1. INFLAMMATORY BOWEL DISEASES Dr. Asim Siddig Dr. Sara Samir 9 August 2014

2. WHAT IS CD AND WHAT IS UC ? Dr. Asim Siddig 9 August 2014 3. BY THE END OF THIS SESSION You will know what is IBD. You will know what is UC. You will know what is CD. You will be able to differentiate between UC and CD. You will know what is the management of both of them. 9 August 2014 4. 9 August 2014 5. 9 August 2014 6. 9 August 2014 7. THANK YOUUUUUUUUUUUUU UUUU 9 August 2014 8. GENERAL PRINCIPLES The term inflammatory bowel disease (IBD) includes : - Crohn disease (CD) and - ulcerative colitis (UC) and others. and they are chronic, relapsing, and remitting inflammatory conditions of the gastrointestinal (GI) tract. The incidence of IBD in developed countries is approximately 3 per 100,000 to 16 per 100,000 population, the prevalence 0.1% to 0.2%. The most common age of presentation is from adolescence to 30 years with a smaller increase in incidence in the 50 to 80 year age group.9 August 2014 9. PATHOLOGY CD is characterized by : a granulomatous, transmural inflammatory infiltrate located at any level of the GI tract from mouth to anus, most commonly found in the ileocecal area. CD is a patchy, non continuous process. UC : is limited to the colon, usually involves only the superficial layers of the bowel, and is continuous in nature. UC virtually always involves the rectal mucosa.9 August 2014 10. CD UC 9 August 2014 11. OTHER FORMS OF IBD Collagenous colitis Lymphocytic colitis Ischemic colitis Behcets syndrome Infective colitis Intermediate colitis 9 August 2014 12. ETIOLOGY remains obscure Genetic : Ulcerative colitis is more common in DR2-related genes. Crohns disease is more common in DR5 DQ1 alleles. 3-20 times higher incidence in first degree relatives. Environmental. 9 August 2014 13. PATHOGENESIS OF IBD American Gastroenterological Association Institute, Bethesda, MD. Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407. Normal Gut Tolerance- controlled inflammation Environmental trigger (Infection, NSAID, other) Acute Injury Complete Healing Genetically Susceptible Host Acute Inflammation Immunoregulation, failure of repair or bacterial clearance Tolerance 9 August 2014 14. DIAGNOSIS : CROHNS The most common presentation is : I. ileitis, which may manifest only as diarrhea and abdominal pain, or may include systemic features such as anorexia, fevers, weight loss, anemia, increased white blood cell count, erythrocyte sedimentation rate, or C-reactive protein levels. II. Bloody diarrhea usually indicates colonic involvement. III. Another presentation : small bowel obstruction or localized peritonitis accompanied by fever, abdominal pain, and leukocytosis. This presentation is often mistakenly diagnosed as an acute appendicitis or diverticulitis.9 August 2014 15. LESS COMMON PRESENTATIONS INCLUDE I. Refractory oral ulceration. II. Perianal fistula or abscess. III. Gastroduodenal disease (dyspepsia, anorexia, nausea and vomiting, epigastric pain). IV. Intra-abdominal abscess. V. Symptoms of enterovesical fistula (urinary tract infection, fecaluria). 9 August 2014 16. ALSO CD confined to the colon may be confused with UC. In patients experiencing mainly weight loss and diarrhea, diseases associated with malabsorption (celiac) are possibilities. In women, gynecologic disease should be considered. 9 August 2014 17. DIAGNOSIS : ULCERATIVE COLITIS Patients experience symptoms of proctitis : I. Rectal bleeding. II. Urgency. III. Tenesmus. Occasional incontinence of stool is seen in >50%. Rectal disease may cause constipation and hard stools streaked with blood. In severe colitis bloody diarrhea developed (>6 to 10 bowel movements/day), fever, weight loss, volume depletion, and anemia.9 August 2014 18. 9 August 2014 19. ULCERATIVE COLITIS CONT. At presentation in an adult, 55% will have proctitis alone, 30% left sided colitis, and 15% will have more extensive disease. In children, disease involvement is usually more extensive. The differential diagnosis of UC includes infectious ischemic colitis or radiation colitis, and CD limited to the colon. Irritable bowel syndrome (IBS) often mimics the9 August 2014 20. PHYSICAL EXAMINATION Right lower quadrant tenderness or the sensation of a mass may be active CD. The presence of left lower quadrant tenderness in a patient with rectal bleeding should always raise the possibility of active UC. Patients with severe UC or toxic megacolon will appear acutely ill with abdominal tenderness, dehydration, tachycardia, hypotension, and often fever. In the rare case of perforation, peritoneal signs and/or abdominal rigidity will be present. 