What is the next step in evaluating a patient with altered bowel habits and left lower quadrant abdominal pain who has a normal colonoscopy?

Next Step: Proceed Directly to Irritable Bowel Syndrome Diagnosis with Targeted Exclusions

In a patient with variable stools and left lower abdominal pain who has a normal colonoscopy, the next step is to complete basic blood work (CBC, CRP, comprehensive metabolic panel, thyroid function, celiac serology with total IgA) and measure fecal calprotectin to exclude inflammatory bowel disease, celiac disease, and microscopic colitis before making a positive diagnosis of irritable bowel syndrome. 1, 2

Critical Exclusions Before IBS Diagnosis

The normal colonoscopy has already ruled out colorectal cancer and macroscopic inflammatory bowel disease, but several treatable organic conditions remain that can mimic IBS and must be systematically excluded:

Mandatory Blood Work Panel

• Complete blood count to screen for anemia suggesting occult bleeding or malabsorption 1, 2
• C-reactive protein to assess for systemic inflammation 1, 2
• Comprehensive metabolic panel to evaluate electrolyte disturbances and renal/hepatic function 1, 2
• Thyroid function tests because thyroid disorders commonly present with altered bowel habits 1
• Anti-tissue transglutaminase IgA with total IgA for celiac disease screening—this is mandatory, not optional, as celiac disease affects 3-10% of patients with chronic diarrhea in secondary care 1, 2

Essential Stool Testing

• Fecal calprotectin is the single most important test at this stage because it distinguishes inflammatory from non-inflammatory causes with high sensitivity 1, 2
• If calprotectin is elevated (>50 μg/g), this indicates colonic inflammation and warrants repeat colonoscopy with mandatory biopsies from both right and left colon (not rectum) to diagnose microscopic colitis, which has entirely normal-appearing mucosa on endoscopy 1, 2

Common Pitfall: Missing Microscopic Colitis

The most critical error at this juncture is assuming the normal colonoscopy excluded all organic disease. 1, 2 Microscopic colitis accounts for 15% of chronic diarrhea cases in older adults and is diagnosed only by histology, not by endoscopic appearance. 2 If the initial colonoscopy did not include biopsies from the right and left colon, and if fecal calprotectin is elevated, the patient requires repeat colonoscopy with proper biopsy protocol. 1, 2

Bile Acid Diarrhea Evaluation

If the above workup is negative and diarrhea-predominant symptoms persist, objective testing for bile acid diarrhea with SeHCAT scanning or serum 7α-hydroxy-4-cholesten-3-one is required—empiric cholestyramine trials are not recommended as a diagnostic strategy. 1 This condition is highly treatable but frequently missed.

Positive IBS Diagnosis After Exclusions

Once the above investigations return normal, a positive diagnosis of irritable bowel syndrome can be made using Rome IV criteria (recurrent abdominal pain at least 1 day per week in the last 3 months, associated with 2 or more of: related to defecation, change in stool frequency, change in stool form). 1, 3

However, recognize that Rome IV criteria have only 52-74% specificity, meaning they cannot reliably exclude organic disease on their own—this is why the systematic exclusion process above is mandatory. 1

Red Flags That Change the Algorithm

• Weight loss is an absolute exclusion criterion for functional disorders and mandates aggressive workup for malignancy and malabsorption 2, 3
• Nocturnal diarrhea suggests organic pathology rather than IBS 1
• Age >45 years with new-onset symptoms increases colorectal cancer risk and requires full colonoscopy (already completed in this case) 1, 2
• Blood in stool requires fecal immunochemical testing (FIT) and consideration of repeat colonoscopy 4, 2

Timeline for Completion

• Blood work and fecal calprotectin should be completed within 1-2 weeks 2
• If calprotectin is elevated or celiac serology is positive, proceed to appropriate confirmatory testing (repeat colonoscopy with biopsies or upper endoscopy with duodenal biopsies) within 2-4 weeks 4, 2
• If all testing is negative, initiate IBS-directed therapy without further delay 1

Symptomatic Management Can Begin Immediately

While awaiting test results, loperamide 4 mg initially, then 2 mg after each unformed stool (maintenance 4-8 mg daily) can be started for diarrhea-predominant symptoms, as this provides symptomatic relief regardless of the underlying diagnosis. 1