Crohn's disease in Stockholm County : epidemiological panorama and associated gallstone disease

Abstract

Crohn's disease is a chronic inflammatory bowel disease of obscure etiology, affecting any part of the gastrointestinal tract but the ileocaecal region in particular. The annual incidence has gradually been increasing, and the clinical pattern has changed; a shift towards colorectal involvement as well as an increasing number of elderly patients has been observed. Gallstone disease has been a common extraintestinal complication among patients with Crohn's disease, but the true relative risk and the pathogenesis remain unclear.

The aims of this thesis were to investigate the epidemiological time trends in Crohn's disease in Stockholm County during a 35 year period between 1955-1989, and to evaluate the clinical course of the expanding entity of colorectal Crohn's disease. Furthermore, relative risk and risk factors for developing gallstone disease in patients with Crohn's disease were assessed in patients born 1933-1935 and 1953-1955. An additional aim, in a separate study, was to investigate what type of gallstones these patients may be prone develop, by examining the bile composition in patients having had ileal resections due to Crohn's disease. The annual incidence of Crohn's disease in Stockholm County increased from 1.4 to 4.9 per 100,000 inhabitants between the 1955-1959 and 1985-1989 periods, stabilizing at 4.6 per year during the last two decades. The age specific incidence among those aged 15-29 years decreased, whereas the incidence in those aged > 60 years increased. The median age at diagnosis increased from 25 to 32 years. The annual incidence of colorectal Crohn's disease increased from 0.2 to 1.6 per 100,000 inhabitants between 1955-1959 and 1985-1989. The overall proportion of colorectal Crohn's disease increased from 15% to 32% with a corresponding decrease of ileocaecal disease.

The frequency of major surgery at first flare-up of colorectal Crohn's disease decreased over time, although the cumulative probability of resection remained unchanged. Half of the patients with colorectal Crohn's disease had at least one surgical resection within ten years from diagnosis and slightly more than half of those patients ultimately received an ileostomy. Patients with left-sided colorectal Crohn's disease were less likely to undergo major surgery, while patients with perianal and rectal fistulas had the highest probability of surgical intervention. A relapse-free course during the initial five years after the first flare-up implied a high probability of remaining in remission. Around 20% of the patients with colorectal Crohn's disease subsequently developed changes also in the small bowel. Regardless of gender or age, patients with Crohn's disease had almost twice the prevalence of gallstone disease compared to the general population. The number of previous intestinal resections was the only significant risk factor. Site of disease or type of intestinal resection were not found to be associated with an increased risk for gallstone formation. Short or long ileal resections due to Crohn's disease did not have any major influence on the biliary lipid composition. Nevertheless the cholesterol saturation of bile was significantly lower among the patients than the controls. The bile acid pattern after ileal resection was characterized by a significantly decreased proportion of deoxycholic acid and an increased proportion of ursodeoxycholic acid. Patients having undergone short or long ileal resections due to Crohn's disease had a 50% higher ratio of bilirubin to bile acids compared with the controls. Patients with Crohn's disease may therefore develop pigment rather than cholesterol gallstones. It still remains unclear whether the increased prevalence of gallstone disease in patients with Crohn's disease is attributed to secondary morbidity (i.e. surgical management) or Crohn's disease per se. Circumstances at the time of laparotomy, such as use of total parenteral nutrition and/or bowel rest must also be considered in the pathogenesis of gallstone formation in patients with Crohn's disease.