> Table of Contents > Diarrhea, Chronic
Diarrhea, Chronic
Aung S. Myint, DO
Matthew Chandler, MD
Marie L. Borum, MD, EdD, MPH
image BASICS
  • An increase in frequency of defecation or decrease in stool consistency (typically >3 loose stools per day) for >4 weeks (1,2,3):
    • Etiologies include osmotic, secretory, malabsorptive, inflammatory, and hypermotility.
    • Infectious etiologies are less common in chronic diarrhea.
  • System(s) affected: gastrointestinal (GI)
Variable depending on etiology, but overall ˜3-5% of the U.S. population is affected (3)
In most cases, chronic diarrhea is the result of disturbances in the intestinal luminal water and electrolyte balance. This varies depending on etiology.
  • Osmotic (fecal osmotic gap >125 mOsm/kg) (2,3)
    • Carbohydrate malabsorption
      • Disaccharides including lactose
      • Monosaccharides including fructose
      • Polyols including sorbitol, xylitol, sucralose, and saccharin (common sugar substitutes)
      • These substances cannot be metabolized, thus creating an osmotic gradient.
    • Substances including magnesium, phosphate, and sulfate
  • Secretory (fecal osmotic gap <50 mOsm/kg) (2,3)
    • Stimulant laxative ingestion
    • Postcholecystectomy
      • Excessive bile salts in intestinal lumen cause cholerheic diarrhea; often resolves in 6 to 12 months
    • Ileal bile acid malabsorption
      • Ileal resection of <100 cm leads to cholerheic 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
    • Systemic mastocytosis
    • Protein-losing enteropathy
  • Malabsorption (2,3)
    • 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 fatsoluble vitamin malabsorption.
    • Small intestinal bacterial overgrowth
    • Pancreatic exocrine insufficiency (CF, chronic pancreatitis)
    • Inadequate bile acid production/secretion
  • Inflammatory (2,3)
    • Ulcerative colitis
    • Crohn disease
    • Microscopic colitis (lymphocytic or collagenous)
    • Vasculitis
    • Radiation enterocolitis
    • Eosinophilic enterocolitis
  • Hypermotility (normal fecal osmotic gap) (1,2,3)
    • Irritable bowel syndrome (IBS)
    • Functional diarrhea
  • Drugs: NSAIDs, colchicine, metformin, digoxin, SSRIs (3)
  • Herbal products: St. John's wort, echinacea, garlic, saw palmetto, ginseng, cranberry extract, aloe vera
  • Infectious (2,3)
    • Bacterial: Clostridium difficile, Mycobacterium avium intracellulare
    • Viral: cytomegalovirus
    • Parasitic: Giardia lamblia, Cryptosporidium, Isospora
    • Helminthic: Strongyloides
  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes on major histocompatibility complex (MHC) class II antigen-presenting cells (4).
  • IBD is polygenic (5).
  • Cystic fibrosis (CF) is caused by a mutation in the CF transmembrane conductance regulator (CFTR), resulting in abnormal exocrine gland secretions.
  • Familial diarrhea syndrome is linked to a missense mutation in GUCY2C resulting in hyperactivation of CFTR (6).
  • 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
    • Dysmotility syndromes
  • Malabsorptive
    • 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
  • Variable depending on etiology of the diarrhea
  • Treat the underlying disorder.
  • 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.
  • A significant number of patients with IBS have psychiatric comorbidities.
  • General: Assess for volume depletion, nutritional status, recent weight loss (2,3).
  • Skin: flushing (carcinoid), erythema nodosum (IBD), pyoderma gangrenosum (IBD), ecchymoses (vitamin K deficiency), dermatitis herpetiformis (celiac disease) (1,2,3)
  • HEENT: iritis/uveitis (IBD)
  • Neck: goiter (hyperthyroid), lymphadenopathy (Whipple disease)
  • Cardiovascular: tachycardia (hyperthyroid)
  • Pulmonary: wheezing (carcinoid)
  • Abdomen: hyperactive bowel sounds (IBD), abdominal distention (IBD/IBS), diffuse tenderness (IBD/IBS)
  • Anorectal: anorectal fistulas (IBD), anal fissures (IBD)
  • Extremities: arthritis (IBD)
  • Neurologic: tremor (hyperthyroid)
See above.
