2. INFLAMMATORY BOWEL DISEASE DEFINITION: IBD are chronic inflammatory disorders of unknown etiology involving the gastrointestinal tract, characterized by relapsing and remitting course of abdominal pain with diarrhoea with or without blood and variable constitutional symptoms. Two major forms are recognized: ulcerative colitis( UC) which affects only the large bowel, and Crohns disease (CD) which can affect any part of the GI tract from mouth to anus. Less frequently, three other forms of IBD are also recognized, microscopic ulcerative, microscopic lymphocytic,and microscopic collagenous colitis.

3. Epidemiology Incidence of CD varies from country to country, it is about 4-10 per 100 000 annually, with a prevalence of 27-106 per 100 000. Incidence of UC is stable at 6-15 per 100 000 annually, with a prevalence of 80-150 per 100 000. Incidence of IBD is higher in North America, northern Europe & UK. Race & Ethnic origin affects the incidence, Jewish people are more affected than any other group. CD is slightly more common in females (M:F=1:1.2) & at a younger age group (mean 26), while UC is slightly more common in male (M:F = 1.2 : 1, mean 34y)

4. PATHOPHYSIOLOGY It is thought that IBD develops because of an abnormal host response to an environmental trigger in genetically susceptible individuals.

5. PATHOPHYSIOLOGY This causes inflammation of the intestine and release of inflammatory mediators, such as TNF, IL-12 and IL-23, which cause tissue damage. In both diseases the intestinal wall is infiltrated with acute and chronic inflammatory cells. However there are important differences in the distribution of disease and in histological features.

7. PATHOPHYSIOLOGY ULCERATIVE COLITIS: 1. Inflammation invariably involves the rectum(proctitis) but can spread to involve the sigmoid colon(procto-sigmoiditis) or the whole colon(pancolitis). 2. In longstanding pancolitis the bowel can become shortened and pseudopolyps develop which are normal or hypertrophied residual mucosa within areas of atrophy. 3. The inflammatory process is limited to the mucosa and spares the deeper layers of bowel wall. 4. Both acute and chronic inflammatory cell infiltrate the lamina propria and the crypts (cryptitis). Crypt abscesses are typical. Goblet cells lose their mucus and in long-standing cases glands become distorted. 5. Dysplasia, charaterised by heaping of cells within the crypts, nuclear atypia and increased mitotic rate may herald the development of colonic cancer.

8. PATHOPHYSIOLOGY CROHNS DISEASE: 1. The sites most commonly involved, inorder of frequency, are the terminal ileum and right side of colon, colon alone, terminal ileum alone and ileum and jejunum. 2. The entire wall of the bowel is oedematous and thickened, and there are deep ulcers which often appear as linear fissures, thus the mucosa between them is described as cobblestone. These my penetrate through the bowel wall to initiate abscesses of fistulas. 3. CD has a patchy distribution and the inflammatory process is interrupted by islands of normal mucosa(Skipped lesions). 4. Histologically, the bowel wall is thickened with a chronic inflammatory infiltrate throughout all layers, occasionally with granuloma.

9. Distinguishing characteristics of CD and UC UCCDFeature Only colon (rarely “ backwash ileitis ” SB or colonLocation Continuous, begins distally Skip lesionsAnatomic distribution Involved in >90%Rectal spareRectal involvement UniversalOnly 25%Gross bleeding Rare75%Peri-anal disease NoYesFistulization No50-75%Granulomas

10. Endoscopic features of CD and UC UCCDFeature ContinuousDiscontinuousMucosal involvement RareCommonAphthous ulcers AbnormalRelatively normal Surrounding mucosa RareCommonLongitudinal ulcer NoIn severe casesCobble stoning CommonUncommonMucosal friability distortedNormalVascular pattern

11. Pathologic features of CD and UC UCCDFeature UncommonYesTransmural inflammation No50-75%Granulomas RareCommonFissures NoCommonFibrosis UncommonCommonSubmucosal inflammation

