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Inflammatory Bowel Disease: Advances in Immunopathogenesis and Treatment

This article discusses the pathophysiology, genetic components, and immunopathogenesis of inflammatory bowel disease (IBD), as well as current and novel treatment strategies. It also explores the evaluation of patient disease activity, quality of life, and patient education resources for optimal understanding and adherence.

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Inflammatory Bowel Disease: Advances in Immunopathogenesis and Treatment

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  1. Inflammatory Bowel Disease: Advances in Immunopathogenesis and Treatment

  2. Faculty

  3. Learning Objectives • Discuss the pathophysiology, genetic components, and immunopathogenesis of IBD and how this translates to individualizing treatment strategies • Understand current and novel therapies, their mechanisms of action, side effects, and monitoring requirements • Evaluate patient disease activity, quality of life, and patient education resources on treatment therapies to support optimal understanding and adherence

  4. Overview of Inflammatory Bowel Disease

  5. General Overview • Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  6. Katy S: Presenting Symptoms • Katy is a 25-year-old elementary school teacher. • She became an established patient at your practice when she moved to the area 3 years ago after graduating from college and accepting a teaching position at a local school. • Until today, Katy’s medical history is significant only for seasonal allergies. • At today’s appointment, Katy reports she has experienced intermittent abdominal pain and diarrhea for the past 2 to 3 months.

  7. Katy S: Presenting Symptoms • When you ask her to describe her symptoms, Katy reports: • Onset of the pain ~1 hour after eating, with more severe pain in the evening • The pain occurs almost daily and is most noticeable in the right lower quadrant • Katy indicates the pain persists for a few hours and may be accompanied by nausea • She reports no relief from ibuprofen but indicates a heating pad is sometimes helpful • Katy tells you she has 4 to 6 episodes of diarrhea each day, although the timing is variable • Occasionally she awakens a night with diarrhea and she experiences urgency • She expresses concerns about having an accident while teaching • She denies taking any other-the-counter medications for the diarrhea • Katy also denies seeing any blood in her stool

  8. Crohn’s Disease Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Diagnosis and management of Crohn's disease. Am Fam Physician. 2011;84(12):1365-75.

  9. Brian P: Presenting Symptoms • Brian is a 19-year-old college freshman attending a local university. • He presents to your university health center with a history of ulcerative colitis diagnosed at age 15. • He has been maintained for the past 2 years on mesalamine 800 mg DR BID with good symptom control. • Brian reports worsening diarrhea over the last 3 months. • He has multiple, loose, watery, bloody stools ~6 to 8 times a day.

  10. Brian P: Presenting Symptoms • Brian complains of fatigue and weakness. • He also expresses concern that his symptoms prevent him from attending class and he has fallen behind on his class assignments. • He is afraid he will have to drop out of school and does not want to tell his parents of his worsening illness. • Brian reports successful treatment of past relapses with prednisone prescribed by his local gastroenterologist.

  11. Ulcerative Colitis Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705

  12. Disease Activity in Ulcerative Colitis Truelove SC, Witts LF. Br Med J. 1955;2(4947):1401-48. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  13. Epidemiology

  14. Crohn’s Disease Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  15. Ulcerative Colitis • Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  16. Pathogenesis and Risk Factors

  17. Interaction of Risk Factors • Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. AnanthakrishnanAN. Nat Rev GastroenterolHepatol. 2015;12(4):205-17.Triantafillidis JK, et al. Drug Des DevelTher. 2011;5:185-210. Zhang YZ, Li YY. World J Gastroenterol. 2014;20(1):91-9.

  18. Genetics Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. Ananthakrishnan AN. Nat Rev GastroenterolHepatol. 2015;12(4):205-17. Tsianos EV, et al. World J Gastroenterol. 2012;18(2):105-18. Zhang YZ, Li YY. World J Gastroenterol. 2014;20(1):91-9.

  19. Environmental Risk Factors • Ananthakrishnan AN. CurrGastroenterol Rep. 2013;15(1):302. AnanthakrishnanAN. GastroenterolHepatol (N Y). 2013;9(6):367-74. Cohen AB, et al. Dig Dis Sci. 2013;58(5):1322-8.Cabre E, Domenech E. World J Gastroenterol. 2012;18(29):3814-22. Cohen AB, et al. Dig Dis Sci. 2013;58(5):1322-8. Zhang YZ, Li YY. World J Gastroenterol. 2014;20(1):91-9.

  20. Environmental Risk Factors Ananthakrishnan AN. CurrGastroenterol Rep. 2013;15(1):302. AnanthakrishnanAN. GastroenterolHepatol (N Y). 2013;9(6):367-74. Cabre E, Domenech E. World J Gastroenterol. 2012;18(29):3814-22.

  21. Altered Immune Response Triantafillidis JK, et al. Drug Des DevelTher. 2011;5:185-210. Zhang YZ, Li YY. World J Gastroenterol. 2014;20(1):91-9.

