Inflammatory Bowel Disease

1. Inflammatory Bowel Disease

2. Inflammatory Bowel Disease (IBD) • Immune-mediated chronic intestinal condition • “Inflammation of the intestines” Source: p.1886

3. Types of IBD Source: p.1886

4. Ulcerative Colitis (UC) • Mucosal disease • Involves the rectum and extends proximally to involve all parts of the colon • Produces mucosal friability and areas of ulceration Source: p.1887 Source: p.570

5. Crohn’s disease (CD) • Chronic inflammatory disorder that produces ulceration, fibrosis, and malabsorption • Can affect any part of the GI tract from the mouth to the anus • Terminal ileum and colon are the more common sites Source: p.1888 Source: p.569

6. Pathophysiology

7. Possible factors • a pathogenic organism (as yet unidentified) • an immune response to an intraluminal antigen (eg, protein from cow milk) • or an autoimmune process whereby an appropriate immune response to an intraluminal antigen and an inappropriate response to a similar antigen is present on intestinal epithelial cells.

8. Predisposing factors • genetic predisposition [NOD2 gene (now called CARD15), chromosomes 5 (5q31) and 6 (6p21 and 19p)] • abnormal immune reactivity • smoking, diet, drugs, geography and social status, the enteric flora, alteredintestinal permeability, and appendectomy

10. Pathophysiology of IBD - pt. 2

12. Pathophysiology of IBD - Summary

13. EPIDEMIOLOGY

14. CLINICAL FEATURES

15. CLINICAL FEATURES

16. ENDOSCOPIC FEATURES

17. RADIOGRAPHIC FEATURES

18. TREATMENT

19. Treatment Goals • Relieve symptoms by suppressing the chronic inflammation of the intestines • Induce remission • periods of time that are symptom-free • Maintain remission • prevent flare-ups of disease • Improve the patient's quality of life • a

20. Treatment Options • Pharmacologic • 5-ASA • Glucocorticoids • Antibiotics • Azathiprine and 6-MP • Methotrexate • Cyclosporine • Tacrolimus • Anti-TNF Antibody

21. Treatment Options • Non-Pharmacologic • Nutritional Therapy • Bowel Rest and TPN • Surgery • Resection • Strictureplasty

22. Pharmacologic: 5-ASA • 5-aminosalicylate acid • Mainstay of therapy • For mild to moderate UC and CD • Effective at inducing remission in both UC and CD • Maintains remission in UC

23. Pharmacologic: 5-ASA • Example: Sulfasalazine • Combined sulfapyridine and 5-ASA • MOA: anti-inflammatory • Side effects: allergic and hypersensitivity reactions, headache, nausea and vomiting, anorexia

24. Pharmacologic: 5-ASA • Example: Mesalamine • Sulfa-free 5-ASA • Similar MOA to Sulfasalazine, less side effects • Olsalazine • Asacol, an enteric coated mesalamine liberates 5-ASA in pH>7.0 • Balsalazide • Claversal • Pentasa uses an ethylcellulose coating to allow water absorption

25. Pharmacologic: Glucocorticoids • For moderate to severe UC and CD unresponsive to 5-ASA • Induces remission but has no role in maintenance therapy • Should be tapered once clinical remission has been induced

26. Pharmacologic: Glucocorticoid • Oral Glucocorticoid • Prednisone 40-60mg/day • Parenteral • Hydrocortisone 300mg/day • Methylprednisone 40-60 mg/day • ACTH – for glucocorticoid naïve patients • Side effects • Fluid retention, hyperglycemia, osteonecrosis, withdrawal symtoms

27. Pharmacologic: Antibiotics • Indicated for post-colectomy and IPAA complication (pouchitis) in UC patients • Metronidazole • 15-20mg/kg/day in 3 divided doses for several months • SE: metallic taste, nausea, disulfiram-like reaction • Ciprofloxacin • 500mg id • 2nd DOA for active CD after 5-ASA • 1st DOA in perianal and fistulous CD

28. Pharmacologic: Azathioprine and 6-MP • Purine analogs employed in the management of gluocorticoid-dependent IBD • MOA: • is metabolized into thionosinic acid which inhibits the purine ribonucleotide synthesis and cell proliferation • Glucocorticoid-sparing agents • Effective for post-operative prophylaxis of CD

29. Pharmacologic: Azathioprine and 6-MP • Azathioprine • 2-3 mg/kg/day • 6-MP • 1-1.5 mg/kg/day • Side effects • Pancreatitis (reversible), nausea, fever, rash and hepatitis, dose-related leukopenia

30. Pharmacologic: Azathioprine and 6-MP • Patients should be monitored (CBCs and liver function) since they are at a four-fold increased risk of developing a lymphoma

31. Pharmacologic: Methotrexate (MTX) • MOA: inhibits dihydrofolate reductase leading to impaired DNA synthesis • IM or SC route • Effective in inducing remission and reducing glucocorticoid dosage, and in maintaining remission in active CD • SE: leukopenia, hepatic fibrosis, HPS pneumonitis

32. Pharmacologic: Cyclosporine (CSA) • For severe UC patients refractory to glucocorticoids • MOA: inhibits calcineurin →blocks production of IL-2 and function of B-cells→ blocks helper T-cells→ inhibits both the cellular and humoral immune system by

33. Pharmacologic: Cyclosporine (CSA) • Best given IV 2-4 mg/kg/day • Oral 7.5 mg/kg/day only effective with 6-MP/azathioprine • AE: HPN, gingival hyperplasia, etc • Monitor renal function (Creatinine cleaance)

34. Pharmacologic: Tacrolimus • Macrolide antibioitc with immunomodulatory properties similar to CSA • 100x as potent as CSA, has good oral absorption • For children with refractory IBD and adults with extensive small bowel involvement, steroid dependent or refractory UC or CD

35. Pharmacologic: Anti-TNF Ab • MOA: Blocks TNF→ blocks inflammatory cytokine → blocks intestinal inflammation • Examples: • Infliximab • Thalidomide • Adalimumab • Certolizumab Pegol • SE: increased risk of infections, serum sickness

36. Non-Pharmacologic: Nutritional Therapies • Bowel rest and TPN/EN • Induces remission • Use of peptide-based preparations • Dietary intervention helpful in CD but not in UC • a

37. Non-Pharmacologic: Srugery

38. Non-Pharmacologic: Surgery

39. Non-Pharmacologic • Reduce stress • Stop smoking • Do not take NSAIDs if not indicated to prevent ulcerations