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Pathogenesis of Gall Stones in Crohn's Disease

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Pathogenesis of Gall Stones in Crohn's Disease 94 Gutl994;35:94-97 Pathogenesis ofgall stones in Crohn's disease: an alternative explanation Gut: first published as 10.1136/gut.35.1.94 on 1 January 1994. Downloaded from R Hutchinson, P N M Tyrrell, D Kumar, J A Dunn, J K W Li, R N Allan Abstract that other factors are necessary for gall stone The increased prevalence of gall stones in formation including nucleation factors and gall Crohn's disease is thought to be related to bladder stasis.78 depletion of the bile salt pool due either to Clinically we noted a high incidence of gall terminal ileal disease or after ileal resection. stones in patients with Crohn's disease but there This study was designed to examine whether was no obvious correlation with terminal ileal this hypothesis is correct and explore alterna- disease, which suggested that gall stones were tive explanations. Two hundred and fifty one not necessarily attributable to the disturbance in randomly selected patients (156 females, 95 the enterohepatic circulation of bile salts. We males, mean age 45 years) were interviewed therefore surveyed a large number of patients and screened by ultrasonography to determine with Crohn's disease to determine the prevalence the prevalence ofgall stones in a large popula- of gall stones and the risk factors for their tion of patients with Crohn's disease. Sixty development. nine (28%) patients had gall stones proved by ultrasonography (n=42), or had had chole- cystectomy for gail stone disease (n=27). The Patients and methods risk factors for the development of gall stones Two hundred and fifty one consecutive patients including sex, age, site, and duration of with Crohn's disease attending the inflammatory disease, and previous intestinal resection were bowel disease clinic were studied and clinical examined by multivariate analysis. Age and details of their Crohn's disease and any biliary duration of disease were positive risk factors disease was recorded. The details of Crohn's for gail stones and were covariables. The site disease, which were recorded and verified from of disease and of previous intestinal resection the case notes, included duration, site of disease http://gut.bmj.com/ did not predispose to gail stones. Previous (small bowel, large bowel or both), and site and surgery was an independent risk factor for the extent of any previous resection. Site of macro- development of gall stones, the risk increasing scopic Crohn's disease was determined by radio- with number of laparotomies. It is suggested logical methods, supplemented with information that mechanisms other than ileal dysfunction from surgical exploration and histological exami- may predispose to gall stones. Postoperative nation when available. The case notes, operation gall bladder hypomotility with biliary sludge notes, and histology reports of all patients on September 25, 2021 by guest. Protected copyright. formation may be precursors of gall stone previously treated by cholecystectomy were formation in patients with Crohn's disease. reviewed and the diagnosis of gall stones estab- (Gut 1994; 35: 94-97) lished. Patients were questioned about symp- toms characteristic of cholelithiasis, and on this basis, those treated by cholecystectomy were Several studies have shown an increased preval- divided into symptomatic and non-symptomatic ence of gall stones in patients with inflammatory groups. bowel disease. Surveys using cholecystography Those patients with an intact gall bladder had have shown gall stones in 30-34% of patients abdominal ultrasound scanning on the same day with Crohn's disease.'2 The high prevalence of as their clinic attendance. gall stones has been established in an ultrasono- graphic study,3 where 34% of terminal ileal Crohn's disease patients had gall stones com- ANALYSIS OF DATA pareu with 8% among healthy, age and sex The overall prevalence of gall stones in patients matched controls. The prevalence of gall stones with Crohn's disease was determined and related The General Hospital, is lower in patients with colonic Crohn's disease4 to sex, age, duration of disease, site of disease, Steelhouse Lane, or and number Birmingham and is 24-5% in patients after ileostomy ileal and site of previous intestinal resec- R Hutchinson resection for inflammatory bowel disease.5 tions. The BMDP statistical software package P N M Tyrrell The pathogenesis of gall stones in these was used for data analysis.9 The Mann-Whitney D Kumar patients is usually attributed to the disturbance U test, the X2 test, and the X2 test for linear trend J A Dunn J K W Li in the enterohepatic