Crohn's disease Flashcards
Define
• Chronic granulomatous inflammatory disease that can affect any part of the gastrointestinal tract. Grouped with ulcerative colitis and known, together, as inflammatory bowel disease.
What’s the aetiology?
- Cause unknown but thought to be due to interplay between genetic, host immune response and environmental factors including smoking, oral contraceptive pill, diet high in refined sugar, zinc deficiency and measles.
- Genetic susceptibility – stronger in CD, mutations in CARD15 (NOD2) gene on Chr16 increase susceptibility of structuring small bowel CD. Also increased incidence of HLA-B27 with ankylosing spondylitis.
- Host immune response: In the genetically predisposed individual, there is an exaggerated immune response with effector T cells (T helper (Th)1, Th2 and Th17) predominating over regulatory T cells. Pro-inflammatory cytokines (interleukin (IL)-12, interferon (IFN)-γ, IL-5, IL-17) released by these activated T cells stimulate macrophages to produce tumour necrosis factor (TNF)-α, IL-1 and IL-6. There is also activation of other cells (neutrophils, mast cells and eosinophils) that together lead to increased production of a wide variety of inflammatory mediators, all of which can lead to cell damage.
- Though inflammation can occur anywhere from mouth to anus, 40% involves the terminal ileum and caecum
- Tend to be ‘skip lesions’ – discontinuous inflammation. Cobblestone appearance – deep ulcers and fissures. Transmural inflammation and granulomas present in 50%
What are the risk factors?
- White ethnicity
- Family history
- Age 15 to 40 or 60 to 80
- Smoking
Epidemiology
- UK annual incidence: 5-8/100,000
- UK prevalence: 50-80/100,000
- Affects any age and gender but peaks in 15 and 40 and 60 to 80
- More common in white people and Ashkenazi Jews
What are the presenting symptoms?
- Crampy abdominal pain (due to inflammation, fibrosis or bowel obstruction), right lower quadrant (ileitis – mimic appendicitis)
- Diarrhoea (may be bloody or steatorrhoea or nocturnal)
- Bowel obstruction (bloating, distension, constipation)
- Fever, malaise, weight loss
- Symptoms of complications (fever etc.)
- Sometimes right iliac fossa pain due to inflammation of terminal ileum
- May have perianal lesions (skin tags, fistulae, abscesses or sinuses)
- Oral lesions (mouth ulcers, pain in mouth and gum)
What are the signs?
- Weight loss
- Clubbing
- Signs of anaemia
- Aphthous ulcers in mouth
- Uveitis, erythema nodosum, pyoderma gangrenosum
What are the appropriate investigations?
• Blood:
o FBC - low Hb, high platelets, high WCC
o U&Es
o LFTs - low albumin
o High ESR (suggests chronic inflammation)
o CRP may be high or normal
o Vit B12 (normal or low), iron studies and folate
• Stool microscopy and culture: exclude infective colitis
• Comprehensive metabolic panel (CMP) – chronic or severe disease. Hypoalbuminaemia, hypocholesterolaemia, hypocalcaemia.
• Yersinia enterocolitica serology: important to exclude Y enterocolitica, causes acute ileitis
• AXR: could show evidence of toxic megacolon
• Erect CXR: if there is a risk of perforation
• Small bowel barium follow-through could show:
o Fibrosis/strictures (string sign of Kantor - part of the intestine looks like a piece of string, showing incomplete filling of the intestinal lumen)
o Deep ulceration (rose thorn ulcers)
o Cobblestone mucosa
• Endoscopy (OGD, colonoscopy, sigmoidoscopy) and biopsy may show:
o Could help differentiate UC and CD
o Useful for monitoring malignancy and disease progression
o Can show mucosal oedema and ulceration with ‘rose thorn fissures’ (occurs when there is a cobblestone mucosa)
o Fistulae and abscesses
o Transmural chronic inflammation with infiltration of macrophages, lymphocytes and plasma cells
o Granulomas with epithelioid giant cells may be seen in blood vessels and lymphatics
• Radionucide-labelled neutrophil scan: can localise the inflammation (when other investigations are contraindicated)
What’s the management plan?
Treatment depends on site and severity of disease and also if the disease is stricturing or fistulating.
• Acute Exacerbation
o Fluid resuscitation
o IV/oral corticosteroids
o 5-ASA analogues (e.g. mesalazine and olsalazine)
o Analgesia
o Parenteral nutrition may be necessary
o Monitor markers of disease activity e.g. fluid balance, ESR, CRP, platelets, Hb
• Long-Term
o Steroids - for acute exacerbations. Oral prednisolone (40mg/day) for mild/moderate disease over 8 weeks.
o 5-AminoSalicylic Acid analogues - decreases the frequency of relapses (useful for mild to moderate disease)
• NOTE: more commonly used in UC
o Immunosuppression: using steroid-sparing agents (e.g. azathioprine, 6-mercaptopurine, methotrexate) reduces the frequency of relapses
o Anti-TNF agents: (e.g. infliximab and adalimumab) - very effective at inducing and maintaining remission. Usually reserved for refractory Crohn’s.
• General Advice:
o Stop smoking
o Dietician referral (low fibre diet necessary if there are stricture present)
• Surgery indicated it:
o Medical treatment fails
o Failure to thrive in children in the presence of complications
o Involves resection of affected bowel and stoma formation - NOTE: there is a risk of disease recurrence
What are the side effects of some drugs?
Side effects of azathioprine are bone marrow suppression, acute pancreatitis and allergic reactions.
Rare potentially serious side effects of 5-ASA are bloody diarrhoea (resembling acute colitis), Stevens–Johnson syndrome, acute pancreatitis and renal impairment.
Side effects of methotrexate: hepatotoxicity, pulmonary fibrosis,
What are the possible complications?
• GI: o Haemorrhage o Obstruction o Complications in pregnancy associated with immunosuppressant therapy (methotrexate should be stopped 6 weeks before! Tetratogenic) o Intraabdominal sepsis (on immunosuppressants so increased risk of infective colitis or C.diff with antibiotic use) o Strictures o Perforation o Fistulae (between bowel, bladder, vagina) o Perianal fistulae and abscesses o GI cancer o Malabsorption • Extraintestinal Features: o Uveitis o Episcleritis o Gallstones o Kidney stones (severe disease, increased absorption of oxalate) o Arthropathy o Sacroiliitis o Ankylosing spondylitis o Erythema nodosum o Pyoderma gangrenosum o Amyloidosis
What’s the prognosis?
- It is a chronic relapsing condition
- 2/3 of patients will require surgery at some stage
- 2/3 of these patients require more than 1 operation
- Associated with a decrease in life expectancy
