Diarrhea, Chronic

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Basics

Description

  • An increase in frequency of defecation, urgency, or decrease in stool consistency (typically >3 loose stools per day) for >4 weeks (1)
    • 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.
  • Infectious causes of chronic diarrhea are uncommon in immunocompetent patients. Parasitic etiologies are more common than bacterial.

Epidemiology

Incidence
Difficult to estimate as definitions may vary from patient to patient, though it has been estimated that the average American has an episode of diarrhea every other year

Prevalence
Varies by etiology; about 6.6% of the U.S. population (2) is affected.

Etiology and Pathophysiology

Chronic diarrhea is typically the result of disturbances in luminal water and electrolyte balance within the intestine that causes increased water volume in the stool.

  • Osmotic (fecal osmotic gap >75 mOsm/kg) (1)
    • Carbohydrate malabsorption
      • Disaccharides, including lactose
      • Monosaccharides, including fructose
      • Polyols, including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)—cannot be metabolized and create an osmotic gradient.
    • Magnesium, phosphate, and sulfate ingestion
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1,3)
    • Alcoholism
    • Bacterial enterotoxins (i.e., cholera)
    • Stimulant laxative ingestion
    • Postcholecystectomy
      • Excessive intestinal bile salts cause choleretic diarrhea; often resolves in 6 to 12 months
    • Ileal bile acid malabsorption
    • Ileal resection of <100 cm leads to choleretic diarrhea due to excessive colonic bile salts.
    • Disordered motility
      • Postvagotomy
      • Diabetic autonomic neuropathy
      • Hyperthyroidism
    • Neuroendocrine tumors
      • VIPoma
      • Gastrinoma
      • Somatostatinoma
      • Carcinoid syndrome
    • Metastatic medullary carcinoma of the thyroid
    • Adrenal insufficiency
    • Hyperthyroidism
    • Noninvasive infection: giardiasis, cryptosporidiosis
    • Microscopic colitis (lymphocytic or collagenous)
    • Protein-losing enteropathy
    • Idiopathic secretory diarrhea
  • Malabsorption (1,3)
    • Celiac disease
    • Whipple disease
    • Tropical sprue
    • Giardiasis
    • Chronic mesenteric ischemia
    • Lymphatic obstruction
    • 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 (cystic fibrosis [CF], chronic pancreatitis)
    • Inadequate bile acid production/secretion
  • Inflammatory (1,3)
    • Ulcerative colitis; Crohn’s disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Diverticulitis
    • Vasculitis; radiation enterocolitis
    • Eosinophilic enterocolitis
    • Invasive or inflammatory infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
    • Neoplasms: colon cancer, lymphoma, villous adenocarcinoma
  • Hypermotility (normal fecal osmotic gap) (1)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
  • Drugs (1,3)
    • Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, newer gliptins, theophyllines, antibiotics, SSRIs, antineoplasic agents
    • Factitious diarrhea: excessive laxative use
  • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, Aloe vera
  • Infectious (1)
    • Bacterial: C. difficile, Mycobacterium avium intracellulare
    • Viral: cytomegalovirus
    • Parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. histolytica
    • Helminthic: Strongyloides
  • Food allergies (1)
Genetics
  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II antigen-presenting cells.
  • Inflammatory bowel disease (IBD) is polygenic.
  • CF is caused by a mutation in the CF transmembrane conductance regulator (CFTR), resulting in abnormal exocrine gland secretions.

Risk Factors

  • Osmotic
    • Excess ingestion of nonabsorbable carbohydrates
    • Lactose intolerance
    • Celiac disease
  • Secretory (1)
    • Postsurgical: extensive small bowel resection/ileal surgery, vagotomy, bile acid malabsorption
    • History of neuroendocrine disease
    • History of stimulant laxative abuse
    • Dysmotility syndromes
  • Malabsorptive
    • CF
    • Chronic alcohol abuse
    • Chronic pancreatitis/pancreatic insufficiency
    • Celiac disease
    • Medications (i.e., orlistat, acarbose)
  • Inflammatory
    • IBD
    • NSAID use
    • Thoracoabdominal radiation
    • HIV/AIDS
    • Antibiotic use
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress
    • Preceding infection
  • Genetic predisposition

ALERT
Diabetes mellitus and/or prior cholecystectomy both 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 primary sclerosing cholangitis.
  • Celiac disease is associated with dermatitis herpetiformis, type 1 diabetes, other autoimmune disorders, and IgA deficiency.
  • Many patients with IBS have behavioral comorbidities.
  • Latex-food allergy syndrome: associated allergies to latex and banana, avocado, kiwi, and walnut (1)

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Basics

Description

  • An increase in frequency of defecation, urgency, or decrease in stool consistency (typically >3 loose stools per day) for >4 weeks (1)
    • 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.
  • Infectious causes of chronic diarrhea are uncommon in immunocompetent patients. Parasitic etiologies are more common than bacterial.

