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INFLAMMATORY BOWEL DISEASE

INFLAMMATORY BOWEL DISEASE. Norman H. Gilinsky, M.D., FACP, FACG Associate Professor of Medicine Medical Director, Digestive Diseases Center University of Cincinnati. Objectives At completion of this lecture, the student will be able to:.

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INFLAMMATORY BOWEL DISEASE

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  1. INFLAMMATORY BOWEL DISEASE Norman H. Gilinsky, M.D., FACP, FACG Associate Professor of Medicine Medical Director, Digestive Diseases Center University of Cincinnati

  2. ObjectivesAt completion of this lecture, the student will be able to: • Describe the main manifestations of each of the inflammatory bowel disorders • State the main clinical features that differentiate Crohn’s disease from ulcerative colitis • Formulate a management plan for diagnosis of disease extent and severity of each disorder • Develop a strategy to treat each disease • Differentiate treatment modalities that are more applicable to the management of Crohn’s disease than ulcerative colitis

  3. Inflammatory Bowel DiseaseUlcerative Colitis and Crohn’s Disease Similarities • Chronic inflammation, usually limited to GIT • Majority young, therefore life-long disorder • Natural history: tends to relapse • Medications utilized generally similar Differences • Anatomic location and pathology (and therefore, presentation) • Nutritional consequences • Response to medical therapies • Surgical strategy, if required

  4. IBD: Location and Extent 5% Gastroduodenitis 40% Distal/ Left-sided colitis 30% Proctitis 25% Colitis 40% Ileocolitis 30% Ileitis 30% Extensive/ Pancolitis Ulcerative Colitis Crohn’s Disease

  5. IBD: PATHOGENESIS Chromosome 16 (IBD1) Chromosome 12 (IBD2) Chromosome 6 (IBD3-HLA) Chromosome 14 NOD2 Genetic susceptibility IBD Infection Diet Smoking NSAIDs Immune dysregulation Environmental trigger TH 1 TH 2 Ahmad et al, Aliment Pharmacol Ther 2001; Hugot et al, Science 2001

  6. Inflammatory Bowel DiseaseExtra-Intestinal Manifestations Joints • Peripheral arthritis • Ankylosing spondylitis, sacroileitis Skin • Pyoderma gangrenosum, Erythema nodosum Eyes • Episcleritis, uveitis, keratoconjunctivitis Biliary • Sclerosing cholangitis,cholangiocarcinoma Other • Hypercoagulability

  7. Ulcerative Colitis – Clinical Features Presents with bloody diarrhea • Majority have limited left-sided disease • Majority consitutionally well • Majority safely managed in office setting • Profuse bloody diarrhea; >6 stools/day • Weight loss, anemia, hypoalbuminemia • Fever, abdominal pain, distension Red Flags

  8. Ulcerative Colitis: Differential Diagnosis Infection • Salmonella, shigella, campylobacter, amebiasis, etc. Ischemia Radiation Vasculitis Medications Toxins Practice Point: Consider clinical setting, stool studies

  9. Ulcerative Colitis: Consequences of Disease Acute • Fluid, electrolyte disturbance • Anemia • Fulminant colitis, toxic megacolon, perforation Chronic • Related to chronic disease, treatment • Related to extra-intestinal manifestations • Cancer

  10. Colorectal Cancer in IBD • Increased risk associated with: • Duration of disease • Anatomic extent of disease • Cancers develop in a dysplasia-to-cancer sequence • Cancers often flat, multiple, at advanced stage. Practice Point: Colonoscopy with biopsy necessary for periodic cancer surveillance in patients with IBD.

  11. Ulcerative Colitis - Diagnostic Work-Up • Clinical suspicion • Stool studies • Endoscopy (with biopsy) • (Radiology) • Hematology and biochemistry (especially if clinically severe – i.e. CBC, albumin, electrolytes) • Serologies (if uncertainties remain, e.g. amebiasis; specific IBD serologies experimental)

  12. IBD: Treatment Modalities 5-Aminosalicylic Acid [sulfasalazine, mesalamine] Administered topically PO and/or PR Corticosteroids Administered PO, PR or IV Immunomodulation [6-MP, Azothioprine, Cyclosporine, etc] Surgery

  13. Inflammatory Bowel DiseaseSulfasalazine / 5-Aminosalicylates • Ulcerative colitis • Induction therapy in mild to moderate disease (anticipate about 80% response) • Maintenance therapy, to reduce chances of relapse, once remission obtained • Crohn’s disease • Data not convincing • Best effects with high doses and for ileal disease • Balsalazide

  14. Inflammatory Bowel DiseaseSulfasalazine / 5-Aminosalicylates 5-ASA-diazo bond-sulfapyradine • Action • Topical / mucosal anti-inflammatory • Side-effects • Intolerance [gastric distress, headache] • Allergy • Cytopenias, hemolysis, folate deficiency • Nephritis, hepatitis • Pneumonitis, pancreatitis • Hypospermia • Balsalazide