Initial Tests (lab, imaging)
  • Blood: CBC with differential, electrolytes (Mg, P, Ca), total protein, albumin, thyroid-stimulating hormone (TSH), free T4, erythrocyte sedimentation rate, iron studies (2,3)
  • Stool: WBCs, culture, ova and parasites, Giardia stool antigen, C. difficile toxin, stool electrolytes (fecal osmotic gap), fecal occult blood, qualitative fecal fat (Sudan stain) (2,3).
  • Plain film of the abdomen to evaluate for obstruction, toxic megacolon, bowel ischemia (1)
  • CT to rule out chronic pancreatitis if abnormal pancreatic enzymes or evidence of malabsorption (1,2)

Follow-Up Tests & Special Considerations
  • Celiac disease: antiendomysial antibody IgA, antitissue transglutaminase (TTG) IgA, antigliadin (AGA) IgA, serum IgA (10% of celiac patients have IgA deficiency that may result in false-negative results) (4)[A]
  • Chronic pancreatic insufficiency: fecal elastase (2)[A]
  • Protein-losing enteropathy: fecal &agr;1 antitrypsin (2)[A]
  • Carbohydrate malabsorption: fecal pH (3)[A]
  • Small bowel overgrowth: hydrogen breath test
  • Prior history of hospitalization or antibiotics: C. difficile toxin (3)[A]
  • HIV ELISA, special stains for Isospora and Cryptosporidium (2)[A]
  • Allergy testing (2)[C]
  • Neuroendocrine tumor
    • Serum: chromogranin A, VIP, gastrin (1,3)
    • Urine: 5-HIAA, histamine (1,3)
Diagnostic Procedures/Other
  • Ileocolonoscopy with biopsies: to diagnose IBD, microscopic colitis, CMV colitis, and colorectal neoplasia (7)[A]
  • Flexible sigmoidoscopy: especially if pregnant, with comorbidities, or if left-sided symptoms predominate (tenesmus and urgency) (7)[A]
  • Esophagogastroduodenoscopy (EGD) with small bowel biopsies if malabsorption is suspected:
    • Celiac, Giardia infection, Crohn disease, eosinophilic gastroenteropathy, Whipple disease, intestinal amyloid, pancreatic insufficiency (7)[A]
  • Capsule endoscopy if further evaluation of small bowel is needed (7)[C]
  • Upper GI series with small bowel follow-through
  • CT or magnetic resonance (MR) enterography (1,2)
Test Interpretation
  • Celiac disease: Marsh classification:
    • Intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy (4)
  • Crohn disease: cobblestoning, linear ulcerations, skip lesions, noncaseating granulomas
  • Ulcerative colitis: crypt abscesses, superficial inflammation
  • Lymphocytic colitis: increased intraepithelial infiltration of lymphocytes, increased inflammatory cells within the lamina propria, normal mucosal architecture (8)
  • Melanosis coli suggests laxative abuse (2).
  • Volume resuscitation if necessary (2)[A]
  • Electrolyte replacement if indicated (2)[A]
  • If stable, treatment is generally outpatient.
