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Tuesday, August 12, 2025

Inflammatory bowel disease


Definition

Inflammatory Bowel Disease (IBD) is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract, primarily encompassing Ulcerative Colitis (UC) and Crohn’s Disease (CD). Both conditions are immune-mediated but differ in their location, depth, and pattern of inflammation.

Classification

  1. Ulcerative Colitis

    • Affects only the colon and rectum

    • Inflammation is continuous and limited to the mucosa and submucosa

    • Always involves the rectum and extends proximally in a continuous pattern

  2. Crohn’s Disease

    • Can involve any part of the gastrointestinal tract from mouth to anus

    • Inflammation is transmural (affecting the full thickness of the bowel wall)

    • Characterized by “skip lesions” – areas of affected bowel interspersed with normal segments

Etiology and Risk Factors

Multifactorial origins including:

  • Genetic susceptibility (NOD2/CARD15 mutations in Crohn’s)

  • Immune dysregulation with abnormal response to gut microbiota

  • Environmental factors: Smoking (risk ↑ in Crohn’s, protective in UC), diet, stress

  • Infections triggering immune activation in predisposed individuals

Pathophysiology

IBD results from an inappropriate, sustained immune response to intestinal microbes in genetically susceptible hosts.

  • Crohn’s Disease: Th1/Th17-mediated immune response with granuloma formation

  • Ulcerative Colitis: Predominantly Th2-mediated response without granulomas
    Cytokines such as TNF-α, IL-12, IL-23 play central roles in perpetuating inflammation.

Clinical Features

Ulcerative Colitis

  • Bloody diarrhea

  • Rectal urgency, tenesmus

  • Abdominal discomfort, typically in the lower abdomen

  • Continuous symptoms correlating with extent of colonic involvement

Crohn’s Disease

  • Chronic diarrhea (may be bloody or non-bloody)

  • Abdominal pain (often in right lower quadrant)

  • Weight loss, fatigue

  • Perianal disease (fistulas, abscesses, fissures)

  • Small bowel involvement → malabsorption, nutrient deficiencies

Extraintestinal manifestations (both conditions)

  • Musculoskeletal: arthritis, ankylosing spondylitis

  • Dermatologic: erythema nodosum, pyoderma gangrenosum

  • Ocular: uveitis, episcleritis

  • Hepatobiliary: primary sclerosing cholangitis (more common in UC)

Diagnosis

Laboratory Tests

  • Elevated inflammatory markers: ESR, CRP

  • Anemia, hypoalbuminemia

  • Stool tests to exclude infection (e.g., C. difficile, parasites) and measure fecal calprotectin

Endoscopy

  • UC: continuous inflammation starting at rectum, friable mucosa, superficial ulcerations

  • CD: patchy (“skip”) lesions, cobblestone mucosa, deep ulcerations, strictures

Histology

  • UC: crypt abscesses, mucosal inflammation

  • CD: transmural inflammation, granulomas (non-caseating) in ~30% of cases

Imaging

  • MR enterography or CT enterography for small bowel disease in Crohn’s

  • Barium studies less commonly used today

Management

Goals: induce and maintain remission, prevent complications, improve quality of life.

1. Lifestyle and Supportive Care

  • Smoking cessation (especially in Crohn’s)

  • Nutritional optimization: correct deficiencies (iron, vitamin B12, folate, vitamin D)

  • Stress management

  • Vaccinations before starting immunosuppressants (e.g., influenza, pneumococcal, hepatitis B)

2. Pharmacological Therapy

A. Induction of Remission

  • Aminosalicylates (5-ASA) – first-line for mild to moderate UC

    • Mesalazine: 2.4–4.8 g/day orally in divided doses; rectal preparations for distal disease

    • Sulfasalazine: 2–4 g/day orally in divided doses; monitor for sulfa-related side effects

  • Corticosteroids – for moderate to severe flares, not for maintenance

    • Prednisolone: 40 mg orally once daily, taper over 6–8 weeks

    • Budesonide: 9 mg orally once daily for mild to moderate ileocecal Crohn’s or mild colitis

  • Antibiotics (Crohn’s with abscesses, perianal disease)

    • Metronidazole: 400 mg orally three times daily

    • Ciprofloxacin: 500 mg orally twice daily

B. Maintenance of Remission

  • Aminosalicylates – continued in UC

  • Immunomodulators – for steroid-dependent or refractory cases

    • Azathioprine: 1.5–2.5 mg/kg orally once daily

    • 6-Mercaptopurine: 0.75–1.5 mg/kg orally once daily

    • Methotrexate (for Crohn’s): 15–25 mg once weekly IM/SC with folic acid supplementation

  • Biologic agents – moderate to severe disease unresponsive to conventional therapy

    • Anti-TNF agents: Infliximab 5 mg/kg IV at weeks 0, 2, 6 then every 8 weeks; Adalimumab 160 mg SC at week 0, 80 mg at week 2, then 40 mg every other week

    • Anti-integrin: Vedolizumab 300 mg IV at weeks 0, 2, 6 then every 8 weeks

    • Anti-IL-12/23: Ustekinumab 6 mg/kg IV induction then 90 mg SC every 8–12 weeks

3. Surgical Management

Ulcerative Colitis

  • Indicated for fulminant colitis, perforation, uncontrolled bleeding, dysplasia/cancer, or refractory disease

  • Total proctocolectomy with ileal pouch–anal anastomosis can be curative

Crohn’s Disease

  • Surgery is not curative; reserved for complications such as strictures, fistulas, abscesses, or refractory disease

  • Resection of affected segment, stricturoplasty

Complications

  • UC: severe bleeding, toxic megacolon, colorectal cancer

  • CD: strictures, fistulas, abscesses, malnutrition, small bowel cancer

  • Both: increased thromboembolic risk, osteoporosis from chronic inflammation or corticosteroid use

Prognosis

  • Chronic, lifelong conditions with relapsing-remitting course

  • Advances in biologic therapy have improved outcomes, reducing hospitalizations and surgery rates

  • Early aggressive treatment in selected patients can prevent disease progression and complications




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