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The aetiology of ulcerative colitis and Crohn’s disease remains an enigma. There is, however, a growing consensus that early events/exposure are of importance and constitute a “window of opportunity”. Both analytical and observational studies as well as animal models give credence to this hypothesis. Smoking has, until recently, been the only factor that has been consistently associated with an increased risk of Crohn’s disease and a decreased risk of ulcerative colitis. Appendicectomy has now been added to this very short list as there has been a consistent finding in several studies that this operation is associated with a decreased risk of ulcerative colitis.1 ,2 Duggan et al’s study (see page 494) confirms these results. Their findings for childhood hygiene are in accordance with previous studies where the availability of hot running water is associated with Crohn’s disease but not ulcerative colitis.3 However, no other aspects of childhood hygiene were associated with either Crohn’s disease or ulcerative colitis, including Helicobacter pylori serology. In the case of appendicectomy, their results are also in accordance with previous studies, showing that appendicectomy is associated with a strong protective effect against ulcerative colitis1 ,2 which is even more pronounced if surgery was performed before the age of 20 years.
How should the findings be interpreted?
Duggan et al are extremely cautious when interpreting their results especially with regard to hot water supply in childhood, but underline that their findings constitute further evidence that exposure to certain environmental factors during childhood is important. However, with regard to appendicectomy the authors emphasise that removal of the appendix could be causally linked to the decreased risk of ulcerative colitis. This emphasis is supported by results in an animal model4 but an alternative explanation, not necessarily mutually exclusive, is that appendicitis could be inversely associated with the risk of ulcerative colitis. In Sweden there has been a dramatic decline, from 13 000 to 10 000 operations annually, in the number of appendicectomies performed over the past 10 years. This decline is most pronounced in younger age groups.5Moreover, there are strong indications that this effect is not due to better diagnostic procedures but actually reflects a decrease in the incidence of appendicitis. The underlying reason for this decline is unclear, but unspecified childhood exposure could also be relevant to the lifetime risk of appendicitis as illustrated by the hypothesis put forward by Barker ...“That the rise of appendicitis in western Europe since the late 19th century could be due to improvement in sewage disposal and water supplies, leading to an enteric infection in childhood at an older age.”6 The increased use of day care centres for very young children since the late 1960s could be the underlying reason for the decreasing trend.
Previous observational studies have shown an association between both ulcerative colitis and Crohn’s disease and early infectious events.7 ,8 Moreover, in studies from the 1960s and 1970s early weaning was implicated as a risk factor for both diseases and a similar finding has been reported for high socio-economic status.8 ,9 Later studies have not confirmed these associations.2 ,7 The assumption that hot water supply during the first part of this century was crucial for the better survival of young children with severe infections, which were more likely to occur after early weaning, could explain Duggan et al’s findings. In later studies the absence of an association with both socio-economic status and early weaning outside the United Kingdom could be explained by better hygiene and a decrease in infant mortality. The two diverging trends of an increase in the incidence of ulcerative colitis and Crohn’s disease and a decrease in that of appendicitis could therefore be different sides of the same coin.
One way of resolving this issue would be to examine the need for appendicectomy in a larger data set. Such studies should focus on the extent to which there is a difference in the protective effect against ulcerative colitis among those undergoing appendicectomy for appendicitis compared with those subsequently found to have a normal appendix at surgery. The results from such studies should reveal whether appendicectomy alone protects against ulcerative colitis or whether appendicitis is necessary.
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