PATHOGENESIS OF IBDAlthough genetic susceptibility, luminal antigenic drive, and environmental triggers are each important, animal models demonstrate that no single factor is sufficient to induce chronic relapsing, immune-mediated intestinal inflammation. Chronic inflammatory bowel diseases depend on the interaction of these essential components, each of which is necessary but not sufficient to induce disease.
1-The main difference between Crohn's disease and UC is the location and nature of the inflammatory changes. Crohn's can affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. Ulcerative colitis, in contrast, is restricted to the colon and the rectum.Crohn's & Colitis Foundation of America".2-Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohn's disease affects the whole bowel wall ("transmural lesions").3-Finally, Crohn's disease and ulcerative colitis present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions.
Optimal treatment of inflammatory bowel disease depends on what form it consists of. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptom, such as prednisone, TNF inhibition, azathioprine (Imuran), methotrexate, or 6-mercaptopurine. More commonly, treatment of IBD requires a form of mesalazine.
Often, steroids are used to control disease flares and were once acceptable as a maintenance drug. In use for several years in Crohn's disease patients and recently in patients with ulcerative colitis, biologicals have been used such as TNF inhibitors. Severe cases may require surgery, such as bowel resection, strictureplasty or a temporary or permanent colostomy or ileostomy. Alternative medicine treatments for bowel disease exist in various forms, however such methods concentrate on controlling underlying pathology in order to avoid prolonged steroidal exposure or surgical excisement.
InflammatoryBowel Disease (IBD)Presented by:M. Sufianstudent of Nutrition Sciences(B/Sc)Science & Research Branch of Islamic Azad University(SRBIAU) All Rights Reserved by M Sufian 1/13/2012 1 email@example.com
Contents:• Introduction• Occurrence & Commonness• Pathophysiology• Diagnosis Symptoms Signs• Complications• Treatments Medical Surgical• Q&A• References All Rights Reserved by M Sufian1/13/2012 2 firstname.lastname@example.org
Introduction: • IBD:Chronic inflammatory diseases of GI tract of unknown etiology • Commonly refers to 1) ulcerative colitis Ulcerative colitis (UC) affects only the large intestine (*) 2) Crohn’s disease Crohn’s disease (CD) can affect any part of the gastrointestinal tract but most frequently attacks the distal third of the small intestine & the colon All Rights Reserved by M Sufian1/13/2012 3 email@example.com
Introduction (continued) • Diagnosed using clinical, endoscopic, and histologic criteria • No single finding is absolutely diagnostic for one disease or the other • Approx. 20% of patients have clinical picture that falls between ulcerative colitis and Crohn’s disease (indeterminate colitis) • Many of the treatments available are effective for both diseases • Extraintestinal manifestations may be present in both All Rights Reserved by M Sufian1/13/2012 4 firstname.lastname@example.org
Occurrence & Commoness • Approx. 1 million people in U.S. have ulcerative colitis (UC) or Crohn’s disease (CD) • Most commonly observed in industrialized nations; lowest in developing regions (also higher rate in urban areas vs. rural areas) • Incidence higher in Ashkenazi Jews • Incidence is slightly higher in females than males • Vast majority diagnosed between ages 15-40 All Rights Reserved by M Sufian1/13/2012 5 email@example.com
Pathophysiology • Still under investigation • ? Defect in function of the intestinal immune system (breakdown in defense barrier) • Exposure of mucosa to microorganisms results in inflammatory process causing ulceration, bleeding and loss of fluids and electrolytes • ? Genetic predisposition (esp. when ileal disease involved) All Rights Reserved by M Sufian1/13/2012 6 firstname.lastname@example.org
Pathophysiology(Cont’d) All Rights Reserved by M Sufian1/13/2012 7 email@example.com
Pathophysiology(Cont’d) Pathophysiology in Crohns disease vs. ulcerative colitis Crohns disease Ulcerative colitis Autoimmune Widely regarded as disease an autoimmune No consensus disease Cyypkine Associated with Vaguely associated response Th17 with Th2 All Rights Reserved by M Sufian1/13/2012 8 firstname.lastname@example.org
Diagnostic: Symptoms Symptoms in Crohns disease vs. ulcerative colitis Crohns disease Ulcerative colitis Often porridge-like, Often mucus-like Defecation sometimes steatorrhea and with blood Tenesmus Less common More common Fever Common Indicates severe disease Fistulae Common Seldom Weight loss Often More seldom All Rights Reserved by M Sufian1/13/2012 9 email@example.com
