Inflammatory Bowel Disease

1. Inflammatory Bowel Disease Dr. WM Simmonds Internal Medicine Gastroenterology 29/08/2011

2. Inflammatory Bowel DiseaseObjectives • Understand the pathogenesis of inflammatory bowel disease • Know the differences between Crohn`s disease and ulcerative colitis • Have an approach to the new patient with bloody diarrhoea • Know the differential diagnosis of IBD • Know the exta-intestinal manifestations of IBD • Know the principles of therapy of inflammatory bowel disease

3. Inflammatory Bowel DiseaseIntroduction • Inflammatory bowel disease (IBD) is an immune mediated, heterogeneous syndrome which is divided into 2 major phenotypes: • Crohn`s disease (CD) • Ulcerative Colitis(UC). • There is no pathognomomic test for either CD or UC. • Diagnosis is made on a combination of clinical, radiological, endoscopic and histological grounds.

4. Inflammatory Bowel DiseaseEpidemiology IBD is a condition of developed countries and outside of Europe, the United Kingdom and North America, is seen in Australia, South-Africa, and Israel at an appreciable frequency. IBD is more common in urban areas and in high socioeconomic settings. It is more common in caucasians, and especially those of Jewish extraction. It occurs less frequently in other race groups. Smokers have double the risk of developing CD as opposed to non-smokers. In contrast to this, smoking protects against UC. First degree relatives of those with IBD have an increased risk of developing IBD.

5. Inflammatory Bowel DiseaseEtiology and pathogenesis IBD is currently thought to be due to a dysregulated immune response to an as yet unidentified environmental antigen (possibly enteric microbes). As such the abnormal immune response develops in those with a genetic predisposition, and is modified by certain factors (smoking). The current hypothesis holds that the immune response in patients with IBD is against normal bowel flora which is erroneously perceived as being pathogenic.

6. Inflammatory Bowel DiseaseEtiology and pathogenesis Numerous genetic polymorphisms have been identified to date which confer a certain risk, and in certain cases predict disease behaviour (e.g. NOD2/CARD15 on chromosome 16, which is associated with CD of the terminal ileum). Some genetic polymorphisms are specific for CD or UC and some are shared. Genes implicated are involved in regulation of the innate immune system, the adaptive immune system and autophagy. An alternative hypothesis that patients with IBD have an abnormalities in mucosal defence (defensin production).

7. Ulcerative Colitis Disease is confined to the large bowel (that is apart from extra-intestinal manifestations). The disease is characterised by mucosal inflammation of the large bowel. Perianal disease, fistulas and small bowel strictures are NOT part of the clinical picture and are suggestive of CD.

8. Ulcerative ColitisClinical picture Blood per rectum Bloody diarrhoea (including nocturnally). Blood macroscopically visible in 95% of active disease. Cramps (especially before bowel movements) Urgency and at times incontinence Tenesmus Tenderness over inflamed colon Extra intestinal manifestations

9. Ulcerative ColitisEndoscopic characteristics Rectum almost always involved Extends continuously for varying distances proximally 20% have pan-colitis Pan-colitics may have “backwash ileitis” Longstanding colitis may manifest as a featureless colon, which is narrow and shortened Pseudopolyps are a manifestation of prior severe inflammation

10. Ulcerative Colitis

11. Ulcerative Colitis Severity:Truelove en Witts Classification

12. Ulcerative ColitisEndoscopic grading of UC • Mayo grade: • Loss of vascular pattern • Friability • Spontaneous haemorrhage

13. Ulcerative ColitisMicroscopic characteristics • Inflammation is limited to mucosa and superficial sub mucosa, except with fulminant colitis when it may become transmural • Features of chronicity • Crypt architectural distortion (branching and fallout) • Basal plasma cells and lymphoid aggregates • Active disease • Neutrophyl infiltration of epithelium and crypt abscesses

14. Ulcerative Colitis

15. Ulcerative ColitisRadiological Characteristics • Plain abdominal x-ray • Collapse of involved segment • Haustral thickening (“thumb printing”) • Dilated colon (>6 cm dilatation of caecum or transverse implies megacolon) • Ba enema (not used much now) • Ulceration • Featureless, shortened colon (chronicity features) “lead pipe” • CT scan • Dilated loops of colon • Enhancement of colonic wall

16. Ulcerative Colitis

17. Ulcerative ColitisComplications Colonic haemorrhage Toxic megacolon Perforation Longstanding disease (> 10 years) increases the risk of colon Ca.

18. Crohn’s Disease • Transmural inflammation of bowel, which may affect any part of the GI tract from the mouth to the anus, but tends to affect individual patients in a particular location, which remains stable over time. • It follows that resected Crohn`s disease tends to recur at the site of resection.

