What is the diagnostic and treatment approach for differentiating between Irritable Bowel Syndrome (IBS) and Crohn's Disease?

Differentiating IBS from Crohn's Disease

Use fecal calprotectin as the initial screening test to differentiate IBS from Crohn's disease—a level above 100-250 μg/g stool warrants ileocolonoscopy with biopsies, while a normal level (<50 μg/g) effectively rules out inflammatory bowel disease. 1

Initial Non-Invasive Testing

Fecal calprotectin is the cornerstone of differentiation between IBS and Crohn's disease, with pooled sensitivity of 93% and specificity of 96% for diagnosing IBD in adults. 1, 2 The negative predictive value of a normal calprotectin is extremely high, making it highly effective at excluding inflammatory bowel disease. 1

• Set your threshold at 100-250 μg/g stool (not the assay reference of 50 μg/g) to trigger colonoscopy, as this improves positive predictive value with minimal reduction in negative predictive value. 1
• Fecal lactoferrin serves as an alternative biomarker with similar utility for differentiating IBD from functional disease. 1, 2
• Critical caveat: Fecal calprotectin will be elevated in acute infectious gastroenteritis, so stool culture must be performed first to exclude infection before interpreting results. 1

When to Proceed to Endoscopy

Ileocolonoscopy with biopsies of both affected and normal-appearing areas is mandatory when fecal calprotectin exceeds your local threshold or when clinical suspicion remains high despite normal biomarkers. 1, 2

Key Endoscopic Features Distinguishing Crohn's Disease:

• Discontinuous "skip" lesions with segments of normal mucosa between inflamed areas 1, 3
• Cobblestoning, strictures, and fistulas are highly suggestive of Crohn's disease 1
• Perianal disease strongly indicates Crohn's rather than IBS 1, 3
• Terminal ileal involvement with ulceration or stenosis 1

Biopsy Protocol:

• Take at least two biopsies from every colonic segment, the rectum, and terminal ileum, including both abnormal and normal-appearing areas. 1
• This documents skip lesions and provides histological confirmation of transmural inflammation and granulomas characteristic of Crohn's disease. 1, 3

Baseline Laboratory Assessment

When Crohn's disease is suspected, obtain comprehensive baseline labs before endoscopy:

• Complete blood count to assess for anemia (common in Crohn's but not IBS) 1, 2
• CRP level, recognizing that approximately 20% of patients with active Crohn's disease may have normal CRP—so a normal value does not exclude the diagnosis. 1, 2
• Albumin, liver profile, iron studies, renal function, and vitamin B12 to establish baseline nutritional status 1, 2
• Stool culture and C. difficile toxin to exclude infectious causes 2

Important pitfall: Do not rely on CRP alone—its sensitivity and specificity are insufficient for screening, though it has prognostic value once diagnosis is established. 1

Cross-Sectional Imaging

MR enterography (or CT enterography if MRI unavailable) should be performed in all patients at diagnosis to assess small bowel involvement, disease extent, and complications like strictures or fistulas that cannot be reached by standard colonoscopy. 1, 2

• Small bowel involvement occurs in approximately one-third of Crohn's patients and cannot be adequately assessed by colonoscopy alone. 3
• Imaging detects transmural inflammation, abscesses, and penetrating disease characteristic of Crohn's but absent in IBS. 1, 3

Additional Diagnostic Considerations

Upper endoscopy with biopsies should be performed in pediatric patients and adults with upper GI symptoms, as upper tract involvement suggests Crohn's disease. 1

Small bowel capsule endoscopy may aid diagnosis when ileocolonoscopy, gastroscopy, and cross-sectional imaging are inconclusive but clinical suspicion for Crohn's remains high. 1, 2 Ensure cross-sectional imaging is performed first to exclude strictures that could cause capsule retention. 2

Serological Markers: Limited Utility

Do not rely on pANCA or ASCA antibodies for differentiating Crohn's disease from IBS—their diagnostic accuracy is limited and they provide minimal additional value beyond clinical assessment and objective testing. 2

Management Implications When Diagnosis Remains Unclear

If symptoms persist despite normal fecal calprotectin and negative endoscopy, consider:

• Serial calprotectin monitoring to detect emerging inflammation, as 53% of patients with initially elevated levels show reduction on repeat testing. 1
• Alternative mechanisms: small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance based on symptom patterns 1
• Functional symptom management: low FODMAP diet, psychological therapies (CBT, hypnotherapy), antispasmodics, and avoidance of opiates 1

Critical distinction: Overtreatment of functional symptoms with immunosuppression or biologics appropriate for Crohn's disease exposes patients to significant adverse effects without benefit. 1