Aetiology

The cause of Crohn's disease (CD) is unknown. It is thought to be caused by environmental triggers in genetically vulnerable people (1). The following risk factors and genetic association have been identified:

• genetic –
  • plays a stronger role in Crohn’s disease than in Ulcerative colitis (1)
  • in up to 20% of patients with Crohn's disease there is another family member affected by Crohn's or ulcerative colitis
  • there is a weak association with HLA-DR1 and DRQ5 in California, USA
  • mutation of CARD15/NOD2 gene located on the 16th chromosome has been shown in small intestinal CD in white (but not oriental) populations (1)
    
    
• environmental -
  • “westernization” of lifestyle - changes in diet, smoking, exposure to sunlight, pollution, and industrial chemicals
  • smoking – is a significant risk factor in developing of Crohn's
  • diet – although inconclusive the following have been implicated
    • low intake of fibre from fruit and vegetables and higher intake of fatty acids
    • frequent fast food intake – 3 to 4 fold risk (2)
      
      
• occupation – common in white-collar than in blue-collar occupations (2)
  
  
• infective organism - the following are suggestions, none are proven:
  • Mycobacterium paratuberculosis causes a granulomatous inflammation in the small intestine of cattle
  • persistence of measles virus; those born at the time of measles epidemics seem to be at higher risk
  • other associated pathogens include - M paramyxovirus, Listeria monocytogenes, and Helicobacter hepaticus (2)
    
    
• immune mechanisms - may be a down-regulating of the normal mucosal immune response in Crohn's Disease
  
  
• NSAID’s – several studies have revealed the risk of relapse and exacerbation of inflammatory bowel disease after NSAID treatment though the evidence is not strong (3)
  
  
• oral contraceptives – an association between the risk of developing inflammatory bowel disease (especially Crohn’s) and the use of oral contraceptive agents have been identified (4)
  
  
• appendectomy – there is a significant risk of developing Crohn’s disease following an appendectomy. The risk falls to a baseline level after about 5 years (5)

Reference:

• (1) Carter MJ et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53 Suppl 5:V1-16
• (2) Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12 Suppl 1:S3-9
• (3) Kefalakes H et al. Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality? Eur J Clin Pharmacol. 2009;65(10):963-70
• (4) Cornish JA et al. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2008;103(9):2394-400
• (5) Kaplan GG et al. The risk of developing Crohn's disease after an appendectomy: a meta-analysis. Am J Gastroenterol. 2008;103(11):2925-31