1 / 15

Crohn’s Disease & Mycobacterial Infections

Explore the epidemiology, etiopathogenesis, antibiotic therapy, and relationship between Mycobacteria and IBD spectrum diseases. Learn about genetic influences, NOD2 function, IBD treatment options, histology, and the detection of MAP in mucosal biopsies.

bvirgil
Download Presentation

Crohn’s Disease & Mycobacterial Infections

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Crohn’s Disease &Mycobacterial Infections Kimberly Persley, MD October 19, 2005

  2. Outline • Epidemiology • Presumed Etiopathogenesis • Antibiotic Therapy • Mycobacteria and IBD

  3. IBD Spectrum Ulcerative colitis Crohn’s Disease Indeterminant colitis

  4. Normal Intestine Vs. IBD Environmental triggers (infection, bacterial products) Failure to down- regulate Chronic uncontrolled inflammation = IBD Moderately inflamed Down-regulate Normal gut controlled inflammation Normal gut controlled inflammation

  5. Evidence of Genetic Influence • Prevalence varies among different populations • risk in increased among first degree relatives • greater concordance among monozygotic than diazygotic twins • identification of “susceptibility genes” (NOD2/CARD 15)

  6. NOD2/CARD15 • Intracellular pattern recognition receptors • Participates in host defense against microbial pathogens • recognition or molecular pattern present of pathogens • activation of nuclear factor kB • induction and secretion of pro/anti-inflammatory cytokines and chemokines • induction of antimicrobial pathways

  7. Defective NOD2 Function • Ineffective clearance of intracellular MAP infection • Decrease in defensin secretion • permits increased mucosal adherence and epithelial invasion of ingested organisms

  8. IBD Treatment Pyramid Biologics severity Immunomodulators Steroids Antibiotics 5-ASA

  9. Antibiotics • Lack of well-designed, placebo-controlled trials • Large “Antibiotic” underground • Ciprofloxacin and Metronidazole are the two most widely studied abx • Rifaximin may have a promising role in CD • Antimycobacterial drugs results are inconclusive

  10. Histology Normal SB histology Crohn’s Disease

  11. Infection and IBD • Histopathology • NOD2 mutations • High bacterial concentrations in the TI and colon are preferentially involved in IBD • Altered composition of commensal enteric bacteria • Clinical improvement with antibiotics

  12. Detection of MAP from Mucosal Biopsies • Sardinia • 1.6 million people • 3.5 million sheep and MAP infection endemic • determine the proportion of MAP infected people Sechi, Leonard et al. AJG 2005:100:1529

  13. Prevalence of MAP • Germany • 100 CD, 100 UC and 100 normals • IS900 PCR in resected bowel specimens Autschback F. et al. Gut 2005;54:944

  14. Culture of MAP in CD • University of Florida • 52 patients • 28 CD • 9 UC • 15 Controls • presence of viable MAP in peripheral blood of pts with CD Nasser S. et al. Lancet 2004;364:1039

  15. Does MAP cause Crohn’s disease? • I just don’t KNOW!!! • MAP infection may cause CD in a subset of patients • MAP colonize ulcerated mucosa of CD but not initiate or perpetuate intestinal inflammation

More Related