What tests are recommended to diagnose Crohn's disease?

Diagnostic Testing for Crohn's Disease

Perform ileocolonoscopy with systematic biopsies from at least five sites (including terminal ileum and rectum, even from normal-appearing mucosa) as the diagnostic cornerstone, combined with MR enterography to evaluate small bowel disease beyond endoscopic reach, and obtain fecal calprotectin and stool cultures to exclude infection. 1, 2, 3

Initial Endoscopic Evaluation

• Complete ileocolonoscopy with biopsies is mandatory, taking at least two biopsies from five different sites including the terminal ileum and rectum, even from normal-appearing mucosa 3
• Biopsies from unaffected areas are critical to document histologically the spared segments between inflammatory areas 3
• Look for discontinuous (skip) lesions throughout the GI tract, rectal sparing, strictures, fistulae, and perianal involvement as key endoscopic features 3
• In acute severe presentations, sigmoidoscopy alone may be sufficient 3

Common pitfall: Failing to biopsy normal-appearing mucosa will miss the characteristic skip lesions that help differentiate Crohn's from ulcerative colitis.

Cross-Sectional Imaging

MR enterography should be performed at diagnosis in all patients to detect small bowel involvement beyond endoscopic reach, assess transmural disease, identify strictures and fistulae, and evaluate extraluminal complications 1, 3

• MRI is preferred as first-line imaging over CT due to lack of radiation exposure and superior ability to detect active inflammation 1, 3
• Cross-sectional imaging should evaluate both luminal and extraluminal disease 1
• For diagnosis and determining disease extent, MRI is the preferred modality 1

Laboratory Testing

Obtain a comprehensive laboratory panel including:

• Complete blood count to assess for anemia (from chronic inflammation, blood loss, or nutritional deficiencies), leukocytosis, and thrombocytosis 2
• C-reactive protein (preferred over ESR as it is more sensitive and correlates better with endoscopic disease activity) 2
• Erythrocyte sedimentation rate for complementary inflammatory assessment 2
• Comprehensive metabolic panel including electrolytes, liver enzymes (ALT, AST, alkaline phosphatase, bilirubin), and renal function (creatinine, BUN) 2
• Serum albumin and pre-albumin to assess nutritional status 2
• Iron studies (serum iron, ferritin, total iron-binding capacity) 2
• Vitamin B12 level (commonly deficient in terminal ileal disease) 2

Critical caveat: Approximately 20% of patients with active Crohn's disease have normal CRP levels, so normal inflammatory markers do not exclude active disease 2

Stool Studies

Fecal calprotectin is highly valuable with pooled sensitivity of 93-95% and specificity of 91-96% for diagnosing IBD 2, 3

• Use a cutoff of 100 μg/g for greater diagnostic precision than 50 μg/g 2
• Mandatory stool cultures to exclude bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia) 2, 3
• Clostridium difficile toxin testing is essential to rule out this infectious trigger which can precipitate or mimic Crohn's flares 2, 3

Small Bowel Capsule Endoscopy

• Perform small bowel capsule endoscopy when small bowel Crohn's disease is suspected despite normal or inconclusive investigations 1
• A patency capsule should be considered before capsule endoscopy 1
• In cases of indeterminate colitis, capsule endoscopy can establish a definitive diagnosis by demonstrating small bowel lesions compatible with Crohn's disease in 17-70% of patients 3

Important limitation: A negative capsule endoscopy does not definitively exclude future diagnosis of Crohn's disease 3

Perianal Disease Assessment

When perianal involvement is suspected:

• Perform clinical assessment, pelvic MRI scan, and examination under anesthesia by a colorectal surgeon experienced in fistulising perianal Crohn's disease 1
• Endoscopic assessment of the rectal mucosa should be undertaken 1
• Depending on local availability and expertise, endoanal ultrasound may have a role 1

Upper GI Evaluation

• Oesophagogastroduodenoscopy may be warranted in patients experiencing upper gastrointestinal symptoms, but is otherwise not routinely needed 1

What NOT to Do

Do NOT use genetic testing for diagnosing Crohn's disease in routine clinical practice, as NOD2/CARD15 testing lacks adequate sensitivity and specificity for diagnosis 2

• Limited exception: Consider genetic testing only in very early onset inflammatory bowel disease, patients with family history suggesting Mendelian inheritance, or severe refractory disease 2

Diagnostic Integration

No single test serves as a gold standard—diagnosis requires a combination of clinical, biochemical, endoscopic, radiological, and histological investigations 2

• At initial diagnosis, use all four assessment modalities where resources allow: symptom assessment, endoscopic evaluation, laboratory markers, and cross-sectional imaging to establish baseline values for future comparison 2
• The combination of elevated CRP and fecal calprotectin provides the most reliable assessment of inflammatory activity 2