Conditions with similar symptoms	Testing to consider	Clinical features/comments
Celiac disease	Tissue transglutaminase and total immunoglobin A (to rule out immunoglobin A deficiency; if present, follow up with deaminated gliadin)25,26 Positive findings on serologic testing should be confirmed with biopsy	Patients cannot be on a gluten-free diet at time of testing; serologic tests and biopsies may be falsely negative (absence of HLA-DQ2 and HLA-DQ8 can rule out celiac disease) Consider in patients with diarrhea, steatorrhea, weight loss, bloating, distention, and flatulence or if local prevalence of celiac disease is > 1%7,8 Extraintestinal symptoms include anemia, dermatitis herpetiformis, oral lesions, osteoporosis, or osteopenia
Colorectal cancer	Complete blood count26 Colonoscopy usually not necessary	Fear of cancer is a common concern for patients with IBS symptoms, and this should be discussed Consider in patients 55 years and older who have alarm features (e.g., family history, abdominal pain, abdominal mass, weight loss), if the patient is due for routine screening, or if colonoscopy is otherwise indicated 4,43
Dyssynergic defecation (pelvic floor dysfunction)	Perineal and rectal examination (if negative, further testing, such as anorectal manometry, can be deferred)27	Incomplete evacuation, straining with defecation, manual removal of stool, history of sexual or physical abuse
Functional abdominal distention/functional abdominal bloating	Testing similar to IBS	Functional gastrointestinal disorder distinct from IBS, but overall management is similar Subjective symptoms of recurrent abdominal pressure with objective increases in abdominal girth (functional abdominal distention) or sensation of trapped gas (functional abdominal bloating), fewer stool abnormalities, more likely related to abdominal wall distention than to retained gas13
Functional diarrhea	Testing similar to IBS	Functional gastrointestinal disorder distinct from IBS, but overall management is similar Pain and bloating are not predominant symptoms, as in IBS13
Inflammatory bowel disease (ulcerative colitis, Crohn disease)	C-reactive protein or fecal calprotectin If positive, colonoscopy with biopsies and ileoscopy 26	Family history; abdominal pain and tenderness, perianal disease or fissuring, skin manifestations
Medications commonly associated with constipation (secondary constipation)	Medication history; usually no further testing necessary	Calcium-containing antacids, iron supplements, anticholinergics, opioids
Medications commonly associated with diarrhea; alcohol use	Medication and substance use history; usually no further testing necessary	Nonosmotic or stimulant laxatives, magnesium-containing antacids, sugar alcohols (mannitol, sorbitol, xylitol), antibiotics, metformin, alcohol abuse
Metabolic abnormalities commonly associated with constipation (secondary constipation)	Thyroid-stimulating hormone, chemistry panel, A1C, serum magnesium	Hypothyroidism, diabetic neuropathy, hypomagnesemia, hypokalemia, and hypercalcemia can cause constipation13
Noninvasive small bowel parasite (e.g., Giardia)	Stool test for giardiasis26	Testing for other ova and parasite diseases not routinely indicated unless specifically indicated
Opioid-induced constipation	Medication history, review of Prescription Drug Monitoring Program database, review of electronic health record; usually no further testing necessary	May coexist with constipation-predominant IBS or functional constipation Straining, incomplete evacuation, hard/lumpy stools, manual removal of stool Patients may also report dysphagia, reflux, nausea, bloating13 Assess for opioid use disorder, refer for treatment if needed