Diagnostic: Signs Findings in diagnostic workup in Crohns disease vs. ulcerative colitis Sign Crohns disease Ulcerative colitis Terminal ileum involvement Commonly Seldom Colon involvement Usually Always Rectum involvement Seldom Usually Involvement around Common Seldom the anus No increase in rate of primary Bile duct involvement Higher rate sclerosing cholangitis All Rights Reserved by M Sufian1/13/2012 10 firstname.lastname@example.org
Diagnostic: Signs Findings in diagnostic workup in Crohns disease vs. ulcerative colitis Sign Crohns disease Ulcerative colitis Patchy areas of inflammation Continuous area of Distribution of Disease (Skip lesions) inflammation Deep geographic and Endoscopy Continuous ulcer serpiginous (snake-like) ulcers May be transmural, deep into Depth of inflammation Shallow, mucosal tissues Stenosis Common Seldom May have non- necrotizing Non-peri-intestinal crypt Granulomas on biopsy non-peri- intestinal crypt granulomas not seen granulomas All Rights Reserved by M Sufian1/13/2012 11 email@example.com
Ulcerative colitis vs. Crohn’s • Rectal bleeding common • Occasional rectal bleeding • Abdominal pain uncommon • Abdominal pain common • Rectal involvement almost 100% • Rectal involvement 50% • Fistula formation rare • Fistula formation common • Stricture & obstruction rare • Stricture and obstruction common • Perirectal, perianal abscesses • Perirectal, perianal abscesses uncommon common • Continuous involvement • Discontinuous involvement • Mucosa & submucosa involved • Transmural • Small bowel not involved (*) • Small bowel often involved • Risk of malignancy greatly • Risk of malignancy increased increased All Rights Reserved by M Sufian1/13/2012 23 firstname.lastname@example.org
Treatment Management in Crohns disease vs. ulcerative colitis Crohn’s disease Ulcerative colitis Mesalazine less useful More useful Antibiotics Effective in long-term Generally not useful Often returns following Usually cured by Surgery removal of affected part removal of colon All Rights Reserved by M Sufian1/13/2012 45 email@example.com
Treatment (Medical) 1. Anti-inflammatory agents(aminosalicylates,corticosteroids) 2. Immunosuppressant 3. Antibiotics 4. TNF (Tumor Necrosis Factor) inhibitors 5. Anti-diarrheal agents 6. Antispasmodic agents 7. Supportive therapy ** 75% of ulcerative colitis patients respond well to medical management All Rights Reserved by M Sufian1/13/2012 46 firstname.lastname@example.org
1-Anti-inflammatories (aminosalicylates) • Sulfasalazine (Azulfidine)-combination of sulfapyradine (anti- bacterial) + 5-aminosalicylic acid (5-ASA) – Greatest effect on IBD; mainstay of outpatient medical treatment for mild-mod. active UC & CD – Originally used to treat rheumatoid arthritis – Possesses both anti-inflammatory & antibacterial properties – Partially absorbed in jejunum but remainder passes to colon – Therapeutic action of 5-ASA compounds: inhibition of prostaglandin & leukotriene synthesis, free radical scavenging, impairment of white cell adhesion and function, inhibition of cytokine synthesis – Watch for folate deficiency, abdominal discomfort & allergies to sulfa compounds All Rights Reserved by M Sufian1/13/2012 47 email@example.com
1-Anti-inflammatories (aminosalicylates) • Mesalamine group- Asacol, Pentasa, Rowasa – Coating 5-ASA with acrylic resins- permits drug delivery to distal bowel & colon – Effective for ileal & colon involvement – Rapid absorption – Enemas and suppositories – Fewer side effects than sulfasalazine – Olsalazine-delayed absorption;useful in colonic disease All Rights Reserved by M Sufian1/13/2012 48 firstname.lastname@example.org
1-Anti-inflammatories (corticosteroids) • Treatment of choice for acute attack IBD (including IV treatment; enemas for acute proctitis) • Generally used for moderate-severe IBD • Not to be used for maintaining remission due to multiple & severe side effects * • Prednisone-synthetic glucocorticoid;powerful anti-inflammatory action – Usually tapered doses – IV use- methylprednisolone, dexamethasone • Budesonide (Entocort EC)- newer type – Synthetic steroid coated with ethylmethylcellulose which delays its release until ileum & descending colon • **Side effects often outweigh benefits if used for prolonged period of time All Rights Reserved by M Sufian1/13/2012 49 email@example.com
2-Immunosuppressants • Reduce inflammation by suppressing immune system’s response (which might damage digestive tissue) to invading virus or bacterium • Azathioprine (Imuran) & mercaptopurine (6-MP, Purinethol) – help reduce signs and sx of IBD and heal fistulas from CD – inhibits mitosis – Increases risk of neoplasia – Serious hepatic, renal, & hematological side effects All Rights Reserved by M Sufian1/13/2012 50 firstname.lastname@example.org
