Crohns Disease Mycobacterial Infections Kimberly Persley MD October

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 Environmental triggers (infection, bacterial products) Failure to downregulate Chronic uncontrolled inflammation = IBD Moderately inflamed Normal gut controlled inflammation Down-regulate Normal gut controlled inflammation

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” (NOD 2/CARD 15)

NOD 2/CARD 15 • Intracellular pattern recognition receptors • Participates in host defense against microbial pathogens – recognition or molecular pattern present of pathogens – activation of nuclear factor k. B – induction and secretion of pro/antiinflammatory cytokines and chemokines – induction of antimicrobial pathways

Defective NOD 2 Function • Ineffective clearance of intracellular MAP infection • Decrease in defensin secretion – permits increased mucosal adherence and epithelial invasion of ingested organisms

IBD Treatment Pyramid s e v e r i t y Biologics Immunomodulators Steroids Antibiotics 5 -ASA

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

Histology Normal SB histology Crohn’s Disease

Infection and IBD • Histopathology • NOD 2 mutations • High bacterial concentrations in the TI and colon are preferentially involved in IBD • Altered composition of commensal enteric bacteria • Clinical improvement with antibiotics

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

Prevalence of MAP • Germany • 100 CD, 100 UC and 100 normals • IS 900 PCR in resected bowel specimens Autschback F. et al. Gut 2005; 54: 944

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

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