  22. Clinical Features

  23. Symptoms Associated with Intestinal Inflammation • Diarrhea • May contain mucus or blood • Nocturnal diarrhea • Incontinence • Pain or rectal bleeding with bowel movement • Severe bowel movement urgency • Constipation • Can be primary symptom in UC limited to rectum (proctitis) • Can be as severe with obstipation and no passage of flatus when bowel obstruction is present Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  24. Symptoms Associated with Intestinal Inflammation • Tenesmus • Nausea and vomiting; more common in CD • Abdominal cramps and pain • Frequently located in RLQ in CD • Around the umbilicus or in the LLQ in moderate-to-severe UC In most cases, CD and UC are chronic, intermittent conditions. Symptoms range from mild to severe during relapses and may completely resolve during remissions. Symptoms typically depend on the segment of the intestinal tract that is affected. Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  25. Constitutional Symptoms • Fever • Loss of appetite • Weight loss • Night sweats • Growth delays • Primary amenorrhea Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  26. Evaluation and Diagnosis

  27. Katy S: Diagnostic Evaluation • Your physical exam reveals: • A low-grade fever of 100°F • A 5-pound weight loss since Katy’s last visit 6 months ago • Tenderness and guarding in her RLQ • You perform blood tests including a CBC, TSH, comprehensive metabolic panel, sedimentation rate, and C-reactive protein. • You also order a stool test for C. difficile, culture, giardia, ova and parasites, fecal lactoferrin, and fecal immunohistochemical test.

  28. Katy S: Diagnostic Evaluation • Results: • Hemoglobin: 8.2 • Sedimentation rate: elevated • C-reactive protein: elevated • Fecal lactoferrin: 175 • Other stool tests: negative • You refer Katy to a nurse practitioner colleague in gastroenterology for possible inflammatory bowel disease.

  29. History Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  30. Physical Exam Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  31. Laboratory and Blood Tests Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Cioffi M, et al. World J GastrointestPathophysiol. 2015;6(1):13-22. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  32. Imaging and Endoscopy Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  33. Brian P: Diagnostic Evaluation • As Brian’s NP, what steps would you take next? • Obtain a thorough history of his medication adherence • Perform a complete physical exam • Perform CBC, complete metabolic panel, ESR, and iron studies

  34. Brian P: Diagnostic Evaluation • Your physical exam of Brian reveals: • Weight: 153 lbs., a 7-pound weight loss from his usual weight of 160 • Pulse: 83 bpm • Temperature: 36.2°C • Skin: pale and dry • Upon furthering questioning, Brian reports: • Increased frequency of headaches • Difficulty sleeping

  35. Brian P: Diagnostic Evaluation • Perform CBC, complete metabolic profile, ESR, and iron studies • Results: • CBC: mild anemia with Hgb 12.0 g/dL • Complete metabolic panel: potassium 3.3 mEq/L • ESR: elevated • Iron studies: elevated ferritin levels

  36. Complications

  37. Intestinal Complications • Abraham C, Cho JH. N Engl J Med. 2009;361(21):2066-78. Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  38. Extra-intestinal Complications Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  39. Extra-intestinal Complications Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705. Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Lima FD, et al. Rev Assoc Med Bras. 2012;58(4):481-8. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  40. Treatment Goals

  41. Treatment Goals • Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  42. Factors to Guide Management • Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  43. Diet and Lifestyle Interventions

  44. Nutrition • Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009.

  45. Nutrition • Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705. Bernstein CN, et al. World Gastroenterology Organisation Global Guidelines. 2009.

  46. Lifestyle Adams SM, Bornemann PH. Am Fam Physician. 2013;87(10):699-705.Bernstein CN, et al. Inflammatory bowel disease: a global perspective. World Gastroenterology Organisation Global Guidelines. 2009. Wilkins T, et al. Am Fam Physician. 2011;84(12):1365-75.

  47. Primary Pharmacologic Interventions

  48. Pharmacologic Interventions • Major classes of pharmacologic agents approved for UC and CD include: • 5-aminosalicylic acids • Corticosteroids • Immunomodulators • TNF inhibitors and monoclonal antibodies • Severity of disease at presentation should guide therapy • Emerging research suggests aggressive treatment at earlier stage of disease may improve clinical outcomes and increase likelihood of mucosal healing. • Step-up, Top-down Study revealed CD patients randomized to early treatment with immunomodulator plus TNF inhibitor were more likely to achieve clinical remission, steroid-free remission, and mucosal healing compared to patients treated with corticosteroids sequentially followed (as needed) by azathioprine and infliximab • Bernstein CN, et al. World Gastroenterology Organisation Global Guidelines. 2009. D'HaensGR, et al. J Crohns Colitis. 2014;8(8):726-34. KrishnareddyS, Swaminath A. World J Gastroenterol. 2014;20(5):1139-46. PacheI, et al. Swiss Med Wkly. 2009;139(19-20):278-87. TriantafillidisJK, et al. Drug Des DevelTher. 2011;5:185-210.

  49. 5-aminosalicylic Acid • Bernstein CN, et al. World Gastroenterology Organisation Global Guidelines. 2009. D'HaensGR, et al. J Crohns Colitis. 2014;8(8):726-34. KrishnareddyS, Swaminath A. World J Gastroenterol. 2014;20(5):1139-46. PacheI, et al. Swiss Med Wkly. 2009;139(19-20):278-87. TriantafillidisJK, et al. Drug Des DevelTher. 2011;5:185-210.

  50. Corticosteroids • Bernstein CN, et al. World Gastroenterology Organisation Global Guidelines. 2009. D'HaensGR, et al. J Crohns Colitis. 2014;8(8):726-34. KrishnareddyS, Swaminath A. World J Gastroenterol. 2014;20(5):1139-46. PacheI, et al. Swiss Med Wkly. 2009;139(19-20):278-87. TriantafillidisJK, et al. Drug Des DevelTher. 2011;5:185-210.

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