What’s So Special about Pediatric IBD ?

1. What’s So Special about Pediatric IBD ? David Tuchman, MD Division of Pediatric Gastroenterology and Nutrition Herman and Walter Samuelson Children’s Hospital at Sinai CSGNA Fall Educational Program November 8, 2014

2. Educational Objectives • Review the different types of IBD • Discuss etiology of IBD • Learn the differences between Pediatric IBD and Adult IBD • Learn the effects of IBD on growth and development • Discuss the effects of IBD on bone development • Learn about the transition of care in IBD

3. Inflammatory Bowel Disease (IBD) • IBD is an term for a group of diseases which Crohn’s disease and Ulcerative colitis • Chronic, debilitating conditions • Distinctly different diseases but are grouped together as IBD • Produce similar signs and symptoms • Intestinal inflammation, abdominal pain and diarrhea

4. IBD – Type and Anatomic Distribution

5. IBD – Facts and Figures • Health care costs: $1.7 billion dollars annually • 1.4 million Americans have been diagnosed with IBD • About 10% of these individuals are children and adolescents under the age of 17 years • Peak age incidence is between 15 and 25 years

6. IBD in Children • Impact on children • 25% of IBD occurs in childhood • Incidence and prevalence • 1.4 million people in the US have IBD • Crohns disease is diagnosed in 5000 children each year • It is estimated that 50,000 – 100,000 children have IBD NASPGHAN 2nd Edition

7. Burril Crohn, Leon Ginzburg and Gordon Oppenhiemer Regional ileitis. Journal of American Medical Association (October 1932) • … to describe, in pathologic and clinical details, a disease of the terminal ileum, affecting mainly young adults, characterized by subacute or chronic necrotizing and cicatrizing inflammation. The ulceration of the mucosa is accompanied by a disproportionate connective tissue reaction of the remaining walls of the involved intestine… (which) leads to stenosis … with formation of multiple fistulas. Aufses, Surgical Clinics of North America, 2001; 81(1) Feb 2001.

8. IBD Presentation

9. Crohns Disease vs. Ulcerative Colitis

10. IBD – Diagnostic Approach • Suspect diagnosis • History (“red flags”), Family History • Labs: • Iron deficiency anemia, elevated ESR, CRP, low serum albumin • Exclude other etiologies • Stools studies • Enteric pathogens, C. difficile, amebiasis, TB skin test • Classify disease • Crohns, UC • Determine extent of disease – “stage” the disease • Evaluate for extra-intestinal manifestations • Evaluate growth and development

11. Laboratory Studies in the Initial Evaluation for IBD • CBC with differential • ESR/CRP • Comprehensive Metabolic Panel • Serum albumin • Liver chemistries • Stool studies • Enteric pathogens • Fecal calprotectin • Stool for occult blood

12. Imaging Studies • Upper GI series and small bowel follow through • Abdominal and pelvic CT scan • Magnetic Resonance Imaging

14. Imaging Studies in IBD MR enterography Abdominal CT Scan

15. Endoscopic appearance of normal terminal ileum and colon Terminal Ileum Colon Normal vascular pattern No friability Smooth and shiny Normal folds Smooth and shiny Villi seen Lymphoid follicles (Peyer’s patches)

16. Endoscopic Appearance of Crohns Disease • Deep fissures • Cobblestoning • Segmental distribution • Relative rectal sparing • Terminal ileal involvement • Granulomas on biopsy

17. Endoscopic Appearance of Ulcerative Colitis • Loss of vascular pattern • Granularity • Exudates • Diffuse continuous disease • No ileal involvement

18. IBD Histology

19. IBD – Perianal Disease • Perianal abscesses, fistulae and fissures • Perianal disease is noted in about 10 % of children with newly diagnosed Crohn’s disease 1 1 Keljo et al. Inflamm Bowel Dis. 2009;15 :383-387.

20. IBD - Extraintestinal Manifestations Eye UVEITIS EPISCLERITIS

21. IBD - Extraintestinal Manifestations Skin Erythema Nodosum Pyoderma Gangrenosum

22. IBD - Extraintestinal Manifestations Hepatobiliary Disease Oral Disease

23. Inflammatory Bowel Disease • Etiology – Unknown • IBD occurs in genetically susceptible individuals whose immune systems react abnormally to environmental agents in the gastrointestinal tract

24. Pathogenesis of IBD - Multifactorial IBD

25. Nature Reviews Immunology 8, 458-466 (June 2008)

27. IBD - Genetics • High degree of concordance among monozygotic twins • Increased susceptibility to IBD among first- or second-degree relatives of affected individuals • Linkage between IBD and several genomic regions • Several mutations/single-nuceotide polymorphisms (SNPs) have been found to be associated with increased susceptibility to IBD • Age of onset: younger the onset, more likely a family history of IBD Bousvaros et. Inflamm Bowel Dis 2006; 12(9), 885- 913

