What is the treatment for large intestine inflammation?

Treatment of Large Intestine Inflammation (Inflammatory Bowel Disease)

For large intestine inflammation (ulcerative colitis or Crohn's colitis), initiate treatment with corticosteroids (prednisolone 40 mg daily) for moderate to severe disease, or high-dose mesalazine (≥2g daily) for mild disease, followed by immunosuppression with azathioprine or biologics if conventional therapy fails. 1

Initial Treatment Strategy Based on Disease Severity

Mild Disease

• Start with high-dose mesalazine at 4g daily for mild ileocolonic or colonic inflammation 1, 2
• Mesalazine doses below 2g/day are ineffective and should not be used 1
• Topical mesalazine may be added for left-sided colonic disease 1

Moderate to Severe Disease

• Initiate oral prednisolone 40 mg daily as first-line therapy 1, 2
• Taper gradually over 8 weeks according to clinical response to prevent early relapse 2
• Critical pitfall: Rapid steroid reduction leads to early relapse and should be avoided 2

Alternative First-Line Options

• Elemental or polymeric diets are less effective than corticosteroids but can be used in patients with contraindications to steroids or those preferring to avoid them 1, 2
• Metronidazole 10-20 mg/kg/day is effective but not recommended first-line due to side effects; reserve for colonic or treatment-resistant disease 1

Second-Line Immunosuppression

When to Escalate

• Initiate immunosuppression if patients relapse more than once or fail to respond to conventional therapy 1

Conventional Immunosuppressants

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day are effective for maintaining remission 1
• These agents work slowly and should be used as adjunctive therapy with steroids during active disease, not as sole therapy 1
• Methotrexate 15-25 mg IM weekly is effective for patients intolerant of or who failed azathioprine/mercaptopurine 1
• Add folic acid 5 mg once weekly (3 days after methotrexate) to reduce side effects 1

Biologic Therapy

Anti-TNF Agents (First-Line Biologics)

• Infliximab is the preferred first biologic due to lower costs with biosimilars and good effectiveness/safety profile 1
• Dosing for induction: 5 mg/kg at weeks 0,2, and 6 3
• Maintenance: 5 mg/kg every 8 weeks (can increase to 10 mg/kg or every 4 weeks if response is lost) 1, 3
• Reserve biologics for patients with insufficient response to immunosuppression or intolerance 1
• Critical warning: Infliximab carries increased risk of serious infections including tuberculosis; test for latent TB before initiating and monitor during treatment 3
• Black box warning: Risk of lymphoma and hepatosplenic T-cell lymphoma, especially in young males with Crohn's disease receiving concomitant azathioprine or mercaptopurine 3

Alternative Biologics

• Adalimumab and golimumab are additional anti-TNF options 1
• Vedolizumab (anti-integrin) prevents leukocyte homing to the gut 1
• Ustekinumab blocks IL-12/23 pathway for Crohn's disease 1
• Tofacitinib (JAK inhibitor) is approved specifically for ulcerative colitis 1

Special Situations

Fistulating and Perianal Disease (Crohn's)

• First-line: Metronidazole 400 mg three times daily and/or ciprofloxacin 500 mg twice daily for simple perianal fistulae 1
• Azathioprine/mercaptopurine are effective after excluding distal obstruction and abscess 1
• Infliximab (5 mg/kg at weeks 0,2,6) for refractory fistulae, used as part of strategy including immunomodulation and surgery 1
• Surgical options include Seton drainage, fistulectomy, and advancement flaps in combination with medical treatment 1

Strictures and Obstruction

• Surgery is mandatory for symptomatic strictures not responding to medical therapy and not amenable to endoscopic dilation 1
• Always biopsy colorectal strictures to exclude malignancy 1
• Endoscopic balloon dilation has 89-92% technical success for fibrotic strictures but 43% require surgery within 2 years 1
• Inflammatory strictures deserve a trial of steroids before intervention 1

Emergency Indications for Surgery

• Free perforation with generalized peritonitis requires immediate open surgery 1
• Toxic megacolon without improvement after 24-48 hours of medical treatment mandates surgery 1
• Life-threatening bleeding with persistent hemodynamic instability despite resuscitation 1
• Subtotal colectomy with ileostomy is the procedure of choice for acute severe ulcerative colitis with refractory hemorrhage 1

Maintenance of Remission

Lifestyle Modification

• All smokers must be strongly advised to stop smoking - this is the most important factor in maintaining remission 1
• Provide counseling, nicotine patches, or substitutes to achieve smoking cessation 1

Pharmacologic Maintenance

• Mesalazine has limited benefit for maintenance and is ineffective in those who needed steroids for induction 1
• Azathioprine/mercaptopurine are effective but reserved as second-line due to potential toxicity 1
• Infliximab 5-10 mg/kg every 8 weeks is effective for up to 44 weeks in patients who responded to initial infusion 1
• Corticosteroids including budesonide are NOT effective for maintenance and should not be used long-term 1

Critical Pitfalls to Avoid

• Never use mesalazine doses below 2g/day - they are ineffective 1
• Do not delay surgery in critically ill patients with toxic megacolon or perforation 1
• Avoid infliximab in patients with obstructive symptoms 1
• Screen for latent tuberculosis before starting anti-TNF therapy 3
• Carefully assess risk/benefit of combining azathioprine/mercaptopurine with anti-TNF in young males with Crohn's disease due to hepatosplenic T-cell lymphoma risk 3
• Development of antibodies to infliximab increases clearance and reduces effectiveness 3

Treatment Goals

The paradigm has shifted from symptom control to achieving mucosal healing and suppression of mucosal inflammation 1, 4. This involves early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation, and therapeutic drug monitoring 4.