First Line
  • Based on underlying cause:
    • Lactose intolerance: lactose-free diet (9)[A]
    • Cholecystectomy or ileal resection: cholestyramine or colestipol 2 to 16 g/day PO divided (10)[A]
    • Diabetes: aggressive diabetes management and glucose control
    • Hyperthyroidism: methimazole 5 to 20 mg/day PO, propylthiouracil (PTU) 100 to 150 mg/day PO divided; thyroid ablation
    • C. difficile: vancomycin 125 mg PO q6h or metronidazole (Flagyl) 500 mg PO q8h or fidaxomicin 200 mg PO BID
    • G. lamblia: metronidazole 250 mg PO Q8H, nitazoxanide 500 mg PO q12h (2)[A]
    • Whipple disease: ceftriaxone 2 g IV for 14 days then Bactrim DS 160/800 mg PO BID for 1 to 2 years (11)[A]
    • Small intestinal bacterial overgrowth: rifaximin 550 mg PO BID, fluoroquinolones 250 to 750 mg PO BID, metronidazole 500 mg PO q6-8h, penicillins (12)[A]
    • Pancreatic insufficiency: pancreatic enzyme replacement (1)[A]
    • HIV/AIDS: antiretroviral therapy
    • Microscopic colitis: budesonide 9 mg/day PO, mesalamine 800 mg PO TID, Pepto-Bismol 786 mg PO TID (8)[A]
    • IBD: 5-aminosalicylic acid (5-ASA), corticosteroids (short-term only), antibiotics (short-term only), immunomodulators (6-mercaptopurine [6-MP], azathioprine, methotrexate), anti-TNF therapy (infliximab, adalimumab, certolizumab) (5)[A]
    • Neuroendocrine tumor: octreotide 100 to 600 &mgr;g/day SC (2,13)[A]
    • Celiac disease: gluten-free diet (wheat/barley/rye avoidance) (4)[A]
    • IBS diarrhea predominant: rifaximin 550 mg PO BID, alosetron 0.5 to 1 mg PO BID, peppermint oil (14)[A]
  • Symptom relief:
    • Loperamide (Imodium) 4 to 8 mg/day PO divided
    • Diphenoxylate-atropine (Lomotil) 1 to 2 tabs PO BID-QID (2)[A]
  • Resection of neuroendocrine tumors (13)[A]
  • Intestinal resection for medically refractory IBD
  • Fecal transplant for recurrent C. difficile infection (14)[A]
Many homeopathic and naturopathic formulations are available; most have not been evaluated by the FDA.
Abstain from gluten-containing foods, nonabsorbable carbohydrates, lactose-containing products, and food allergens depending of etiology of diarrhea.
  • Reassure patient of wide variation in what is accepted as “normal” bowel habits.
  • Restrict colon stimulants.
  • Specific education and dietary changes based on underlying etiology.
Depends on etiology
1. Schiller LR. Definitions, pathophysiology, and evaluation of chronic diarrhoea. Best Pract Res Clin Gastroenterol. 2012;26(5):551-562.
2. Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 1999;116(6):1464-1486.
3. Juckett G, Trivedi R. Evaluation of chronic diarrhea. Am Fam Physician. 2011;84(10):1119-1126.
4. Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5): 656-676.
5. Talley NJ, Abreu MT, Achkar JP, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(Suppl 1):S2-S25.
6. Fiskerstrand T, Arshad N, Haukanes BI, et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N Engl J Med. 2012;366(17):1586-1595.
7. Shen B, Khan K, Ikenberry SO, et al. The role of endoscopy in the management of patients with diarrhea. Gastrointest Endosc. 2010;71(6): 887-892.
8. Temmerman F, Baert F. Collagenous and lymphocytic colitis: systematic review and update of the literature. Dig Dis. 2009;27(Suppl 1):137-145.
9. Shaukat A, Levitt MD, Taylor BC, et al. Systematic review: effective management strategies for lactose intolerance. Ann Intern Med. 2010;152(12): 797-803.
10. Wilcox C, Turner J, Green J. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther. 2014;39(9):923-939.
Additional Reading
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415.
See Also
Algorithm: Diarrhea, Chronic
K52.9 Noninfective gastroenteritis and colitis, unspecified
Clinical Pearls
  • Consider IBS, IBD, malabsorption syndromes (such as lactose intolerance), celiac disease, over-the-counter medications, and herbal products and chronic infections (particularly in patients who are immunocompromised).
  • The appropriate workup is based on a comprehensive medical history.