Crohn

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Crohns Disease Mycobacterial Infections

• Kimberly Persley, MD
• October 19, 2005

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Outline

• Epidemiology
• Presumed Etiopathogenesis
• Antibiotic Therapy
• Mycobacteria and IBD

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IBD Spectrum
Ulcerative colitis
Crohns Disease
Indeterminant colitis
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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
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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)

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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

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Defective NOD2 Function

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

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IBD Treatment Pyramid
Biologics
severity
Immunomodulators
Steroids
Antibiotics
5-ASA
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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

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Histology
Normal SB histology
Crohns Disease
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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

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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 20051001529
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Prevalence of MAP

• Germany
• 100 CD, 100 UC and 100 normals
• IS900 PCR in resected bowel specimens

Autschback F. et al. Gut 200554944
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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 20043641039
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Does MAP cause Crohns disease?

• I just dont KNOW!!!
• MAP infection may cause CD in a subset of
  patients
• MAP colonize ulcerated mucosa of CD but not
  initiate or perpetuate intestinal inflammation