Conditions with similar symptoms	Testing to consider	Clinical features/comments
Bile acid diarrhea	SeHCAT where available, serum C4, FGF19, 48-hour fecal bile acidsA1 Empiric trial of a bile acid sequestrant (e.g., colesevelam [Welchol], colestipol [Colestid], cholestyramine [Questran]) is an alternative to testing but is limited by patient compliance and tolerance; some authorities recommend with caution,A2 whereas others recommend againstA3,A4	Consider if diarrhea developed following cholecystectomy Community prevalence of bile acid diarrhea may be greater than that of celiac disease; testing initiated earlier in the evaluation process may result in decreased health care utilizationA5
Carbohydrate malabsorption (e.g., lactose, fructose)	Breath tests, trial of food avoidance	Can also cause a fatty malabsorptive diarrhea Inquire about food triggers, family historyA6,A7
Dyssynergic defecation (pelvic floor dysfunction)	Referral for expert perineal and rectal examination and anorectal manometryA8 (anorectal manometry may be required to justify insurance coverage of pelvic floor retraining or therapy)	Incomplete evacuation, straining with defecation, manual removal of stool, history of sexual or physical abuseA9
Functional dyspepsia	Helicobacter pylori testing (stool antigen testing is most cost-effective, urea breath tests are more accurate but more expensive, serologic tests are least accurate) If patient is older than 55 years or has alarm features, esophagogastroduodenoscopy is indicated	IBS and functional dyspepsia may coexist; both may cause postprandial discomfort, bloating, and distention that are relieved by bowel movementA1,A10,A11
Microscopic colitis	Colonoscopy with multiple biopsies (even if mucosa appears normal) and ileoscopy	Consider in patients with chronic unexplained watery diarrheaA7
Nonceliac gluten sensitivity	Tissue transglutaminase IgA, total IgA, upper gastrointestinal endoscopy with duodenal biopsy to rule out celiac disease	Gluten food trigger, can have systemic symptoms similar to celiac diseaseA12
Pseudomembranous colitis (Clostridioides difficile)	Stool nucleic acid amplification tests for toxin genes (only diarrheal stools should be tested to avoid false-positive results)	Antibiotic use, patient is in a health care environment, patient is immunocompromisedA7
Slow transit constipation	Colonic transit study (consider only after ruling out dyssynergic defecation)	Rare condition, false-positive results are not uncommon
Small intestinal bacterial overgrowth	Lactulose hydrogen breath testing (appropriate only in patients with risk factors for this condition)	Risk factors for small intestinal bacterial overgrowth: Structural abnormalities (small bowel diverticula, strictures, surgical blind loops, or ileocecal valve resection) Disordered motility (scleroderma, type 1 diabetes mellitus, opioid use) Acid suppression (chronic proton pump inhibitor use, achlorhydria, gastric resection)A7,A9