what’s so special about pediatric ibd ?
DESCRIPTION
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. Educational Objectives. Review the different types of IBD - PowerPoint PPT PresentationTRANSCRIPT
What’s So Special about Pediatric IBD ?
David Tuchman, MDDivision of Pediatric Gastroenterology and Nutrition
Herman and Walter Samuelson Children’s Hospital at SinaiCSGNA Fall Educational Program
November 8, 2014
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
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
IBD – Type and Anatomic Distribution
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
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
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.
IBD PresentationSymptom/Sign Crohns Disease Ulcerative Colitis
Abdominal Pain ++ ++++
Diarrhea ++++ +++
Rectal bleeding ++ ++++
Weight loss ++++ ++
Growth Failure +++ +
Perianal disease ++
Mouth ulcers ++ +
Fever + +
Erythema nodosum ++ +
Anemia +++ +++
Arthritis + +
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
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
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
Imaging Studies
• Upper GI series and small bowel follow through
• Abdominal and pelvic CT scan• Magnetic Resonance Imaging
Imaging Studies in IBD
MR enterography Abdominal CT Scan
Endoscopic appearance of normal terminal ileum and colon
Normal vascular patternNo friabilitySmooth and shinyNormal folds
Terminal Ileum Colon
Smooth and shinyVilli seenLymphoid follicles (Peyer’s patches)
Endoscopic Appearance of Crohns Disease
• Deep fissures• Cobblestoning• Segmental distribution• Relative rectal sparing• Terminal ileal
involvement• Granulomas on biopsy
Endoscopic Appearance of Ulcerative Colitis
• Loss of vascular pattern• Granularity• Exudates• Diffuse continuous
disease• No ileal involvement
IBD Histology
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.
IBD - Extraintestinal Manifestations Eye
UVEITIS EPISCLERITIS
IBD - Extraintestinal Manifestations Skin
Pyoderma GangrenosumErythema Nodosum
IBD - Extraintestinal Manifestations
Hepatobiliary Disease Oral Disease
Inflammatory Bowel Disease
• Etiology – Unknown• IBD occurs in
genetically susceptible individuals whose immune systems react abnormally to environmental agents in the gastrointestinal tract
Pathogenesis of IBD - Multifactorial
IBD
Nature Reviews Immunology 8, 458-466 (June 2008)
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
Pediatric IBD
• Severity of Disease• Growth (Weight and height gain)• Sexual maturation• Health Supervision• Psycho-social well being• Healthcare Provider Transitioning
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
1Goodhand et al. Inflammatory Bowel Disease 2010:16:947-9522 VanLimbergen et al. Gastroenterology 2008;135:1114-1122Abraham and Kahn Gastro and Hepatol 2014;10:633-640
“Idiopathic “ IBD is rare in the young child
Pediatric Reference Cutoff Proportion of young children
Gupta 2008 (n=989) 5 years 10% (Crohn’s only)
Kugathasan 2003 (n=199) 10 years 20 %
Cannioto 2007 (n=184) 2 years 9%
Bousvaros Boston Children’s Hospital Symposium 2014
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
IBD in young children
• Immunodeficiencies frequently 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
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;118:124-9Tigas et al J Pediatr Gastroenterol Nutr 1993;16:373-80Kocoshis - Presention
Growth Failure in IBDPatients Occurrence (%)
Pediatric IBD 35
Prepubertal CD 60-85
Children with UC 6-12
Kirschner in Kirsner, ed. IBD 5th ed. 2000NASPGHAN
Growth Failure in Pediatric IBD
Growth Failure
Malnutrition
Increased energy needs
Malabsorption of nutrients
Suboptimal intake of calories
Increased GI losses
Corticosteroids Inflammation
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)
Growth Velocity Curves
Evaluating Growth
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
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
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
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
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
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”
Immunomodulators and IBD
• 6 MP, Azathioprine, Methotrexate• Measure TPMT phenotype• Closely monitor CBC, LFT’s• Other adverse effects:
– Pancreatitis
• Increased risk of lymphoma– Slight increased risk for EBV associated lymphoma– Minimal if any risk of non-Hodgkin’s lymphoma
Mercaptopurine in Maintaining Remission in CD
Markowitz, et al; Gastroenterology 2000: 119:895-902
