Transcript Pediatric IBD

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
• 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
Crohn’s
Diseae
Ulcerative
Colitis
Indeterminate
Colitis
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 Presentation
Symptom/Sign
Crohns Disease
Ulcerative Colitis
Abdominal Pain
++
++++
Diarrhea
++++
+++
Rectal bleeding
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++++
Weight loss
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++
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
Terminal Ileum
Smooth and shiny
Villi seen
Lymphoid follicles (Peyer’s patches)
Colon
Normal vascular pattern
No friability
Smooth and shiny
Normal folds
Endoscopic Appearance of Crohns
Disease
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•
•
•
•
Deep fissures
Cobblestoning
Segmental distribution
Relative rectal sparing
Terminal ileal
involvement
• Granulomas on biopsy
Endoscopic Appearance of Ulcerative
Colitis
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•
•
•
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
Erythema Nodosum
Pyoderma Gangrenosum
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
Genes
IBD
Environment
Mucosal
Immune
System
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 2010:16:947-952
VanLimbergen et al. Gastroenterology 2008;135:1114-1122
Abraham and Kahn Gastro and Hepatol 2014;10:633-640
2
“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)
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•
•
•
•
•
•
•
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
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–
–
–
Corticosteroids
Inadequate calorie intake
Malabsorption
Increased energy expenditure from chronic
inflammation – Pro-inflammatory cytokines,
decreased IGF -1
Sawczenko et al Pediatrics 2006;118:124-9
Tigas et al J Pediatr Gastroenterol Nutr 1993;16:373-80
Kocoshis - Presention
Growth Failure in IBD
Patients
Occurrence (%)
Pediatric IBD
35
Prepubertal CD
60-85
Children with UC
6-12
Kirschner in Kirsner, ed. IBD 5th ed. 2000
NASPGHAN
Growth Failure in Pediatric IBD
Suboptimal intake of
calories
Increased energy needs
Malabsorption of nutrients
Increased GI losses
Malnutrition
Growth
Failure
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
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•
•
•
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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
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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
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•
•
•
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
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–
–
–
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; 148:461-466
NASPGHAN 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 noncompliance
• 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
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•
•
•
Pediatric Care
Family centered
Multi-disciplinary
Parent primary caregiver
and decision-maker
May ignore growing
independence and
increasingly adlt behavior
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•
•
•
Adult Care
Patient centered
Single physician
Acknowledges patient
autonomy and
independence
May neglect family
concerns
Healthcare Provider Transitioning Checklist
from Digestive Health for Life, CDHNF, NASPGHAN
Age
Patient
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
•
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
•
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
•
14-17
17 +
Health Care Team
•
•
•
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
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
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 selfmanagement 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