What distinguishes Crohn's disease from ulcerative colitis?

Distinguishing Crohn's Disease from Ulcerative Colitis

Crohn's disease is distinguished from ulcerative colitis by its transmural inflammation, patchy distribution with skip lesions, potential involvement of any GI tract segment (especially terminal ileum), rectal sparing, and presence of granulomas on histology, whereas ulcerative colitis shows continuous mucosal-only inflammation starting from the rectum and extending proximally. 1, 2

Anatomical Distribution and Location Patterns

Ulcerative colitis begins in the rectum and extends proximally in a continuous, uninterrupted fashion with gradually decreasing inflammation severity, while Crohn's disease demonstrates patchy, discontinuous inflammation with skip lesions that can affect any part of the GI tract from mouth to anus. 1, 2

Key location-based distinctions:

• Rectal involvement occurs in >97% of untreated ulcerative colitis cases, making rectal sparing extremely rare (only up to 3% of UC patients). 1, 2
• Rectal sparing strongly suggests Crohn's disease and is a key distinguishing feature, occurring commonly in CD. 1, 2
• The terminal ileum is the most commonly affected site in Crohn's disease, which can involve small intestine alone, colon alone, or both. 2
• Approximately 20% of UC patients with extensive colitis may develop "backwash ileitis," but this differs from the primary terminal ileitis characteristic of CD. 3

Depth and Transmural Characteristics

The single most important pathophysiologic distinction is that ulcerative colitis inflammation is limited to the mucosa and occasionally submucosa only, while Crohn's disease exhibits transmural inflammation extending through all layers of the intestinal wall. 2, 3

This transmural nature drives critical clinical differences:

• Fibrosis in UC is restricted to mucosa or submucosa, whereas in CD it extends through all intestinal wall layers. 2, 3
• Fistulas represent a hallmark complication of Crohn's disease due to transmural inflammation, with approximately one-quarter of perianal fistulas presenting at or before diagnosis. 2, 4
• Serositis (serosal layer inflammation) is typically absent in UC except in fulminant colitis, but is commonly present in CD. 3
• Strictures in UC result from mucosal/submucosal fibrosis, whereas CD strictures involve all layers. 2, 3

Microscopic and Histological Features

Granulomas (non-cryptolytic) are absent in ulcerative colitis but present in Crohn's disease, serving as the most specific distinguishing histological feature. 1, 2, 4

Additional microscopic distinctions:

• Crypt abscesses are more common in UC (41%) than in CD (19%). 1, 3
• The inflammatory infiltrate in UC is diffuse without variations in intensity, while in CD it varies in intensity within and between biopsies. 1, 3
• Mucin depletion is pronounced in UC but uncommon and mild in CD. 2, 3
• Crypt architectural irregularity and chronic inflammation are diffuse and continuous in UC but focal and discontinuous in CD. 3
• Fissures are characteristically absent in UC but present in CD. 3

Diagnostic Approach Algorithm

Perform a complete ileocolonoscopy with at least two biopsies from five different sites (including ileum and rectum) to differentiate CD from UC, even if initial sigmoidoscopy suggests UC. 1, 2

Systematic diagnostic steps:

• Systematically examine the terminal ileum and all colonic segments with detailed description of lesion type, location, depth, and extent. 1
• Take biopsies from unaffected areas to document histologically the spared segments between inflammatory areas, which is essential for identifying skip lesions. 1
• Systematically complete with cross-sectional imaging (MRI or CT enterography) to evaluate small intestine involvement, as about one-third of CD patients have small intestine disease not detectable by colonoscopy. 1, 2
• Fecal calprotectin has 93% sensitivity and 96% specificity for diagnosing IBD in adults, with optimal threshold 100 μg/g. 1

When Differentiation Remains Unclear

In 5-15% of IBD cases, endoscopic and histological evaluation cannot distinguish between CD and UC (termed IBD-unclassified). 1, 2

In these challenging cases:

• Capsule endoscopy of the small intestine can establish a definitive CD diagnosis by demonstrating small intestine lesions in 17-70% of patients with unclassified IBD. 1, 2
• A negative capsule endoscopy does not definitively exclude a future diagnosis of Crohn's disease. 1
• In fulminant colitis, the macroscopic appearance may not be sufficiently distinct to differentiate UC from CD. 3

Clinical Implications and Pitfalls

Primary sclerosing cholangitis is more commonly associated with ulcerative colitis than with Crohn's disease. 1

Critical considerations:

• Growth failure is far more severe in Crohn's colitis and may precede intestinal symptoms by months to years. 4
• Colorectal cancer risk is increased in both conditions, but the risk appears to be the same in Crohn's colitis as in UC when matched for extent and duration of colonic involvement. 2
• Always exclude infectious causes before finalizing diagnosis, as these can mimic IBD. 1
• In longstanding UC, mucosal haustration disappears resulting in an atrophic, smooth mucosa. 3