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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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
Alliment Pharm May 2015; 42(2) 4
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
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
Crohn s Endoscopy 8
UC Endoscopy 9
Histology Small Bowel Imaging Upper GI with small bowel follow through MR Enterography Small Bowel Imaging Capsule Endoscopy 10
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
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
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
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
Biologics Anti TNF-α monoclonal antibodies ~ Pro-inflammatory cytokine involved in IBD ~ Neutralizes TNF-α and down-regulates other proinflammatory 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
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
THANK YOU 18