Scandinavian Journal of Gastroenterology

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Prevalence of Inflammatory Bowel Disease among Relatives of Patients with Crohn's Disease U. Monsén, O. Bernell, C. Johansson & G. Hellers To cite this article: U. Monsén, O. Bernell, C. Johansson & G. Hellers (1991) Prevalence of Inflammatory Bowel Disease among Relatives of Patients with Crohn's Disease, Scandinavian Journal of Gastroenterology, 26:3, 302-306, DOI: 10.3109/00365529109025046 To link to this article:

Published online: 08 Jul 2009.

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Prevalence of Inflammatory Bowel Disease among Relatives of Patients with Crohn’s Disease u. MONSBN, 0.BERNELL, c. JOHANSSON & G. HELLERS Dept. of Medicine and Dept. of Surgery, Huddinge University Hospital, Stockholm, Sweden

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MonsCn U, Bernell 0, Johansson C, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with Crohn’s disease. Scand J Gastroenterol 1991, 26, 302-306 The prevalence of familial inflammatory bowel disease was 13.4% in a populationbased study of 1048 patients with Crohn’s disease (CD). Seventy-two of the index cases had 82 first-degree relatives. Forty-nine were more distantly related (19 first cousins from the same generation as the index patient). The prevalence of CD among first-degree relatives was 21 times higher than among non-relatives. Four of six monozygotic twins were concordant. The age at onset was 25 years in the patients with familial CD, compared with 33 years in the entire group. An additional 53 relatives were found to have ulcerative colitis (UC). The prevalence of UC among first-degree relatives of patients with CD was six times higher than among nonrelatives. Key words: Crohn’s disease; familial Crohn’s disease; inflammatory bowel disease; ulcerative colitis

Ulla MonsCn, M . D., Dept. of Medicine, Huddinge Sjukhus, S-141 86 Huddinge, Sweden

Two years after his first presentation of regional MATERIALS AND METHODS enteritis Crohn published the first report on familial occurrence of Crohn’s disease (CD) (1). Patients were collected from two epidemiologic Since then there have been numerous reports of studies of IBD in Stockholm County (12,13; multiple cases among relatives (2-5), although unpublished observations) during 1955-1984. very few have been from defined populations Only patients who were registered citizens of Stockholm County at the time of definite diagnosis 67). The etiology of CD is still unknown, but the were included. presence of familial aggregation suggests that a All patients admitted to hospitals in Stockholm genetic factor is of importance for the suscepti- County are registered in a central admissions bility to the disease. CD has also been shown to register, and this register was searched for posbe associated with other genetically determined sible cases of CD. Details’of the search procedure diseases such as ankylosing spondylitis (8) and have been published previously (12,13). During Turner’s syndrome (9). However, a definite the period of study 1297 patients were diagnosed association with a particular HLA haplotype has as having CD. so far not been proved (10,ll). The diagnostic criteria were in accordance with The aim of the present study was to investigate the previous studies (12,13) and included a the prevalence of inflammatory bowel disease history of typical symptoms and two unequivocal (IBD) among relatives of patients with verified roentgenograms with at least a 3-month time CD in a population in which the prevalence of interval. For the operated patients the scoring the disease is known. table suggested by Lennard-Jones (14) was used.

IBD among Crohn’s Disease Relatives

Table I. Number of persons in 10 CD families with both CD and UC among the relatives Families (no.)

CD relative (no.)

UC relative

6 1 2 1

1 2 3

1 2 1 1




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In 1955 Stockholm County had a population of 1.18 million. It increased to 1.59 million at the end of 1984. The mean male to female ratio during the period of study was 1: 0.96 in the age group 45-49 years. The follow-up data were obtained through personal telephone calls or letters. At the time of follow-up 183 patients were dead and 19 were living in other countries. Nine were adopted and had no children of their own and did not know of their relatives. Three patients had senile dementia, and another three were mentally retarded. Thirty-two patients were lost to followup (unlisted telephone number, no telephone, not answering letters, or no address). Thus, follow-up was complete for 1048 patients with CD . Those who answered that they had a relative with IBD received an extended questionnaire. The relatives who were said to have IBD were contacted and had their diagnosis verified. The follow-up was carried out between September 1988 and June 1989. One hundred and seventy-three answered positively about having a relative with IBD. In 33 cases IBD in the relative could not be proved or the index patient refused to give the name of the relative. The pedigrees of the remaining 140 index cases were then drawn. RESULTS General prevalence and family patterns There were 88 patients with a positive family history of CD only and 10 with both CD and ulcerative colitis (UC). This corresponds to a prevalence of CD of 9.4%. Another 42 patients


