Pediatric Inflammatory Bowel Disease in Less Than 30 Minutes Shervin Rabizadeh, M.D., M.B.A. Director, Pediatric Gastroenterology and Pediatric Inflammatory Bowel Disease Program Cedars-Sinai Medical Center
Objective Review Diagnosis and Treatment of Pediatric Inflammatory Bowel Disease in Children Understand risks and benefits of treatments in children with IBD
IBD is not IBS Inflammatory Bowel Disease Epidemiology Up to 350 per 100,00 1 in 5 people Symptoms Testing Treatment Prognosis Diarrhea, blood stools, abdominal pain, fever, weight loss, growth issues, fatigue Non-intestinal manifestations Abdnormal blood test Inflammation on biopsies Immunomodulators Surgery Lifelong Increased risk of intestinal cancer Irritable Bowel Syndrome Diarrhea predominant Constipation predominant Diarrhea and constipation Bloating Abdominal pain and cramps Normal blood work and pathology Dietary modification Anti-diarrhea agents Anti-depressants Antibiotics Affects quality of life but not life threatening No increased risk of cancer
Inflammatory Bowel Disease Crohn Disease and Ulcerative Colitis Disregulated immune response Incidence and prevalence 1-1.5 million people in U.S. with IBD 7-10 children out of 100,000 develop IBD in any given year in U.S. Estimated over 100,000-150,000 children are presently believed to have IBD 25% of IBD diagnosed at pediatric age usually >6yrs Barton et al. Gut. 1989 Kugathasan et al. J Pediatr. 2003 Baldassano et al. Gastroenterol Clin North Am. 1999 Markowitz. IBD. 2004
Pathogenesis of IBD
Pathogenesis Rabizadeh et al. 2011
IBD Presentation Rabizadeh et al. 2013
Differential Diagnosis Primary Presenting Symptom Right lower quadrant abdominal pain, with or without mass Chronic periumbilical or epigastric abdominal pain Rectal bleeding, no diarrhea Bloody diarrhea Watery diarrhea Perirectal disease Growth delay Anorexia, weight loss Arthritis Liver abnormalities Diagnostic Considerations Appendicitis, infection (e.g., Campylobacter, Yersinia), lymphoma, intussusception, mesenteric adenitis, Meckel s diverticulum, ovarian cyst Irritable bowel, constipation, lactose intolerance, peptic disease, celiac disease Fissure, polyp, Meckel s diverticulum, rectal ulcer syndrome Infection, hemolytic-uremic syndrome, Henoch-Schönlein purpura Irritable bowel, lactose intolerance, giardiasis, Cryptosporidium, sorbitol, laxatives Fissure, hemorrhoid (rare), streptococcal infection, condyloma (rare) Celiac disease, endocrinopathy Anorexia nervosa Collagen vascular disease, infection Chronic hepatitis
Impaired Linear Growth More Common in Crohn s Krischner et al. 2000
Growth Failure Poor weight gain/short stature Crohndisease > ulcerative colitis 15-40% prevalence May be presenting symptom May be irreversible
Assessment of Short Stature Height < 3% Low Wt/Ht * Ht velocity < 3% Delayed Bone Age IBD Related + + + + Endocrine + 0 + + Constitutional Delay + 0 0 + Genetic + 0 + 0 * % ideal weight for height
Common Pediatric IBD Extraintestinal Manifestations Rabizadeh et al. 2012
Extraintestinal Manifestations
Diagnosis
Fecal Calprotectin Protein derived from neutrophils Marker of inflammation Noninvasive Good for following flares Possible role is diagnosis
Endoscopic Findings Granuloma Ulcer
Imaging Small bowel imaging is strongly recommended Especially if unsuccessful ileal intubation Diagnosis is indeterminate Small bowel follow through (SBFT) examination Good for strictures Oldest test Ultrasonography Noninvasive radiation-free Detects bowel wall thickening with sensitivity of 75% to 95% and specificity of 67% to 100% Limitations Operator dependency Technical difficulties depending on body habitus Inability to evaluate superficial lesions
Imaging Computer tomography (CT) especially with negative luminal contrast in CT enterography or CT enteroclysis studies Visualization of bowel wall inflammation as well as fistulas and abscesses Limitation is significant radiation Magnetic resonance imaging (MRI) Limits radiation Oral enterographywith intraluminal contrast and intravenous gadolinium has made MRI equal or better than CTE or SBFT Limitations Costly Requires lying still for long periods Video wireless capsule endoscopy Allows for visualization of superficial mucosa of small bowel Limitations Hard to swallow Retention
TREATMENT
Treatment Goals Therapeutic goal is mucosal healing and long-lasting remission Treatment of pediatric patients with IBD should focus on the individual patient and requires a commonsense approach with consideration of Symptoms Quality of life Growth Minimizing side effects There is a paucity of therapies approved specifically for children Most of the treatment regimens are extrapolated from adult studies.
