How is ulcerative colitis diagnosed?

Diagnosis of Ulcerative Colitis

The diagnosis of ulcerative colitis requires colonoscopy with histology combined with clinical history and non-invasive biomarkers—no single test can establish the diagnosis alone. 1

Initial Assessment and Laboratory Screening

When a patient presents with suggestive symptoms (bloody diarrhea, rectal urgency, tenesmus), immediately order:

• Complete blood count to assess for anemia, leukocytosis, or thrombocytosis 1, 2
• C-reactive protein (CRP) as the preferred inflammatory marker over ESR 2
• Serum albumin to evaluate nutritional status and disease severity 1, 2
• Liver enzymes and renal function as baseline and to assess extraintestinal involvement 2
• Fecal calprotectin which has excellent sensitivity for IBD (though poor specificity) 1, 2
• Stool cultures and C. difficile toxin to exclude infectious causes—this is mandatory 1, 2

Critical pitfall: Normal inflammatory markers do not exclude ulcerative colitis, particularly in mild disease or proctitis. 2 Infections and drugs commonly elevate fecal biomarkers, so always exclude these first. 1

Endoscopic Evaluation: The Definitive Diagnostic Step

Ileocolonoscopy with biopsies from both inflamed and uninflamed segments is required to establish the diagnosis. 1 Take a minimum of two biopsies from at least five sites around the colon including the rectum and terminal ileum. 1

Key Endoscopic Features Supporting UC Diagnosis:

• Continuous and confluent colonic involvement starting from the rectum and extending proximally 1
• Clear demarcation between inflamed and normal mucosa 1
• Rectal involvement (nearly universal) 1
• Loss of vascular pattern, granularity, friability, spontaneous bleeding, and ulcerations 1, 3

Important caveat: No endoscopic feature is absolutely specific for UC versus Crohn's disease. 1 Endoscopic appearance may significantly underestimate true disease extent, particularly in quiescent disease, which is why segmental biopsies are essential. 1

Exception for Acute Severe Colitis:

In patients presenting with acute severe colitis as their first manifestation, perform an unprepared flexible sigmoidoscopy during the acute phase, followed by a planned colonoscopy later to assess disease extent. 1 Avoid full colonoscopy in acute severe disease due to perforation risk.

Histological Confirmation

Histopathology is the definitive tool for diagnosis. 3 The pathologist needs clinical information including endoscopic findings, disease duration, and current treatment. 1

Classic Histological Features:

• Basal plasmacytosis (earliest diagnostic feature with highest predictive value) 1
• Widespread crypt architectural distortion (cryptitis, crypt abscesses, crypt atrophy) 1, 4
• Diffuse transmucosal inflammatory infiltrate 1
• Mucosal atrophy 1
• Absence of granulomas (which would suggest Crohn's disease) 3

Critical distinction in early disease: Only 20% of patients show crypt distortion within 2 weeks of first symptoms. 1 Preserved crypt architecture does not rule out UC at early stages—repeat biopsies after an interval may be necessary to establish the diagnosis. 1

Disease Extent Classification

Establish disease extent using the Montreal classification (adults) or Paris classification (children), as this determines prognosis and treatment. 1

• Extensive colitis: 19% 10-year colectomy rate 1
• Left-sided colitis: 8% 10-year colectomy rate 1
• Proctitis: 5% 10-year colectomy rate 1

Disease extent can change over time—up to 50% with proctitis will develop more extensive disease. 1 Always classify by maximal extent ever documented. 1

Imaging for Complications

Use abdominal X-ray, CT, or ultrasound to define disease extent and detect complications, particularly in acute presentations. 1 CT scanning shows characteristic mural thickening (mean 8mm versus normal 2-3mm). 3

What NOT to Use for Diagnosis

Serological markers (pANCA, ASCA) have limited accuracy and are ineffective at differentiating colonic Crohn's from UC—do not use them for routine diagnosis or therapeutic decisions. 1, 2 Genetic testing for IBD-associated SNPs does not allow diagnosis. 1

Diagnostic Algorithm Summary

1. Clinical suspicion → Order labs (CBC, CRP, albumin, fecal calprotectin) + stool studies
2. Exclude infections → Stool cultures and C. difficile toxin mandatory
3. Ileocolonoscopy with biopsies → Minimum 2 biopsies from ≥5 sites including rectum and ileum
4. Histological confirmation → Look for basal plasmacytosis, crypt distortion, diffuse inflammation
5. Classify extent → Use Montreal classification to guide prognosis and treatment
6. Assess severity → Mayo Score can be applied clinically and endoscopically 1