Inflammatory Bowel Disease Francisco A. Sylvester, MD Associate Professor of Pediatrics.

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Presentation transcript:

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 - Colon Crohn DiseaseUlcerative Colitis

IBD – Disease Location Crohn disease Ulcerative colitis

Distribution of Crohn Disease

Types of Crohn Disease

Diagnostic Certainty Crohn DiseaseUlcerative Colitis IBD-U

Dr. Burrill B. Crohn ( )

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 (< 20 years of age) Appendicitis - Appendectomy Smoking Crohn’s Disease

North-To-South Gradient

Pathophysiology

Intestinal Flora Stomach 0-10² Duodenum 10² Distal Ileum Colon Jejunum 10² Proximal Ileum 10 3 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 DNA Lipopolysaccharide (LPS)

Intestine: Steady State ~ ~ ~ ~ ~ ~ ~ ~ Microbes DC Intestinal Lumen T cells Intact Epithelial Cell Barrier ~ MLN Treg Intestinal LP ~ ~ ~ Blood ~ M Cells

“Controlled Inflammation”

~ ~ ~ ~ ~ ~ ~ ~ ~ Microbes Activated T cells Cytokines/Chemokines DC Intestinal Lumen T cells Damage to Epithelial Cell Barrier Microbial Invasion ~ ~ ~ ~ Intestinal Inflammation Intestinal LP ~

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

GenesEnvironment 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-MP CD: MTX Biologics Steroids/ 5_ASA AZA/6-MP CD: 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)