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  • 1. Inflammatory Bowel Disease Francisco A. Sylvester, MD Associate Professor of Pediatrics
  • 2. Goals - IBD
    • Definitions: Crohn disease – ulcerative colitis
    • Epidemiology
    • Pathophysiology - Genetics
    • Diagnosis
    • Treatment
  • 3. Definitions Crohn disease – Ulcerative colitis
  • 4. Normal colon
  • 5. IBD - Colon Crohn Disease Ulcerative Colitis
  • 6. IBD – Disease Location http://www.hopkins-gi.org/ Crohn disease Ulcerative colitis
  • 7. Distribution of Crohn Disease http://www.hopkins-gi.org/
  • 8. Types of Crohn Disease http://www.hopkins-gi.org/
  • 9. Diagnostic Certainty Crohn Disease Ulcerative Colitis IBD-U
  • 10. Dr. Burrill B. Crohn (1884-1983)
  • 11. Epidemiology
    • ~1.4 million Americans have IBD
    • Mean age at diagnosis ~30 years of age
    • 25% diagnosed as children
    • M = F (in children with Crohn M > F)
    • At CCMC: ~80-90 new patients/year
  • 12. Crohn’s Disease Ulcerative Colitis Ulcerative Colitis (< 20 years of age) Appendicitis - Appendectomy Smoking Crohn’s Disease
  • 13. North-To-South Gradient
  • 14. Pathophysiology
  • 15.  
  • 16. Intestinal Flora Stomach 0-10² Duodenum 10² Distal Ileum 10 7 - 10 8 Colon 10 11 - 10 12 Jejunum 10² Proximal Ileum 10 3 Sartor B. Gastroenterology 2008;134:577-94 * *
  • 17. “ Our” DNA 90% Bacterial 10% Human
  • 18. So, Why Doesn’t Everybody Have IBD ?
  • 19. Microbial Molecular Patterns Muramyl dipeptide (MDP) Flagellins Bacterial DNA Lipopolysaccharide (LPS)
  • 20. Intestine: Steady State ~ ~ ~ ~ ~ ~ ~ ~ Microbes DC Intestinal Lumen T cells Intact Epithelial Cell Barrier ~ MLN Treg Intestinal LP ~ ~ Blood M Cells ~ ~
  • 21. “ Controlled Inflammation”
  • 22. ~ ~ ~ ~ ~ ~ ~ ~ ~ Microbes Activated T cells Cytokines/Chemokines DC Intestinal Lumen T cells Damage to Epithelial Cell Barrier Microbial Invasion ~ ~ ~ ~ Intestinal Inflammation Intestinal LP ~
  • 23. http://www.randymays.com/Rugersr9-1.jpg
  • 24. IBD - Genetics
    • NOD2/CARD15 (chromosome 16q12)
      • 20-40-X risk in individuals carrying 2 abnormal alleles
      • Ileal Crohn disease
      • Stricturing – penetrating
      • Caucasians only
  • 25. IBD - Genetics
    • GWAS
      • ATG16L1 (Crohn disease)
      • IL-23R (Crohn disease and ulcerative colitis)
      • IL-23/Th17 pathway
      • > 30 novel loci
  • 26. What is Changing? Genes vs. Jeans?
  • 27. Environmental Factors
    • Microbial Ecology
      • Hygiene (Parasites )
      • Antibiotics
      • Refrigeration
      • Diet
      • Vaccines
    • Tobacco
    • North-to-south gradient
      • Vitamin D deficiency?
  • 28. Pathophysiology - IBD
    • Genetic predisposition
    • Defective innate immunity
    • Hyperactivation of effector cells
    • Microbial ecology alterations
    • Environmental factors
  • 29. Genes Environment Microbiota
  • 30. Diagnosis
    • History – Physical Exam
    • Laboratory
      • CBC, ESR, CRP, albumin
      • Stool culture
      • Serology (antibodies to PAMPs)
    • Endoscopy
    • Imaging
  • 31. Extraintestinal Manifestations
    • Skin
    • Mouth
    • Joints
    • Bone
    • Liver
    • Hypercoagulability
    • Kidney
    • Eye
    • Present in ~50% patients
    • 25% patients may have more than one
    • May be presenting symptom!
  • 32. Growth Failure – Pediatric IBD
  • 33. Complications
    • Intra-abdominal sepsis (Crohn disease)
    • Fecal incontinence
    • Short gut syndrome (Crohn disease)
    • Colon cancer
    • Infertility
    • Medication adverse effects (infection, cancer)
  • 34. Arrow shows narrowing of the distal ileum
  • 35. Arrow shows a phlegmon
  • 36. Step Up vs. Top Down Mesalamine (5-ASA)/ Corticosteroids AZA/6-MP CD: MTX Biologics Steroids/ 5_ASA AZA/6-MP CD: MTX Biologics Crohn disease: Nutritional therapy
  • 37. Challenges for School-Aged Children
    • School absences
    • Bathroom needs
    • Psychosocial issues
      • Self-perception and self-esteem
      • Peer relationships
    • Special diets (nutritional therapy)