What are the typical presentation, differential diagnosis (ddx), investigations (invx), management (mx), and complications of Ulcerative Colitis (UC)?

Ulcerative Colitis: Clinical Presentation, Diagnosis, Management, and Complications

Ulcerative colitis (UC) is a chronic inflammatory condition characterized by continuous mucosal inflammation of the colon, beginning in the rectum and extending proximally to a variable extent, with bloody diarrhea as its cardinal symptom. 1 The disease follows a relapsing and remitting course, with approximately 50% of patients experiencing a relapse in any given year 1.

Typical Presentation (Signs and Symptoms)

Cardinal Symptoms

• Bloody diarrhea - The hallmark symptom of UC 1
• Colicky abdominal pain
• Urgency to defecate
• Tenesmus (painful straining)
• Rectal bleeding
• Nocturnal diarrhea
• Incontinence in severe cases 1

Disease Patterns

• Relapsing-remitting course - Most common pattern
• Frequently relapsing disease - Seen in a significant minority
• Chronic continuous disease - Seen in some patients 1

Disease Severity Classification (Truelove & Witts)

Parameter	Mild	Moderate	Severe
Bloody stools/day	< 4	4 or more	≥ 6
Pulse	< 90 bpm	≤ 90 bpm	> 90 bpm
Temperature	< 37.5°C	≤ 37.8°C	> 37.8°C
Hemoglobin	> 11.5 g/dl	≥ 10.5 g/dl	< 10.5 g/dl
ESR	< 20 mm/h	≤ 30 mm/h	> 30 mm/h
CRP	Normal	≤ 30 mg/l	> 30 mg/l

1

Differential Diagnosis

• Infectious colitis - Including bacterial (C. difficile, Salmonella, Shigella), viral, and parasitic causes
• Crohn's disease - Especially Crohn's colitis
• Ischemic colitis - Particularly in older patients
• Radiation colitis - In patients with history of pelvic radiation
• Microscopic colitis - Lymphocytic or collagenous colitis
• Diverticular disease-associated colitis
• Medication-induced colitis - Particularly NSAIDs
• Colorectal malignancy - May present with similar symptoms
• Irritable bowel syndrome with diarrhea - But without blood or inflammation 1, 2

Investigations (Invx)

Initial Laboratory Tests

• Full blood count - May show anemia, thrombocytosis
• Inflammatory markers - CRP, ESR
• Electrolytes and liver function tests
• Iron studies and vitamin D level
• Stool samples for:
  • Microbiological analysis (infectious causes)
  • C. difficile toxin
  • Fecal calprotectin (sensitive marker of intestinal inflammation) 1

Endoscopic Evaluation

• Sigmoidoscopy/colonoscopy - Gold standard for diagnosis
• Macroscopic features:
  • Loss of vascular pattern
  • Granularity
  • Friability
  • Ulceration of rectal mucosa
  • Continuous inflammation from rectum proximally 1

Histopathology

• Rectal biopsy - Essential even if no macroscopic changes
• Characteristic findings:
  • Decreased crypt density
  • Crypt architectural distortion
  • Irregular mucosal surface
  • Heavy diffuse transmucosal inflammation
  • Absence of granulomas (which would suggest Crohn's) 2

Imaging

• Abdominal radiography - Essential in severe disease to exclude toxic megacolon
• CT scan - For complications or atypical presentations
• MRI - For assessment of disease extent and activity 1

Management (Mx)

Treatment Goals

• Improve symptoms
• Achieve and maintain remission
• Promote mucosal healing
• Prevent complications and disease progression
• Improve quality of life 2, 3

Treatment Based on Disease Extent and Severity

Mild to Moderate Disease

1. Proctitis (distal disease)

   • First-line: Topical 5-aminosalicylic acid (5-ASA) suppositories
   • Alternative: Topical corticosteroids if 5-ASA not tolerated

2. Left-sided colitis

   • First-line: Combination of oral and topical 5-ASA
   • Alternative: Add topical corticosteroids if inadequate response

3. Extensive colitis

   • First-line: Oral 5-ASA (with topical therapy if accessible)
   • Alternative: Oral corticosteroids if inadequate response 2

Moderate to Severe Disease

1. Outpatient management

   • Oral corticosteroids (prednisolone)
   • Consider early introduction of immunomodulators (azathioprine, 6-mercaptopurine)
   • Biologic agents for steroid-dependent or refractory disease:
     • TNF inhibitors (infliximab)
     • Anti-integrin agents (vedolizumab)
     • IL-12/23 inhibitors (ustekinumab)
     • JAK inhibitors (tofacitinib)

2. Severe acute UC (requiring hospitalization)

   • Intravenous corticosteroids
   • Thromboprophylaxis
   • Correction of fluid/electrolyte imbalances
   • Nutritional support if needed
   • Monitor for response (clinical symptoms, CRP, albumin)
   • If no response after 3-5 days, initiate rescue therapy:
     • Infliximab or cyclosporine
   • Consider colectomy if medical therapy fails 4, 2

Maintenance Therapy

• 5-ASA for mild disease
• Immunomodulators or biologics for moderate to severe disease
• Regular monitoring of disease activity:
  • Clinical assessment
  • Fecal calprotectin (every 3-6 months)
  • Periodic endoscopic evaluation 3

Complications

Acute Complications

• Acute severe colitis - Potentially life-threatening condition requiring hospitalization
• Toxic megacolon - Severe dilatation of the colon with systemic toxicity
• Perforation - Rare but life-threatening complication
• Massive hemorrhage - May require urgent colectomy 4

Chronic Complications

• Colorectal cancer - Risk increases with disease duration and extent
  • 4.5% risk after 20 years of disease
  • 1.7-fold higher risk compared to general population
• Strictures - Due to chronic inflammation and fibrosis
• Functional bowel problems - Even during remission
• Extraintestinal manifestations:
  • Primary sclerosing cholangitis (most serious)
  • Inflammatory arthropathies
  • Erythema nodosum
  • Pyoderma gangrenosum
  • Uveitis/episcleritis 3, 5, 6

Long-term Outcomes

• Colectomy rates - Approximately 20% of patients are hospitalized and 7% undergo colectomy within 5 years of diagnosis
• Mortality - Life expectancy is approximately 5 years shorter than the general population
• Quality of life - Significantly impacted during active disease 3

Surveillance

• Colonoscopic surveillance for dysplasia/cancer:
  • Begin 8 years after diagnosis for extensive colitis
  • Begin 15 years after diagnosis for left-sided colitis
  • Not required for proctitis 1

Key Pitfalls to Avoid

• Failing to exclude infectious causes, especially C. difficile, before diagnosing a flare
• Delaying escalation of therapy in non-responders to steroids
• Missing extraintestinal manifestations
• Inadequate cancer surveillance in long-standing disease
• Overlooking the psychological impact of chronic disease