Inflammatory Bowel Disease

Francisco A. Sylvester, MD

Associate Professor of Pediatrics

Goals - IBD

1. Definitions: Crohn disease – ulcerative colitis

2. Epidemiology

3. Pathophysiology - Genetics

4. Diagnosis

5. Treatment

Definitions

Crohn disease – Ulcerative colitis

Normal colon

IBD - ColonCrohn Disease Ulcerative Colitis

IBD – Disease Location

http://www.hopkins-gi.org/

Crohn disease Ulcerative colitis

Distribution of Crohn Disease

http://www.hopkins-gi.org/

Types of Crohn Disease

http://www.hopkins-gi.org/

Diagnostic Certainty

Crohn Disease Ulcerative Colitis

IBD-U

Dr. Burrill B. Crohn(1884-1983)

Epidemiology

• ~1.4 million Americans have IBD

• Mean age at diagnosis ~30 years of age

• 25% diagnosed as children

• M = F (in children with Crohn M > F)

• At CCMC: ~80-90 new patients/year

Crohn’s Disease

Ulcerative Colitis

Ulcerative Colitis(< 20 years of age)

Appendicitis - Appendectomy

Smoking

Crohn’s Disease

North-To-South Gradient

Pathophysiology

Intestinal Flora

Stomach 0-10²Duodenum 10²

Distal Ileum 107 - 108

Colon 1011 - 1012

Jejunum 10²Proximal Ileum 103

Sartor B. Gastroenterology 2008;134:577-94

“Our” DNA

90% Bacterial

10% Human

So, Why Doesn’t Everybody Have IBD?

Microbial Molecular Patterns

Muramyl dipeptide (MDP) Flagellins

Bacterial DNALipopolysaccharide (LPS)

Intestine: Steady State

~ ~~~~

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~Microbes

DC

Intestinal Lumen

T cells

IntactEpithelial Cell Barrier

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MLN

TregIntestinal LP

~ ~

~

Blood

~

M Cells

“Controlled Inflammation”

~ ~~~~

~~

~ ~Microbes

Activated T cellsCytokines/Chemokines

DC

Intestinal Lumen

T cells

Damage toEpithelial Cell Barrier

Microbial Invasion

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~~

Intestinal Inflammation

Intestinal LP

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http://www.randymays.com/Rugersr9-1.jpg

IBD - Genetics

• NOD2/CARD15 (chromosome 16q12)– 20-40-X risk in individuals carrying 2

abnormal alleles– Ileal Crohn disease– Stricturing – penetrating– Caucasians only

IBD - Genetics

• GWAS– ATG16L1 (Crohn disease)– IL-23R (Crohn disease and ulcerative colitis)– IL-23/Th17 pathway– > 30 novel loci

What is Changing?

Genes vs. Jeans?

Environmental Factors

• Microbial Ecology– Hygiene (Parasites)– Antibiotics– Refrigeration– Diet– Vaccines

• Tobacco

• North-to-south gradient– Vitamin D deficiency?

Pathophysiology - IBD

• Genetic predisposition

• Defective innate immunity

• Hyperactivation of effector cells

• Microbial ecology alterations

• Environmental factors

Genes Environment

Microbiota

Diagnosis

• History – Physical Exam

• Laboratory– CBC, ESR, CRP, albumin– Stool culture– Serology (antibodies to PAMPs)

• Endoscopy

• Imaging

Extraintestinal Manifestations

• Skin• Mouth• Joints• Bone

• Liver• Hypercoagulability• Kidney• Eye

•Present in ~50% patients•25% patients may have more than one•May be presenting symptom!

Growth Failure – Pediatric IBD

Complications

• Intra-abdominal sepsis (Crohn disease)

• Fecal incontinence

• Short gut syndrome (Crohn disease)

• Colon cancer

• Infertility

• Medication adverse effects (infection, cancer)

Arrow shows narrowing of the distal ileum

Arrow shows a phlegmon

Mesalamine (5-ASA)/Corticosteroids

AZA/6-MPCD: MTX

Biologics

Steroids/5_ASA

AZA/6-MPCD: MTX

Biologics

Step Up vs. Top Down

Crohn disease: Nutritional therapy

Challenges for School-Aged Children

• School absences

• Bathroom needs

• Psychosocial issues– Self-perception and self-esteem– Peer relationships

• Special diets (nutritional therapy)