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Crohn’s disease

Crohn’s disease. Dr Bernard Stacey. “ DAPPSSICAMP ”. Description Aetiology Pathophysiology Predisposing factors Symptoms Signs Investigations Complications Alternatives Management Prognosis. Areas of Interest. “Causes” (Genetics and others) Treatments (Drugs and surgery)

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Crohn’s disease

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  1. Crohn’s disease Dr Bernard Stacey

  2. “DAPPSSICAMP” • Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  3. Areas of Interest • “Causes” (Genetics and others) • Treatments (Drugs and surgery) • Assessment

  4. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  5. Crohn’s disease • Chronic inflammatory condition • Can affect any part of the gut • Commonly: • large bowel • terminal ileum • small bowel - localised, diffuse • perianal

  6. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  7. Crohn’s disease • Prevalence: 40 per 100,000 • Incidence: approx 0.7 - 1 per 1000 people • Western world • Clusters • Affecting all ages • Peaks in 20s and 60s

  8. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  9. Macroscopic features • Bowel thickened and narrowed • Deep fissuring ulcers • cobblestoning • Fistulae and abcesses

  10. Microscopic features(histology) • Inflammation extends throughout all layers of bowel • Chronic inflammatory cells • Granulomas • 60-75% only • Lymphoid hyperplasia

  11. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  12. SMOKING ! • Increased risk of: • Getting it in the first place • Aggressive disease • Relapse • Hospital admissions • Surgery • Cancer

  13. Genetics • Long known that Crohn’s / UC is commoner in families / twins • Not simple inheritance • Sibling with CD/UC means 15-30x the risk • 1 in 7 patients have a relative with the illness

  14. Genetics (2) THE HUMAN GENOME PROJECT • 1996: Oxford group • Showed Crohn’s and UC share some susceptibilty genes • Chromosomes 3, 7 and 12

  15. An Infective Cause for Crohn’s? • M. Paratuberculosis • E. Coli • Viruses eg: measles • Post-infective bacteria • Clostridium • Bacteroides • Toothpaste • Cornflakes • Hygiene • “Allergy” • Refined sugars • Trauma • Pollutants

  16. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  17. Symptoms-depend on site of disease • Abdominal pain • Weight loss • Diarrhoea +/- blood • Obstructive symptoms • Complications of fistulae • Complications of malabsorption • B12, Ca/Vit D, Zn, etc

  18. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  19. Oral apthous ulceration

  20. Episcleritis

  21. Erythema Nodosum • IBD • TB/ Sarcoid • OCP, sulphonamides • Streptococcal infections • Yersinia, psitticosis • Lymphogranuloma venereum • Connective tissue disorders • Tuleraemia

  22. Pyoderma Gangrenosum

  23. Arthropathy with effusion (supra-patellar)

  24. Sacro-ileitis

  25. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  26. Investigations • Blood tests and markers of nutrition • Hb, ESR/CRP, Albumin, LFTs • Endoscopy • OGD, enteroscopy, colonoscopy  HISTOLOGY • X-ray / ultrasound • SB meal/enema, Ba enema, fistulogram, CT • Nuclear medicine • Labelled leucocyte scan • Laparoscopy

  27. Fissuring “rose thorn” ulceration in terminal ileum

  28. “Skip lesions” in the small bowel

  29. Non-invasive imaging • Virtual colonoscopy • Fast CT scan after usual bowel prep • Large memory computer • Accompanying software

  30. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  31. Complications • Social / financial – days off work • Psychosexual – surgery, stomas • Nutritional – osteoporosis, B12 • Multiple resections  short bowel syndrome • Fistulae • Toxic megacolon • Primary sclerosing cholangitis • Cancer • risk  after 10 years in total colitis

  32. 0 2 4 6 8 10 15 20 25 30 Increasing risk of colorectal cancer in colitis – years after diagnosis

  33. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  34. Differential diagnosis • Initially often “IBS” • Ulcerative colitis • Infective diarrhoea • especially amoebic • Differential diagnosis of malabsorption and malnutrition • Ileal TB / lymphoma • Behçet’s disease

  35. Description • Aetiology • Pathophysiology • Predisposing factors • Symptoms • Signs • Investigations • Complications • Alternatives • Management • Prognosis

  36. Current treatments • 5-ASA drugs • Steroid enemas • Budesonide • Steroids • (Elemental diets) • Azathioprine • Methotrexate • Infliximab, adalimumab • Surgery • Diversion • Resection

  37. What’s new in IBD treatment?

  38. DEXA scanning

  39. Steroids

  40. 5-ASA drugs • Role in prevention of colorectal cancer • Sulphasalazine • 3% compliant patients • 31% non-compliant patients • Mesalazine • Reduces risk by 81% at >1.2g/day

  41. Surveillance • Total colitis • Every 3 yrs after 8 years • Every 2 years from 20-30 years • Annually thereafter • Left sided colitis • After 15 years • Proctitis • nil

  42. IBD and azathioprine • Remission rates: Crohn’sUC Overall 45% 58% >6/12 Rx 64% 87% Fraser et al : Gut. 2002;50(4):485-9

  43. IBD patients on azathioprine • Up to 1/3 of patients with IBD discontinue azathioprine because of side-effects or lack of a clinical response • Life-threatening haematotoxicity • Neutropenia • Thrombocytopenia • Pancytopenia

  44. IBD patients on azathioprine • 15% suffer early toxicity • Most of these (77%) are within 12 weeks of starting therapy • Nausea within 2 weeks • Deranged LFTs within 8 weeks • Bone marrow toxicity within up to 12 weeks • Step up dosing???

  45. Azathioprine metabolism

  46. Human RBC TPMT TPMTH/TPMTH TPMTL/TPMTH TPMTL/TPMTL

  47. TPMT levels in Southampton 2002-3 10% 5%

  48. Pharmacogenetic based prescribing • ‘Tailored’ azathioprine doses • Case reports of successful treatment of homozygous TPMTL patients with low dose azathioprine: 0.1 – 0.3 mg/kg (eg: 70kg  7mg od) Kaskas BA et al. Gut 2003; 52: 140-2

  49. Non-responders • Inverse correlation between TPMT and 6-TGN • 6-TGN levels > 235 correlate with remission • Increasing AZA dose: • 1/3 will achieve remission • 2/3 will not  6-TGN levels No change in 6-TGN levels BUT  in mercaptopurine metabolites Hepatotoxicity in 1/4

  50. Allopurinol • Used at 200mg with reduction of azathioprine dose to 25% • Drives pathway towards 6TG by blocking XO arm • Needs careful monitoring

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