What is the approach to diagnose and manage a patient suspected of having Crohn's disease versus another condition (CHS)?

Distinguishing Crohn's Disease from Other Conditions

When evaluating a patient for suspected Crohn's disease, perform ileocolonoscopy with biopsies from at least five sites (including terminal ileum and rectum, even from normal-appearing mucosa) combined with MR enterography as first-line imaging to establish the diagnosis and differentiate from mimics. 1, 2

Initial Diagnostic Algorithm

Step 1: Endoscopic Evaluation

• Perform complete ileocolonoscopy examining the terminal ileum and all colonic segments, not just sigmoidoscopy, as approximately one-third of Crohn's disease patients have small bowel involvement that would be missed 2, 3
• Obtain at least two biopsies from five different sites: terminal ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum 1, 2, 4
• Critically, biopsy normal-appearing mucosa to document histologically the spared segments between inflammatory areas, which distinguishes Crohn's disease from continuous inflammatory patterns 1, 2, 3
• Use standardized endoscopic scoring (CDEIS or SES-CD) to document severity, though this may not be practical in routine practice 1

Step 2: Cross-Sectional Imaging

• Perform MR enterography as first-line imaging in all patients at diagnosis to evaluate small bowel involvement beyond endoscopic reach and assess for transmural disease, strictures, fistulae, and extraluminal complications 1
• MR enterography is preferred over CT enterography because it avoids ionizing radiation exposure and has superior ability to detect active inflammation 4
• CT enterography should be reserved for emergency presentations or when MRI is contraindicated or unavailable 1, 4
• Intestinal ultrasound (IUS) may be used where local expertise exists, as it appears similar in value to MRE for monitoring transmural healing 1

Step 3: Laboratory Assessment

• Obtain baseline blood work: complete blood count, CRP, ESR, albumin, liver function tests, iron studies, renal function, and vitamin B12 1, 4
• Measure fecal calprotectin (sensitivity 93%, specificity 96% for IBD diagnosis; use 100 μg/g threshold rather than 50 μg/g for greater diagnostic precision) 1, 3, 4
• Note that approximately 20% of patients with active Crohn's disease may have normal CRP levels, so do not rely on CRP alone 1

Step 4: Exclude Infectious Mimics

• Mandatory stool cultures and C. difficile toxin assay before finalizing any IBD diagnosis 2, 4
• Loose stools for more than 6 weeks usually discriminate IBD-associated colitis from most infectious diarrhea 4

Key Distinguishing Features of Crohn's Disease

Distribution Pattern

• Patchy, discontinuous (skip) lesions throughout the GI tract, contrasting with the continuous proximal extension from rectum seen in ulcerative colitis 2, 3, 4
• Rectal sparing is common in Crohn's disease (occurs in >97% of cases), whereas rectal involvement is nearly universal in untreated ulcerative colitis 2, 3
• Any portion of the GI tract from mouth to anus can be affected: 25% colitis only, 25% ileitis only, 50% ileocolitis 5

Depth of Inflammation

• Transmural inflammation affecting all layers of the intestinal wall, versus mucosal/submucosal limitation in ulcerative colitis 2, 3
• This transmural nature leads to complications like strictures, fistulae, and abscesses that are characteristic of Crohn's disease 1, 4

Histological Features

• Non-caseating granulomas are pathognomonic for Crohn's disease when present (absent in ulcerative colitis) 2, 3
• Crypt abscesses are less common in Crohn's disease (19%) compared to ulcerative colitis (41%) 2, 3
• Variable intensity of inflammatory infiltrate within and between biopsies, versus diffuse uniform infiltrate in ulcerative colitis 2, 3

Clinical Features

• Perianal disease (fistulae, abscesses) occurs in 15-25% of patients and is highly characteristic of Crohn's disease 1, 4
• Upper GI symptoms warrant esophagogastroduodenoscopy, particularly in pediatric patients 1, 6

Management of Diagnostic Uncertainty

When Initial Evaluation is Inconclusive (5-15% of cases)

• Perform small bowel capsule endoscopy when Crohn's disease is suspected despite normal or inconclusive ileocolonoscopy and imaging 1
• Use a patency capsule first in patients with obstructive symptoms to prevent capsule retention 1
• Capsule endoscopy can establish definitive Crohn's disease diagnosis by demonstrating small bowel lesions in 17-70% of patients with unclassified IBD 2, 3, 4
• Critical caveat: A negative capsule endoscopy does not definitively exclude future diagnosis of Crohn's disease 2, 3, 4

Alternative Advanced Techniques

• Balloon-assisted enteroscopy permits tissue sampling beyond conventional endoscopy reach with similar diagnostic yield to capsule endoscopy and greater sensitivity than MRE (perforation risk 0.15%) 1
• Consider when biopsy confirmation would alter therapeutic approach in diagnostically uncertain cases 1

Common Diagnostic Pitfalls

False Patterns Mimicking Other Conditions

• Rectal sparing can occur in ulcerative colitis if patients received empirical topical therapy before evaluation 2
• "Cecal patch" (isolated peri-appendiceal inflammation) and backwash ileitis (up to 20% of extensive ulcerative colitis) can confuse the picture 2
• Uneven inflammation distribution can occur in long-standing or treated ulcerative colitis 2

Monitoring Considerations

• Use fecal calprotectin for disease monitoring in patients with known Crohn's disease location and baseline value 1
• Fecal calprotectin may be less reliable in small bowel disease than colonic Crohn's disease; changes over time in an individual patient are more meaningful than absolute numbers 1
• Multimodal monitoring combining clinical assessment, biochemical markers (CRP, fecal calprotectin), imaging, and endoscopy with histology is advised 1

Assessment of Complications

• Prioritize cross-sectional imaging and IUS for stricture assessment, supplemented by ileocolonoscopy when clinically safe, with biopsies to exclude dysplasia and distinguish fibrotic from inflammatory strictures 1
• For perianal disease, use clinical assessment, pelvic MRI, and examination under anesthesia by an experienced colorectal surgeon; endoanal ultrasound may have a role depending on local expertise 1