Upload
regina-mccoy
View
213
Download
0
Tags:
Embed Size (px)
Citation preview
Goals - IBD
1. Definitions: Crohn disease – ulcerative colitis
2. Epidemiology
3. Pathophysiology - Genetics
4. Diagnosis
5. Treatment
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
Intestinal Flora
Stomach 0-10²Duodenum 10²
Distal Ileum 107 - 108
Colon 1011 - 1012
Jejunum 10²Proximal Ileum 103
Sartor B. Gastroenterology 2008;134:577-94
Microbial Molecular Patterns
Muramyl dipeptide (MDP) Flagellins
Bacterial DNALipopolysaccharide (LPS)
Intestine: Steady State
~ ~~~~
~~
~Microbes
DC
Intestinal Lumen
T cells
IntactEpithelial Cell Barrier
~
MLN
TregIntestinal LP
~ ~
~
Blood
~
M Cells
~ ~~~~
~~
~ ~Microbes
Activated T cellsCytokines/Chemokines
DC
Intestinal Lumen
T cells
Damage toEpithelial 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
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
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!
Complications
• Intra-abdominal sepsis (Crohn disease)
• Fecal incontinence
• Short gut syndrome (Crohn disease)
• Colon cancer
• Infertility
• Medication adverse effects (infection, cancer)
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