Crohn's disease : Studies on epidemiology, twins, aetiological factors and clinical course with special reference to smoking

Abstract: In an epidemiological study of the incidence of Crohn's disease in Orebro county during the 25-year period 1963-1987, the mean annual incidence was 6.1/105 inhabitants. During the first five year period the mean incidence was 4.3 but during the following four quinquennia the incidence was stable at around 6.6/105 inhabitants. The point prevalence at 31/12 1987 was 146/105, with male to female ratio of 1:1.15. The mean age at diagnosis increased from 23 to 32 years. No cohort more prone to develop the disease was found. Of the 246 incidence cases 5 patients had died of Crohn's disease.The genetic influence was analysed in 18 monozygotic and 26 dizygotic twin palrs with Crohn's disease. Eight of the monozygotic palrs were concordant for the disease but only one of the dizygotic pairs. The proband concordance rate was 58.3% for monozygotic twins and the heritability of liability (r) 1.0. The corresponding figures for dizygotic twins were 3.9% and 0.47. When comparing with ulcerative colitis the heritability was found to be significantly stronger in Crohn's disease.A case-control study of smoking habits in 144 patients and 259 matched population controls showed that smoking doubled the risk of aquiring Crohn's disease. In former smokers a non-significant increased risk was observed.The effects of smoking on the localization and course of Crohn's disease was evaluated in 231 patients. Patients with high life time tobacco exposure (>150 cig.years) had small bowel disease more often than patients with low life time exposure. Heavy smokers(> 10 cig./day) had a slightly increased risk to be operated at least once, odds ratios after 5 and 10 years of follow up for heavy smokers compared to never smokersbeing 1.14 and 1.24 respectively. The risk for heavy smokers to be operated twice or more was even higher after 10 years offollow up, the odds ratio being 1.79. The accumulated number of fistulae and/or abscesses was higher in smokers than never smokers.Twenty-six monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbuntin, betalactoglobulin, gliadin, whole yeast (Saccharomyces cerevisiae) and mannan. Twins that had developed Crohn's disease displayed higher titers of all three antibodies towards mannan, and also higher IgA towards yeast. Their healthy twin hadhigher IgA to mannan and yeast. These results suggest that yeast cell wall material for instance mannan or some antigen rich in mannose and cross reacting with mannan might play an aetiological role in Crohn's disease.Conclusion: The incidence of Crohn's disease has been stable during the last 20 years. The genetic influence is important. Smoking increases the risk of aquiring Crohn's disease and heavy smokers have a worse outcome of the disease. Patients with high life time tobacco exposure more often have small bowel disease. Mannan or agents cross-reacting with mannan may play a role in the pathogenesis of the disease. However, not even similar smoking and dietary (as ntirrored by dietary antibodies) habits in identical twins are sufficient to cause disease. Additional factors are needed.