What are the differences and similarities in presentation, characteristics, and treatment management between Ulcerative Colitis (UC) and Crohn's Disease (CD) in terms of induction and maintenance therapy?

Ulcerative Colitis vs. Crohn's Disease: Presentation, Characteristics, and Treatment

Clinical Presentation

Ulcerative Colitis

The cardinal symptom of UC is bloody diarrhea, typically accompanied by urgency and tenesmus 1. Patients present with:

• Rectal bleeding as the dominant feature 1
• Colicky abdominal pain (less prominent than in CD) 1
• Urgency and tenesmus 1
• Systemic symptoms are less common than in CD 1

Crohn's Disease

CD presents with more heterogeneous symptoms, typically abdominal pain, diarrhea, and weight loss 1. Key features include:

• Abdominal pain as a dominant symptom (more prominent than UC) 1
• Diarrhea (often non-bloody initially) 1
• Weight loss is characteristic 1
• Systemic symptoms of malaise, anorexia, and fever are more common than in UC 1
• Perianal disease (fistulae, ulcers) is common in CD but rare in UC 2

Disease Characteristics

Anatomic Distribution

UC always begins in the rectum and spreads proximally in a continuous, diffuse pattern 2. Disease extent includes:

• Proctitis: limited to rectum (<15-20 cm from anus) 1
• Left-sided disease: extends to splenic flexure (<50 cm from anus) 1
• Extensive/pancolitis: extends proximal to splenic flexure 1

CD has a patchy, discontinuous distribution and may spare the rectum entirely 2. Location patterns include:

• Ileal or ileocolonic disease (most common) 3, 4
• Isolated colonic disease 1
• Upper gastrointestinal involvement (unique to CD) 1
• Perianal involvement is common in CD but rare in UC 2

Histopathology

UC is limited to the mucosa and occasionally submucosa, while CD involves all layers of the intestinal wall (transmural) 2. Distinguishing features:

• UC shows continuous mucosal inflammation 1
• CD demonstrates focal, asymmetric inflammation with granulomas in the majority of cases 1, 2
• Giant cells are found in CD but not UC 2
• CD shows transmural inflammation, while UC does not 2

Complications and Natural History

CD causes intestinal obstruction from strictures, fistulae, and abscesses—complications not seen in UC 1. Key differences:

For UC:

• 50% of patients relapse in any given year 1
• 20-30% with pancolitis require colectomy 1
• Total colectomy is curative 2
• 90% fully capable of work after first year 1
• Slight excess mortality only in first 2 years after diagnosis 1

For CD:

• 50% require surgery within first 10 years, 70-80% within lifetime 1
• Surgery is not curative; disease recurs 1, 2
• Only 75% fully capable of work after diagnosis 1
• 15% unable to work after 5-10 years 1
• Greater disability burden than UC 1
• Mortality slightly higher than normal population, greatest in first 2 years or with upper GI disease 1

Cancer Risk

Both UC and CD are associated with increased colorectal cancer risk, but the risk is higher in UC 1, 2. Risk factors include:

• Disease duration >8 years 1
• Extensive disease (pancolitis) 1
• Primary sclerosing cholangitis (4-fold increased risk in UC) 1
• Family history of sporadic CRC (doubles risk) 1

Treatment Management

Induction Therapy for Ulcerative Colitis

For proctitis, mesalamine 1g suppository once daily is the preferred initial treatment 4. The treatment algorithm:

• Combination topical mesalamine with oral mesalamine ≥2.4 g/day is more effective than either alone 4
• Topical mesalamine is more effective than topical steroids 4

For left-sided colitis, combination therapy with mesalamine enema ≥1 g/day plus oral mesalamine ≥2.4 g/day is more effective than either alone 4. Key points:

• Once-daily dosing is as effective as divided doses 4
• This combination is more effective than topical steroids 4

For extensive colitis, initial treatment should be mesalamine enema 1 g/day combined with oral mesalamine ≥2.4 g/day 4. Escalation strategy:

• Systemic corticosteroids (prednisolone 40 mg daily) for moderate to severe activity or when mesalamine fails 4
• Severe extensive colitis requires hospital admission for intensive intravenous treatment 4
• Budesonide MMX 9 mg/day for left-sided disease inadequately controlled with oral 5-ASA 4

Induction Therapy for Crohn's Disease

For mild ileal or ileocolonic CD, high-dose mesalamine 4 g daily is appropriate first-line therapy 3, 4. However, CD has limited response to aminosalicylates compared to UC 4.

For moderate to severe CD, oral prednisolone 40 mg daily is recommended, with taper over 8 weeks to prevent early relapse 1, 3, 4. Evidence base:

• 60% remission with 0.5-0.75 mg/kg/day prednisone vs. 30% placebo (NNT=3) 1
• 83% remission with 1 mg/kg/day vs. 38% placebo (NNT=2) 1
• Doses <15 mg/day are ineffective for active disease 1
• Too rapid reduction is associated with early relapse 1

For isolated ileo-caecal disease with moderate activity, budesonide 9 mg daily can be used, though marginally less effective than prednisolone 3, 4.

For severe ileitis, intravenous steroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) are indicated 3, 4. Important consideration:

• Concomitant intravenous metronidazole is advisable when distinguishing active inflammation from septic complications is difficult 3, 4

Maintenance Therapy

For UC, mesalamine remains the cornerstone of maintenance therapy 1, 4. Key principles:

• Continue the same formulation and dose that induced remission 1
• Corticosteroids have no role in maintenance therapy for either UC or CD 1

For CD, thiopurines are the mainstay of maintenance and steroid-sparing therapy 1, 3. Indications:

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day serve as adjunctive therapy and steroid-sparing agents 3, 4
• Consider thiopurines for patients requiring ≥2 corticosteroid courses within a calendar year 1
• Disease relapse as steroid dose reduced below 15 mg 1
• Relapse within 6 weeks of stopping steroids 1
• Postoperative prophylaxis of complex (fistulating or extensive) CD 1
• Thiopurines provide steroid-sparing benefit (NNT=3) 1

Monitoring and Biomarkers

In patients with UC in symptomatic remission, use a biomarker- and symptom-based monitoring strategy over symptom-based alone 1. Specific thresholds:

• Fecal calprotectin <150 mg/g, normal fecal lactoferrin, and/or normal CRP rule out active inflammation and avoid routine endoscopy 1
• In moderate to severe symptoms, fecal calprotectin >150 mg/g, elevated fecal lactoferrin, or elevated CRP inform treatment decisions and avoid routine endoscopy 1
• In symptomatic remission but elevated biomarkers, perform endoscopic assessment 1
• In moderate to severe symptoms with normal biomarkers, perform endoscopic assessment 1
• In mild symptoms, perform endoscopic assessment to inform treatment decisions 1

Critical Distinguishing Features for Treatment

Ulcerative colitis responds well to aminosalicylates across all disease severities, making mesalamine the clear first-line choice 1, 4. In contrast, Crohn's disease has limited response to aminosalicylates, which are only appropriate for mild ileal/ileocolonic disease; corticosteroids are required earlier in the treatment algorithm 4.

The most important pitfall: Do not overlook topical therapy in UC—combination topical plus oral mesalamine is significantly more effective than oral alone 4. For CD, consider alternative explanations for persistent symptoms, such as bacterial overgrowth, bile salt malabsorption, or fibrotic strictures, rather than assuming active inflammation 4.

Avoid rapid corticosteroid tapers in both conditions, as this increases early relapse rates 1, 4. Specifically, doses of prednisolone <15 mg/day are ineffective for active disease 1.