9 August 2014 21. PHYSICAL EXAMINATION CONT. Rectal examination should be performed, to check for rectal tenderness and the presence of blood. The perianal region and oral mucosa should be examined, as up to one third of patients with CD will develop perianal disease, and many will have oral ulcers. 9 August 2014 22. 9 August 2014 23. DIAGNOSTIC TESTS Laboratory Testing : Hemoglobin-decreased (bleeding, malabsorption of iron, folic acid or vitamin B12. Serum albumin concentration falls as a consequence of protein losing enteropathy. C-reactive protein is increased. ESR is increased with exacerbations or because of abcess. Platelet count-increased. 9 August 2014 24. DIAGNOSTIC TESTS Stool culture to exclude superimposed enteric infection in patient who present with exacerbations of IBD. 9 August 2014 25. ENDOSCOPY Sigmoidoscopy is the first diagnostic test to perform in the patient with bloody diarrhea. CD can be diagnosed by colonoscopy. This is often the only method of diagnosing early ileal or colonic CD. Colonoscopy is also an effective method of assessing the extent of UC Typically, there is a cobblestone appearance of the colon in CD, with areas of normal mucosa between involved areas. In UC, inflammation is continuous with erosions and friability apparent. However, in about 10% of sufferers, the differentiation between CD and UC is impossible based on9 August 2014 26. 9 August 2014 27. 9 August 2014 28. RADIOGRAPHY If severe colitis or obstruction is suspected, a three- position abdominal series should be obtained (upright chest film, abdominal decubitus, and flat plate or kidney, ureters, bladder, KUB, views) to rule out perforation, obstruction, or toxic megacolon. 9 August 2014 29. BARIUM ENEMA 9 August 2014 30. 9 August 2014 31. COMPLICATIONS: UC can lead to toxic megacolon resulting in perforation and intra-abdominal sepsis. CD may cause fibrosis, stricture, intestinal obstruction, fistulas, and intra-abdominal abscesses, as well as perianal disease. Colonic mucosa that is involved with IBD is more likely to develop dysplasia and carcinoma. With extensive colonic involvement by CD, the rate of malignant transformation is probably similar to that seen with UC. The frequency of screening for carcinoma in IBD is controversial, but after 8 years of disease it is prudent to perform colonoscopy and biopsy regularly. This9 August 2014 32. CROHNS COMPLICATIONS 9 August 2014 33. 9 August 2014 34. Extraintestinal Manifestations of UC 9 August 2014 35. MANAGEMENT OF IBD Dr. Sara Monier. 9 August 2014 36. GENERAL GOALS IN TREATING CROHNS DISEASE 9 August 2014 37. LIFESTYLE CHANGES 9 August 2014 38. GENERAL GOALS IN TREATING CROHNS DISEASEManagement options for Crohn's disease include drug therapy, attention to nutrition, smoking cessation and, in severe or chronic active disease, surgery The aims of drug treatment are to reduce symptoms and maintain or improve quality of life, while minimizing toxicity related to drugs over both the short- and long-term. Glucocorticosteroid treatment, 5-aminosalicylate (5-ASA) treatment, antibiotics, immunosuppressives and tumour necrosis factor (TNF) alfa inhibitors are currently considered to be options for treating Crohn's disease. Between 50 and 80% of people with Crohn's disease will eventually need surgery for strictures causing symptoms of9 August 2014 39. DRUG THERAPY FOR CROHNS DISEASE When treating Crohn disease using medications, there are two goals to achieve : 1. Induce remission 2. Maintain remission 9 August 2014 40. 