What labs should I order to rule out other causes of diarrhea aside from Irritable Bowel Syndrome with Diarrhea (IBS-D)?

Laboratory Testing to Rule Out Other Causes of Diarrhea Besides IBS-D

For patients with suspected IBS-D, a focused laboratory evaluation should include fecal calprotectin or fecal lactoferrin, stool testing for Giardia, celiac disease serologies, and consideration of bile acid diarrhea testing to rule out other causes of chronic diarrhea. 1

First-Line Laboratory Tests

Essential Tests

• Complete Blood Count (CBC) - To screen for anemia, inflammation, or infection 1, 2
• Fecal Calprotectin or Fecal Lactoferrin - To screen for inflammatory bowel disease (IBD) 1
  • These are more sensitive than ESR or CRP for detecting intestinal inflammation
• Stool Test for Giardia - Strongly recommended regardless of travel history 1
• Celiac Disease Testing 1
  • IgA Tissue Transglutaminase (tTG)
  • Second test to detect celiac disease in IgA deficiency (IgG tTG or IgG/IgA deaminated gliadin peptides)
• Basic Metabolic Panel - To assess for electrolyte abnormalities 2

Conditional Tests Based on Clinical Scenario

• Stool Hemoccult (Fecal Occult Blood Test) - To screen for GI bleeding 1
• Bile Acid Diarrhea Testing - Suggested in patients with chronic diarrhea 1
  • In the US, options include:
    • 48-hour stool collection for total bile acids
    • Serum fibroblast growth factor 19
  • If testing unavailable, consider empiric trial of bile acid binders 1

Second-Line Tests Based on Specific Concerns

For Patients with Risk Factors or Warning Signs

• Stool Culture - For bacterial pathogens if infectious etiology suspected 1
• Stool for Ova and Parasites - Only if travel to or immigration from high-risk areas 1
• C. difficile Testing - For patients with:
  • Recent antibiotic use (within 8-12 weeks)
  • Healthcare-associated diarrhea 1
• Inflammatory Markers - ESR or CRP if other inflammatory markers unavailable 1
  • Note: These are less sensitive than fecal calprotectin/lactoferrin for intestinal inflammation

For Persistent or Severe Symptoms

• Colonoscopy with Biopsies - Consider for:
  • Patients over 50 years (higher risk of colon cancer)
  • Persistent diarrhea with weight loss
  • To evaluate for microscopic colitis 1, 2

Important Considerations

When to Avoid Certain Tests

• Stool for Ova and Parasites (other than Giardia) - Not recommended without travel history to high-risk areas 1
• ESR or CRP for IBD Screening - Less sensitive than fecal calprotectin/lactoferrin 1
• Serologic Tests for IBS - Currently available tests lack sufficient diagnostic accuracy 1

Diagnostic Pitfalls to Avoid

• Overlooking Bile Acid Diarrhea - Present in 20-30% of patients diagnosed with IBS-D 3
• Missing Celiac Disease - Can present with IBS-like symptoms; testing is strongly recommended 1, 2
• Neglecting to Test for Giardia - Important cause of chronic diarrhea even without travel history 1
• Assuming IBS-D Without Excluding Other Causes - At least two-thirds of IBS-D cases may have identifiable causes (food intolerances, bile acid diarrhea, disturbed microbial flora) 3

Testing Algorithm

1. Start with CBC, fecal calprotectin/lactoferrin, stool for Giardia, celiac disease serologies
2. If negative and symptoms persist:
   • Consider bile acid diarrhea testing or empiric trial of bile acid binders
   • Test for C. difficile if recent antibiotic use
3. For patients >50 years or with concerning symptoms (weight loss, persistent diarrhea):
   • Consider colonoscopy with biopsies to rule out microscopic colitis and malignancy

By following this systematic approach to laboratory testing, clinicians can effectively rule out other causes of diarrhea and more confidently diagnose IBS-D when appropriate.