had a positive family history of UC only. Thus, the overall prevalence of IBD among the CD patients was 13.4%. The male to female ratio was 1: 1.25 among all the CD patients, whereas it was 1: 1.5 among the patients with a positive family history of CD (not significant; chi-square test). The 98 patients had 131 relatives with CD, and in these families there were an additional 11 relatives with UC (Table I). In 65 cases only 1 relative had CD. Nineteen index cases had two affected family members, two had three, and two index cases had. four. Fourteen CD family members were found in the CD and UC mixed families (Table I). Mean age at follow-up and age at onset The mean age at diagnosis was 25 years for the index patients with a positive family history (range, 9-69) and 33 years for the remaining CD patients (range, 3-83). The mean age of the 98 index patients was 48.9 years at the time of follow-up. The mean age of the index patients’ children was 24 years at the time of follow-up. First-degree relatives Among the 98 patients with a positive family history of CD 72 (30 males and 42 females) had 1or 2 first-degree relatives (parent, sibling, child) with the disease. There were 10 index patients with 2 first-degree relatives with CD. Altogether there were 82 first-degree relatives with the disease (Table 11). Among the first-degree relatives with CD 18% were mothers and 11% fathers. Among the diseased siblings there was no major difference between the sexes-28% were females and 24% males. Among the children 16% were females and 18% males. Each CD patient in Stockholm County can be estimated to have five first-degree relatives (M. WalldCn, unpublished observations, 1984). The number of first-degree relatives at risk can be estimated to be 5240. In this series 82 first-degree relatives with CD were found. With a CD prevalence of 74: 100,000 in the county in 1985 (unpublished observation) there is an estimated relative risk (observed prevalence/expected prevalence) of 21.


U.Monstn et al.

Table 11. Seventy-two families with 82 diseased first-degree relatives Relatives (no.)

Healthy relative

CD (no.)

UC (no.) ~-


Mothers Fathers Daughters Sons Sisters Brothers All

72 71 58 62 80 80 423

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There was no married couple with CD in the present series. Second- and third-degree relatives Thirteen second-degree relatives were found in this survey and an additional 36 more distantly related patients. Nineteen of these were first cousins, of whom 14 were females and 5 males. Most of the cousins came from the mother’s side, and notably, there was no male cousin with CD on the paternal side of the family. Twins There were six pairs of twins in this series; all were monozygotic. Four pairs were concordant with regard to CD (two male and two female pairs), CD and UC in the same family In our series of 1048 patients with CD there were 42 index patients who had 1 family member with UC. In an additional six families there was a first-degree relative with both UC and CD and, in four CD families, more distant relatives with

uc .

Altogether there were 53 relatives with UC in the families of the index patients. More than half of them (28 of 53) were first-degree relatives. The estimated relative risk is 6, when using the same calculation as above and on the basis of a background prevalence of 87 of 100,000 for UC (13; unpublished observations). DISCUSSION Most previous studies are from major gastroenterologic centers with selected patient popu-

57 62 46 53 54 59

13 8 11 22 19

1 0 2 0 3 0





lations (2-5, 15-17). The prevalence of IBD in the background population is not known in these series. In some studies a questionnaire has been used (7,15), and in one of these (15) the response rate was low (61%). In other series the diagnosis of the relatives was not verified (15,17). To calculate the relative risk for each family member, it is necessary to draw pedigrees for all patients. This was done in some of the recent studies (15-17) in which the number of patients was fairly limited. Therefore, approximate numbers of firstdegree relatives were used to calculate the relative risk. The relative risk for IBD could then be calculated for parents only when the exact number was known. It was found to be 1.53% (only CD among the parents, 1.0%). This is in the same range as for other series (5,15,16). The prevalence of a family history of CD in some previous studies is shown in Table 111. The crude family rate varies from 6% to 22%. The significance of the discrepancies is difficult to evaluate, since the quality of the studies varies considerably. Most American studies have shown a high family prevalence rate (4,15,17), which may be due to bias of ascertainment and, in some cases, a high percentage of Jews in the index population (17, 18). In all previous studies, as in the present, more first-degree relatives than second- and thirddegree relatives were found. It is notable that more first cousins (third-degree relative) than second-degree relatives have IBD. The reason could be that the index patient and first cousins are from the same generation and have the same environmental influence. It could also reflect a general increase in IBD incidence (12,13).

IBD among Crohn’s Disease Relatives


Table 111. The prevalence of family history of CD in previously published studies and in the present study

Author Mayberry et al., 1980 (7)* Weterman & Pena, 1984 (5)* Lasher et al., 1986 (15) Kiister et al., 1987 (16) Present study Present study*

CD patients (no.)

Index patients

Diseased relatives



CD (no.)


139 400 100 265 1048 1048

13 32 40 16 140 94

9 8 22 6 13.4 8.9

7 34 18 17 122 82

8 6 6 2 53 28

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* First-degree relatives only.

