Crohn’s disease is a serious chronic condition belonging to the inflammatory bowel disease (IBD) group.
Although its etiology is still unknown, everyone agrees that both genetic and environmental factors are
present. The opinions differ when it comes to the weight of each of the two factors, and to their interpretation. The  exciting field of genetics has been lately getting a lot of attention and funding, but results have so far fallen short of expectation. On the other hand, the most apparent argument for the environmental factor is a several fold increase in incidence in the developed world from the 1960s, and more recently a similar trend in developing countries.

The observation that the number of Crohn's patient spouses developing the same disease during marriage
is greater than expected by chance has been slowly gaining acceptance. Introduced cautiously in the 1980s by the U.K. researchers (1), supported by studies from the U.S. (2) and France (3) in the early 1990s, this has recently made the title prominence in follow-up study from France and Belgium (4). Initial study from 1994 reported 10 IBD cases in married couples of Northwestern France and Belgian county of Liege. The recent study has found 14 in NW France and 13 in all of Belgium, concluding that this number is higher than expected by chance both in NW France (p < 0.00001) and Belgium (p < 0.05). Half of the IBD couples were concordant for Crohn's disease, while the other half was shared between mixed couples and couples concordant for ulcerative colitis. French IBD register used for these studies has been established in 1988 as a detailed database of all reported cases from NW France, and 1994 study reported that 95% of all gastroenterologists have participated.

A study of increased intestinal permeability, believed to be an early event in pathogenesis of Crohn's
disease, in relatives and spouses of patients have shown a trend where length of association and frequency of contacts with a patient correlated to abnormal permeability (5), although a statistical significance was not reached due to small number of spouses and first degree relatives.

In the view of Crohn's disease rarity (roughly 1 in a 1000 population), its communicability has been
suspected in clusters of unrelated affected individuals that have shared a close relationship or a household
(6, 7). Four young adult females who have been close friends in their teens have developed Crohn’s disease several years after parting to attend college (6). A young woman who was adopted lived with her "grandmother" and they both had Crohn's disease (7). Geographical clusters have also been reported (8-10). The most investigated cluster was in the parish of Blockley, U.K. (10), where the observed number of mostly unrelated patients (twelve) was much higher than expected (less than two) for parish population of about 2000, with no excess of patients in adjacent parishes. The parish has its own water supply, but extensive microbiological sampling have not identified a possible waterborne infectious agent. A study from Holland investigating water supply and disease incidence also was not able to establish the link between them (11). Blockley study was also negative for trace metal deficiencies in the soil and HLA genetic typing of patients. Most recently, a cluster was discovered in a small town in southeast Brazil (12, unpublished data), with 9 patients in a community of 15000, in a country that has a much lower prevalence compared to the developed countries. Contacts between patients before the onset of their symptoms were not investigated in any of the above geographical clusters.

Looking for factors in postoperative recurrence of Crohn’s disease a study examined intestinal mucosal
inflammation induced by the contact with intestinal fluids in surgically excluded ileum (13). It was shown
that recurrence may be triggered by agents in the fecal stream, pointing to fecal-oral route in suspected
transmission of Crohn's disease to genetically predisposed individuals.

Familial Crohn's disease has been always interpreted as a sign of genetic factors, but some reports have
shown that temporal succession of occurrence may indicate infectious origin as well. A family where the
father, the mother, and their 4 children all had Crohn's disease was described (14). The wife of one of the sons subsequently developed the disease as well. In another family, 7 of 11 children developed Crohn's disease, although neither parent was affected. There was no Crohn's disease in previous generations of either family, and no linkage to HLA haplotypes was found. The authors concluded that data presents circumstantial evidence in favor of infectious etiology in these 2 clusters, although they were unable to identify any common infectious agent. Recently there has been a lot of research in the earlier onset in subsequent generations of familial cases. This was initially attributed to genetic anticipation, yet later studies could not find proof for such claims (15). A letter from a physician commenting on this issue has explained earlier onset as a result of higher probability of acquiring an infectious agent due to increased frequency of contacts with patient in a familial setting (16).

Patients are reluctant to consider this evidence, feeling that they are already isolated enough and don't need additional reasons to be avoided by friends and family. Clinicians and patient organizations (CCFA) are also slow to recognize this research. Although the putative infectious agent(s) has not yet been identified, the message of a potential infectious origin should not be confined to the research community but cautiously introduced into clinical practice in order to possibly prevent or reduce occurrence of familial and communal Crohn's disease (16).
 

Acknowledgment - The author would like to thank Pedro D. Gaburri for contributing unpublished data for
Southeast Brazil study.
 
 

References:
 

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