Crohn’s disease

Background

Chronic relapsing-remitting, non-infectious inflammatory disease of the GI tract

  • Can affect any part of the GI tract from mouth to anus, and usually presents as ‘skip’ lesions i.e. abnormal lesions with normal mucosa between (this is in contrast to UC)
    • Around 30% involve small bowel (terminal ileum most common); 20% only the colon; 45% involve both
  • It has an incidence of around 10 per 100,000 per year and a prevalence of around 115000 in the UK
    • It usually presents around either 15-30 or 60-80.  More common in adult females (1.8:1)

Aetiology

  • The exact cause(s) is unknown but there are several risk factors
    • Genetics- 15-20% will have an affected family member; siblings of an affected individual are 17-35 times more likely to develop crohn’s
      • At least 200 genes have been identified- complex polygenic factors
    • Smoking
      • In contrast to UC, smoking increases the risk of CD (OR 1.76 compared to general population)
    • Appendectomy
      • Relative risk after 1 year was 6.7 and after 5 years was 1.1

Pathophysiology

  • Chronic inflammation from inappropriate T cell activation
  • Initially, focal inflammatory lesions form around the crypt cells of the GI mucosa, followed by ulceration of the superficial mucosa.
    • Invasion of inflammatory cells into the deep mucosa allows the formation of noncaseating granulomas.
    • Crypt and villous atrophy is a consequence of neutrophillic infiltration into the crypts

Presentation

  • Crohn’s is a relapsing/remitting disease- as such symptoms/signs will often be episodic in nature
  • Symptoms
    • Change in bowel habit- most commonly diarrhoea
      • May be bloody (not frequently); more often with mucus
      • May be chronic
      • Bowel movements may partially relieve abdominal pain
    • Abdominal pain- most commonly in the right lower quadrant
    • Weight loss
  • On examination,
    • the abdomen may be tender or distended
    • there may be mouth ulcers or perianal lesions (e.g. fistulae, skin tags etc)
  • Extraintestinal features
    • More common in crohn’s than in UC, particularly with related colitis
    • Can be split into
      • Related to disease activity
        • Pauci-articular arthritis
          • <5 large joints e.g. ankles, knees, hips, wrists, elbows, shoulders
          • usually asymmetric, acute and self-limiting (~few weeks rather than months)
          • although the joints aren’t usually permanently damaged, there is often associated enthesitis (tendon attachment); tenosynovitis (tendon + sheath) or dactylitis.
        • Erythema nodosum
        • Aphthous ulcers (painful, clearly defined, shallow ulcers of the mouth and underside of the tongue)
        • Episcleritis
        • Osteoporosis (both a manifestation and a complication of treatment)
      • Not related to disease activity
        • Axial arthritis (e.g. ankylosing spondylitis); polyarticular arthritis (small joints; >5 joints; symmetrical; persistent; damaging)
        • Pyoderma gangrenosum (erythematous papules/pustules that can ulcerate; most commonly on the shins/previous trauma sites)
        • Uveitis (bilateral)
        • Hepatobiliary conditions
          • e.g. primary sclerosing cholangitis (mainly in UC- serious, cholangitis, steatosis, chronic hepatitis, cirrhosis, gallstones
          • May be a complication or secondary to treatment; most commonly detected with deranged LFTs
      • Rarer manifestations include bronchial disease; pancreatitis; renal stones; VTE

Investigations

  • Blood tests
    • FBC
      • Anaemia- chronic disease; iron deficient; chronic blood loss; malabsorption of B12/folate
      • Leucocytosis- inflammation, abscess or steroid treatment
    • U&Es
      • Hydration status- hyponatraemia
      • Kidney function
      • Micronutrient/electrolyte deficiencies e.g. hypocalcaemia/hypomagnesaemia
    • LFTs
      • Check liver/biliary status for extraintestinal manifestations
      • Hypoalbuminaemia
    • Inflammatory markers
      • Raised CRP
    • Serology
      • Anti-S cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA)
        • Crohn’s more likely to be ASCA positive
        • UC more likely to be p-ANCA positive (can be positive in CD too)
  • Imaging
    • First line used to be contrast studies (barium or otherwise; swallow + follow through and enema studies)
      • ‘Cobblestone appearance’- patches of normal and ulcerated mucosa
      • fistulae
    • CT is being used more often
  • Endoscopy
    • Ileocolonoscopy with biopsy is the gold-standard investigation for Crohn’s disease

Assessment of Severity

Management

  • Patient support and information
    • Smoking cessation
  • Inducing remission
    • Glucocorticosteroid treatment (prednisolone; methylprednisolone or IV hydrocortisone)
    • NB In children where growth is a concern, enteral nutrition (nutrition shakes) may be an alternative
      • Budesonide (a steroid with low bioavailability) is preferred in mild-moderate crohn’s)
    • Consider adding azathioprine or mercaptopurine in patients who do not respond adequately to glucocorticoids or who have had a previous episode within the last 12 months
      • NB Do NOT use as monotherapy.  If glucocorticoids are not suitable, try 5-aminosalicylate (5-ASA) for first/mild presentations
      • IMPORTANT: Before starting either- assess thiopurine methyltransferase (TPMT) activity.
        • Do NOT offer if activity is very low/absent
      • ALSO MONITOR WCC, and drug levels
      • Major side-effects of azathioprine include myelosuppression, hepatitis and pancreatitis; minor, often transient effects, include nausea, vomiting and flu-like symptoms.
      • If these are not suitable, consider methotrexate
  • Cytokine modulators (Infliximab/adalimumab- block TNF-alpha activity)
    • Infliximab can be considered for severe Crohn’s disease, where conventional treatment has failed or is contraindicated
      • Severe disease is defined as very poor general health and one or more symptoms of weight loss, fever, severe abdominal pain, and diarrhoea (CDAI >300; HBI >=8)
        • Active fistulating Crohn’s disease is also a relative indication
      • Treat until treatment failure (e.g. need for surgery) or for 12 months
      • Treat only if active disease i.e. not in remission
  • Total parenteral nutrition may be suitable in severe disease too
  • Surgery
    • Only offer surgery as an alternative to medical therapy in early Crohn’s disease limited to the distal ileum/proximal  caecum
    • Surgery may be offered for the management of secondary strictures (balloon dilation)
    • Surgery is not routinely offered in Crohn’s as disease is systemic and recurrence is almost certain (only really used for complications)
  • Maintenance of remission
    • Smoking cessation
    • Azathioprine/mercaptopurine may be used as monotherapy (particularly in those who have required their use in inducing remission)
      • Where these are not suitable, consider methotrexate
      • Do NOT offer glucocorticosteroids unless this is required for the management of extraintestinal manifestations e.g. erythema nodosum/uveitis
    • Offer colonoscopic surveillance for colorectal cancer; monitor for osteopenia/osteoporosis

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