para>Diabetes mellitus and/or prior cholecystectomy both cause secretory and osmotic diarrhea. á
GENERAL PREVENTION
- Variable depending on etiology of the diarrhea
- Treat the underlying disorder.
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.
- A significant number of patients with IBS have psychiatric comorbidities.
DIAGNOSIS
HISTORY
- Detailed history of symptoms, including the following (1,2 and 3):
- Onset, pattern, and frequency
- Stool volume and quality (including presence of blood or mucus)
- Presence of nocturnal symptoms
- Travel history
- Antibiotic exposure
- Dietary habits
- Current medications
- Family history
- Determine aggravating or alleviating factors, including changes with oral intake or improvement with selective food avoidance (e.g., dairy products).
- Evaluate for recent unintentional weight loss.
- Complete review of systems, including rashes, arthritis, ocular problems, heat intolerance, polyuria/polydipsia, headache, fever, flushing, alcohol intake
- IBS or functional diarrhea by Rome III criteria (3):
- IBS: recurrent abdominal pain or discomfort at least 3 days/month in last 3 months. ≥2 of the following criteria must be met:
- Improvement with defecation
- Onset associated with change in frequency of stool
- Onset associated with change in form of stool
- Functional diarrhea: loose or watery stools ≥75% of the time without pain for >3 months (symptoms >6 months)
PHYSICAL EXAM
- 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 and 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)
DIFFERENTIAL DIAGNOSIS
See above. á
DIAGNOSTIC TESTS & INTERPRETATION
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 ╬▒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).
TREATMENT
GENERAL MEASURES
- Volume resuscitation if necessary (2)[A]
- Electrolyte replacement if indicated (2)[A]
- If stable, treatment is generally outpatient.
MEDICATION
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 ╬╝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]
SURGERY/OTHER PROCEDURES
- Resection of neuroendocrine tumors (13)[A]
- Intestinal resection for medically refractory IBD
- Fecal transplant for recurrent C. difficile infection (14)[A]
COMPLEMENTARY & ALTERNATIVE MEDICINE
Many homeopathic and naturopathic formulations are available; most have not been evaluated by the FDA. á
ONGOING CARE
DIET
Abstain from gluten-containing foods, nonabsorbable carbohydrates, lactose-containing products, and food allergens depending of etiology of diarrhea. á
PATIENT EDUCATION
- Reassure patient of wide variation in what is accepted as "normal"Ł bowel habits.
- Restrict colon stimulants.
- Specific education and dietary changes based on underlying etiology.
PROGNOSIS
Depends on etiology á
COMPLICATIONS
- Fluid and electrolyte abnormalities (1,3)
- Malnutrition (1); anemia (1,3)
- Malignancy (colon cancer in IBD, small bowel cancer in celiac disease and Crohn disease, lymphoma with IBD therapies) (5)
- Infection with immunomodulator, biologic, and corticosteroid therapies for IBD (5)
REFERENCES
11 Schiller áLR. Definitions, pathophysiology, and evaluation of chronic diarrhoea. Best Pract Res Clin Gastroenterol. 2012;26(5):551-562.22 Fine áKD, Schiller áLR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 1999;116(6):1464-1486.33 Juckett áG, Trivedi áR. Evaluation of chronic diarrhea. Am Fam Physician. 2011;84(10):1119-1126.44 Rubio-Tapia áA, Hill áID, Kelly áCP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656-676.55 Talley áNJ, Abreu áMT, Achkar áJP, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(Suppl 1):S2-S25.66 Fiskerstrand áT, Arshad áN, Haukanes áBI, et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N Engl J Med. 2012;366(17):1586-1595.77 Shen áB, Khan áK, Ikenberry áSO, et al. The role of endoscopy in the management of patients with diarrhea. Gastrointest Endosc. 2010;71(6):887-892.88 Temmerman áF, Baert áF. Collagenous and lymphocytic colitis: systematic review and update of the literature. Dig Dis. 2009;27(Suppl 1):137-145.99 Shaukat áA, Levitt áMD, Taylor áBC, et al. Systematic review: effective management strategies for lactose intolerance. Ann Intern Med. 2010;152(12):797-803.1010 Wilcox áC, Turner áJ, Green áJ. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther. 2014;39(9):923-939.
ADDITIONAL READING
van Nood áE, Vrieze áA, Nieuwdorp áM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415. á
SEE ALSO
Algorithm: Diarrhea, Chronic á
CODES
ICD10
K52.9 Noninfective gastroenteritis and colitis, unspecified á
ICD9
787.91 Diarrhea á
SNOMED
236071009 Chronic diarrhea (disorder) á
CLINICAL PEARLS
- Consider IBS, IBD, malabsorption syndromes (such as lactose intolerance), celiac disease, over-thecounter medications, and herbal products and chronic infections (particularly in patients who are immunocompromised).
- The appropriate workup is based on a comprehensive medical history.