Biologic Agents – Adverse Events• Infusion reactions
– Acute/delayed• Rare complications
– HSTCL– TB and increased risk of infection– Lupus – like reaction
• Monitor – PPD– CXR– Skin examnations– Labs: CBC, LFT’s
Immunomodulators and Biologics for Ulcerative Colitis
• 6 MP and AZA used to reduce steroid exposure
• Started soon after induction with other agents• Not indicated for acute treatment of
fulminant UC• Role of biologics still being defined
Immuno-compromised patient
• No live virus vaccines– Intra-nasal influenza– MMR, OPV, Varicella
• Killed vaccines should be given accroding to recommended schedule– Influenza– Pneumococcus– Hepatitis B– Meningococcus– HPV
Melmed. Inflamm Bowel Dis 2009;15:1410-1416
Bone Health in children with IBD
• Bone mineral density if often reduced in children with IBD
• Pathogenesis is multifactorial• Decreased bone turnover more likely than
increased resorption• Vertebral compression fractures can occur
Sylvester et al J Pediatr 2006; 148:461-466NASPGHAN slide set
Therapy for Decreased Bone Density
• Control the underlying disease• Optimize nutrition
– Calories/protein– Calcium/Vitamin D
• Promote physical activity• Consider referral to a specialist in bone health
Nutritional Complications of IBD
• Osteopenia and osteoporosis• Anemia• Micronutrient deficiencies
– Iron– Folate– B12– Zinc
Depression and Anxiety in Children with IBD
• 25 -30% of children with IBD have symptoms of depression and/or anxiety
• 10-30% meet criteria for clinical depression or an anxiety disorder
• Predictors of depression– Stressful life events; maternal depression– Family dysfunction; steroid treatment; older age
• These rates are similar to children with other chronic illnesses
Mackner et al . Inflamm Bowel Dis 2006;12:239-244
MESSAGE Acronym for Depression Screening
M Mood (depressed or irritable) and Motor (hyper or hypo)
E Energy (fatigue)
S Sleep (insomnia or hypersomnia)
S Suicide or Self-Esteem
A Anhedonia (lack of pleasure)
G Guilt
E Eating (change of appetite)
Rufo et al. NASPGHAN monograph - June 1 2011
Pediatric and Adult IBD - Transitions
Compared with adults, adolescents with IBD had •Fewer clinic visits•More documented non-compliance•More active IBD on endoscopic evaluation•Higher Crohn’s disease activity1
1 Bollegala et al. J Crohns Colitis 2013; 7:e55-e60
Pediatric vs. Adult Healthcare
Pediatric Care• Family centered• Multi-disciplinary• Parent primary caregiver
and decision-maker• May ignore growing
independence and increasingly adlt behavior
Adult Care• Patient centered• Single physician• Acknowledges patient
autonomy and independence
• May neglect family concerns
Healthcare Provider Transitioning Checklistfrom Digestive Health for Life, CDHNF, NASPGHAN
Age Patient Health Care Team
12-14 Early Adolescence – New knowledge and responsibilities•I can describe my GI condition•I can name my medications, the amount and times I take them•I can describe the common side effects of my medications•I know my doctors and nurses names and roles
• Discuss the idea of visiting the office without parents or guardians in the future
• Encourage independence by performing part of the exam with the parents or guardians out of the examining room
14-17 Mid Adolescence – Building knowledge and practicing independence•I know the names and purposes of the tests that are done•I know what can trigger a flare of my disease•I know my medical history
• Always focus on the patient instead of the parents or guardians when providing any explanations
• Allow the patientto select when the parent or guardian is in the room for the exam
17 + Late Adolescence – Taking Charge•I can describe what medications I should not take because thety might interact with the medication I am taking for my health condition•I carry insurance information (card) with me in my wallet/purse/backpack
• Remind patient and family that at age 18 the patient has the right to make his or her own health choices
• Develop specific plans for self-management outside the home (work/school)
Resources and Tools for Successful Transition
Educational Resources for Providers
Transition in IBD www.ibdtransition.org.uk/
Transition Guidelines for Providers
NASPGHAN guidelines (Baldassano et al J Pediatr Gastroenterol Nutr 2002;34:245-248
Transition Readiness Assessment and Tools
www.naspghan.org
Resources and Tools for Adolescents and Parents
Crohns and Colitis Foundation of America (CCFA)
Transition Advocacy and Support for Patients, Parents and Providers
Society for Adolescent Health and Medicine
Abraham and Kahn Gasto and Hepatol 2014:10:633-640