  15. Inflammatory Bowel DiseaseMesalamine (5-ASA preparations) • Route of administration • Oral • Enema • Suppository • Side-effect profile • Less intolerance • No hypospermia, folate deficiency • Efficacy • No better (than sulfasalazine) for colitis • Cost • More expensive • Balsalazide

  16. Inflammatory Bowel DiseaseRole of Corticosteroids • Good drug for controlling acute flare (available oral, rectal or IV – use depending on disease location, clinical severity) • Of no value in maintenance situation • High frequency side-effects • Symptoms may flare with tapering • Steroid dependency common

  17. Inflammatory Bowel DiseaseRole of Immunosuppressive Agents 6-Mercaptopurine, azathioprine, methotrexate, cyclosporine • Steroid-sparing • Induces remission in majority • Speed of onset variable • Maintains remission • Useful in chronic grumbling disease, wish to avoid surgery, compliant patient • Requires periodic monitoring • Generally acceptable side-effect profile

  18. Inflammatory Bowel DiseaseManagement of Severe Colitis • Hospitalize, IV therapy • IV steroids, antibiotic cover • May require nutritional support • Rule out infection, megacolon • Frequent monitoring • Clinical condition, vitals • CBC, albumin • Radiology • Surgery if deteriorates, doesn’t settle • Concern = perforation, high relapse rate

  19. Crohn’s Disease: Main Characteristics (1) • Any or > 1 region of GIT involved (perianal, skip areas) • Colon spared in > 20% • Small bowel involved in > 60%; therefore predisposed to nutritional sequelae, malabsorption, metabolic disorders, trace element and vitamin deficiencies • Inflammation transmural, therefore efficiency of topical therapy limited

  20. Crohn’s Disease: Main Characteristics (2) • Disease pathology diverse • Inflammatory • Stricturing • Perforating • Presentation and outcome therefore diverse • No ‘cure’, therefore surgery (if required) limited to localized complications • Recurrences post-surgery not unusual

  21. Crohn’s Disease - Presentation Inflammatory • Pain, tenderness, diarrhea, RLQ mass Obstuction • Cramps, distension, vomiting, obstruction Fistulizing • Enererocutaneous, enteroenteric, rectovaginal, enterovesical, etc.

  22. Crohn’s Disease: Disease Consequences Constitutional • Fevers, weight loss, debilitation, pain Nutritional sequelae • Malabsorption, depletion syndromes • Growth retardation Perianal involvement • Abscess, fissure, fistula Other • Short-bowel syndrome • Renal calculi, gallstones • QOL, Psychologic

  23. Crohn’s Disease: Differential Diagnosis • Infectious etiologies • CMV, TB, Yersinia, C difficile, toxigenic E coli, etc. • Appendicitis • Diverticulitis • Ischemia • Carcinoma, lymphoma • Ulcerative colitis • Celiac disease Practice Point: Great mimicker

  24. Crohn’s Disease - Diagnostic Work-Up • Clinical suspicion • Stool studies • Endoscopy (with biopsy) • Radiology • Abdominal X-ray • Small bowel follow-through • CT scan, etc. • Hematology and biochemistry (especially if clinically severe – i.e. CBC, albumin, electrolytes) • Malabsorption • Serologies (specific IBD serologies experimental)

  25. Crohn’s Disease: Treatment Modalities 5-Aminosalicylic Acid Biologic Agents [Monoclonal antibodies – Infliximab] Antimicrobials Surgery Corticosteroids Nutritional Aspects Immunosuppressive Psychologic Support

  26. The future – Biologic Therapies? • Approved TNF- antibodies (infliximab, Remicade®) • Experimental • CDP-571 • Interleukin 10 • Gene therapies?

  27. Inflammatory Bowel DiseaseOther Issues for the Specialist and Primary Care Physician • Perineal / ano-rectal disease [CD] • Symptomatic fistula [CD] • Short bowel syndrome / nutritional support [CD] • The pediatric and adolescent patient • The pregnant patient • Bone disease • Work and Psychologic issues

  28. Panproctocolectomy Failure of medical therapy Dysplasia or carcinoma Debility, poor QOL Intolerant of medications Massive hemorrhage, perforation Intractable pyoderma, hemolysis Directed to specific complication Symptomatic obstruction Symptomatic fistulae Perforation Hemorrhage Dysplasia or carcinoma Perianal disease IBD: Indications for Surgery Ulcerative Colitis Crohn’s Disease

  29. IBD: Other Key References • Your Internal Medicine Textbook – plus: • Hanauer et al. Management of Crohn’s disease in adults. Am J Gastroenterol 2001; 96:634-43 • Kornbluth et al. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol 1996; 92:204-211 • Lichtenstein. Inflammatory bowel disease. Gastroenterol Clin N Am 1999; 28:2

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