Pediatric Crohn’s diseases

Hiren Chatrola

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 in Children

• Impact on children• 25% of IBD occurs in childhood

• Incidence and prevalence• Crohns disease is diagnosed in 5000 children each

year• It is estimated that 50,000 – 100,000 children have

IBD

NASPGHAN 2nd Edition

• … 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.

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)

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

IBD in Younger Children (< 5 years)

• Chronic granulomatous disease• Glycogen storage disease 1b• Hermansky – Pudlak syndrome• Wiskott-Aldrich syndrome• Hyper IgM syndrome• Common Variable Immune Deficiency

Bousvaros Boston Children’s Hospital Symposium 2014

IBD Presentation

Symptom/Sign Crohns Disease Ulcerative ColitisAbdominal 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 ColitisAny portion of GI tract Colon onlySkip areas ContinuousRectal Sparing No rectal sparingNon-caseating granulomas No granulomasTransmural inflammation Mucosal inflammationFistulae and abscesses Abscesses rareStictures commom Strictures rareIleum and cecum commonly involvedPerianal 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 IBDMR 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

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• Inadequate calorie intake• Malabsorption• Increased energy expenditure from chronic

inflammation – Pro-inflammatory cytokines, decreased IGF -1

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. 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)

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

Treatment of Crohn’s Disease

• Mild to moderate CD• Aminosalicylates• 400 mg PO 2t/d (6 weeks)

• Enteral feeds• Corticosteroids

• Budesonide 4 mg PO• Prednisone 0.5-2 mg/kg/d

• Moderate to severe CD–Enteral feeds (induction)–Corticosteroids (induction)

• Budesonide vs. prednisone– Immunomodulators (maintenance)

• 6-mercaptopurine 1.25-2.5 mg/kg• Azathioprine 1 mg/kg/day PO • Methotrexate 10 mg/m² PO/IM/SC

–Biologics (Induction and maintenance)• Infliximab 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks• Adalimumab

Induction: 80 mg SC on Day 1 (administer as two 40 mg injections in one day); THEN 2 weeks later (Day 15) give 40 mg

Maintenance (beginning Week 4 [Day 29]): 20 mg SC q2wk

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

Immunomodulators and IBD

• 6 MP, Azathioprine, Methotrexate• Closely monitor CBC and LFT• Other adverse effects:

• Pancreatitis• Increased risk of lymphoma

• Slight increased risk for EBV associated lymphoma• Minimal if any risk of non-Hodgkin’s lymphoma

Nutritional Complications of IBD

• Osteopenia and osteoporosis (Vit D and Calcium supplements should be given)

• Anemia• Micronutrient deficiencies

• Iron• Folate• B12• Zinc

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