What is the diagnostic approach to confirm Crohn's disease?

How to Confirm Crohn's Disease

Confirm Crohn's disease by performing ileocolonoscopy with systematic biopsies from at least five sites (including terminal ileum and rectum, even from normal-appearing mucosa) combined with MR enterography to evaluate small bowel disease beyond endoscopic reach, plus fecal calprotectin and stool cultures to exclude infection. 1, 2

Initial Clinical Assessment

Suspect Crohn's disease when patients present with:

• Diarrhea or abdominal pain persisting more than 6 weeks 1
• Weight loss, fever, or growth failure 1
• Perianal disease (fistulas, abscesses, skin tags) 1, 3
• Extraintestinal manifestations including arthritis/arthralgia, pyoderma gangrenosum, or primary sclerosing cholangitis 1

Mandatory First-Line Investigations

Ileocolonoscopy with Biopsies

Perform complete ileocolonoscopy with systematic biopsies as the diagnostic cornerstone - this is non-negotiable at initial presentation before starting therapy. 1, 2

• Take at least two biopsies from five different sites: terminal ileum, ascending colon, transverse colon, descending colon, and rectum 2, 3
• Biopsy even normal-appearing mucosa to document skip lesions and histologically spared segments 3
• Look for key endoscopic features: discontinuous (skip) lesions, rectal sparing, aphthous ulcers, cobblestoning, strictures, and fistulae 3
• In acute severe presentations, sigmoidoscopy alone may suffice 3

Cross-Sectional Imaging

MR enterography is the preferred first-line imaging modality to assess small bowel involvement beyond endoscopic reach. 1, 2

• MRE detects: transmural inflammation, strictures, fistulae, abscesses, and proximal small bowel disease 1
• Avoid CT enterography for initial diagnosis in young patients due to radiation exposure (15.5% of patients accumulate >75 mSv, increasing cancer mortality risk by 7.3%) 1
• Reserve CT only for acute presentations when MRI is unavailable 1
• Intestinal ultrasound is an acceptable alternative with similar diagnostic accuracy to MRE (92% vs 97% sensitivity), though less sensitive for deep pelvic pathology 1

Laboratory Testing

Obtain a comprehensive panel to assess inflammation and nutritional status:

• Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) - but note that 20% of patients with active Crohn's disease have normal CRP, so normal values do not exclude disease 2, 4
• Complete blood count: assess for anemia (common in Crohn's disease) and leukocytosis 2, 4
• Nutritional markers: albumin, prealbumin, vitamin B12, iron studies 2, 5
• Liver function tests and electrolytes 4

Stool Studies

Mandatory stool testing to exclude infectious mimics before confirming IBD diagnosis: 2, 3, 4

• Fecal calprotectin: highly valuable with 93-95% sensitivity and 91-96% specificity for IBD; use cutoff of 100 μg/g for optimal diagnostic precision 2, 4
• Stool cultures for bacterial pathogens 2, 3
• Clostridium difficile toxin testing - essential to rule out this infectious trigger 2, 3, 4
• Withdraw NSAIDs at least 4 weeks prior to capsule endoscopy or evaluation, as they can cause small bowel ulcerations mimicking Crohn's disease 1

When Initial Tests Are Negative

Capsule Endoscopy Indications

If clinical features strongly suggest Crohn's disease but ileocolonoscopy and MRE are negative, proceed with small bowel capsule endoscopy. 1

• Capsule endoscopy has superior diagnostic yield compared to ileoscopy, radiography, and CT enterography for proximal small bowel lesions 1
• Enhance pre-test probability by selecting patients with: typical symptoms PLUS elevated inflammatory markers (CRP, ESR) OR elevated fecal calprotectin OR extraintestinal manifestations 1
• Critical caveat: Small bowel ulcerations on capsule endoscopy are not specific for Crohn's disease - they occur in Behçet's disease, vasculitis, and NSAID-induced enteropathy. In one study, only 13% of patients with small bowel ulcerations on capsule endoscopy had confirmed Crohn's disease at one-year follow-up 1
• Use patency capsule first if stricture is suspected to reduce retention risk 1

Balloon-Assisted Enteroscopy

Consider balloon-assisted enteroscopy when diagnostic uncertainty persists and tissue diagnosis would alter management. 1

• Similar diagnostic yield to capsule endoscopy but allows biopsy collection 1
• Perforation risk is 0.15% for diagnostic procedures 1

Diagnostic Integration

No single test serves as a gold standard - diagnosis requires combining clinical symptoms, biochemical markers, endoscopic findings, radiological imaging, and histological evidence. 2, 4

The strongest diagnostic combination includes:

• Supportive clinical history (>6 weeks symptoms, weight loss, perianal disease) 1
• Elevated fecal calprotectin (>100 μg/g) 2, 4
• Ileocolonoscopy showing characteristic features with histological confirmation 1, 2
• MRE demonstrating small bowel involvement or transmural disease 1, 2

Critical Pitfalls to Avoid

• Never rely on laboratory markers alone - they must be interpreted alongside endoscopic and imaging findings 4
• Do not assume normal CRP excludes active disease - approximately 20% of active Crohn's disease patients have normal CRP 2, 4
• Always exclude infectious causes first before confirming IBD diagnosis to avoid inappropriate immunosuppressive treatment 3, 4
• Do not use serological markers (pANCA, ASCA) for diagnosis - they have limited accuracy and cannot differentiate colonic Crohn's from ulcerative colitis 4
• Avoid repeated CT scans in young patients due to cumulative radiation exposure and cancer risk 1
• Recognize that capsule endoscopy findings require clinical correlation - small bowel ulcerations alone do not confirm Crohn's disease 1