Inflammatory Bowel Disease

1. Inflammatory Bowel Disease

2. Definition Inflammatory bowel disease (IBD) is a term encompassing a number of chronic inflammatory disorders leading to damage of the gastrointestinal tract.

3. Crohns disease

4. Symptoms of CD The presentation depends on the site, extent, severity, and complications of intestinal and extraintestinal disease. • Fevers, night sweats, and weight loss. • Abdominal pain • Nausea and vomiting • Diarrhea • Rectal bleeding

5. Musculoskeletal Peripheral arthritis Sacroiliitis Ankylosing spondylitis Osteoporosis Dermatologic Erythema nodosum Pyoderma gangrenosum Aphthous stomatitis Hepatobiliary Disease Primary sclerosing cholangitis Ocular Uveitis Scleritis Episcleritis Vascular Thromboembolic events Renal Nephrolithiasis Extraintestinal Manifestations of Inflammatory Bowel Disease

6. Physical Examination in CD • Weight loss and pallor. • Clubbing of the fingers. • Abdominal distension • Tenderness in the area of involvement • Abnormal bowel sounds. • Presence of an inflammatory mass are common. • Perianal abscess, fistula, skin tags, or anal stricture.

7. Laboratory Studies • Anemia • Deficiencies of iron, vitamin B12, or folic acid • Anemia of chronic disease. • Leukocytosis • Thrombocytosis • Elevated ESR and C-reactive protein levels • Decreased Serum albumin levels • Urinalysis commonly demonstrates calcium oxalate crystals. • Stoolanalysis for fecal leukocytes • Serologic markers with high specificity for CD. • Anti-Saccharomyces cerevisiae antibody(ASCA) • Antibody to the outer core membrane of E. coli (OmpC)

8. Imaging Studies • Plain abdominal x- ray • Barium studies • Small bowel enema (enteroclysis) / follow-through • Large bowel enema • U/S Abdomen and Pelvis / Transrectal U/S • CT Abdomen and Pelvis • MRI

9. CD Typical features of Crohn's disease of the distal ileum including fissure ulcers (small arrows), longitudinal ulcers (arrowhead), "cobblestoning" (open arrows), aphthoid ulcers (curved arrow) and stricturing. ic=ileocaecal valve. Aphthoid ulceration of terminal ileum (small arrows)- Note also "cobblestoning" (larger arrows).

10. Endoscopy • Upper and Lower Endoscopy • Capsule Endoscopy

11. CD

12. CD

13. CD

14. Granuloma in CD

15. ACG Practice Guidelines:Definitions of Disease Severity • Ambulatory patients • Patients who are able to tolerate oral alimentation • Patients without manifestations of • Dehydration • Toxicity ( high fever, rigors, prostration ) • Abdominal tenderness • Painful mass • Obstruction • >10% weight loss Mild – Moderate CD : Hanauer et al A J Gastroenterology 2001,96,635

16. ACG Practice Guidelines:Definitions of Disease Severity (cont.) • Patients who have failed to respond to treatment for mild-moderate disease • Patients with more prominent symptom of: • Fever • Significant weight loss • Abdominal pain or tenderness • Intermittent nausea or vomiting (without obstructive findings) • Significant anemia Moderate-Severe CD: Hanauer et al A J Gastroenterology 2001,96,635

17. ACG Practice Guidelines:Definitions of Disease Severity (cont.) • Patients with persistent symptoms despite the introduction of steroids as out patient • Individuals presenting with: • High fever • Persistent vomiting • Evidence of intestinal obstruction • Rebound tenterness • Cachexia, or • Evidence of abscess Sever –Fulminant CD: Hanauer et al A J Gastroenterology 2001,96,635

18. ACG Practice Guidelines:Definitions of Disease activity • Patients who are asymptomatic or without inflammatory sequelae • Patients who have responded to acute medical interventionorhave udergone surgical resection without gross evidence of residual disease NB: Patients requiring steroids to maintain well-being are considered to be “steroid-dependen”and are usually notcosidered to be “in remission.” CD in remission: Hanauer et al A J Gastroenterology 2001,96,635

19. Long-term disease evolution behavior in CD Cosnes J et al. Inflamm Bowel Dis 2002;8;244

20. Medical treatment of IBD Yousef A. Qari MD,FRCPC,ABIM Consultant Gastroenterologist King Abdulaziz University Hospital Jeddah, Saudi Arabia

21. Current Expectations for IBD Therapy • Induce clinical remission • Maintain clinical remission • Improve quality of life Plus • Heal mucosa • Decrease hospitalization / surgery / overall costs • Minimize disease- related and therapy-related complications

22. ACG Practice Guidelines:Recommended treatment • Aminosalicylates • Sulphasalazine (3-6g/d) • Mesalamine (3.2-4.0g/d) 40-50% • Antibiotics (CD involving colon) • Metronidasole (10-20mg/kg) 50% • Ciprofloxacin (1g/d) • Metro+Cipro (250mg 2-3 times/d +500mg 2 times/d) 76% • Budesonide (CIR) (9mg/d) • For ileal & Rt colonic disease 69% Mild – Moderate CD : Remission

23. ACG Practice Guidelines:Recommended treatment • Corticosteroids • Appropriate antibiotics therapy or drainage (surgical/percutaneous) required for infection or abscess • Inflximab infusion • Effective adjunct • Possible alternative to steroid therapy in selected patients in whom corticosteroids are contraindicated or ineffective. Moderate –Severe CD