9 August 2014 41. HOW TO INDUCING REMISSION IN CROHN'S DISEASE offer monotherapy with a conventional glucocorticosteroid (prednisolone, methylprednisolone or intravenous hydrocortisone) to induce remission in people with a first presentation or a single inflammatory exacerbation of Crohn's disease in a 12- month period In children, enteral nutrition is used as a treatment to induce remission instead of glucocorticoids in which a feeding tube is placed to deliver the predigested food needed to be absorbed early in the small intestine allowing the remaining bowel to rest9 August 2014 42. Consider Budesonide or 5-aminosalicylate (5-ASA) for a first presentation or a single inflammatory exacerbation in a 12 month period in people: -with one or more of distal ileal, ileocaecal or right- sided colonic Disease who decline, cannot tolerate or in whom a conventional glucocorticosteroid is contraindicated. Note that budesonide and 5-aminosalicylate (5-ASA) are less effective than glucocorticosteroid but may have fewer side effects and they are not used to treat severe presentations of Crohn disease 9 August 2014 43. IMMUNOSUPPRESSIVE DRUGS ( ADD-ON TREATMENT) Consider adding azathioprine or mercaptopurine to a glucocorticosteroid or budesonide to induce remission if: -there are two or more inflammatory exacerbations in a 12- month period Assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine -if TPMT activity is deficient (very low or absent), dont offer such immunosuppressives -if TPMT activity is below normal but not deficient, you can consider azathioprine or mercaptopurine at a lower dose.9 August 2014 44. TPMT is responsible for catalyzing the S-methylation of thiopurine drugs so any defect in TPMT activity leads to decreased methylation eventually leading to enhanced bone marrow toxicity which may cause myelosuppression, anemia, bleeding tendency, leukopenia & infection. Note: Monitor for neutropenia in those taking azathioprine or mercaptopurine even if they have normal TPMT activity 9 August 2014 45. METHOTREXATE Consider adding methotrexate to a glucocorticosteroid or budesonide to induce remission in people who cannot tolerate azathioprine or mercaptopurine, or in whom TPMT activity is deficient but only in patients with: -two or more inflammatory exacerbations in a 12- month period. 9 August 2014 46. SEVERE CROHNS DISEASE Severe active Crohn's disease which is defined as very poor general health with one or more symptoms such as weight loss, fever, severe abdominal pain and usually frequent (34 or more) diarrhoeal stools daily. People with severe active Crohn's disease may or may not develop fistula or have extra-intestinal manifestations of the disease. 9 August 2014 47. TREATING SEVERE CROHNS DISEASE TNF INHIBITORS Infliximab and adalimumab are recommended as treatment options for adults with severe active and fistulising Crohn's disease whose disease has not responded to conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy. These medications should only be USED and CONTINUED if there is clear evidence of ongoing active disease as determined by clinical symptoms, biological markers and investigation, including9 August 2014 48. A trial of withdrawal from treatment should be considered for all patients who reach a stable clinical remission but if the disease relapses later on after treatment has been stopped, these medications should be restarted again. Note for People who continue treatment with TNF Inhibitors should have their disease reassessed at least every 12 months to determine whether ongoing treatment is still clinically appropriate. 9 August 2014 49. SURGERY Consider surgery as an alternative to medical treatment early in the course of the disease for people whose disease is limited to the distal ileum, taking into account the following: -benefits and risks of medical treatment and surgery -risk of recurrence after surgery -individual preferences 9 August 2014 50. HOW TO MAINTAIN REMISSION AFTER INDUCTION Offer azathioprine or mercaptopurine as monotherapy to maintain remission in people who have not or have previously used them with glucocorticosteroid or budesonide to induce remission. Consider methotrexate to maintain remission only in - people who: -needed methotrexate to induce remission -or have tried but did not tolerate azathioprine or mercaptopurine for maintenance or have contraindications to them9 August 2014 51. Consider surgery early in the course of the disease or before or early in puberty for children and young people whose disease is limited to the distal ileum and who have growth impairment despite optimal medical treatment and/or refractory disease Consider balloon dilation particularly in people with a single stricture that is short, straight and accessible by colonoscopy 9 August 2014 52. MAINTAINING REMISSION IN CROHN'S DISEASE AFTER SURGERY Consider azathioprine or mercaptopurine to maintain remission after surgery in people with adverse prognostic factors such as: -more than one resection, -or previously complicated disease (for example, abscess, involvement of adjacent structures, fistula or penetrating disease). Consider 5-ASA treatment to maintain remission after surgery 9 August 2014 53. MANAGEMENT OF ULCERATIVE COLITIS 9 August 2014 54. SEVERITY OF UC The term mild or moderate or severe UC for adults are based on the Truelove and Witts' severity criteria 9 August 2014 55. MILD MODERATE SEVERE 9 August 2014 56. 