What is the diagnostic approach for suspected Crohn’s disease?

How to Diagnose Crohn's Disease

The diagnosis of Crohn's disease requires ileocolonoscopy with systematic biopsies from at least five sites (including terminal ileum and rectum, even from normal-appearing mucosa) combined with cross-sectional imaging—preferably MR enterography—to evaluate disease extent beyond endoscopic reach, plus exclusion of infectious causes through comprehensive stool studies. 1, 2

No Single Gold Standard Exists

There is no single reference standard for diagnosing Crohn's disease—diagnosis is based on integrating clinical presentation, biochemical markers, stool studies, endoscopic findings, cross-sectional imaging, and histological evaluation. 1, 3

Step 1: Clinical Assessment and Initial Laboratory Workup

Key Clinical Features to Identify:

• Chronic gastrointestinal symptoms lasting >6 weeks (abdominal pain, diarrhea, weight loss) help distinguish inflammatory bowel disease from acute infectious causes 2
• Presence of arthralgias supports Crohn's disease over celiac disease 2
• Absence of bloody diarrhea favors Crohn's disease over ulcerative colitis 2

Mandatory Laboratory Tests:

• Complete blood count (assess for anemia—hemoglobin <13 g/dL in men, <12 g/dL in women) 1
• C-reactive protein and erythrocyte sedimentation rate (note: ~20% of active Crohn's disease patients have normal CRP) 3
• Comprehensive metabolic panel, albumin, liver function tests 3
• Iron studies (ferritin <30 μg/L indicates iron deficiency without inflammation; ferritin 30-100 μg/L with inflammation suggests mixed picture) 1
• Vitamin B12 level 3
• Fecal calprotectin (sensitivity 93-95%, specificity 91-96% for IBD; optimal cutoff 100 μg/g) 4, 3

Step 2: Exclude Infectious Causes (Mandatory)

Before confirming IBD diagnosis, obtain stool specimens to exclude:

• Common bacterial pathogens 1, 4
• Clostridioides difficile toxin (specifically test for this) 1, 4, 3
• Ova, cysts, and parasites (if travel history or relevant exposure) 1
• Mycobacterial pathogens when appropriate 2

Loose stools persisting >6 weeks typically discriminate IBD from most infectious diarrhea. 1, 2

Step 3: Ileocolonoscopy with Systematic Biopsies (First-Line Investigation)

Perform complete ileocolonoscopy with biopsies from:

• At least five different sites including terminal ileum and rectum 2, 4, 3
• Both inflamed AND normal-appearing segments (at least two biopsies per site) 1, 2, 4
• This documents histologically the spared segments between inflammatory areas 4

Exception: In acute severe colitis, sigmoidoscopy alone may be sufficient. 1, 4

Key Endoscopic Features of Crohn's Disease (None Are Pathognomonic):

• Discontinuous (skip) lesions throughout the GI tract 1, 2, 4
• Rectal sparing 4
• Presence of strictures and fistulae 1, 2, 4
• Perianal involvement 1, 2, 4

Step 4: Cross-Sectional Imaging (Essential for Complete Evaluation)

MR enterography is the preferred first-line imaging modality to: 1, 4, 3

• Evaluate small bowel disease beyond endoscopic reach (up to 20% have isolated proximal small bowel disease) 1
• Assess transmural disease, strictures, fistulae, and extraluminal complications 2, 4
• Detect active inflammation without radiation exposure 1, 4

Alternative Imaging Options:

• Intestinal ultrasound (IUS) has similar value to MRE for monitoring but lower sensitivity for disease extent (70% vs 80% for MRE) 1
• CT enterography should be reserved for acute presentations or when MRI is contraindicated, due to radiation exposure concerns (15.5% of patients accumulate >75 mSv, increasing cancer mortality risk by 7.3%) 1, 4
• Small bowel capsule endoscopy (SBCE) may be considered when other imaging is inconclusive, but requires prior cross-sectional imaging or patency capsule to exclude strictures (retention risk in established Crohn's disease) 1, 5

Step 5: Special Considerations

Upper GI Endoscopy:

Not routinely required unless patient has upper gastrointestinal symptoms. 1

Indeterminate Colitis (IBDU):

If unable to distinguish Crohn's disease from ulcerative colitis after ileocolonoscopy and imaging, capsule endoscopy demonstrates small bowel lesions compatible with Crohn's disease in 17-70% of IBDU patients, though negative SBCE does not definitively exclude future Crohn's disease diagnosis. 1, 4

Device-Assisted Enteroscopy:

May be performed when diagnosis needs endoscopic confirmation after positive MRI or SBCE findings, allowing tissue sampling and potential therapeutic intervention. 1

Critical Pitfalls to Avoid

• Do not rely on serological markers (pANCA, ASCA, anti-OmpC, CBir1)—accuracy is limited and ineffective at differentiating colonic Crohn's disease from ulcerative colitis 1
• Genetic testing for IBD-associated SNPs does not allow diagnosis 1
• Normal CRP does not exclude active disease (present in ~20% of active cases) 3
• Always biopsy normal-appearing mucosa to document skip lesions histologically 2, 4
• Avoid repeated CT scans in young patients due to cumulative radiation exposure—use MRE or ultrasound for monitoring 1