12. Extra GI manifestation These occur in both UC & CD. Eyes Eyes: uveitis, episcleritis, conjunctivitis. Joints Joints: type I (pauci-articular) arthropathy, type II (polyarticular) arthropathy, arthralgia, Ankylosing spondylitis, inflammatory bak pain. Skin Skin: erythema nodosum, pyoderma gangrenosum. Liver & biliary tree Liver & biliary tree: sclerosing cholangitis, fatty liver, chronic hepatitis, cirrhosis, gallstones. Nephrolithiasis Nephrolithiasis Venous thrombosis Venous thrombosis

13. CD ….. Clinical features CD ….. Clinical features - Diarrhoea abdominal pain weight loss, malaise, lethargy, anorexia, nausea, vomiting & low-grade fever. - In 15% of cases no GI symptoms. - Diarrhoea in 80% of cases, & in colonic disease it contains blood making differentiation from UC difficult. - Steatorrhoea may be present if small bowel involved. - CD may present as acute appendicitis. - Anal & perianal disease may be the presenting feature in 25% of cases. - Enteric fistulae (external & internal), e.g. to bladder or vagina occur in 20-40% of cases. - External fistula usually after surgery.

14. CD ….. Examination CD ….. Examination - Loss of weight may be present. - Aphthus ulceration of mouth is often seen. - R.I.F. tenderness or mass may be detected. - Anus should be examined for oedematous anal tags, fissures or perianal abscesses. - Look for extra-GI manifestations. - Sigmoidoscopy should be done: rectum is usually normal, biopsy must be taken, patchy oedematous haemorrhagic mucosa may be seen.

15. CD …..Investigations Blood tests: anaemia, normochromic normocytic. Def. of iron and/or folate occurs. Serum B12 levels can be below normal, however Megaloblastic anaemia is unusual. Raised WBC, ESR,CRP. Hypoalbuminaemia in severe disease. Liver biochemistry may be abnormal. Blood cultures & stool cultures.

16. CD …. Radiology & imaging Barium follow-through, or CT scan with oral contrast. Plain abdominal x-ray, US or CT in acute colonic symptoms to outline the colon. High-resolution US and CT Scanning to define thickness of bowel wall & intra-abdominal abscesses. Endo-anal US & MRI to evaluate perianal disease. Radionuclide scans with gallium-labelled polymorphs or technitium-labelled leucocytes to identify small intestine or colon disease & to localize extra intestinal abscesses.

19. CD….. Disease activity Hb, WBC, inflammatory markers (ESR, CRP & platelet count) & serum albumin. CD activity index in research studies. Calprotectin is a calcium-binding protein & accounts for 60% of cytosolic protein of neutrophils. Faecal calprotectin is a cheap & useful marker for diseas activity in IBD.

20. CD ilitis: DDx Lymphoma Yersinea Enterocolitis TB

21. CD ….. Medical Management The aim is to induce & maintain a remission. Mild symptoms : symptomatic treatment, stop cigarette smoking, loperamide or codeine phosphate for diarrhoea or give colestyramine if diarrhoea is due to bile acid malabsorption. Anaemia if due to iron or B12 def. : haematinics. Erythropoeitin may be given if anaemia normocytic normochromic.

22.  Induction of remmision  Induction of remmision: Oral or IV glucocorticosteroids. Enteral nutrition. Oral glucocorticosteroids + azathioprine or 6mercaptopurine.  Maintainance of remmision  Maintainance of remmision: Aminosalicylates (colonic disease). Azathioprine, 6MP, mycophenolate mofetil.  Perianal disease  Perianal disease: Ciprofloxacin and metronidazole. CD ….. Medical Management

23. Treatment of corticosteroid / immunosuppressive therapy-resistant disease. Methotrexate. IV cyclosporine. Infliximab (TNF-α antibody). Adalimumab. Certolizumab. New biological agents.

24. Infliximab - mucosal healing Baseline Week 10Week 54

25. CD….. Surgical management Try to avoid surgery, & do minimum resection because recurrence rate is high (15% per year). Nearly 80% of patients will require an operation at sometime. Azathioprine or 6MP should be used in patients undergoing second surgery to decrease the chance of recurrence.

