Celiac Disease and Its Complications: A Time Traveller's Perspective

Abstract

From the perspective of people with celiac disease, the case-control study confirms that there is an association between clinically diagnosed celiac disease and an increased risk of lymphoproliferative malignancy and gives a precise estimate of the contemporary risk. Taken with the other available estimates the relative risk of NHL is around 3- to 4-fold compared with the general population. If we instead focus on absolute risks as measured by incidence rates the available estimates from Derby, United Kingdom, showed that for people with celiac disease the absolute risk of NHL was 1 in 1421 person-years and for small bowel lymphoma 1 in 5684 person-years.18 From a wider, population-based study also from the United Kingdom, the risk beyond 1 year after a diagnosis of celiac disease of any lymphoproliferative malignancy was approximately 1 in 1200 person-years.19. From the perspective of the general population and the possibility of preventing cases of NHL we can use the figures from the current case-control study to calculate the population attributable fraction. To do this we must assume that the relationship between NHL and celiac disease is causal. From the overall estimate from the current study the population attributable fraction is about 0.1%; that is, if we were to remove celiac disease as a risk factor for NHL, then we would prevent 0.1% of NHL occurrence. One could argue that "undetected celiac disease" if diagnosed and treated might prevent a greater proportion of NHL. However, evidence from the 2 case-control studies that included screening for undetected celiac disease suggest that the association with this condition is not as strong as in clinically diagnosed disease.6,20 In addition, there is no evidence that imposing a gluten-free diet on such "screen-detected" individuals prevents malignant complications. From a general population perspective, the incidence of EATL in the Netherlands is reported to be approximately 1 per million person-years21 and is of a similar order of magnitude in Scotland.22 Of the 43 people with refractory celiac disease II in the current study,13 16 developed lymphoma. Thus, we can crudely estimate that refractory celiac disease II is about 3 times more common than EATL itself-perhaps around 0.3 per 100,000 population. From the perspective of people with celiac disease, the current study highlights the severity of the clinical course in refractory celiac disease while not giving us an absolute risk for the majority of people with celiac disease. Nevertheless, taking the data from Derby presented into account, we can be fairly confident that this serious complication of celiac disease is unusual. In summary, Samuel Gee's likely understanding of the state of celiac disease were he to visit us in 2008 is as follows. Celiac disease is now commonly found, but severe and fatal outcomes from it remain rare. Lymphoproliferative malignancy is such an infrequent complication of celiac disease that the majority of gastroenterologists may never see it among the population of celiacs they diagnose and follow-up. Although dietary treatment, which works for almost all, is now available for those unlucky few who do not respond, aside from long-term corticosteroids and the associated side effects thereof, no good alternative yet exists. The precise size of this group of patients, and the magnitude of the risk to them, is still being elucidated, and we can only hope that a visit a further 120 years in the future will reveal progress in these respects. © 2009 AGA Institute.