation or decrease in stool consistency (typically >3 loose stools per day) for > 4 weeks:
  • Etiologies include: Osmotic, secretory, malabsorptive, inflammatory, and hypermotility
  • Infectious etiologies are possible, but less common in a chronic setting.
• System(s) affected: Gastrointestinal

Epidemiology

Prevalence
Variable depending on etiology, but overall ~5% of the US population is affected

Risk Factors

• Osmotic:
  • Excessive ingestion of nonabsorbable carbohydrates
  • Lactose intolerance
  • Celiac disease
• Secretory:
  • Extensive small bowel resection/ileal surgery
  • History of neuroendocrine disease
  • History of stimulant laxative abuse (e.g., senna)
  • Dysmotility syndromes
• Malabsorptive (1):
  • CF
  • Chronic alcohol abuse
  • Chronic pancreatitis/pancreatic insufficiency
  • Celiac disease
  • Medications (e.g., Orlistat, Acarbose)
• Inflammatory:
  • Inflammatory bowel disease (IBD)
  • NSAID use
  • Thoracoabdominal radiation
  • HIV/AIDS
  • Antibiotic use
  • Immunosuppressant therapy
• Hypermotility:
  • Psychosocial stress
  • Preceding infection
• Genetic predisposition (2)

ALERT
Diabetes mellitus and history of cholecystectomy can cause both secretory and osmotic diarrhea.

• Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on MHC Class II antigen-presenting cells.
• IBD is polygenic, and new genome-wide association studies continue to demonstrate new polymorphisms.
• Cystic fibrosis (CF) is caused by a mutation in the CF transmembrane conductance regulator resulting in abnormal exocrine gland secretions.
• Familial diarrhea syndrome is linked to a missense mutation in GUCY2C resulting in hyperactivation of CFTR.

General Prevention

• Variable depending on etiology of the diarrhea
• Treat the underlying disorder.

Pathophysiology

In most cases, chronic diarrhea is the result of disturbances in luminal water and electrolyte balance, but can vary depending on etiology.

Etiology

• Osmotic (fecal osmotic gap >125 mOsm/kg):
  • Carbohydrate malabsorption:
    • Disaccharides including lactose
    • Monosaccharides including fructose
    • Polyols including sorbitol, xylotil, sucralose and saccharin are commonly used as a sugar substitutes.
    • These substances cannot be metabolized, thus creating an osmotic gradient.
  • Substances including magnesium, phosphate, sulfate
• Secretory (fecal osmotic gap <50 mOsm/kg):
  • Stimulant laxative ingestion
  • Postcholecystectomy:
    • Leads to excessive bile salts in intestinal lumen causing cholerheic diarrhea; often resolves in 6–12 months
  • Ileal bile acid malabsorption:
    • Ileal resection of <100 cm leads to cholerheic diarrhea due to excessive presentation of bile salts to colon.
  • Disordered motility (3):
    • Postvagotomy
    • Diabetic autonomic neuropathy
    • Hyperthyroidism
  • Neuroendocrine tumors:
    • VIPoma
    • Gastrinoma
    • Somatostatinoma
    • Carcinoid syndrome
  • Metastatic medullary carcinoma of the thyroid
  • Systemic mastocytosis
  • Protein-losing enteropathy
• Malabsorption:
  • Whipple disease
  • Giardiasis
  • Celiac disease
  • Short bowel syndrome:
    • Ileal resection of >100 cm leads to insufficient bile salt concentrations in the duodenum for optimal fat absorption, leading to fat and fat-soluble vitamin malabsorption.
  • Small intestinal bacterial overgrowth
  • Pancreatic exocrine insufficiency (CF, chronic pancreatitis)
  • Inadequate bile acid production/secretion
• Inflammatory:
  • Ulcerative colitis
  • Crohn disease
  • Microscopic colitis (lymphocytic or collagenous)
  • Vasculitis
  • Radiation enterocolitis
  • Eosinophilic enterocolitis
• Hypermotility (normal fecal osmotic gap):
  • Irritable bowel syndrome
  • Functional diarrhea
• Drugs: NSAIDs, colchicine, metformin, digoxin, SSRIs
• Herbal products: St. John's wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, aloe vera
• Infectious:
  • Bacterial: Clostridium difficile, Mycobacterium avium intracellulare
  • Viral: Cytomegalovirus
  • Parasites: Giardia lamblia, Cryptosporidium, Isospora
  • Helminths: Strongyloides

Commonly Associated Conditions

• Extraintestinal manifestations of IBD include arthralgias, aphthous stomatitis, uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, perianal fistulas, ankylosing spondylitis, and primary sclerosing cholangitis.
• Celiac disease is associated with dermatitis herpetiformis.
• A significant number of patients with IBS have psychiatric comorbidities.