19. Crohn’s Disease • Disease behaviour may follow one of 3 patterns or combinations there of, i.e. • Luminal inflammatory disease • Stricturing disease • Fistulating /penetrating disease.

20. Crohn’s Disease • Disease pattern/behaviour /ultimate phenotype may not be apparent initially and develops over a period of years. • 30% of patients have isolated ileal disease • 30% have ileo-colitis • 30% have isolated colitis. • Peri-anal disease with fisures and fistulas is common. • Upper gastrointestinal involvement occurs less frequently.

21. Crohn’s DiseaseClinical features • Weight loss • Diarrhoea (only bloody in 50% of patients with colonic disease) • Abdominal pain • Symptoms of obstruction (if stricturing disease) • Peri-anal symptoms and disease • Palpable abdominal mass • High fever suggests abscess formation (intra-abdominal, ischio-rectal) • General features of chronic inflammation with pallor, cachexia if severe uncontrolled disease.

22. Crohn’s DiseaseEndoscopic characteristics • Depends on distribution • Ileitis • Colitis • Rectum involved in 50% of patients with colitis • Ulceration: • Aphthous • Stellate • Serpigenous • Skip lesions

23. Crohn’s Disease

24. Crohn’s DiseaseMicroscopic characteristics • Transmural inflammation • Granulomas (non-caseating) • Only seen in 20% of mucosal biopsies and 50% of full thickness biopsies

25. Crohn’s DiseaseRadiological characteristics • Ba small bowel enemas • Strictures (“string sign”) • Separation of loops (inflammation with thickening of the bowel wall) • Mucosal ulceration • Fistulous tracts • CT scan • Abscesses/fluid collections • Thickened bowel • MRI • Especially good for perianal disease • Fistulas

26. Crohn’s Disease

27. Crohn’s DiseaseComplications • Strictures • Fistulas • Entero-enteric • Entero-vaginal (usually only after hysterectomy) • Entero-cutaneous • Recto-vaginal • Peri-anal • Abscess formation • Gallstones • Kidney stones (oxalate)

28. Extra-intestinal manifestations

29. Uveitis

30. Erythema nodosum

31. Pyoderma gangrenosum

32. Differential diagnosis of IBD

33. Clinical approach to a patient with bloody diarrhoea • History and clinical examination • Stool sample • Microscopy, Culture and sensitivity • Clostridium difficile toxin assay • Sigmoidoscopy and biopsy (if biopsy available) • Full length colonoscopy in the absence of a diagnosis and persistent disease or alarm features • weight loss • anaemia, • age >50 years)

34. Truelove en Witt’s Classification

35. Therapy • Induction of remission with corticosteroids • Hydrocortisone 100 mg q 6 hourly IVI for 3 days • Then: • Prednisolone 40 mg per day po 1 week • Prednisolone 30 mg per day po 1 week • Prednisolone 20 mg per day po 1 month (Initiation of maintenance therapy) • Prednisolone 15 mg per day po 1 week • Prednisolone 10 mg per day po 1 week • Prednisolone 5 mg per day po 1 week • Stop.

36. Therapy • Maintenance of remission (UC) • Mild to moderate UC • 5-ASA preparations • Sulphasalazine • Mesalazine • Balsalazide • Severe or steroid dependant UC • Thiopurines • Azathioprine 2-2.5 mg per kg per day • 6 mercaptopurine 1-1.5 mg per kg per day • Steroid refractory UC • Cyclosporine • Anti-TNFα • Colectomy

37. Therapy • Maintenance of remission (CD) • Crohn`s disease(5 ASA probably does NOT work) • Very mild disease (nothing) • Moderate to severe disease • Azathioprine or 6 MP • Methotrexate • Primary prophylaxis • Azathioprine or 6 MP • Severe disease unresponsive to immunomodulators • Biological agents/antibodies • Infliximab (Anti-TNF) • Adalimumab • Vedolizumab • ?“Top down” therapy – Biologic agents first.

38. General measures • Stop smoking (especially CD patients) • Avoid NSAID`s • Drug compliance • Remember complications of therapy • Steroids: osteoporosis, diabetes, cataracts, osteonecrosis, Cushingoid habitus, hypertension, mood changes • 5-ASA: bone marrow suppression (rare), and male infertility • Thiopurines hepatitis, pancreatitis, bone marrow suppression • Methotrexate: teratogenic, liver fibrosis • All drugs may be used in pregnancy & before conception (according to indication) except Methotrexate which is absolutely contraindicated. • If you are a GP, remember initial correct diagnosis and therapy should be followed by timely referral to a specialist.

39. Indications for surgery • UC • Treatment refractory disease • Toxic megacolon • Colonic haemorrhage • Dysplasia/cancer • CD • Strictures/obstruction • Treatment refractory fistulae • Abscesses • Dysplasia/cancer • Massive haemorrhage(rare)

40. Thank you