What laboratory, endoscopic, imaging, and histologic tests are used to diagnose Crohn’s disease?

Diagnostic Testing for Crohn's Disease

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 is the diagnostic cornerstone for Crohn's disease. 1

Endoscopic Evaluation

Complete ileocolonoscopy with biopsies is mandatory for diagnosis. 1, 2

• Take at least two biopsies from five different sites: terminal ileum, rectum, and multiple colonic segments, including both inflamed and normal-appearing mucosa 1, 2
• Biopsies from unaffected areas are critical to document histologically the spared segments between inflammatory areas—a hallmark of Crohn's disease 2
• Key endoscopic features to identify include discontinuous (skip) lesions throughout the GI tract, rectal sparing, strictures, fistulae, and perianal involvement 2, 3
• Use standardized scoring systems like CDEIS or SES-CD when feasible to document severity 4
• In acute severe colitis, sigmoidoscopy alone may be sufficient 2
• Upper GI endoscopy with biopsies should be performed in pediatric patients and adults with upper GI symptoms 4, 3
• When standard endoscopy is inconclusive but clinical suspicion remains high, consider capsule endoscopy or balloon enteroscopy 4, 2

Cross-Sectional Imaging

MR enterography is the preferred first-line imaging modality over CT due to lack of radiation exposure and superior ability to detect active inflammation. 1, 2

• MRI should be systematically performed in all patients at diagnosis to evaluate disease extent beyond endoscopic reach, assess transmural inflammation, identify strictures and fistulae, and detect extraluminal complications like abscesses 1, 2
• MRI provides high soft-tissue contrast with static, dynamic, and multiplanar imaging capabilities, optimized with luminal and intravenous contrast 4
• Pelvic MRI is the modality of choice for imaging perianal disease 4
• CT enterography has similar accuracy to MR enterography for detecting penetrating complications (fistulas, inflammatory masses, abscesses) and should be reserved for situations where MRI is contraindicated, unavailable, or in emergency presentations 4, 2
• Ultrasonography is a relatively accessible, radiation-free tool for urgent assessment of disease activity and exclusion of complications, with high reproducibility 4
• Contrast-enhanced ultrasonography allows quantitative differentiation between inflamed and normal bowel segments but cannot distinguish inflammatory from fibrotic stenosis 4

Laboratory Testing

Obtain a comprehensive laboratory panel including CBC, CRP, ESR, comprehensive metabolic panel, albumin, iron studies, and vitamin B12 to assess for anemia, inflammation, and nutritional status. 1

• The combination of elevated CRP and fecal calprotectin provides the most reliable assessment of inflammatory activity 1
• Critical caveat: Approximately 20% of patients with active Crohn's disease have normal CRP levels, so normal inflammatory markers do not exclude active disease 1
• Fecal calprotectin has pooled sensitivity of 93-95% and specificity of 91-96% for diagnosing IBD, with a cutoff of 100 μg/g providing greater diagnostic precision 1, 2
• Serological markers (pANCA and ASCAs) may support diagnosis but have limited accuracy and should not be relied upon as primary diagnostic tools 3

Stool Studies

Mandatory stool cultures and C. difficile toxin testing must be obtained to exclude infectious causes before confirming IBD diagnosis. 1, 2, 3

• Test for common bacterial pathogens and specifically for C. difficile toxin 1, 2
• Loose stools for more than 6 weeks usually discriminate IBD-associated colitis from most infectious diarrhea 2

Diagnostic Integration

No single test serves as a gold standard—diagnosis requires integration of clinical, biochemical, endoscopic, radiological, and histological investigations. 1, 5, 6

• All four assessment modalities (symptom assessment, endoscopy, laboratory markers, and cross-sectional imaging) should be used at diagnosis where resources allow to establish a baseline for future disease monitoring 4
• Histology is particularly important when the colon is predominantly involved to distinguish Crohn's disease from ulcerative colitis 6
• 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, though a negative capsule endoscopy does not definitively exclude future diagnosis 2
• Endoscopy combined with biopsy provides diagnostic accuracy in nearly all cases when performed systematically 7