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Saturday, August 16, 2025

Crohn's disease


Introduction

Crohn’s disease (CD) is a chronic, relapsing-remitting inflammatory bowel disease (IBD) characterized by transmural inflammation of the gastrointestinal (GI) tract. Unlike ulcerative colitis (UC), which affects only the colon and rectum in a continuous manner, Crohn’s disease can involve any part of the GI tract from mouth to anus, most commonly the terminal ileum and proximal colon, and tends to be discontinuous (skip lesions).

The disease follows a variable course, alternating between flares of active inflammation and periods of remission. Because inflammation is transmural, Crohn’s disease is associated with fistulae, strictures, and abscesses.

Epidemiology

  • Global prevalence is increasing, particularly in industrialized and rapidly urbanizing regions.

  • Peak incidence: 15–35 years of age; smaller peak in 50s–60s.

  • Slight female predominance in Western countries.

  • More common in North America and Northern Europe, though incidence is rising in Asia, the Middle East, and South America.

  • Family history increases risk 3–20 fold.

Etiology and Pathophysiology

Crohn’s disease is multifactorial, involving genetic, immune, microbial, and environmental factors.

  1. Genetic Factors

    • NOD2/CARD15 mutations increase susceptibility.

    • Other implicated loci: ATG16L1, IL23R.

  2. Immune Dysregulation

    • Overactive Th1 and Th17 responses → excess cytokines (TNF-α, IL-12, IL-23).

    • Breakdown of intestinal mucosal barrier.

  3. Microbiome Alterations

    • Dysbiosis with reduced protective bacterial species.

  4. Environmental Triggers

    • Smoking (doubles risk, worsens prognosis).

    • NSAID use.

    • High-fat, low-fiber diets.

    • Stress as a flare trigger (not causative).

Clinical Features

1. Gastrointestinal Manifestations

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

  • Abdominal pain (often crampy, right lower quadrant if ileocecal disease).

  • Weight loss, anorexia, fatigue.

  • Fever during flares.

  • Perianal disease: fissures, fistulas, abscesses, skin tags.

2. Extraintestinal Manifestations

  • Musculoskeletal: peripheral arthritis, ankylosing spondylitis.

  • Dermatologic: erythema nodosum, pyoderma gangrenosum.

  • Ocular: uveitis, episcleritis.

  • Hepatobiliary: primary sclerosing cholangitis, fatty liver.

Complications

  • Intestinal strictures → obstruction.

  • Fistulae (enterocutaneous, enteroenteric, perianal, enterovesical).

  • Abscess formation.

  • Malabsorption (vitamin B12, iron, folate deficiencies).

  • Growth failure in children.

  • Increased risk of colorectal cancer with long-standing disease.

Diagnosis

1. Laboratory Tests

  • CBC: anemia (iron deficiency or anemia of chronic disease).

  • Elevated CRP and ESR.

  • Low albumin.

  • Stool tests: exclude infection (stool culture, C. difficile).

  • Fecal calprotectin: sensitive marker for intestinal inflammation.

2. Endoscopy

  • Colonoscopy with ileoscopy: gold standard for diagnosis.

    • Findings: aphthous ulcers, deep linear ulcers, cobblestoning, skip lesions.

    • Biopsy: transmural inflammation, granulomas (non-caseating, but only in 30–40%).

3. Imaging

  • CT or MR enterography: identifies strictures, fistulas, abscesses.

  • Capsule endoscopy: useful for small bowel disease (avoid if strictures suspected).

4. Differentiation from Ulcerative Colitis

  • Crohn’s: patchy involvement, transmural, fistulas, anywhere in GI tract.

  • UC: continuous disease, limited to mucosa, confined to colon/rectum.

Management

Treatment aims to induce and maintain remission, relieve symptoms, prevent complications, and improve quality of life.

1. Lifestyle and Supportive Measures

  • Smoking cessation (critical).

  • Nutritional support:

    • High-calorie, high-protein diet.

    • Vitamin supplementation (B12, iron, vitamin D, folate).

    • Enteral nutrition in pediatric patients.

  • Psychosocial support.

2. Pharmacological Treatment

a) Induction of Remission

  • Corticosteroids (for moderate-severe flares, short-term only):

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

    • Budesonide: 9 mg orally daily (preferred in ileocecal disease, fewer systemic effects).

b) Maintenance of Remission

  • Immunomodulators:

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

    • 6-Mercaptopurine (6-MP): 0.75–1.5 mg/kg orally daily.

    • Methotrexate: 15–25 mg weekly (subcutaneous or IM).

  • Aminosalicylates (5-ASA):

    • Less effective in Crohn’s than UC, sometimes used for mild disease.

    • Mesalamine: 2–4 g orally daily.

c) Biologic Therapies (moderate to severe, refractory disease)

  • Anti-TNF agents:

    • Infliximab: 5 mg/kg IV at weeks 0, 2, 6, then every 8 weeks.

    • Adalimumab: 160 mg SC day 1, 80 mg day 15, then 40 mg every 2 weeks.

    • Certolizumab pegol: 400 mg SC at weeks 0, 2, 4, then every 4 weeks.

  • Anti-integrin therapy:

    • Vedolizumab: 300 mg IV at weeks 0, 2, 6, then every 8 weeks.

  • Anti-IL12/23 therapy:

    • Ustekinumab: IV induction dose (260–520 mg), then 90 mg SC every 8–12 weeks.

d) Antibiotics (for fistulas, abscesses, perianal disease)

  • Metronidazole: 400 mg orally every 8 hours.

  • Ciprofloxacin: 500 mg orally twice daily.

3. Surgical Management

Indications:

  • Failure of medical therapy.

  • Complications: strictures, fistulas, abscesses, obstruction.

  • Perianal disease.

Surgery is not curative (unlike UC) and recurrence is common.

Monitoring and Follow-Up

  • Regular assessment of symptoms, weight, nutritional status.

  • Blood tests: CBC, CRP, liver function.

  • Fecal calprotectin for monitoring mucosal inflammation.

  • Endoscopic evaluation for mucosal healing.

  • Cancer surveillance colonoscopy after 8–10 years of colonic involvement.

Prognosis

  • Lifelong disease with variable course.

  • Most patients require long-term medication; up to 70% undergo surgery within 20 years of diagnosis.

  • Early aggressive therapy with biologics has improved outcomes.

  • Mortality is only slightly higher than the general population, but morbidity from complications is significant.

Future Directions

  • Precision medicine: genetic and microbiome profiling to guide therapy.

  • Novel biologics targeting JAK-STAT pathways and other immune mediators.

  • Stem-cell therapies for refractory perianal fistulas.

  • Advances in non-invasive monitoring tools (blood and stool biomarkers, imaging).





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