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