Guideline sources The following summarized guidelines for the evaluation and management of chronic diarrhea are prepared by our editorial team based on guidelines from the Canadian Association of Gastroenterologists (CAG 2020), the American Gastroenterological Association (AGA 2019), the British Society of Gastroenterology (BSG 2018), the Chronic Diarrhea Expert Group (CD-EG 2017), the American College of Gastroenterology (ACG 2013), and the American Society for Gastrointestinal Endoscopy (ASGE 2010). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis Definition: Recognize that patients report diarrhea as loose stools, increased stool frequency, or urgency. B Define chronic diarrhea by the duration of > 4 weeks. B 2. Diagnostic investigations https://web.pathway.md/diseases/recqLmnFvUW93houD 1/6 6/29/23, 3:53 AM Chronic diarrhea Pathway Initial evaluation: As per BSG 2018 guidelines, elicit a detailed history to plan investigations in patients with chronic diarrhea. A Show 2 more As per CD-EG 2017 guidelines, assess comorbid symptoms and epidemiologic clues when constructing a differential diagnosis for chronic diarrhea. B Show 5 more Evaluation for inflammatory bowel disease: As per AGA 2019 guidelines: Consider obtaining fecal calprotectin or fecal lactoferrin to screen for IBD in patients with chronic diarrhea. C Avoid obtaining ESR or CRP to screen for IBD in patients presenting with chronic diarrhea. D As per BSG 2018 guidelines, consider obtaining FITing for fecal blood loss in primary or secondary care, either as an exclusion test or to guide the priority of investigations, in patients with chronic diarrhea without rectal bleeding. C Show 2 more As per CD-EG 2017 guidelines, consider obtaining fecal lactoferrin or calprotectin as surrogate measures for fecal leukocytes. B Show 3 more As per ASGE 2010 guidelines: Consider performing a colonoscopy with random biopsies of the right and left sides of the colon in patients with chronic unexplained diarrhea. Consider performing sigmoidoscopy as an alternative option, although it may miss the right-sided organic disease. C Perform intubation of the terminal ileum during colonoscopy in patients undergoing evaluation of chronic diarrhea. B Insufficient evidence to recommend a routine biopsy of the endoscopically normal-appearing terminal ileum. Evaluation for malabsorption: As per BSG 2018 guidelines, consider obtaining hydrogen breath testing, if available, or withdrawing dietary lactose/carbohydrates from the diet in patients with suspected lactose maldigestion. C Show 4 more As per ASGE 2010 guidelines, perform upper gastrointestinal endoscopy with small bowel biopsy in patients with chronic diarrhea or suspected malabsorption and inconclusive evaluation after colonoscopy with biopsy. B Show 2 more Evaluation for celiac disease: As per AGA 2019 guidelines, obtain serum IgA tissue transglutaminase for celiac disease in patients with chronic diarrhea. Obtain a second test to detect celiac disease in the setting of IgA deficiency. B https://web.pathway.md/diseases/recqLmnFvUW93houD 2/6 6/29/23, 3:53 AM Chronic diarrhea Pathway As per BSG 2018 guidelines, obtain blood testing to exclude celiac disease in patients with chronic diarrhea. A As per ACG 2013 guidelines, obtain testing for celiac disease in patients with symptoms, signs, or laboratory evidence suggestive of malabsorption, such as chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating. A As per ASGE 2010 guidelines, perform upper gastrointestinal endoscopy with small bowel biopsy in patients with positive celiac serology. Obtain a minimum of 4 duodenal biopsy specimens for evaluation of suspected celiac disease. B Evaluation for bile acid diarrhea: As per CAG 2020 guidelines, ask about risk factors (history of terminal ileal resection, cholecystectomy, or abdominal radiotherapy) in the initial assessment of patients presenting with chronic non-bloody diarrhea to identify possible bile acid diarrhea. B Show 4 more As per AGA 2019 guidelines, consider obtaining testing for bile acid diarrhea in patients with chronic diarrhea. C As per BSG 2018 guidelines: Obtain SeHCAT testing or serum bile acid precursor 7-alpha-hydroxy-4-cholesten-3-one, depending on local availability, for the diagnosis of bile acid diarrhea in patients with functional bowel or IBS-diarrhea. A Insufficient evidence to recommend an empirical trial of treatment for bile acid diarrhea. I Evaluation of small intestinal bacterial overgrowth: As per BSG 2018 guidelines, insufficient evidence to recommend routine hydrogen or methane breath testing in patients with suspected small bowel bacterial overgrowth. Administer an empirical trial of antibiotics. I As per CD-EG 2017 guidelines: Perform upper gastrointestinal endoscopy or enteroscopy with biopsies of the duodenum or jejunum in patients with unexplained steatorrhea. Insufficient evidence to recommend aspiration of enteric contents for quantitative bacterial culture. B Consider obtaining breath tests to assist with the diagnosis of carbohydrate malabsorption and SIBO. C Evaluation for pancreatic insufficiency: As per BSG 2018 guidelines, obtain MRI to assess for structural anomalies of the pancreas in patients with suspected chronic pancreatitis. B As per CD-EG 2017 guidelines: Consider obtaining stool chymotrypsin and elastase as screening tests for pancreatic insufficiency. C Consider obtaining imaging in selected patients with steatorrhea and secretory diarrhea. B Consider offering an empiric trial of pancreatic enzyme replacement therapy to assess for pancreatic insufficiency in patients with steatorrhea. C https://web.pathway.md/diseases/recqLmnFvUW93houD 3/6 6/29/23, 3:53 AM Chronic diarrhea Pathway Evaluation for parasites: Obtain testing for giardiasis in