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PPT

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  • 1. Inflammatory Bowel Disease Francisco A. Sylvester, MD Associate Professor of Pediatrics
  • 2. Goals - IBD <ul><li>Definitions: Crohn disease – ulcerative colitis </li></ul><ul><li>Epidemiology </li></ul><ul><li>Pathophysiology - Genetics </li></ul><ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul>
  • 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 <ul><li>~1.4 million Americans have IBD </li></ul><ul><li>Mean age at diagnosis ~30 years of age </li></ul><ul><li>25% diagnosed as children </li></ul><ul><li>M = F (in children with Crohn M &gt; F) </li></ul><ul><li>At CCMC: ~80-90 new patients/year </li></ul>
  • 12. Crohn’s Disease Ulcerative Colitis Ulcerative Colitis (&lt; 20 years of age) Appendicitis - Appendectomy Smoking Crohn’s Disease
  • 13. North-To-South Gradient
  • 14. Pathophysiology
  • 15. &nbsp;
  • 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 <ul><li>NOD2/CARD15 (chromosome 16q12) </li></ul><ul><ul><li>20-40-X risk in individuals carrying 2 abnormal alleles </li></ul></ul><ul><ul><li>Ileal Crohn disease </li></ul></ul><ul><ul><li>Stricturing – penetrating </li></ul></ul><ul><ul><li>Caucasians only </li></ul></ul>
  • 25. IBD - Genetics <ul><li>GWAS </li></ul><ul><ul><li>ATG16L1 (Crohn disease) </li></ul></ul><ul><ul><li>IL-23R (Crohn disease and ulcerative colitis) </li></ul></ul><ul><ul><li>IL-23/Th17 pathway </li></ul></ul><ul><ul><li>&gt; 30 novel loci </li></ul></ul>
  • 26. What is Changing? Genes vs. Jeans?
  • 27. Environmental Factors <ul><li>Microbial Ecology </li></ul><ul><ul><li>Hygiene (Parasites ) </li></ul></ul><ul><ul><li>Antibiotics </li></ul></ul><ul><ul><li>Refrigeration </li></ul></ul><ul><ul><li>Diet </li></ul></ul><ul><ul><li>Vaccines </li></ul></ul><ul><li>Tobacco </li></ul><ul><li>North-to-south gradient </li></ul><ul><ul><li>Vitamin D deficiency? </li></ul></ul>
  • 28. Pathophysiology - IBD <ul><li>Genetic predisposition </li></ul><ul><li>Defective innate immunity </li></ul><ul><li>Hyperactivation of effector cells </li></ul><ul><li>Microbial ecology alterations </li></ul><ul><li>Environmental factors </li></ul>
  • 29. Genes Environment Microbiota
  • 30. Diagnosis <ul><li>History – Physical Exam </li></ul><ul><li>Laboratory </li></ul><ul><ul><li>CBC, ESR, CRP, albumin </li></ul></ul><ul><ul><li>Stool culture </li></ul></ul><ul><ul><li>Serology (antibodies to PAMPs) </li></ul></ul><ul><li>Endoscopy </li></ul><ul><li>Imaging </li></ul>
  • 31. Extraintestinal Manifestations <ul><li>Skin </li></ul><ul><li>Mouth </li></ul><ul><li>Joints </li></ul><ul><li>Bone </li></ul><ul><li>Liver </li></ul><ul><li>Hypercoagulability </li></ul><ul><li>Kidney </li></ul><ul><li>Eye </li></ul><ul><li>Present in ~50% patients </li></ul><ul><li>25% patients may have more than one </li></ul><ul><li>May be presenting symptom! </li></ul>
  • 32. Growth Failure – Pediatric IBD
  • 33. Complications <ul><li>Intra-abdominal sepsis (Crohn disease) </li></ul><ul><li>Fecal incontinence </li></ul><ul><li>Short gut syndrome (Crohn disease) </li></ul><ul><li>Colon cancer </li></ul><ul><li>Infertility </li></ul><ul><li>Medication adverse effects (infection, cancer) </li></ul>
  • 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 <ul><li>School absences </li></ul><ul><li>Bathroom needs </li></ul><ul><li>Psychosocial issues </li></ul><ul><ul><li>Self-perception and self-esteem </li></ul></ul><ul><ul><li>Peer relationships </li></ul></ul><ul><li>Special diets (nutritional therapy) </li></ul>

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