circulation of bile salts were used for statistical comparisons. A multi- R N Allan because of disease or removal of terminal ileum.6 variate stepwise discriminant analysis was Correspondence to: The accepted mechanism is that intestinal performed to identify independent factors Mr R Hutchinson, Research Registrar, Department of disease or resection leads to a decrease in the total associated with gall stones. The values from the Surgery, Queen Elizabeth bile acid pool, leading to supersaturated gall final model are presented. The analysis was Medical Centre, Edgbaston, Birmingham B15 2TH. bladder bile, which predisposes to gall stone repeated removing the most influential variable Accepted for publication formation. It is now clear, however, that litho- to determine any correlations inherent in the 10 May 1993 genic bile alone will not lead to cholelithiasis, and data. Pathogenesis oJ gall stones in Crohn's disease: an alternative explanation 995 Resuilts table 251 patients 3 cholecystectomies before diagnosis of (GaIl Stones DlgrL'es Crohn's disease /o)f p Facto (Groups Yes N\o -11'cdoliz valut, IVailue} Gut: first published as 10.1136/gut.35.1.94 on 1 January 1994. Downloaded from I Sex lemales 42 112 Males 27 67 1 0(06 0(08 69 (28%) of 248 have or Age v <20 8 have had gallstones 21-30 10I( 44 31-40 10 43 41-50 18 32 1-60 8 22 >61 22 30 1 10.(* 0(002 Duration of 0-5 9 38 discase (y) 6-10 9 31 Detected on Cholecystectomy 11-15 1 1 40 ultrasonography In 16-20 32 In -t27) 21-25 6 13 -42) 26-30 7 >31 19 18 1 1265* 00004 Site ot disease Ileal 32 87 Colonic 17 58 Both 20 34 2 3 33 0-19 Previous Yes 62 131 Asymptomatic Symptomatic For symptoms 'Incidental' laparotomy No 7 48 1 8-02 0-005 In 3) In 15) In 12) Number of 0 7 48 I(n -39) pres ious 1 19 59 laparotomies 2 10 25 Figure 1: Summarv ofpatients. 3 9 18 4 11 12 13 17 1 14-06* 0 0002 Site ot Ileal 24 57 resection C(olonic 15 26 Results Both 23 48 2 0(61 0-74 There were 156 (62%0) women (mean age 45 years, range 17-75), and 95 (38%) men (mean */ test tfr linear trend. age 45 years, range 14-82). The mean duration of Crohn's disease was 17 years (range 1-54). The site of macroscopic Crohn's disease was ileum in 121 (48%), colon in 76 (30%), and both ileal and UNIVARIATE ANALYSIS OF RISK FACTORS (Table) colonic disease in 54 (22%). Sex Sex did not influence the probability of gall PREVALENCE OF GALL STONES (Fig 1) stones as 42 (27%) of 154 women with Crohn's disease had gall stones at some time, compared Two female patients and one male patient had http://gut.bmj.com/ had cholecystectomy before the diagnosis of with 27 (29%) of94 men (X4=0 06, df= 1, p=0 8, their Crohn's disease and are excluded from the not significant). There was some evidence that sex may be a analysis. Sixty nine (28%) of the remaining 248 stones. Of 42 patients either had gall stones on ultrasono- risk factor for symptomatic gall or women with gall stones, 14 (33%) were sympto- graphic screening (n=42) had previously had 27 men for stone disease matic, whereas only four (15°/) of with cholecystectomy gall (n=27). gall stones had symptoms (x =2 92, df=1, Cholecystectomy had been undertaken for on September 25, 2021 by guest. Protected copyright. symptomatic cholelithiasis in 15 and 'incident- p=0 09). ally' for gall stones detected at laparotomy for Crohn's disease in 12. Only three of 42 cases detected by ultrasound reported recurrent Age attacks of biliary colic. Although the overall The median age at which gall stones were prevalence of gall stones in this series was 28%, detected was 47 years (range 20-82). The median only 7% had symptomatic stones. age of the 179 patients without gall stones was 39 years (range 14-75). The prevalence of gall stones increased with age and was 42°, in patients over 60 years of age (Fig 2). The W association of gall stones with age was statistic- 1 Gall stones ally significant (X2 treid) =10 0, df= 1, p=0 002). No gall stones 60 r Duration ofdisease 54 53 The median duration of Crohn's disease among 50H patients with gall stones was 19 years (range C', 40 F 1-54) at the time of diagnosis of the gall stones. The median duration of Crohn's disease in 30 30H patients without gall stones was 13 years (range 0co 1-50). 0 z 20- Figure 3 shows the prevalence of gall stones related to the duration of Crohn's disease. The 10 prevalence of gall stones increases with duration 360o% 27 412 0o | of disease and rises to 51/, in patients with - 185% () r--- '. - I Crohn's disease for more than 30 years. The < 20 21-30 31-40 41-50 51-60 61 association of gall stones with duration of Age groups (y) Crohn's disease was statistically significant I'gure 2: P'revalence of gall stones in diJJerent age groups.
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