1. Inflammatory Bowel Disease

 

 

Introduction

●      Key Conditions: Ulcerative Colitis (UC) and Crohn’s Disease (CD).

●      Pathophysiology: Chronic inflammatory conditions of the gastrointestinal (GI) tract with relapsing and remitting courses.

●      Epidemiology:

o   Prevalence: Higher in Western countries, decreasing gradient from north to south, less common in Asia-Pacific.

o   Peak incidence:

▪       UC: 15-30 years, smaller peak at 50-70 years.

▪       CD: 20–40 years, more common in Ashkenazi Jews.

o   Genetic predisposition: Stronger in CD (e.g., NOD2 gene mutations).

o   Risk Factors: Smoking cessation (UC), fast food, high sugar/meat, low fiber/fruit diets.

●      Goals of Management: Tailored evidence-based interventions to achieve remission and prevent complications.

Ulcerative Colitis (UC)

Pathophysiology

●      Immune dysregulation involving T-helper (Th2) cells.

●      Overproduction of pro-inflammatory cytokines (IL-5, IL-13).

●      Breakdown of epithelial barrier leading to continuous colonic inflammation.

●      Histology: Goblet cell mucus depletion, crypt abscesses, crypt shortening/distortion.

Diagnosis

●      Presentation: Bloody diarrhea, abdominal pain, urgency, tenesmus.

●      Endoscopic Findings:

o   Continuous mucosal inflammation starting from the rectum.

o   Loss of vascular pattern, friability, ulcers.

●      Histology: Crypt distortion, basal plasmacytosis, diffuse inflammation.

Treatment Targets

●      Clinical Remission: Normal stool frequency, absence of rectal bleeding.

●      Endoscopic Remission: Mayo score ≤2, mucosal healing (subscore ≤1).

●      Histological Remission: Absence of inflammatory infiltrate.

Management of UC

Mild-to-Moderate Disease

  1. 5-ASA: Oral dose 2–4.8 g/day + enema for distal disease.
    • Monitoring: U&E and renal function at baseline, 2–3 months, then annually.
    • Side Effects: Nausea, diarrhea, paradoxical worsening of symptoms (3%).
  2. Steroids: Prednisolone 40–60 mg/day tapered over 8–12 weeks.
  3. Refractory Cases: Budesonide MMX (9 mg/day).
  4. Maintenance: Continue 5-ASA, add thiopurines if steroid-dependent.

Severe Disease

  1. Acute Severe UC (ASUC):
    • Intravenous corticosteroids (hydrocortisone 100 mg QID).
    • Correct hypokalemia and hypomagnesemia.
    • Avoid NSAIDs, opiates, and anticholinergics.
  2. Rescue Therapy:
    • Infliximab: 5 mg/kg IV at weeks 0, 2, 6.
    • Ciclosporin: 2 mg/kg/day IV.
  3. Surgical Options: Colectomy for refractory cases or toxic megacolon.
    • 10-Year Colectomy Rates: Pancolitis 25%, left-sided colitis 8%.

Pouches and Pouchitis

●      Definition: Inflammation of the ileal pouch following colectomy.

●      Risk Factors: Primary sclerosing cholangitis (PSC), retained rectal cuff.

●      Management:

o   Acute: Ciprofloxacin (500 mg BID for 2 weeks) or metronidazole.

o   Chronic: Combination antibiotics, oral budesonide, probiotics for prophylaxis.

o   Surveillance: Annual pouchoscopy for high-risk groups.

Crohn’s Disease (CD)

Pathophysiology

●      Th1/Th17-mediated immune dysregulation.

●      Overproduction of TNF-α, IL-6, IL-12, IL-23.

●      Transmural inflammation causing strictures, fistulas, perforations.

●      Histology: Granulomas, crypt distortion, lymphocytic aggregates.

Management of CD

Medications

  1. Steroids: Budesonide 9 mg/day for mild ileocolonic disease.
  2. Thiopurines: Azathioprine 2–2.5 mg/kg/day.
    • Side Effects: Pancreatitis (0.1–2%), myelotoxicity, nausea.
    • Monitoring: TPMT enzyme; thiopurine metabolites.
  3. Biologics:
    • Anti-TNF: Infliximab, adalimumab.
    • Anti-IL-12/23: Ustekinumab.

Rutgeerts Scoring

●      i0: Normal mucosa, very low recurrence risk.

●      i1: ≤5 aphthous ulcers, low recurrence risk.

●      i2: Larger ulcers confined to the anastomosis, intermediate recurrence risk.

●      i3: Diffuse aphthous ileitis, high recurrence risk.

●      i4: Diffuse inflammation with larger ulcers, very high recurrence risk.

Surgical Management

●      Strictureplasty or segmental resection for obstructive disease.

●      Seton placement for perianal fistulas.

High-Yield Immunology Points

●      Cytokines in UC: IL-5, IL-13 (Th2-mediated).

●      Cytokines in CD: TNF-α, IL-6, IL-23, IL-17 (Th1/Th17-mediated).

●      Therapeutic Targets:

o   Anti-TNF (e.g., infliximab).

o   Anti-integrin (e.g., vedolizumab).

o   Anti-IL-12/23 (e.g., ustekinumab).

Extraintestinal Features

●      Activity-Dependent:

o   Erythema nodosum, aphthous ulcers, episcleritis.

●      Independent of Activity:

o   Pyoderma gangrenosum, uveitis, PSC, sacroiliitis.

●      Management: Treat IBD; consider biologics for refractory conditions.

Pregnancy and IBD

●      Safe Medications:

o   5-ASA, thiopurines, steroids, anti-TNF.

●      Avoid: Methotrexate (teratogenic).

●      Cautions:

o   Ciclosporin linked to low birth weight.

 


 

Risk Factors for Relapse

●      Non-adherence to therapy.

●      Smoking (protective in UC, harmful in CD).

●      CRP >5 mg/L, fecal calprotectin >300 µg/g.

●      Male sex, prior steroid use.

References

  1. Lamb CA, Kennedy NA, Raine T, et al. "British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults." Gut. 2019;68:s1–s106. Link.
  2. European Crohn’s and Colitis Organisation (ECCO) Guidelines. Link.
  3. NICE Guidance for IBD. Link.