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Crohn’s Disease & Mycobacterial Infections

Crohn’s Disease & Mycobacterial Infections. Kimberly Persley, MD October 19, 2005. Outline. Epidemiology Presumed Etiopathogenesis Antibiotic Therapy Mycobacteria and IBD. IBD Spectrum. Ulcerative colitis. Crohn’s Disease. Indeterminant colitis. Normal Intestine Vs. IBD.

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Crohn’s Disease & Mycobacterial Infections

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  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

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