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),(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),(3).
  • 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% (4).

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),(5).
    • Carbohydrate malabsorption
      • Disaccharides, including lactose
      • Monosaccharides, including fructose
      • Polyols, including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)
    • Magnesium, phosphate, and sulfate ingestion
    • Osmotic diarrhea resolved with fasting trial (2)
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1),(6)
    • Alcoholism, stimulant laxative ingestion
    • Bacterial enterotoxins (i.e., cholera)
    • 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
    • Remains unchanged with fasting trial (2)
  • Malabsorption (1),(6)
    • Celiac disease, whipple disease
    • Tropical sprue, giardiasis
    • Chronic mesenteric ischemia, lymphatic obstruction
    • Short bowel syndrome: Ileal resection of >100 cm leads to insufficient bile salts in the duodenum for optimal fat and fat-soluble vitamin absorption.
    • Small intestinal bacterial overgrowth
    • Pancreatic exocrine insufficiency (cystic fibrosis [CF], chronic pancreatitis)
  • Inflammatory (1),(6)
    • Ulcerative colitis; Crohn disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Diverticulitis; vasculitis, radiation enterocolitis
    • Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
    • Neoplasms: colon cancer, lymphoma
  • Hypermotility (normal fecal osmotic gap) (1)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
      • Pain differentiates IBS and functional diarrhea (2),(5)
  • Drugs (1),(3),(6)
    • 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 confirmed by the resolution of symptoms on discontinuation (3).
    • 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, M. 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 (5).
  • Inflammatory bowel disease (IBD) is polygenic. First-degree relative of IBD patients are at 10-fold increase of developing IBD (5).
  • 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
    • Magnesium-containing antacids laxatives (3),(5)
    • 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
    • Medications (i.e., NSAIDs, caffeine, metformin, colchicine, carbamazepine) (3),(5)
  • Malabsorptive
    • CF, chronic alcohol abuse, celiac disease
    • Chronic pancreatitis/pancreatic insufficiency
    • Medications (i.e., orlistat, acarbose)
  • Inflammatory
    • IBD, NSAID use (3), thoracoabdominal radiation
    • HIV/AIDS
    • Antibiotic use (i.e., clindamycin, amoxicillin, ampicillin, cephalosporins) (3)
    • Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan) (3)
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress, preceding infection
    • Medications (i.e., macrolides, metoclopramide, senna) (3),(5)
  • 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, 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),(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),(3).
  • 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% (4).

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),(5).
    • Carbohydrate malabsorption
      • Disaccharides, including lactose
      • Monosaccharides, including fructose
      • Polyols, including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)
    • Magnesium, phosphate, and sulfate ingestion
    • Osmotic diarrhea resolved with fasting trial (2)
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1),(6)
    • Alcoholism, stimulant laxative ingestion
    • Bacterial enterotoxins (i.e., cholera)
    • 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
    • Remains unchanged with fasting trial (2)
  • Malabsorption (1),(6)
    • Celiac disease, whipple disease
    • Tropical sprue, giardiasis
    • Chronic mesenteric ischemia, lymphatic obstruction
    • Short bowel syndrome: Ileal resection of >100 cm leads to insufficient bile salts in the duodenum for optimal fat and fat-soluble vitamin absorption.
    • Small intestinal bacterial overgrowth
    • Pancreatic exocrine insufficiency (cystic fibrosis [CF], chronic pancreatitis)
  • Inflammatory (1),(6)
    • Ulcerative colitis; Crohn disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Diverticulitis; vasculitis, radiation enterocolitis
    • Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis
    • Neoplasms: colon cancer, lymphoma
  • Hypermotility (normal fecal osmotic gap) (1)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
      • Pain differentiates IBS and functional diarrhea (2),(5)
  • Drugs (1),(3),(6)
    • 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 confirmed by the resolution of symptoms on discontinuation (3).
    • 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, M. 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 (5).
  • Inflammatory bowel disease (IBD) is polygenic. First-degree relative of IBD patients are at 10-fold increase of developing IBD (5).
  • 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
    • Magnesium-containing antacids laxatives (3),(5)
    • 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
    • Medications (i.e., NSAIDs, caffeine, metformin, colchicine, carbamazepine) (3),(5)
  • Malabsorptive
    • CF, chronic alcohol abuse, celiac disease
    • Chronic pancreatitis/pancreatic insufficiency
    • Medications (i.e., orlistat, acarbose)
  • Inflammatory
    • IBD, NSAID use (3), thoracoabdominal radiation
    • HIV/AIDS
    • Antibiotic use (i.e., clindamycin, amoxicillin, ampicillin, cephalosporins) (3)
    • Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan) (3)
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress, preceding infection
    • Medications (i.e., macrolides, metoclopramide, senna) (3),(5)
  • 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, 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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