Micronutrients Nutritional Deficiencies Iron Selenium Vitamin B12 Biotin Folate Vitamin D Zinc Rufo et al, JPGN 2012
Psychosocial Concerns Prevalence of depression and anxiety IBD: 24% & 39% General population: 15.7% & 11.3% Higher risk of depression and anxiety compared with youth with other chronic illnesses Complex Etiology Loftus et al. Am J Gastro. Sept 2011 Rufo et al, JPGN 2012
Psychosocial Concerns Contributing factors Chronic illness Embarrassing symptoms Body Image issues related to delayed growth and puberty Perceived loss of control Limited ability of participate in sports and school activities Corticosteroid therapy
Psychosocial Concerns Depression screening should be completed at every visit! Assess parental/family functioning Refer to mental heath specialist Medication management Cognitive behavior therapy Hypnotherapy Support groups Summer IBD camp
Pediatric Versus Adult Healthcare Pediatric Care family-centered multidisciplinary parent primary caregiver and decisionmaker may ignore growing independence and increasingly adult behavior Adult Care patient-centered single physician acknowledges patient autonomy and independence may neglect family concerns
Perspectives on Pediatric IBD Early Age Onset Questions from the parents Adolescent Can I go to school? Is this lifelong? Do I tell my friends? Will he need medicine forever? Do I look like everyone else? Did I give him this? Will I grow? What can I feed him? Can I date? Cancer risk Will I die?
Cumulative Incidence of Surgery From the Time of Diagnosis in Pediatric Patients (1979-2003) 40 % of Patients 30 20 10 0 Years Incidence 95% CI 1 5.7% 4.3% 7.4% 5 17.0% 14.1% 20.4% 10 28.4% 22.5% 35.6% 0 2 4 6 8 10 Years Since Diagnosis Gupta N, et al. Gastroenterology. 2006;130:1069.
Immunomodulators and Biologics Nutritional Treatments Holistic Medications Mesalamine/Aminosalicylates Oral/Rectal Immunomodulators 6-Mercaptopurine (6-MP) 1-1.5 mg/kg/day Azathiopurine 2-2.5 mg/kg/day Methotrexate 15 mg/m2 or 0.4mg/kg sc or orally once a week Cyclosporine Biologics Anti-tumor necrosis factor Infliximab chimeric Adalimumab humanized Certolizumab pegylated Golimumab - humanizaed Antibody to alpha-4 integrin Natalizumab o Risk of progressive multifocal leukoencephalopathy o JC Virus dependent Vedolizumab Anti IL12/23 Ustekinumab Janus Kinase Inhibitor Tofacitinib
Treatment Pyramid Surgery Alternative/ Investigational Drugs Biologic Therapies Corticosteroids Immunomodulators Aminosalicylates Antibiotics Probiotics Fish Oil
The Ultimate Goal of Personalized Medicine Choosing the Right therapy for the Right patient at the Right Time 31
Enteral Nutrition vs. Corticosteroids in Active CD: A Meta-Analysis Study Year Lochs 1991 Malchow 1984 Gonzalez-Huix 1993 Gorard 1993 Lindor 1992 O Morain 1980 Seidman 1993 Seidman 1991 Log Odds Ratio (95% CI) 0.1 0.3 0.5 1 2 4 10 Pooled odds ratio Corticosteroids More Effective Liquid Diet More Effective Reproduced with permission from Griffiths AM et al. Gastroenterology. 1995;108:1056.
Oral and Rectal 5-ASA for UC Safdi et al. Am J Gastro. 1997
Kaplan-Meier Survival Curve of Relapse-Free Duration of Remission 1.00 Fraction in Remission 0.75 0.50 0.25 0.00 0 100 200 300 400 500 600 Days From Start of Remission 6-MP Controls P<0.007 Markowitz J, et al. Gastroenterol. 2000;119:895-902.
REACH Infliximab Trial Pediatric Study Hyams et al. JPGN. 2005
IMAgINE1: Humira in Pediatric CD Hyams et al. Gastro. 2012
Vedolizumab for Pediatric IBD
QUESTIONS?