What is the pathophysiology of ulcerative colitis that differs from Crohn's disease?

Pathophysiological Differences Between Ulcerative Colitis and Crohn's Disease

Ulcerative colitis is characterized by continuous, superficial mucosal inflammation limited to the colon, while Crohn's disease features discontinuous, transmural inflammation that can affect any part of the gastrointestinal tract.1

Anatomical Distribution and Pattern

• Ulcerative colitis (UC) typically begins in the rectum and extends proximally in a continuous fashion with gradually decreasing severity of inflammation, while Crohn's disease (CD) shows a patchy, discontinuous distribution with skip lesions 1
• UC is restricted to the colon and rectum, whereas CD can affect any part of the gastrointestinal tract from mouth to anus 2
• Rectal involvement is almost always present in untreated UC (rectal sparing favors CD), though therapy can alter this pattern 1
• "Backwash ileitis" may occur in approximately 20% of UC patients with extensive colitis but is different from the primary terminal ileitis seen in CD 1

Depth of Inflammation

• UC inflammation is limited to the mucosa and occasionally submucosa, while CD inflammation is transmural (affecting all layers of the intestinal wall) 1, 3
• In UC, fibrosis is commonly restricted to mucosa or submucosa, whereas in CD fibrosis can extend through all layers 1
• Serositis (inflammation of the serosal layer) is typically absent in UC except in fulminant colitis, but is commonly present in CD 1

Microscopic Features

• Crypt architectural irregularity and chronic inflammation are diffuse and continuous in UC but focal and discontinuous in CD 1
• Crypt abscesses (neutrophils within crypt lumina) are more common in UC (41%) than in CD (19%) 1
• Granulomas (non-cryptolytic) are absent in UC but present in CD, serving as a key distinguishing feature 1
• Cryptolytic granulomas may form in UC in reaction to ruptured crypts but are less useful for distinguishing between the two conditions 1
• Mucin depletion is pronounced in UC but uncommon and mild in CD 1

Cellular and Inflammatory Patterns

• Basal plasmacytosis (plasma cells between the base of the crypts and muscularis mucosae) is common in both UC (63%) and CD (62%) 1
• The inflammatory infiltrate in UC is diffuse without variations in intensity, while in CD it varies in intensity within and between biopsies 1
• In UC, the inflammatory infiltrate is proportionate with higher cellularity in the mucosa than submucosa 1
• Lymphoid aggregates are frequent in mucosa and submucosa in UC, but are transmural in CD 1

Tissue Remodeling and Structural Changes

• Paneth cell metaplasia is present in UC but uncommon in CD 1
• Pyloric gland metaplasia is rare in UC but present in CD 1
• Neuronal hyperplasia is rare in UC but common in CD 1
• Muscular hypertrophy is absent in UC but present in CD 1

Complications and Disease Evolution

• Fistulas and perianal disease are rare in UC but common in CD 3
• In longstanding UC, mucosal haustration disappears resulting in an atrophic, smooth mucosa 1
• Strictures may develop in UC (3.2% to 11.2% of cases) due to mucosal/submucosal fibrosis, whereas CD strictures involve all layers 1
• Fissures are characteristically absent in UC but present in CD 1

Diagnostic Challenges

• In fulminant colitis, the macroscopic appearance may not be sufficiently distinct to differentiate UC from CD 1
• Up to 5-10% of IBD cases affecting the colon remain unclassifiable even after considering clinical, radiological, endoscopic, and pathological criteria (termed indeterminate colitis or IBD-unclassified) 1, 4

Understanding these pathophysiological differences is crucial for proper diagnosis, treatment planning, and prognostication, as each disease entity often involves specific therapeutic strategies and outcomes.