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 fall into the following categories: 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). 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
- Carbohydrate malabsorption
- Secretory (fecal osmotic gap <50 mOsm/kg) (1),(6). 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),(6)
- 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),(6)
- 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)
- 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 is confirmed by the resolution of symptoms with medication discontinuation (3).
- Factitious diarrhea: excessive laxative use
- Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, newer gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents
- 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
- Helminthic: Strongyloides
- Food allergies (1)
Genetics
- Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II (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) anion channel, resulting in abnormal exocrine gland secretions of chloride.
Risk Factors
- Osmotic
- Secretory (1)
- Malabsorptive
- CF; chronic alcohol abuse, celiac disease
- Chronic pancreatitis/pancreatic insufficiency (fat malabsorption)
- Medications (e.g., orlistat, acarbose)
- Inflammatory
- Hypermotility
- Genetic predisposition
Diabetes mellitus and cholecystectomy can 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 PSC.
- Celiac disease is associated with dermatitis herpetiformis, T1DM, 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 fall into the following categories: 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). 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
- Carbohydrate malabsorption
- Secretory (fecal osmotic gap <50 mOsm/kg) (1),(6). 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),(6)
- 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),(6)
- 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)
- 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 is confirmed by the resolution of symptoms with medication discontinuation (3).
- Factitious diarrhea: excessive laxative use
- Adverse effect of >700 drugs, most commonly: NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, newer gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents
- 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
- Helminthic: Strongyloides
- Food allergies (1)
Genetics
- Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II (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) anion channel, resulting in abnormal exocrine gland secretions of chloride.
Risk Factors
- Osmotic
- Secretory (1)
- Malabsorptive
- CF; chronic alcohol abuse, celiac disease
- Chronic pancreatitis/pancreatic insufficiency (fat malabsorption)
- Medications (e.g., orlistat, acarbose)
- Inflammatory
- Hypermotility
- Genetic predisposition
Diabetes mellitus and cholecystectomy can 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 PSC.
- Celiac disease is associated with dermatitis herpetiformis, T1DM, 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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