How do you rule out Crohn's disease?

Ruling Out Crohn's Disease: A Comprehensive Diagnostic Approach

The most effective approach to rule out Crohn's disease requires a combination of clinical, biochemical, stool, endoscopic, cross-sectional imaging, and histological investigations, with ileocolonoscopy with biopsies being the gold standard diagnostic procedure. 1

Initial Diagnostic Workup

Laboratory Testing

• Complete blood count: Assess for anemia (Hb <13 g/dL for men, <12 g/dL for women) 1
• Inflammatory markers:
  • Fecal calprotectin: Most sensitive non-invasive marker
    • Values <150 μg/g can rule out active inflammation with high confidence 1
    • Higher sensitivity (88%) for ruling out inflammation at <50 μg/g 2
  • C-reactive protein (CRP): Values <5 mg/L suggest absence of active inflammation 1, 2
  • Erythrocyte sedimentation rate (ESR): Less specific but can be helpful when combined with CRP 2, 3
• Additional tests: Liver profile, albumin, iron studies, renal function 2

Stool Studies

• Infectious workup: Rule out common pathogens including C. difficile toxin, ova, cysts, and parasites 1
• Fecal calprotectin: Key biomarker with highest sensitivity for intestinal inflammation 1, 3

Endoscopic Evaluation

Ileocolonoscopy with Biopsies

• Gold standard diagnostic procedure 1
• Required elements:
  • Complete colonoscopy with terminal ileum intubation
  • Multiple biopsies from inflamed and uninflamed segments 1
  • Look for characteristic findings:
    • Discontinuous lesions
    • Longitudinal ulcers
    • Cobblestone appearance
    • Strictures and fistulae
    • Perianal involvement 1

Upper Endoscopy

• Indicated when:
  • Upper GI symptoms are present
  • To evaluate for upper GI involvement (occurs in up to 13% of patients) 4

Cross-Sectional Imaging

MR Enterography (Preferred First-Line)

• Advantages:
  • No radiation exposure
  • Excellent for small bowel evaluation
  • Can detect transmural inflammation and extraluminal complications 1

CT Enterography

• Consider when:
  • MRI unavailable or contraindicated
  • Requires neutral oral contrast (1300-1800cc) administered over 30-60 minutes 1

Intestinal Ultrasound

• Benefits:
  • Non-invasive, no radiation
  • Well-tolerated, requires no bowel preparation
  • Provides real-time information about disease extent and severity 1

Small Bowel Assessment

Small Bowel Capsule Endoscopy

• Consider when:
  • Small bowel Crohn's is suspected despite normal or inconclusive investigations
  • Patency capsule should be used first to ensure no strictures 1

Small Bowel Follow-Through

• Alternative when more advanced imaging is unavailable 5

Diagnostic Algorithm

1. Initial assessment:

   • Laboratory tests (CBC, CRP, ESR, albumin)
   • Fecal calprotectin
   • Stool studies to rule out infection

2. If fecal calprotectin <150 μg/g AND CRP <5 mg/L:

   • Low probability of Crohn's disease
   • Consider other diagnoses (IBS, functional disorders) 1

3. If fecal calprotectin >150 μg/g OR CRP >5 mg/L:

   • Proceed to ileocolonoscopy with biopsies 1
   • If colonoscopy is negative but suspicion remains high, proceed to small bowel imaging

4. For suspected small bowel involvement:

   • MR enterography (preferred) or CT enterography 1
   • Consider capsule endoscopy if other imaging is negative 1

5. For perianal disease assessment:

   • Pelvic MRI
   • Examination under anesthesia by experienced colorectal surgeon 1

Histopathological Features

Key histological findings to establish diagnosis:

• Focal and patchy chronic inflammation
• Focal crypt irregularity
• Non-caseating granulomas (pathognomonic but present in only 15-60% of cases) 5
• Transmural inflammation 6

Common Pitfalls and Caveats

1. Relying solely on symptoms: Subclinical inflammation can exist despite clinical remission 1

2. Overlooking differential diagnoses: Particularly intestinal tuberculosis and Behçet's enterocolitis, which can mimic Crohn's disease 5

3. Inadequate bowel preparation for imaging: For CT/MR enterography, proper bowel distention is crucial to avoid false negatives 1

4. Misinterpreting biomarkers:

   • CRP may be normal even during active disease
   • Fecal calprotectin can be elevated in other conditions (infections, NSAIDs use) 2

5. Incomplete colonoscopy: Terminal ileum intubation is essential as isolated ileal disease can be missed 1

6. Inadequate biopsies: Multiple biopsies from both inflamed and uninflamed areas are necessary 1

By following this systematic approach, Crohn's disease can be effectively ruled out or diagnosed, allowing for appropriate management decisions to improve patient outcomes.