What are the diagnostic guidelines for ulcerative colitis?

Diagnostic Guidelines for Ulcerative Colitis

The diagnosis of ulcerative colitis (UC) requires a combination of clinical, biochemical, stool, endoscopic, cross-sectional imaging, and histological investigations, as no single reference standard exists for definitive diagnosis. 1

Initial Diagnostic Approach

Clinical Evaluation

• Key symptoms to assess:
  • Bloody diarrhea with or without mucus
  • Rectal urgency and tenesmus
  • Abdominal pain (often relieved by defecation)
  • Nocturnal bowel movements
  • Fever (in severe cases)

Laboratory Testing

• Essential initial tests:
  • Stool cultures and Clostridioides difficile toxin assay to exclude infectious causes 1
  • Fecal calprotectin and lactoferrin (excellent sensitivity for intestinal inflammation) 2
  • Complete blood count
  • C-reactive protein (CRP) and albumin 1, 2
  • Iron studies (serum ferritin, transferrin saturation) 1
    • In patients without active disease: serum ferritin <30 μg/L indicates iron deficiency
    • In patients with inflammation: serum ferritin up to 100 μg/L may still indicate iron deficiency

Endoscopic Assessment

Initial Endoscopic Evaluation

• Full ileocolonoscopy with biopsies is required for diagnosis 1, 2
  • Exception: In acute severe colitis, flexible sigmoidoscopy without bowel preparation is preferred 2
• Minimum of two biopsies from at least five sites throughout the colon, including the ileum and rectum 1, 2

Key Endoscopic Features of UC

• Continuous and confluent colonic inflammation with clear demarcation between inflamed and non-inflamed mucosa 1
• Rectal involvement (typical but not universal - rectal sparing occurs in ~3% of cases) 1
• Erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations 3
• Disease typically starts distally in the rectum with continuous extension proximally 1

Special Endoscopic Considerations

• "Caecal patch" - isolated periappendiceal inflammation can occur in UC 1
• Backwash ileitis - may be present in up to 20% of patients with extensive colitis 1
• If the histology and clinical pattern are atypical for UC, small bowel evaluation is required to exclude Crohn's disease 1

Histological Assessment

Key Histological Features

• No single histological feature is diagnostic of UC 1
• Characteristic findings include:
  • Basal plasmacytosis
  • Diffuse crypt atrophy and distortion
  • Villous surface irregularity
  • Mucus depletion 1
  • Decreased crypt density
  • Heavy diffuse transmucosal inflammation
  • Absence of genuine granulomas 3

Histological Importance

• Histological assessment is a sensitive marker that may outperform endoscopic mucosal healing in predicting clinical course 4
• Significant discordance can exist between endoscopic appearance and histological inflammation, especially in mild disease 5, 6
• Over one-third of patients with chronic inflammation may be underrecognized by clinical impression alone 6

Disease Extent and Severity Assessment

Disease Extent Classification

• Proctitis: Inflammation limited to the rectum
• Left-sided colitis: Inflammation extends to the splenic flexure
• Extensive colitis: Inflammation extends proximal to the splenic flexure

Disease Severity Assessment

• Mayo Score (0-12) assesses: 2

  Mayo Index	0	1	2	3
  Stool Frequency	Normal	1-2/day > normal	3-4/day > normal	≥5/day > normal
  Rectal Bleeding	None	Streaks	Visible	Mostly blood
  Mucosal Appearance	Normal	Mild friability	Moderate friability	Spontaneous bleeding
  Physician's Global Assessment	Normal	Mild	Moderate	Severe

• Truelove and Witts criteria for acute severe colitis 2

• Elevated CRP values >10 mg/L after one year of extensive colitis predict increased risk of surgery 2

Imaging Studies

• Abdominal CT with intravenous contrast:

  • Indicated for patients with pain, fever, or bleeding
  • Not routinely necessary for patients with diarrhea alone 2
  • Hallmark finding: Mural thickening (mean wall thickness ~8 mm vs. normal 2-3 mm) 3

• Intestinal ultrasound (IUS):

  • Potential alternative to endoscopy for assessing response to treatment
  • High concordance between endoscopic and IUS scores (weighted κ between 0.76 and 0.90) 1

Differential Diagnosis Considerations

Key Conditions to Exclude

• Infectious colitis (bacterial, viral, parasitic)
• Crohn's disease
• Microscopic colitis
• Immune checkpoint inhibitor-associated colitis
• Ischemic colitis
• Radiation colitis
• Diverticular disease-associated colitis

UC vs. Crohn's Disease Differentiation

• UC: Continuous inflammation starting from rectum, superficial mucosal involvement 2
• Crohn's: Skip lesions, transmural inflammation, granulomas 2
• In 5-15% of IBD patients, endoscopic and histological assessments cannot definitively distinguish between Crohn's colitis and UC 1

Disease Monitoring

• Response to treatment should be determined by a combination of:

  • Clinical parameters
  • Endoscopy
  • Laboratory markers (CRP, fecal calprotectin) 1

• In patients who clinically respond to therapy, mucosal healing should be assessed:

  • By endoscopy or fecal calprotectin
  • Approximately 3-6 months after treatment initiation 1, 2

• Regular cancer surveillance:

  • Start 8 years after disease onset for extensive colitis
  • Start 12-15 years after disease onset for left-sided disease 2

Common Pitfalls to Avoid

1. Relying solely on clinical assessment:

   • Physician's clinical impression shows poor agreement with endoscopy and histology findings 6
   • Clinical assessment alone may underestimate disease activity in over one-third of patients 6

2. Inadequate biopsy sampling:

   • Multiple biopsies from inflamed and uninflamed segments are essential 1
   • Insufficient sampling may miss patchy inflammation or dysplasia

3. Failure to exclude infectious causes:

   • Always rule out infectious etiologies before diagnosing UC 2
   • Test for C. difficile even in patients with known UC

4. Missing atypical presentations:

   • Rectal sparing can occur in up to 3% of UC patients 1
   • Patchy inflammation may be seen in patients who have received topical therapy 1

5. Inconsistent histological scoring:

   • Multiple histological scoring indices exist but none were developed using formal validation processes 7
   • Standardized assessment is needed for accurate diagnosis and monitoring