Crohn's Disease

Chronic inflammatory and ulcerating condition of the GI tract that can affect anywhere from mouth to anus, most commonly the terminal ileum and colon

Aetiology

  • Genetic predisposition - NOD2 gene found in 10-20% of Caucasian patients with Crohn’s (involved in bacterial recognition)
  • Dysbiosis
  • Faulty immune response
  • Environmental factors - aggravated by smoking and NSAIDs

Pathophysiology

  1. Bacterial lipopolysaccharide triggers persistent activation of T cells and macrophages in a genetically susceptible individual
  1. Normally the reaction against the lipopolysaccharide is self-limiting, but in IBD patients once the inflammation starts it does not stop
  1. Excess pro-inflammatory cytokine production and bystander damage due to neutrophilic inflammation

Disease phenotypes

  • Ileal and/or colonic chronic active mucosal inflammation including cryptitis and crypt abscesses
  • Any area of GI tract can be affected
  • Intestinal strictures - bowel narrowing by scar tissue from inflammation
  • Fissure ulcers - from inflammation
  • Fistula - left behind from draining of fissure ulcer
  • Skip lesions - unaffected areas of bowel (vs. UC - bowel continually affected)

Clinical presentation

Symptoms

  • Symptoms are variable but often include diarrhoea (which may be bloody and become chronic - i.e. present for more than six weeks), abdominal pain and/or weight loss
  • Typically there will be periods of acute exacerbation, interspersed with remissions or less active disease
  • Children may present with poor growth, delayed puberty, malnutrition and bone demineralisation
Extra-intestinal manifestations
  • Skin - pyoderma gangrenosum, erythema nodusum
  • Joints - arthritis, ankylosing spondylitis
  • Eyes - uveitis
  • Oxalate renal stones

Signs

  • Evidence of weight loss
  • Right iliac fossa mass (+ pain)
  • Malaise, fever
  • Peri-anal signs - abscesses, fistulas, skin tags, sphincter damage, anal fissures

Investigations

Blood tests

  • ↑ CRP
  • ↓ albumin and platelets
  • ↓ B12 if terminal ileum affected
  • Faecal calprotectin test - specific for inflammation in the bowel, can distinguish between IBS and IBD

Stool sample

  • To rule out infective causes (of diarrhoea)

Colonoscopy + biopsy

  • Ileocolonoscopy and biopsies from the terminal ileum as well as each affected colonic segment are first-line procedures to establish the diagnosis BUT should not be used in an acute attack
Findings
  • Thickened bowel
  • Strictures
  • ‘Cobble-stoning’
  • Histology:
    • Transmural inflammation
    • Non-caseating granulomas
notion image

Imaging

  • CT/AXR/USS - often used in acute attacks
  • Barium follow through
  • Technetium-labelled white cell scan
  • Small bowel MRI

Management

Lifestyle

  • Smoking cessation

Medical management to induce remission

  • Patients should be offered monotherapy with glucocorticoids (short course PO prednisolone for mild attacks, IV hydrocortisone in hospital for severe flareup)
  • Enteral nutrition may be considered as an alternative in children (as steroids suppress growth)
  • Azathioprine or mercaptopurine may be added on to induce remission if there are 2 or more exacerbations in a 12-month period or the glucocorticoid cannot be tapered

Medical management to maintain remission

  • Immunosuppressants - maintenance therapy for severe chronic disease
    • Azathioprine first line
  • Anti-TNF - last line before surgery
    • Promote apoptosis of activated T-lymphocytes
    • Re-treatment to maintain remission

Surgery

  • Colectomy (resection)
  • Stricturoplasty - for strictured disease

Complications

  • Increased risk of colorectal cancer - colonoscopy 10 years post diagnosis
  • Malabsorption, malnutrition
  • PSC - 80% have associated IBD (more likely to be UC)
  • Toxic megacolon
  • Increased risk of osteoporosis