9 August 2014 57. INDUCE REMISSION STEP1 THERAPY FOR MILD UC To induce remission in people with mild to moderate first presentation or inflammatory exacerbation of proctitis or proctosigmoiditis: -offer a topical aminosalicylate alone (suppository or enema, taking into account the person's preferences) - Or consider adding an oral aminosalicylate to a topical aminosalicylate -Or using an oral aminosalicylate alone, taking into account the person's preferences and explaining that this is not as effective as a topical aminosalicylate alone or combined treatment 9 August 2014 58. To induce remission in people with mild to moderate first presentation or inflammatory exacerbation of proctitis or proctosigmoiditis who cannot tolerate or who decline aminosalicylates, or in whom aminosalicylates are contraindicated: -offer a topical corticosteroid or -consider oral prednisolone 9 August 2014 59. STEP 1 THERAPY FOR MODERATE UC To induce remission in adults with mild to moderate first presentation or inflammatory exacerbation of left-sided or extensive ulcerative colitis: - offer a high induction dose of an oral aminosalicylate with the consideration of adding a topical aminosalicylate 9 August 2014 60. TREATING MILD TO MODERATE ULCERATIVE COLITIS: STEP 2 THERAPY Consider adding oral prednisolone to aminosalicylate therapy to induce remission in people with mild to moderate ulcerative colitis if there is no improvement within 4 weeks of starting step 1 aminosalicylate therapy or if symptoms worsen despite treatment 9 August 2014 61. TREATING ACUTE SEVERE UC STEP 1 THERAPYAdmission For people admitted to hospital with acute severe ulcerative colitis: -offer intravenous corticosteroids to induce remission and -assess the likelihood that the person will need surgery Consider intravenous ciclosporin or surgery for people: -who cannot tolerate or who decline intravenous9 August 2014 62. INDUCING REMISSION STEP2 THERAPY FOR ACUTE SEVERE UC Consider adding intravenous ciclosporin to intravenous corticosteroids Surgery for people: -who have little or no improvement within 72 hours of starting intravenous Corticosteroids -Or whose symptoms worsen at any time despite corticosteroid treatment. 9 August 2014 63. MAINTAINING REMISSION To maintain remission after a mild to moderate inflammatory exacerbation of proctitis or proctosigmoiditis, consider the following options: -a topical aminosalicylate alone or -an oral aminosalicylate plus a topical aminosalicylate or -an oral aminosalicylate alone, explaining that this may not be as effective as combined treatment To maintain remission in adults after a mild to moderate inflammatory exacerbation of left-sided or extensive ulcerative colitis: - offer a low maintenance dose of an oral aminosalicylate9 August 2014 64. To maintain remission after a single episode of acute severe ulcerative colitis: -consider oral azathioprine or oral mercaptopurine -consider oral aminosalicylates in people who cannot tolerate or who decline azathioprine and/or mercaptopurine, or in whom azathioprine and/or mercaptopurine are contraindicated 9 August 2014 65. Agents UC indications dose CD indications use Contraindication Side effects PO steroids as Prednisone Induce remission with a dose of 40- 60mg/day Induce remission with a dose of 0.25-0.75 mg/kg/day Infections, drug sensitivity. Caution if CHF,DM, HTN, TB Adrenal insufficiency, immunosuppressio n, peptic ulcer, osteoporosis IV steroids HCT, methylprednisolon e Induce remission HCT 300mg/d Methyl 40-60mg/d Induce remission HCT 300mg/d Methyl 40-60mg/d Methotrexate Role is unclear Induce remission in refractory disease with a dose of 25 mg IM weekly Pregnancy, breastfeeding, hypersensitivity Caution with renal or hepatic diseases Ulcerative stomatitis, anemia, leucopenia, thrombocytopenia, immune suppression 9 August 2014 66. REFERENCES 1. Taylors Manual of Family Medicine. 2. NICE guidelines. 3. Youtube.com/ 4. Internet. 5. NICE guidelines. 9 August 2014 67. THANK YOU9 August 2014