Epidemiology

Incidence
Difficult to estimate as definitions may vary from patient to patient, though it has been estimated that the average American has an episode of diarrhea every other year

Prevalence
Varies by etiology; about 6.6% of the U.S. population (2) is affected.

Etiology and Pathophysiology

Chronic diarrhea is typically the result of disturbances in luminal water and electrolyte balance within the intestine that causes increased water volume in the stool.

  • Osmotic (fecal osmotic gap >75 mOsm/kg) (1)
    • Carbohydrate malabsorption
      • Disaccharides, including lactose
      • Monosaccharides, including fructose
      • Polyols, including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)—cannot be metabolized and create an osmotic gradient.
    • Magnesium, phosphate, and sulfate ingestion
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1,3)
    • Alcoholism
    • Bacterial enterotoxins (i.e., cholera)
    • Stimulant laxative ingestion
    • Postcholecystectomy
      • Excessive intestinal bile salts cause choleretic diarrhea; often resolves in 6 to 12 months
    • Ileal bile acid malabsorption
    • Ileal resection of <100 cm leads to choleretic diarrhea due to excessive colonic bile salts.
    • Disordered motility
      • Postvagotomy
      • Diabetic autonomic neuropathy
      • Hyperthyroidism
    • Neuroendocrine tumors
      • VIPoma
      • Gastrinoma
      • Somatostatinoma
      • Carcinoid syndrome
    • Metastatic medullary carcinoma of the thyroid
    • Adrenal insufficiency
    • Hyperthyroidism
    • Noninvasive infection: giardiasis, cryptosporidiosis
    • Microscopic colitis (lymphocytic or collagenous)
    • Protein-losing enteropathy
    • Idiopathic secretory diarrhea
  • Malabsorption (1,3)
    • Celiac disease
    • Whipple disease
    • Tropical sprue
    • Giardiasis
    • Chronic mesenteric ischemia
    • Lymphatic obstruction
    • 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 (cystic fibrosis [CF], chronic pancreatitis)
    • Inadequate bile acid production/secretion
  • Inflammatory (1,3)
    • Ulcerative colitis; Crohn’s disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Diverticulitis
    • Vasculitis; radiation enterocolitis
    • Eosinophilic enterocolitis
    • Invasive or inflammatory infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
    • Neoplasms: colon cancer, lymphoma, villous adenocarcinoma
  • Hypermotility (normal fecal osmotic gap) (1)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
  • Drugs (1,3)
    • Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, newer gliptins, theophyllines, antibiotics, SSRIs, antineoplasic agents
    • Factitious diarrhea: excessive laxative use
  • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, Aloe vera
  • Infectious (1)
    • Bacterial: C. difficile, Mycobacterium avium intracellulare
    • Viral: cytomegalovirus
    • Parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. histolytica
    • Helminthic: Strongyloides
  • Food allergies (1)
Genetics
  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II antigen-presenting cells.
  • Inflammatory bowel disease (IBD) is polygenic.
  • CF is caused by a mutation in the CF transmembrane conductance regulator (CFTR), resulting in abnormal exocrine gland secretions.

Risk Factors

  • Osmotic
    • Excess ingestion of nonabsorbable carbohydrates
    • Lactose intolerance
    • Celiac disease
  • Secretory (1)
    • Postsurgical: extensive small bowel resection/ileal surgery, vagotomy, bile acid malabsorption
    • History of neuroendocrine disease
    • History of stimulant laxative abuse
    • Dysmotility syndromes
  • Malabsorptive
    • CF
    • Chronic alcohol abuse
    • Chronic pancreatitis/pancreatic insufficiency
    • Celiac disease
    • Medications (i.e., orlistat, acarbose)
  • Inflammatory
    • IBD
    • NSAID use
    • Thoracoabdominal radiation
    • HIV/AIDS
    • Antibiotic use
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress
    • Preceding infection
  • Genetic predisposition

ALERT
Diabetes mellitus and/or prior cholecystectomy both 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 primary sclerosing cholangitis.
  • Celiac disease is associated with dermatitis herpetiformis, type 1 diabetes, other autoimmune disorders, and IgA deficiency.
  • Many patients with IBS have behavioral comorbidities.
  • Latex-food allergy syndrome: associated allergies to latex and banana, avocado, kiwi, and walnut (1)

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