26. Indications for surgery Failure of medical treatment. Complications: toxic dilatation of colon, obstruction, perforation, abscesses, enterocutaneous fistula. Failure to grow in children.

27. UC ….. Clinical features: The major symptom is bloody diarrhoea with mucus. Malaise, lethargy, anorexia & weight loss. Aphthous ulceration in the mouth. The disease may be mild, moderate or severe. 10% have persistent chronic symptoms, others have a single attack only. Severe attack definition Severe attack definition : bloody diarrhoea > 6 per day, fever, tachycardia, high ESR>30mm/h, low Hb<10gm, albumin < 30g/L

28. UC ….. Examination No specific signs in UC. Slight abd. distension or tenderness. The anus is normal. PR shows blood. Rigid sigmoidoscopy shows rectal inflammation, bleeding, friable mucosa.

29. UC ….. Investigations Blood tests: iron def. anaemia, WBC & platelets increased. ESR &CRP are raised, hypoalbuminaemia, liver biochemistry. Stool cultures: to exclude infective causes. Imaging: Plain abdominal, abdominal U/S. Colonoscopy.: should not be performed in severe attacks for fear of perforation. In chronic disease it is useful to assess the extent & to exclude any malignant changes.

32. DDX of UC Infectious Drug induced Microscopic colitis

33. UC ….. Medical management Aminosalicylates: 5-aminosalicylic acid (5-ASA) Given in a special preparation, e.g. binding to sulfapyridine(sulfasalazine), to be released in the large bowel. Proctitis Proctitis : oral aminosalicylates + local rectal steroid preparation. Mesalazine enemas & budesonide enemas can be tried. In resistant cases try oral steroids alone or combined with azathioprine. Left sided proctocolitis Left sided proctocolitis: oral aminosalicylates + local rectal steroid, but in moderate to severe cases oral prednisolone. Total colitis Total colitis (moderate to severe attacks): Hydrocortisone 100mg i.v. 6 hourly + oral aminosalicylates. Azathioprine may be used in recurrent cases. I.V. cyclosporine in severe cases. When patient responds, we shift to oral prednisolone & doses very slowly tapered, 5-10 mg every week, if flare up again when reducing prednisolone, then azathioprine should be added. Maintainance of remission: by aminosalicylates.

34. UC …. Surgical management Indications: Fulminant acute attack: 1. Failure of medical treatment in 3 days. 2. Toxic dilatation. 3. Haemorrhage. 4. Perforation. Chronic Disease: 1. Incomplete response to medical treatment. 2. Excessive steroid requirement. 3. Non-compliance with medication. 4. Risk of cancer.

35. UC …. Course & prognosis 1/3 of patients with distal inflammatory proctitis due to UC will develop more proximal disease, with 5-10% developing total colitis. 1/3 of patients with UC will have a single attack, & the others will have a relapsing course. 1/3 with UC will undergo colectomy within 20 years of diagnosis.

36. Cancer in IBD Patients with UC & Crohns colitis have increased incidence of developing colon cancer, & patients with CD have more incidence of small bowel cancer. A screening colonoscopy with multiple biopsies should be done every 2 years in patients with total UC & Crohns colitis of 10 y and annually after 20y.

37. Pregnancy & IBD Women with inactive UC have normal fertility. Rate of relapse of D. during pregnancy is the same as in non-pregnant patient, & is usually due to inappropriate discontinuation of mentainance therapy. Aminosalicylates, steroids, & azathioprine are safe at the time of conception and during pregnancy.

38. Microscopic Inflammatory Colitis Chronic or fluctuating diarrhoea. Colonoscopy : normal. BUT Histopathological findings on biopsy are abnormal. There are 3 forms: 1. Microscopic UC 2. Microscopic lymphocytic colitis 3. Collagenous colitis

39. Complications of IBD Bleeding Stricture Fistula Toxic megacolon Cancer: Patients with either UC or CD have an increased risk of intestinal dysplasia & CRC that is related to the duration, extent& severity of the inflammation,so those with extensive/longstanding disease should undergo regular colonoscopic examinations with mucosal biopsies to detect these complications.