2-Immunosuppressants • Methotrexate (Rheumatrex)- used for patients who do not respond to other medications • Cyclosporine (Neoral, Sandimmune)- administered IV for CD with fistulas All Rights Reserved by M Sufian1/13/2012 51 email@example.com
3-Antibiotics • IBD is associated with frequent bacterial infections especially with toxic megacolon, fistulas and fulminant disease • Most effective antibiotics: metronidazole (Flagyl), ampicillin, cephalosporins, amonioglyco sides, ciprofloxacin (Cipro) All Rights Reserved by M Sufian1/13/2012 52 firstname.lastname@example.org
4-TNF (tumor necrosis factor) inhibitors • TNF is a protein produced by immune system; chemical messenger that can cause inflammation & tissue damage • Etanercept (Enbrel) – TNF receptor blocker; binds to alpha & beta TNF – Used to treat RA; not yet FDA approved for treating Crohn’s All Rights Reserved by M Sufian1/13/2012 53 email@example.com
4-TNF Inhibitors • Infliximab (Remicade)- neutralizes cytokine TNF alpha – Increased risk infections (reactivation of TB or granulomatous disease) – Usually for moderate-severe disease – May be used for long-term therapy All Rights Reserved by M Sufian1/13/2012 54 firstname.lastname@example.org
5-Antidiarrheal agents • Decrease peristalsis & therefore intestinal motility • Improves diarrhea& prevents loss of fluid & electrolytes • Loperamide (Imodium), Atropine (Lomotil) • Cholestyramine (Questran)- inhibits enterohepatic reuptake of bile salts All Rights Reserved by M Sufian1/13/2012 55 email@example.com
5-Antispasmodic agents • Treat functional disturbances of GI motility • Dicyclomine (Bentyl)- anticholinergic; blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle & CNS All Rights Reserved by M Sufian1/13/2012 56 firstname.lastname@example.org
6-Supportive therapy • (In addition to adequate nutritional support) – Vitamin B12 – Iron – Folic acid All Rights Reserved by M Sufian1/13/2012 57 email@example.com
Surgical Treatment • **Surgical removal of large bowel (colectomy) will result in cure for ulcerative colitis • Not the case for Crohn’s; surgical removal of the affected bowel segment in CD will not prevent the later appearance of disease at an adjacent or distant site All Rights Reserved by M Sufian1/13/2012 58 firstname.lastname@example.org
Surgical Treatment (Ulcerative Colitis) • Main indications: failure of medical treatment, complications (toxic megacolon, perforation) and risk of malignancy • Resection of colon & rectum (panproctocolectomy) is curative – Fecal diversion via ileostomy or ileo-anal anastomosis in form of ileal pouch • Pouch may cause mechanical problems (40% develop inflammation resembling UC, 15% may need further surgery) All Rights Reserved by M Sufian1/13/2012 59 email@example.com
Surgical Treatment (Ulcerative Colitis) • 10% will have colectomy during 1st year of dx – 4% will have surgery during 2nd year – 1 % annually in subsequent years – Extent of colitis at diagnosis affects need for subsequent surgery (colectomy rate for patients with pancolitis is 32%) All Rights Reserved by M Sufian1/13/2012 60 firstname.lastname@example.org
Surgical Treatment (Crohn’s Disease) • Limited to dealing with complications such as stricture formation, perforation and fistulae • 30% need surgery within 1st year • For the remainder, surgery rate is 5% per year • Following resection, 30% will require further surgery within 5 years, & 50% within 10 years • Complications are frequent; least invasive procedures desirable All Rights Reserved by M Sufian1/13/2012 61 email@example.com
Underwriting IBD: Mild Ulcerative Colitis Distal or rectal involvement only • 5 or fewer stools/day • Tx with retention enemas or oral anti- inflammatory meds • No systemic or extracolonic manifestations All Rights Reserved by M Sufian1/13/2012 62 firstname.lastname@example.org
Moderate Ulcerative Colitis • No currently active pancolitis • No serious complications • No worse than mild anemia • Treatment may require intermittent use of oral steroids or other cytotoxic drugs All Rights Reserved by M Sufian1/13/2012 63 email@example.com
Severe Ulcerative Colitis • Active pancolitis with frequent diarrhea, abdominal pain • Severe & typical systemic findings • Weight loss > 10% of body weight • Lab results reveal moderate-severe anemia and/or hypoalbuminemia • Recent (w/in 5 yrs) toxic megacolon or multiple surgeries • Treatment requires high doses of steroids or multiple cytotoxic medications All Rights Reserved by M Sufian1/13/2012 64 firstname.lastname@example.org
