Chapter 28 Irritable Bowel Disease IBD

1. Chapter 28 Irritable Bowel Disease IBD John Noviasky

2. IBD • Chronic, idiopathic, relapsing inflammatory disorder of gastrointestinal tract (GIT) • Mainly ulcerative colitis (UC) and Crohn’s disease (CD) • >600,000 in U.S. have IBD • Table 28-1

3. Etiology • True cause unclear • may be genetic, infectious, environmental, autoimmunity • generally recognized as dysregulation of mucosal immune system • smoking decreases risk for UC, smoking increases risk for CD • NSAID -exacerbation of IBD

4. Etiology continued • Breast-fed infants decreased risk for IBD • some feel emotional stress plays a part but objective evidence limited • Increased in pro inflammatory cytokines, chemokines, prostaglandins, and reactive oxygen leads to increased inflammation and tissue destruction

5. UC (ulcerative colitis) • Shallow inflammation of the colon ranging from proctitis (rectal involvement only) to disease involving the entire colon, symptom worse in later • no fistulas, no fissures, no abscesses, no small bowel involvement • chronic, loose bloods stools (most common symptom)

6. UC continued • Tenesmus - (urge to defecate) • abdominal pain • mild UC - < 4 stools/day, no systemic signs of toxicity and normal ESR • severe UC - > 6 bloody stools/day, fever, tachycardia, anemia, ESR>30 • Relapse and remission common

7. CD (Crohns Disease) • Chronic, transmural, patchy, granulomatous, inflammatory disease that can involve entire GIT (mouth to anus) • discontinuous ulceration (skip lesions) • fistula formation, peri-anal involvement • severity of disease does not correlate directly with extent of bowel involvement

8. CD continued • Three main patterns of disease (predominantly inflammatory, stricturing, or fissuring) • patients often present with abdominal pain and chronic, often nocturnal diarrhea • weight loss, low grade fever and fatigue also common • mild to moderate CD - ambulatory pts who are able to tolerate oral feeding without systemic toxicity

9. CD continued • Moderate to severe CD - fever, weight loss, abdominal pain, nausea and vomiting and/or significant anemia • surgery often cures UC • disease often recurs after surgery in CD • Table 28-2 • Extra intestinal complications of CD and UC (table 28-3)

10. Treatment • Specific therapy depends on disease location • Goals • relief of symptoms • improve QOL • maintain nutrition • relieve inflammation • maintain remission

11. Aminosalicylates • First class to show benefit • sulfasalzine (Azulfidine) - composed of 5-ASA attached to sulfapyridine. This allows for 5-ASA transport past upper intestine so can work in colon. Sulfapyridine - no benefit but can cause adverse effect. • 80% of dose reaches distal small intestine and colon where the diazo bond is broken. Sulfapyridine liberated in colon is poorly absorbed.

12. Aminosalicylates continued • 15% of pts discontinue d/t adverse effects (eg. Nausea, vomiting, headache, alopecia, anorexia) Table 28-4 • Newer agents contain 5-ASA and are sulfa-free, Also pH-dependent (delays absorption until lower bowel) eg. Aminosalicylate, mesalamine • 90% of sulfasalazine intolerant pts can tolerate the new agents

13. Aminosalicylates continued • Mesalamine formulations • 1)Asacol - pH sensitive -releases in distal ileum and colon • 2)Pentasa- contains acid-resistant microgranules that release 5-ASA in duodenum, jejenum, ileum, and colon • 3) Rowasa- topical enema or suppository works at rectum and distal colon

14. Corticosteroids • Common treatment for moderate to severe flares/Not for maintenance • 40-60 mg prednisone • 30% may not respond • topical steroids (enemas, foams and supp.) can work for distal colitis in those that fail 5-ASA (can have adrenal suppression w/long term use)

15. Immunomodulators • Useful in steroid-dependent IBD • Azathioprine converts to 6-mercaptopurine metabolized to thioinosinic acid which inhibits purine ribonucleotide synthesis and cell proliferation • also, suppresses T-cell function

16. Immunomodulators continued • Some clinicians use steroids/inflixinnals to induce remission then maintain of Azathioprine • adverse effects-rash, nausea and diarrhea, myelosuppression can occur (monitor CBC q month x 3 months then q 3 months) need to d/c drug d/t neutropenia 10% of the time

17. Immunomodulators continued • Methotrexate-folate antagonist-impairs DNA synthesis • inflammatory mediators • decrease IL-1 • decrease T cells - decrease cytokines (IL-2) and interferon) • Not for UC • useful for CD in pts intolerant to azathioprine

18. Immunomodulators continued • Takes weeks to months to work • adverse effects- stomatitis, neutropenia, nausea, pneumonitis, alopecia, hepatotxicity • folic acid 1 mg daily • can decrease nausea/ stomatitis

19. Cyclosporine (CSA) • Selective to T-cell • quicker effect than Azathioprine, methotrexate • can manage severe UC refractory to steroids • 60% of pts with steroid-resistant or fistulizing CD respond to CSA

20. Infliximab • Binds and neutrolizes tumor necrosis factor (TNF) alpha • used to induce and maintain remission of moderate to severe CD (and fistulizing CD) in those with inadequate response to usual therapy • Dose-5mg/kg IV over 2 hours at O,2, and 6 weeks and then q 8 weeks • rapid response-with in days, 60% efficacy