A predominance of females among the index cases was noted in this survey but not in other series (15,17). There is no obvious explanation for this finding. A lower age at diagnosis was also found, as in other series (4, 15). The mean age of the index cases’ children was 24 years at the time of followup, which means that there is still time for more children to develop IBD. McConnell has presented a theory about a common genetic background for C D and U C (6,20). According to this theory, an individual with few susceptibility genes is likely to develop UC, whereas someone with more susceptibility genes is likely to develop CD. This could explain why we found more UC relatives of C D patients in this study than C D relatives of UC patients as we reported in a previous study from the same catchment area (19). Our findings of four concordant twins among six monozygotic twin pairs in combination with the previously published Swedish twin study (21) strengthen this theory. In another recent genetic study (22) we found evidence of a major gene in UC by using a complex segregation analysis. This method of analysis is so far the only way to distinguish between genetic and environmental influence and to characterize the genetic factors involved. Further such genetic studies of CD may confirm McConnell’s theory. ACKNOWLEDGEMENTS This study was supported by grants from the

Foundations of the Karolinska Institute and Professor Nanna Svartz.


1. Crohn BB. The broadening concept of regional enteritis. Am J Dig Dis 1934, 1, 97-99 2. Almy TP, Sherlock P. Genetic aspects of ulcerative colitis and regional enteritis. Gastroenterology 1966, 51.757-761 3. Korelitz BI. Epidemiological and psychosocial aspects of inflammatory bowel disease with observations on children, families and pregnancy. Am J Gastroenterol 1982, 77, 929-933 4. Farmer RG, Michener WM, Mortimer EA. Studies of family history among patients with inflammatory bowel disease. Clin Gastroenterol 1980, 9,271-278 5. Weterman IT, Pena AS. Familial incidence of Crohn’s disease in the Netherlands and a review of the literature. Gastroenterology 1984, 86, 449-452 6. Lewkonia RM, McConnell RB. Progress report. Familial inflammatory bowel disease-heredity or environment? Gut 1976, 17, 235-243 7. Mayberry JF, Rhodes J , Newcombe RG. Familial prevalence of inflammatory bowel disease in relatives of patients with Crohn’s disease. Br Med J 1980, 1, 84 8. Moll JMH. Inflammatory bowel disease. Clin Rheum Dis 1985, 11, 87-111 9. Prise WH. A high incidence of chronic inflammatory bowel disease in patients with Turner’s syndrome. J Med Genet 1979, 16, 263-266 10. Smolen JS, Gang1 A , Poltenhauer P, Menzel EJ, Mayer WR. HLAantigensinIBD. Gastroenterology 1982, 82, 34-38 11. Purrmann J , Bertram J, Cleveland S, Gemsa R , Berges W, Stohmeyer G. Association of Crohn’s disease with the HLA phenotype B44, Cw5. Z Gastroenterol 1988, 26, 658-662 12. Hellers G. Crohn’s disease in Stockholm County 1955-74. A study of epidemiology, results of surgical

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U.MonsCn et al.

treatment and longterm prognosis. Acta Chir Scand 1979 (SUPPI490), 1-84 13. Nordenvall B, Brostrom 0, Berglund M, et al. Incidence of ulcerative colitis in Stockholm County 1955-1979. Scand J Gastroenterol 1985, 20, 783790 14. Lennard-Jones JE. Natural history and characteristics of Crohn’s disease. Postgrad Med J 1968, 44, 674-678 15. Lashner BA, Evans AA, Kirsner JB, Hanauer SB. Prevalence and incidence of inflammatory bowel disease in family members. Gastroenterology 1986, 91, 1396-1400 16. Kiister W, Purrman J, Funk S, Strohmeyer G. Zur Genetic des Morbus Crohn. Med Klin 1987, 679682 17. Roth MP, Petersen G, McElree C, Vadheim C, Panish J, Rotter J. Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews. Gastroenterology 1989, 96, 1016-1020 Received 30 July 1990 Accepted 18 September 1990

18. Singer HC, Anderson JGD, Frischer H, Kirsner JB. Familial aspects of inflammatory bowel disease. Gastroenterology 1971, 61, 423-430 19. MonsCn U, Brostro 0, Nordenvall B, Sorstad J, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis. Scand J Gastroenterol 1987, 22, 214-218 20. McConnell RB. Genetics of inflammatory bowel disease. In: Allan RN, Keighley MRB, AlexanderWilliams J, Hawkins C, eds. Inflammatory bowel disease. Churchill Livingstone, Edinburgh, 1 9 8 3 , s 16 21. Tysk C, Lindberg E, Jarnerot G , FlodCrus-Myrhed B. Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 1988,29, 99C-996 22. Monstn U, Iselius L, Johansson C, Hellers G. Evidence for a major additive gene in ulcerative colitis. Clin Genet 1989, 36, 411-414

Prevalence of inflammatory bowel disease among relatives of patients with Crohn's disease.

The prevalence of familial inflammatory bowel disease was 13.4% in a population-based study of 1048 patients with Crohn's disease (CD). Seventy-two of...
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