What are the characteristics and treatment options for ulcerative colitis?

Pathology of Ulcerative Colitis

Diagnostic Biopsy Requirements

For a reliable diagnosis of ulcerative colitis, obtain a minimum of two biopsies from at least five sites around the colon (including the rectum) and the ileum. 1

• Biopsies must be accompanied by clinical information including endoscopic findings, disease duration, and current treatment 1
• Samples should be fixed immediately by immersion in buffered formalin before transport 1

Microscopic Features: Four Main Categories

The pathological features of UC are classified into four main categories: mucosal architecture, lamina propria cellularity, neutrophil granulocyte infiltration, and epithelial abnormality 1

Early Stage Disease (Within 2 Weeks of Symptoms)

Basal plasmacytosis is the earliest diagnostic feature with the highest predictive value for diagnosing ulcerative colitis. 1

• Only 20% of patients show crypt distortion within 2 weeks of first symptoms 1
• Preserved crypt architecture and absence of transmucosal inflammatory infiltrate do NOT rule out early UC 1
• The major differential diagnosis concern is infectious colitis (acute self-limiting colitis), which shows preserved crypt architecture and acute inflammation 1
• Repeat biopsies after an interval may be necessary to establish definitive diagnosis by showing additional features 1

Established Disease: Classic Histological Features

The microscopic diagnosis of established ulcerative colitis is based on the combination of widespread crypt architectural distortion and mucosal atrophy, diffuse transmucosal inflammatory infiltrate with basal plasmacytosis, and active inflammation causing cryptitis and crypt abscesses. 1

Mucosal Architecture Changes:

• Widespread crypt architectural distortion 1
• Mucosal atrophy 1
• Decreased crypt density with branching and atrophy (shortening) of crypts 1
• Crypt distortion and atrophy persist even in quiescent disease 1

Inflammatory Infiltrate:

• Diffuse transmucosal inflammatory infiltrate 1
• Basal plasmacytosis (plasma cells at the base of the mucosa) 1
• Increased transmucosal lamina propria cellularity 1

Active Inflammation Features:

• Cryptitis (neutrophils infiltrating crypt epithelium) 1
• Crypt abscesses (neutrophils within crypt lumens) 1
• Epithelial damage in association with neutrophils 1

Additional Microscopic Features:

• Paneth cell metaplasia may persist in chronic disease 1
• Mucin depletion in active disease, which restores with reduced epithelial regeneration during remission 1

Distribution Pattern

A decreasing gradient of inflammation from distal to proximal favors a diagnosis of ulcerative colitis. 1

• In untreated patients, UC presents continuous inflammation beginning in the rectum and extending proximally with gradual decrease in severity 1
• The transition between involved and normal mucosa is abrupt 1
• UC is characterized by continuous, confluent colonic involvement with clear demarcation of inflammation and rectal involvement 1
• However, unusual distribution patterns can occur 1

Critical Pitfall: Treatment may change the classical distribution pattern of inflammation, which is important to recognize when evaluating biopsies from treated patients to avoid misdiagnosis 1

Quiescent (Inactive) Disease

In quiescent disease, the mucosa may still show features related to architectural damage and recovery, with disappearance of basal plasmacytosis and increased transmucosal cellularity, but active inflammation is usually not observed. 1

• Quiescent disease is characterized by lack of active inflammation (absence of mucosal neutrophils) 1
• Features of chronic mucosal injury persist: crypt distortion, atrophy, and Paneth cell metaplasia 1
• Histological mucosal healing is characterized by resolution of crypt architectural distortion and inflammatory infiltrate 1
• However, some features of sustained damage may persist: decreased crypt density with branching and atrophy of crypts 1

Histological vs. Endoscopic Healing

Histological healing is distinct from endoscopic mucosal healing—histological inflammation may persist in cases with endoscopically quiescent disease and has been associated with adverse outcomes. 1

• No standard definition of histological remission or "histological mucosal healing" exists 1
• Definitions of pathological remission range from residual inflammation with persistent architectural distortion to normalization of the colonic mucosa 1
• Biopsies can distinguish between quiescent and active disease and assess different grades of disease activity 1

Macroscopic/Endoscopic Features

The most common endoscopic feature of ulcerative colitis is continuous, confluent colonic involvement with clear demarcation of inflammation and rectal involvement. 1

• Endoscopic changes characteristically commence at the anal verge and extend proximally in a continuous, confluent, and concentric fashion 1
• The demarcation between inflamed and normal areas is usually clear and may occur abruptly within millimeters, especially in distal disease 1

Endoscopic Features by Severity:

Endoscopically severe ulcerative colitis is defined by mucosal friability, spontaneous bleeding, and ulcerations. 1

• Granularity, vascular pattern, ulceration, and bleeding/friability predict global assessment of endoscopic severity 1
• A pathognomonic finding is the presence of continuous colonic inflammation characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations 2
• In severe colitis: hemorrhagic mucosa with deep ulceration, mucosal detachment on the edge of ulcerations, and well-like ulceration 1

Imaging Features

The hallmark CT finding of UC is mural thickening with a mean wall thickness of 8 mm, as opposed to 2-3 mm mean wall thickness of normal colon. 2

• Abdominal CT scanning is the preferred initial radiographic imaging study in UC patients with acute abdominal symptoms 2

Clinical Correlation

UC is a chronic inflammatory bowel disorder causing continuous mucosal inflammation extending from the rectum to more proximal colon with variable extents 2. The classic presentation includes bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable degrees of abdominal pain often relieved by defecation 2. UC is characterized by inflammation limited to the mucosa, though over time it may confer transmural effects on the bowel wall 3.