What tests are used to rule out Crohn's disease?

Diagnostic Tests to Rule Out Crohn's Disease

A comprehensive diagnostic approach for ruling out Crohn's disease requires a combination of laboratory tests, endoscopic evaluation with biopsies, and cross-sectional imaging studies, as no single test serves as a definitive "gold standard." 1

Laboratory Tests

First-line Tests

• Complete blood count (CBC) - to assess for anemia, leukocytosis, and thrombocytosis 2, 1
• Inflammatory markers:
  • C-reactive protein (CRP) - values <5 mg/L help rule out active inflammation 2
  • Erythrocyte sedimentation rate (ESR) - often elevated in chronic inflammation 1, 3
  • Liver function tests, albumin, iron studies - to assess nutritional status and complications 2

Stool Tests

• Fecal calprotectin - critical biomarker with high negative predictive value:
  • Values <50 μg/g make IBD unlikely
  • Values 50-150 μg/g suggest possible IBD
  • Values >150 μg/g strongly suggest active inflammation 2, 1
• Stool cultures and C. difficile testing - mandatory to rule out infectious causes 1

Endoscopic Evaluation

• Ileocolonoscopy with biopsies - considered the reference standard for diagnosis 1

  • Multiple biopsies should be taken from both inflamed and non-inflamed areas 2
  • Allows direct visualization of mucosal inflammation and ulceration 2
  • Biopsies help identify characteristic histological features like granulomas 1

• Upper GI endoscopy - recommended when upper GI symptoms are present or in pediatric patients 2, 4

• Small bowel capsule endoscopy (SBCE) - particularly useful when other tests are negative:

  • Has a high negative predictive value for small bowel Crohn's disease 2
  • Should be performed after ruling out strictures 2
  • NSAIDs should be withdrawn at least 4 weeks prior to SBCE to avoid false positives 2

Cross-sectional Imaging

• CT enterography or MR enterography - preferred for small bowel assessment:

  • Evaluates transmural inflammation and extraluminal complications 2
  • Detects bowel wall thickening, strictures, fistulas, and abscesses 2
  • MRI preferred when available to reduce radiation exposure, especially in young patients 2

• Abdominal ultrasound - useful where expertise exists, especially for follow-up 2

Diagnostic Algorithm

1. Initial assessment:

   • Evaluate for alarm symptoms (persistent rectal bleeding, weight loss >10%, nocturnal symptoms, family history of IBD) 1
   • Check inflammatory markers (CRP, ESR) and fecal calprotectin 1

2. If fecal calprotectin <100 μg/g and normal CRP:

   • Crohn's disease is unlikely; consider alternative diagnoses 1

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

   • Proceed to ileocolonoscopy with biopsies 2, 1

4. If ileocolonoscopy is negative but suspicion remains high:

   • Perform cross-sectional imaging (MR enterography preferred) 2
   • Consider small bowel capsule endoscopy if no strictures are present 2

Important Considerations

• No single test can definitively rule out Crohn's disease; the diagnosis relies on a combination of clinical, laboratory, endoscopic, and imaging findings 1
• Fecal calprotectin has higher specificity for intestinal inflammation than serum markers 1
• CRP levels are typically higher in Crohn's disease than in ulcerative colitis for all categories of disease severity 3
• Endoscopic differentiation of small bowel Crohn's disease from drug-induced lesions can be challenging 2
• Cross-sectional imaging is particularly important for assessing disease beyond the reach of the endoscope and for detecting complications 2

By following this comprehensive diagnostic approach, clinicians can effectively rule out Crohn's disease or establish the diagnosis with confidence, allowing for appropriate management decisions that will positively impact patient morbidity, mortality, and quality of life.