Other considerations (UC) • Cirrhosis or sclerosing cholangitis (documented or suspected) • Alkaline phosphatase or LFT elevations w/out liver biopsy or work-up • Fatty liver or pericholangitis confirmed by liver biopsy + significant LFT elevations • (Postpone?) Recent diagnosis • (Postpone?) 0-6 months following surgery All Rights Reserved by M Sufian1/13/2012 65 email@example.com
Underwriting IBD (Mild Crohn’s Disease) • Use of anti-diarrheal meds, no antibiotic or immunosuppressive therapy • Near normal bowel habits • Infrequent attacks • No anemia, normal sed rate All Rights Reserved by M Sufian1/13/2012 66 firstname.lastname@example.org
Moderate Crohn’s Disease • Medications needed to control symptoms (ie, Flagyl, Asacol, Azulfidine) • Limited disease • No more than 2 surgeries • Sed rate up to 2x normal All Rights Reserved by M Sufian1/13/2012 67 email@example.com
Severe Crohn’s Disease • Multiple (3 or more) surgeries • Multiple medications including oral steroids, immunosuppressants, TNF inhibitors • Extensive disease • Anemia, elevated sed rate • Weight loss (> 10% body weight) All Rights Reserved by M Sufian1/13/2012 68 firstname.lastname@example.org
Crohn’s Disease- Favorable factors • Normal CBC • Ileal involvement only • Stable weight • Non-steroidal meds only • Colonoscopies every 12-24 months • Older age All Rights Reserved by M Sufian1/13/2012 69 email@example.com
Crohn’s Disease- Unfavorable Factors • Low blood counts on CBC • Multiple sites in GI tract • Low and/or fluctuating weight • Steroid use • Surgical intervention (multiple) • Poor follow-up/compliance All Rights Reserved by M Sufian1/13/2012 70 firstname.lastname@example.org
Crohn’s Disease – other consideratons • Cirrhosis or sclerosing cholangitis (documented or suspected) • Alkaline phosphatase or LFT elevations w/out liver biopsy or work-up • Fatty liver or pericholangitis confirmed by liver biopsy + significant LFT elevations • Consider postponing if recent diagnosis (0-1 year since dx) • (Postpone?) If CD diagnosed > 10 yrs ago (w/colonic involvement) and there is no recent colonoscopy • (Postpone?) Colonoscopy/biopsy shows any degree of dysplasia All Rights Reserved by M Sufian1/13/2012 71 email@example.com
Questions? All Rights Reserved by M Sufian1/13/2012 72 firstname.lastname@example.org
References 1. ^ Baumgart DC, Carding SR (2007). "Inflammatory bowel disease: cause and immunobiology.". The Lancet 369 (9573): 1627–40. doi:10.1016/S0140-6736(07)60750-8. PMID 17499605. 2. ^ a b Baumgart DC, Sandborn WJ (2007). "Inflammatory bowel disease: clinical aspects and established and evolving therapies.". The Lancet 369 (9573): 1641–57. doi:10.1016/S0140-6736(07)60751-X. PMID 17499606. 3. ^ Xavier RJ, Podolsky DK (2007). "Unravelling the pathogenesis of inflammatory bowel disease.". Nature 448 (7152): 427–34. doi:10.1038/nature06005. PMID 17653185. 4. ^ "Crohns & Colitis Foundation of America". 5. ^ Elson, CO; Cong, Y; Weaver, CT; Schoeb, TR; Mcclanahan, TK; Fick, RB; Kastelein, RA (2007). "Monoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice". Gastroenterology 132 (7): 2359. doi:10.1053/j.gastro.2007.03.104. PMID 17570211. 6. ^ a b c d e f internetmedicin.se > Inflammatorisk tarmsjukdom, kronisk, IBD By Robert Löfberg. Retrieved Oct 2010 Translate. 7. ^ a b c d Hanauer, Stephen B.; William Sandborn (2001-03-01). "Management of Crohns disease in adults" (PDF). American Journal of Gastroenterology 96 (3): 635–43. doi:10.1111/j.1572-0241.2001.03671.x. PMID 11280528. Retrieved 2009-11-07. 8. ^ a b c Kornbluth, Asher; David B. Sachar (July 2004). "Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee" (PDF). American Journal of Gastroenterology 99 (7): 1371–85. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Archived from the original on April 6, 2008. Retrieved 2009-11-07. 9. ^ Broomé, Ulrika; Annika Bergquist (February 2006). "Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer". Seminars in Liver Disease 26 (1): 31–41. doi:10.1055/s-2006-933561. PMID 16496231. 10. ^ Shepherd, NA. (August 2002). "Granulomas in the diagnosis of intestinal Crohns disease: a myth exploded?". Histopathology 41 (2): 166–8. doi:10.1046/j.1365-2559.2002.01441.x. PMID 12147095. 11. ^ Mahadeva, U.; Martin, JP.; Patel, NK.; Price, AB. (July 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohns disease from ulcerative colitis.". Histopathology 41 (1): 50–5. doi:10.1046/j.1365- 2559.2002.01416.x. PMID 12121237. 12. ^ a b c Pages 152-156 (Section: Inflammatory bowel disease(IBD)) in:Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6. All Rights Reserved by M Sufian1/13/2012 73 email@example.com
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