28. Pediatric IBD • Severity of Disease • Growth (Weight and height gain) • Sexual maturation • Health Supervision • Psycho-social well being • Healthcare Provider Transitioning

29. Children with IBD are not just small adults with IBD • Adolescents with IBD have more extensive involvement • 69% of adolescents present with ileo-colonic disease vs. 28% of adults1 • 23% of adolescents with Crohn’spresent with upper tract involvement – uncommon in adults1 • Adolescents more likely to have ulcerative pancolitis compared to adults (67 % vs. 44%)1 • Childhood-onset Crohn’s – more extensive involvement than than adult- onset Crohns (43% vs. 3%)2 1Goodhand et al. Inflammatory Bowel Disease 2010:16:947-952 2 VanLimbergen et al. Gastroenterology 2008;135:1114-1122 Abraham and Kahn Gastro and Hepatol 2014;10:633-640

30. “Idiopathic “ IBD is rare in the young child Bousvaros Boston Children’s Hospital Symposium 2014

31. IBD in Younger Children (< 5 years) • Chronic granulomatous disease • Glycogen storage disease 1b • Hermansky – Pudlak syndrome • NEMO • Wiskott-Aldrich syndrome • IPEX • Hyper IgM syndrome • Common Variable Immune Deficiency Bousvaros Boston Children’s Hospital Symposium 2014

32. IBD in young children • Immunodeficienciesfrequently involve the gi tract and have IBD like symptoms • Most idiopathic IBD in children under the age of 5 years involves the colon • Caution using immunosuppression in patients with immune deficiency • Optimal treatment is determined after multidisciplinary consultation • www.neopics.org Bousvaros Boston Children’s Hospital Symposium 2014

33. Growth Failure • Definition • Height < 5th percentile • Decrease in height velocity below 5th percentile • Fall off of the child’s growth curve • Higher incidence at diagnosis in CD vs. UC • Corticosteroids • Inadequate calorie intake • Malabsorption • Increased energy expenditure from chronic inflammation – Pro-inflammatory cytokines, decreased IGF -1 Sawczenko et al Pediatrics 2006;118:124-9 Tigas et al J Pediatr Gastroenterol Nutr 1993;16:373-80 Kocoshis - Presention

34. Growth Failure in IBD Kirschner in Kirsner, ed. IBD 5th ed. 2000 NASPGHAN

36. Growth Failure in Pediatric IBD Suboptimal intake of calories Increased energy needs Malabsorption of nutrients Increased GI losses Malnutrition Growth Failure Corticosteroids Inflammation

37. Growth Problems in Children with IBD • Increased cytokines act on • Brain affecting appetite and calorie intake • Hepatic expression of IGF 1 • Act on chondrocytes of the growth plate of the long • Growth hormone insensitiviy Sanderson Nature Reviews Gastroenterology & Hepatology11, 601–610 (2014)

38. Growth Velocity Curves

40. Evaluating Growth

41. IBD Treatment Goals • Maximize therapeutic response • Maximize adherence • Minimize toxicity • Improve quality of life • Promote physical growth and pubertal development • Promote psychological growth • Prevent disease complications NASPHGAN slide set

42. IBD – Treatment Approach • Follow up appointment very soon after procedure • Stress that IBD is not rare • Famous people with IBD • President Eisenhower • Review the proposed etiologies • State what IBD is not • allergy, stress, diet • What are the limits? • None, except sky diving and bungee jumping • Introduce the team • Provide literature – CCFA, NASPGHAN

43. Treatment of Crohn’s Disease • Mild to moderate CD • Aminosalicylates • Topical and oral • Antibiotics • Enteral feeds • Corticosteroids • Budesonide • Prednisone • Moderate to severe CD • Enteral feeds (induction) • Corticosteroids (induction) • Budesonide vs. prednisone • Immunomodulators (maintenance) • 6-mercaptopurine • Azathioprine • Methotrexate • Biologics (Induction and maintenance) • Infliximab • Adalimumab • Certolizumab

44. Aminosalicylates (Different formulations)

46. Crohn’s Disease – Antibiotic Therapy • Effect on luminal bacterial concentrations and subsequent down regulation of the local inflammatory response • Selectively eliminate bacterial subsets • Bacterial tissue invasion and microabscess formation • Bacterial translocation and systemic dissemination Sartor; Gastroenterology 2004; 126:1620-1633

47. Enteral Nutrition – IBD • Improves nutrition for all IBD • Effective therapy for pediatric Crohn’s • UC – not shown to be effective • 80-100% calories by formula • NG tube vs. oral • Proposed mechanism - Modulatoin of intestinal bacteria Baldassano and Kim

50. IBD and Corticosteroid Therapy • Steroids are rarely used as monotherapy • If clinical response to initial therapy is inadequate, add corticosteroids early • Steroids are not maintenance drugs • Many side effects including growth impairment But, use of steroids can “get you out of trouble quickly”