PEDIATRIC INFLAMMATORY BOWEL DISEASE Alexis Rodriguez, MD - PDF document

4/6/18 PEDIATRIC INFLAMMATORY BOWEL DISEASE Alexis Rodriguez, MD Pediatric Gastroenterology Advocate Children’s Hospital Disclosers • Abbott Nutrition - Speaker Inflammatory Bowel Disease • Chronic inflammatory disease of the gastrointestinal tract ~ Can affect any area of GI tract • 2 Major Types: ~ Crohn’s Disease ~ Ulcerative Colitis • Other Types: ~ Indeterminate colitis ~ Very Early Onset (VEO-IBD) • Has relapsing and remitting course ~ Goal is to induce and stay in remission • Exact pathogenesis poorly understood 1

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4/6/18 Environmental Factors • Smoking is a risk factor for CD (OR = 1.76; 95% CI: 1.40-2.22) - Protective against UC • Appendectomy is a risk factor for CD - Protective against UC (OR = 0.31; 95% CI: 0.25-0.38) • Vitamin D deficiency risk factor for aggressive CD and UC • Western diet risk factor for both UC and CD - High sugar - High animal protein - Decreased complex carbohydrates/plant fibers 3

4/6/18 Alliment Pharm May 2015; 42(2) 4

4/6/18 How common is IBD? • Incidence increasing among children • Approx 1.6 million Americans with IBD • Pediatric Incidence: ~ CD: 10.7/100,000 ~ UC: 12.2/100,000 • Pediatric Prevalence: ~ 45,000 – 100,000 children with IBD ~ 100,000 cases diagnosed annually Age of Onset 5

4/6/18 Children Vs. Adults • Similarities with adults: ~ Disease pathophysiology similar ~ Many of the same treatments • Differences from adults: ~ Lack of data ~ Not as many treatment options ~ Growth and development issues Presentation Extraintestinal Symptoms • Arthropathies • Optho: ~ Episcleritis ~ Uveitis • Derm: ~ Erythema Nodosum ~ Pyoderma Gangrenosum • Liver: ~ Primary Sclerosing Cholangitis 6

4/6/18 Initial workup • CBC with differential ~ Anemia ~ Thrombocytosis • CMP ~ Hypoalbuminemia • Inflammatory markers ~ CRP, ESR ~ Stool calprotectin • Infectious studies ~ Stool culture, O&P, C.diff Differential Diagnosis • Bacteria: Non Infectious: ~ C.diff ~ HSP ~ Yersinia ~ Behcet’s ~ TB ~ Celiac • Virus: ~ Immunodeficiency ~ HIV ~ Eating disorder ~ CMV ~ Appendicitis ~ EBV ~ Functional • Parasites: ~ Amoebiasis ~ Giardiasis Refer to GI 7

4/6/18 Crohn’s Endoscopy 8

4/6/18 UC Endoscopy 9

4/6/18 Histology Small Bowel Imaging • Upper GI with small bowel follow through • MR Enterography Small Bowel Imaging • Capsule Endoscopy 10

4/6/18 Goals of IBD Treatment • Improve growth and nutrition • Improve quality of life • Maximize therapeutic response • Minimize toxicity • Prevent disease complications • Maximize adherence • Promote psychological health INDUCE REMISSION = CLINICAL RESPONSE 11

4/6/18 Goals of IBD Treatment • Improve growth and nutrition • Improve quality of life • Maximize therapeutic response • Minimize toxicity • Prevent disease complications • Maximize adherence • Promote psychological health INDUCE REMISSION = CLINICAL RESPONSE MUCOSAL HEALING 12

4/6/18 “Step Up” Approach Future Directions – Step Down?? Corticosteroids • Used to induce remission only ~ Try to wean off as soon as possible • Oral, rectal and IV forms available • Suppresses active inflammation • Can be used for Crohn’s and UC ~ Usually started for disease flares ~ Can serve as bridge to maintenance medication • Problem with side effects ~ Less with budesonide (Entocort) 13

4/6/18 Aminosalicylates Aminosalicylates (5-ASA) • Often first line treatment for mild UC ~ unclear efficacy in Crohn’s • Oral and rectal preparations available ~ combination most effective for distal disease • Locally reduce inflammation in the bowel wall ~ no systemic effects • Can be used for induction and maintenance • Generally well tolerated ~ side effects (headaches, GI symptoms) more with sulfasalazine • Adherence can be an issue due to large number of pills Immunomodulators • Thiopurines (6-MP, Azathioprine), Methotrexate • Suppress immune response that triggers intestinal damage • Used for moderate-severe Crohn’s and UC ~ Usually for maintenance therapy ~ Takes weeks to reach maximum efficacy levels • Side effects: ~ Bone marrow suppression ~ Hepatitis ~ Teratogenic ~ LYMPHOMA 14

4/6/18 Biologics • Anti TNF- α monoclonal antibodies ~ Pro-inflammatory cytokine involved in IBD ~ Neutralizes TNF- α and down-regulates other pro- inflammatory cytokines • Anti- integrin antibodies ~ Prevents attachment of T cells to vessel walls in gut • Anti-IL 12 and 23 cytokines ~ Disrupts cytokine signaling in inflammatory response • Used for severe Crohn’s and UC • Side effects include infections, infusion reactions, lymphoma 15

4/6/18 Surgery • Usually last resort for medically refractory disease • Can involve limited resection, partial colectomy, total colectomy with pouch creation • Total colectomy curative for UC 16

4/6/18 Exclusive Enteral Nutrition • First line for induction therapy for Crohn’s in Europe • 100% of nutrition by formula ~ No differences in type of formula • As effective as steroids in inducing mucosal healing • Exact mechanism unknown ~ Possible effect through changing microbiota • Cons: ~ Difficult to sustain ~ Cost ~ Resource demands 17

4/6/18 THANK YOU 18