21. Infliximab • Adverse effects - • immediate • fever, chills, pruritis, urticaria and cardiovascular problems • Delayed- serum sickness, pulmonary symptoms • Infections- pneumonia, cellulitis, sepsis, cholecystitis, endophthalmitis, furunculosis, reactivate TB, reactivate histoplasmosis

22. Infliximab continued • Avoid infliximab- pts with active infection, history of chronic infection, neural demyelinating disorder (exacerbate MS), heart failure (exacerbate heart failure)

23. Antibiotics • Used in CD not UC • flagyl and cipro have been used

24. Nutrition • CD - responds to bowel rest, TPN, or enteral nutrition • Bowel rest and TPN as effective as steroids for CD • not used for maintenance • fish oil - inhibits inflammatory cytokines, modest efficacy for UC and CD

25. Supportive Therapy • Pain relief and diarrhea control • loperamide/lomotil- used when obstruction or toxicity is not evident (watch for toxic megacolon-severe worsening of symptoms and abdominal distention

26. Surgery • Page 28-6

27. Irritable Bowel Syndrome (IBS) • Most common chronic disorder causing pts to seek medical treatment • functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit (diarrhea-predominant/constipation predominant) • incidence ~ 15-20%

28. IBS continued • F:M 3:1 • cost about 33 billion/year

29. Pathophysiology • Psychological stress may exacerbate disease • hypersensitive colon • serotonin may play a role- >95% of 5HT is in GIT, when released, 5HT triggers GI smooth muscle contraction and relaxation and mediates GI sensory function • IBS pts may have more 5HT than normal

30. Diagnosis • No good biochemical or physical markers • diagnosis is by symptoms Table 28-7 • extensive testing not needed unless “alarm” symptoms (table 28-6) • treatment (fig. 28-4)

31. Question 1 • How has drug-induced and parasitic cause of CM’s diarrhea been ruled out? • What is classic triad of UC? • What is diarrhea in UC secondary to ? • What is range of diarrhea frequency? • What is the usual consistency of stools? • Besides diarrhea, what are other secondary results of UC?

32. Question 1 continued • What does bright-red blood mixed in stools indicate? Blood streaked stool? • What can happen to Hb, HCT, and Alb in UC?

33. Question 3 • What is most effective agent to induce remission of acute, severe UC exacerbation? • How often does clinical improvement occur in pts taking prednisone 15-60 mg/day? • When and how should prednisone taper be handled?

34. Question 4 • When should a patient receive parenteral nutrition? • What is definition of adequate response? • When is diarrhea considered resolved? • When might surgery be considered?

35. Question 5 • What should initial dose of oral prednisone for CM be?

36. Question 6 • When prednisone is given in equivalent doses orally and rectally, the incidence of side effects and therapeutic effects are_______? • Which are preferred for distal UC, 5 ASA supp or topical corticosteroids and why?

37. Question 7 • What adverse effects are seen when steroids are used? • Which therapies should be considered in patients on more than 3 months of steroids?

38. Question 8 • What is usual response rate of mild to moderate UC with use of 1.5 to 4.8 g/day of 5-ASA? • Which therapy is first-line for mild to moderate UC; 5-ASA or steroids? • When should steroids be considered? • Which is preferred 5-ASA, sulfasalazine or mesalamine? Fig. 28-2

39. Question 14 • When is a patient considered “toxic” (as in toxic megacolon)? • What are major complications of toxic megacolon?

40. Question 19 • What is classic symptom triad of crohn’s disease (CD) • How do the usual stools of CD differ from UC?

41. Question 20 • What is the most widely used agent for treatment of active symptomatic CD? • What is usual response rate of CD to steroids? • For what degree of severity of CD is sulfasalazine used? • How long does improvement take with use of sulfasalazine?

42. Question 20 continued • With what section of affected GI is sulfasalazine useful? Not useful? • Figure 28-3

43. Question 24 • What is yearly cost of infliximab? • What premedications are sometimes used with infliximab? • What adverse reactions can occur with infliximab? • Which skin test should be given to patients considering infliximab and why?

44. Quesiton 26 • Name some strategies that can help patients with IBS?

45. Quesiton 27 • With which type of IBS is dietary fiber a reasonable first-line treatment?

46. Question 28 • After fiber, what is usual therapy for Constipation Predominant (CP)-IBS • Why should stimulant laxatives generally be avoided for CP-IBS?

47. Question 29 • How does tegaserod work? • What was the efficacy of tegaserod in clinical studies? • What was most common adverse effect reported?

48. Question 29 continued • What type of surgeries were increased in pts on tegaserod compared to control? • Why can’t tegaserod be recommended for use in men? • In which pts is tegaserod contraindicated?

49. Question 30 • Which antispasmodics are options for pain predominant IBS (PP-IBS) • should antispasmodics be used prn or RTC? • In what type of PP-IBS pts are antidepressants a reasonable option? • What dose of amitriptyline should be tried first, what is target dose, what is reasonable trial period?

50. Question 31 • Which is preferred agent for diarrhea-predominent IBS (DP-IBS) • is RTC or prn antidiarrheal use preferred for DP-IBS? • When is prophylactic dosing a reasonable option? • Why is lomotil a second-line agent? • When is cholestyramine used for DP-IBS?