patients with chronic diarrhea. A Avoid testing for ova and parasites (other than Giardia) in patients with chronic diarrhea with no travel history to or recent immigration from high-risk areas. D Evaluation for irritable bowel syndrome: As per AGA 2019 guidelines, insufficient evidence to support obtaining currently available serologic tests for the diagnosis of IBS in patients with chronic diarrhea. I As per BSG 2018 guidelines, diagnose IBS following basic blood and stool screening tests. B As per CD-EG 2017 guidelines: Use the Rome criteria for the diagnosis of IBS. Assess for other etiologies when the criteria are not met. A Do not obtain further testing in patients without alarm features meeting the criteria for IBS. Obtain further evaluation in nonresponders. D Evaluation for colorectal cancer: As per BSG 2018 guidelines: Perform a colonoscopy to exclude colorectal cancer in patients with altered bowel habits, with or without rectal bleeding. A Consider obtaining FITing for fecal blood loss in primary or secondary care, either as an exclusion test or to guide the priority of investigations, in patients with chronic diarrhea without rectal bleeding. C As per ASGE 2010 guidelines: Consider performing a colonoscopy with random biopsies of the right and left sides of the colon in patients with chronic unexplained diarrhea. Consider performing sigmoidoscopy as an alternative option, although it may miss the right-sided organic disease. C Perform intubation of the terminal ileum during colonoscopy in patients undergoing evaluation of chronic diarrhea. B Insufficient evidence to recommend a routine biopsy of the endoscopically normal-appearing terminal ileum. Evaluation for hormone-secreting tumors: As per BSG 2018 guidelines, obtain evaluation for hormone-secreting tumors only when other causes of diarrhea have been excluded, as those tumors are a rare cause of diarrhea. B As per CD-EG 2017 guidelines, reserve measurement of circulating peptide levels for very select patients because of the rarity of peptide-secreting tumors. B Evaluation for structural disorders: As per BSG 2018 guidelines: Obtain anorectal manometry and endoanal ultrasound only after the exclusion of other local pathologies and exhaustion of conservative measures. B Obtain radiological modalities (MRI or CT with contrast follow-through) for the evaluation of fistulae. B https://web.pathway.md/diseases/recqLmnFvUW93houD 4/6 6/29/23, 3:53 AM Chronic diarrhea Pathway As per CD-EG 2017 guidelines, consider obtaining diagnostic evaluation or offering empiric treatment in patients with chronic diarrhea with a history of abdominal surgery. B Evaluation for graft-versus-host disease: consider performing flexible sigmoidoscopy with distal colon biopsies as the initial endoscopic evaluation in patients with suspected GvHD and diarrhea. C Perform upper gastrointestinal endoscopy with biopsies in the event of negative colonic histology findings or when upper gastrointestinal symptoms predominate. C 3. Medical management Non-specific management: offer opioid antidiarrheals (scheduled rather than as needed) for symptomatic management when specific treatment is not possible. B 4. Specific circumstances Patients with HIV: Consider performing flexible sigmoidoscopy or colonoscopy in patients with human immunodeficiency virus and diarrhea if laboratory evaluation is nondiagnostic. C Perform a full colonoscopy with biopsy and/or upper gastrointestinal endoscopy with biopsy in patients with human immunodeficiency virus and persistent diarrhea if flexible sigmoidoscopy is nondiagnostic. B 5. Follow-up and surveillance Indications for referral: As per BSG 2018 guidelines, refer patients for further investigations if symptoms persist despite normal first-line investigations and treatment. E As per CD-EG 2017 guidelines, recognize that failure to make a diagnosis is more likely due to overlooking a common cause than missing a rare cause of chronic diarrhea. Repeat the history and physical examination and review studies already done before ordering additional tests. B Clinical findings Symptoms Past medical history Abdominal pain AUD Diarrhea Bile acid malabsorption Weight loss Celiac disease Chronic mesenteric ischemia Past surgical history Chronic pancreatitis Colorectal cancer Bariatric surgery Diabetes mellitus https://web.pathway.md/diseases/recqLmnFvUW93houD 5/6 6/29/23, 3:53 AM Chronic diarrhea Pathway Cholecystectomy Eosinophilic gastroenteritis Colonic resection Giardiasis HF Hematological findings Hyperthyroidism Anemia IBD IBS Lactose intolerance Pancreatic insufficiency Radiation enteritis SIBO Short bowel syndrome Vipoma Vitamin A deficiency Vitamin D deficiency Vitamin E deficiency Vitamin K deficiency Whipple disease Anthropomorphic exam Malnutrition References 1. Lawrence R Schiller, Darrell S Pardi, Joseph H Sellin. Chronic Diarrhea: Diagnosis and Management. Clin Gastroenterol Hepatol. 2017 Feb;15 2 182 193.e3. Open 2. Arasaradnam RP, Brown S, Forbes A et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 2018 Aug;67 8 1380 1399. Open 3. Walter Smalley, Corinna Falck-Ytter, Alonso Carrasco-Labra et al. AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults IBS D . Gastroenterology. 2019 Sep;157 3 851 854. Open 4. ASGE Standards of Practice Committee, Bo Shen, Khalid Khan et al. The role of endoscopy in the management of patients with diarrhea. Gastrointest Endosc. 2010 May;71 6 887 92. Open 5. Daniel C Sadowski, Michael Camilleri, William D Chey et al. Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea. Clin Gastroenterol Hepatol. 2020 Jan;18 1 24 41.e1. Open 6. Rubio-Tapia A, Hill ID, Kelly CP et al. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2013 May;108 5 656 76;. 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