Inflammatory bowel disease - Hiren Chatrola

1. Pediatric Crohn’s diseases Hiren Chatrola

2. 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

3. IBD – Type and Anatomic Distribution

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

5. • … 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.

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

7. Pathogenesis of IBD - Multifactorial IBD

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

10. 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’s present 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 1 Goodhand 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

11. IBD inYounger Children (< 5 years) • Chronic granulomatous disease • Glycogen storage disease 1b • Hermansky – Pudlak syndrome • Wiskott-Aldrich syndrome • Hyper IgM syndrome • CommonVariable Immune Deficiency Bousvaros Boston Children’s Hospital Symposium 2014

12. IBD Presentation Symptom/Sign Crohns Disease Ulcerative Colitis Abdominal Pain ++ ++++ Diarrhea ++++ +++ Rectal bleeding ++ ++++ Weight loss ++++ ++ Growth Failure +++ + Perianal disease ++ Mouth ulcers ++ + Fever + + Erythema nodosum ++ + Anemia +++ +++

13. Crohns Disease vs. Ulcerative Colitis Crohns Disease Ulcerative Colitis Any portion of GI tract Colon only Skip areas Continuous Rectal Sparing No rectal sparing Non-caseating granulomas No granulomas Transmural inflammation Mucosal inflammation Fistulae and abscesses Abscesses rare Stictures commom Strictures rare Ileum and cecum commonly involved Perianal disease

14. 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

15. 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

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

18. Imaging Studies in IBD MR enterography Abdominal CT Scan

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

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

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

22. IBD Histology

23. 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.

24. IBD - Extraintestinal Manifestations Eye UVEITIS EPISCLERITIS

25. IBD - Extraintestinal Manifestations Skin Pyoderma GangrenosumErythema Nodosum

26. IBD - Extraintestinal Manifestations Hepatobiliary Disease Oral Disease

27. 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 • Inadequate calorie intake • Malabsorption • Increased energy expenditure from chronic inflammation – Pro- inflammatory cytokines, decreased IGF -1

28. Growth Failure in IBD Patients Occurrence (%) Pediatric IBD 35 Prepubertal CD 60-85 Children with UC 6-12 Kirschner in Kirsner, ed. IBD 5th ed. 2000 NASPGHAN

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

31. 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 & Hepatology 11, 601–610 (2014)

32. IBDTreatment 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

33. Treatment of Crohn’s Disease • Mild to moderate CD • Aminosalicylates • 400 mg PO 2t/d (6 weeks) • Enteral feeds • Corticosteroids • Budesonide 4 mg PO • Prednisone 0.5-2 mg/kg/d

34. • Moderate to severe CD –Enteral feeds (induction) –Corticosteroids (induction) • Budesonide vs. prednisone –Immunomodulators (maintenance) • 6-mercaptopurine 1.25-2.5 mg/kg • Azathioprine 1 mg/kg/day PO • Methotrexate 10 mg/m² PO/IM/SC –Biologics (Induction and maintenance) • Infliximab 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks • Adalimumab Induction: 80 mg SC on Day 1 (administer as two 40 mg injections in one day); THEN 2 weeks later (Day 15) give 40 mg Maintenance (beginning Week 4 [Day 29]): 20 mg SC q2wk

36. IBD and CorticosteroidTherapy • 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

37. Immunomodulators and IBD • 6 MP, Azathioprine, Methotrexate • Closely monitor CBC and LFT • Other adverse effects: • Pancreatitis • Increased risk of lymphoma • Slight increased risk for EBV associated lymphoma • Minimal if any risk of non-Hodgkin’s lymphoma

39. Nutritional Complications of IBD • Osteopenia and osteoporosis (Vit D and Calcium supplements should be given) • Anemia • Micronutrient deficiencies • Iron • Folate • B12 • Zinc

40. Thanks

Inflammatory bowel disease - Hiren Chatrola

Inflammatory bowel disease - Hiren Chatrola

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