Pathophysiological Differences Between Ulcerative Colitis and Crohn's Disease

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, 3
Rectal involvement is almost always present in untreated UC, though therapy can alter this pattern 4, 5
"Backwash ileitis" may occur in approximately 20% of UC patients with extensive colitis but is different from the primary terminal ileitis seen in CD 2

UC inflammation is limited to the mucosa and occasionally submucosa, while CD inflammation is transmural (affecting all layers of the intestinal wall) 1, 2
In UC, fibrosis is commonly restricted to mucosa or submucosa, whereas in CD fibrosis can extend through all layers 2
Serositis (inflammation of the serosal layer) is typically absent in UC except in fulminant colitis, but is commonly present in CD 1, 6

Crypt architectural irregularity and chronic inflammation are diffuse and continuous in UC but focal and discontinuous in CD 1, 2
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 3, 4
Mucin depletion is pronounced in UC but uncommon and mild in CD 1

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 4
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

In longstanding UC, mucosal haustration disappears resulting in an atrophic, smooth mucosa 2
Strictures may develop in UC (3.2% to 11.2% of cases) due to mucosal/submucosal fibrosis, whereas CD strictures involve all layers 2
Fissures are characteristically absent in UC but present in CD 1

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) 7