24. Oral Budesonide for active CD Greenberg etal . N Engl J Med 1994;331;836-41

25. ACG Practice Guidelines:Recommended treatment Corticosteroids Budesonide 9mg/d or Prednisone (0.5-0.75mg/kg) or 40mg/d • 5o-70% remission rate in 8-12 weeks • Until resolution of symptoms and resumption of weight gain, generally 7-28 days. • Steroid refractory & steroid dependent ≈ 50% • Smooking • Colonic disease • Not effective for maintenance Moderate –Severe CD:

26. Clinical response and remission in Infliximab-treated patients Moderate-Severe CD: Clinical response : ≥70 points decrease in CDAI from baseline Clinical remission : a CDAI of < 150 Targan SR et al, N Engl J Med. 1997:337:1029

27. Clinical Response at Week 52* P<0.001 P=NS P<0.001 *Week-2 Responders

28. Clinical Remission at Week 54* P<0.001 P=NS P<0.007 *Week-2 Responders

29. ACG Practice Guidelines:Recommended treatment Hospitalization required for : • patients with persistent symptoms despite introduction of oral steroids or infliximab • Patients presenting with high fever, frequent vomiting, evidence of intestinal obstruction, rebound tenderness, cachexia, or an abscess Surgical consultation is warranted for patients with obstruction or tender abdominal mass. Severe-Fulminant CD: Hanaur S et al. Am J Gastroenterology; 96; 635

30. ACG Practice Guidelines:Recommended treatment • Exclude abscess • Abd US • Abd CT • Parentral corticosteroids equivalent to 40-60mg prednisone • If abscess has been excluded • If the patient has been receiving oral setroids Severe-Fulminant CD: Percutaneous Drainage Surgical

31. ACG Practice Guidelines:Recommended treatment • Parentral broad spectrum antibiotics • High fever • Toxic appearance • Inflammatory mass • Nutritional support: (Elemental or TPN) • TPN in addition to steroids plays no specific role • Indications • For patients unable to maintain nutritional requirments after 5-7 days • Preoperative management • Pediatric age groups Severe-Fulminant CD:

32. Possible efficacy Antibiotics AZT/6-MP Cyclosporine Proven efficacy Infliximab Therapeutic Options for Perianal Fistulas in CD

33. Therapeutic Options for Perianal Fistulas in CD AZT/6-MP 22/41 Compleate healing or decreased discharge΅ Pearson DC et al. Ann Intern Med.1995;122;132

34. Therapeutic Options for Perianal Fistulas in CD Infliximab P=0.001 P=0.04 Present DH et al. N Engl J Med. 1999;34;1398

35. Step-up (N = 64) steroids Top-down (N = 65) IFX (0/2/6) + AZA IFX + AZA + IFX + AZA MTX steroids + (epis) IFX steroids relapse steroids Step-up versus Top-down Trial Newly Diagnosed Crohn (N = 129)

38. Step Up treatment paradigm driven by cost, safety and adverse events Surgery Infliximab Immunosuppressives Steroids Elemental diet Antibiotics Aminosalicylates The classical Step-Up-treatment paradigm

39. Placebo (n=30) AZA 2.5 mg/kg per d (n=33) Placebo (n=30) AZA 2.5 mg/kg per d (n=33) Placebo (n=30) AZA 2.5 mg/kg per d (n=33) 80 80 80 60 60 60 % Patients Not Failing Trial 40 40 40 20 20 20 0 0 0 Duration of Trial (Months) Azathioprine is the best conventional drug to maintain clinical remission Remission induced by prednisolone; tapered over 12 wk 100 ster + AZA AZA 0 15 Candy S et al. Gut. 1995;37:674.

40. Continuous Immunotherapy is required to treat a Chronic Disease Patients in clinical remission with AZAfor at least 3.5 yearsbefore randomisation Months after randomisation Lemann et al.Gastroenterol. 2005 Jun;128(7):1812-8.

41. ± 2 SD Cumulative Probability of Surgical Intervention in CD 100 80 60 Probability (%) 40 20 0 0 Dx 2 5 8 11 14 17 20 Years Events (no.)122 26 15 7 7 4 8 1 8 2 2 2 3 2 1 Munkholm P et al. Gastroenterology. 1993; 105:1716.

42. Ulcerative colitis

43. Difinition A chronic disease charecterized by diffuse mucosal inflammation limited to the colon.

44. Age distribution of Ulcerative colitis in east and west provinces of Saudi arabia 188 CASES Age(y) at presentation • Qari Y et al, under publication • 2. Satti M et al, Ann Saudi Med 1996;16(6):637-640.

45. Sex distribution of UC in the Gulf • Qari Y et al, under publication • Hossain J et al. Ann Saudi Med 1991;11:40-6. • Satti M et al, Ann Saudi Med 1996;16(6):637-640. 4. Al-Nakib B et al. Am J Gastroenterology 1984;79:191-4 5. Mir-Madjlessi SH et al. Am J Gastroenterology 1985;11:862-6.

46. Pattern of UC in the Gulf • Qari Y et al, under publication • Hossain J et al. Ann Saudi Med 1991;11:40-6. • Satti M et al, Ann Saudi Med 1996;16(6):637-640. • . 4. Al-Nakib B et al. Am J Gastroenterology 1984;79:191-4 5. Mir-Madjlessi SH et al. Am J Gastroenterology 1985;11:862-6.

47. Epidemiological figures comparing East vs West

48. Ulcerative colitis

49. UC Normal

50. UC