Long-Term Mortality in People With Celiac Disease Diagnosed in Childhood Compared With Adulthood: A Population-Based Cohort Study

Masoud Solaymani-Dodaran, M.D., Ph.D., M.P.H.; Joe West, M.B., Ph.D., M.R.C.P.; Richard F.A. Logan, M.B., M.Sc., F.R.C.P.

Disclosures

Am J Gastroenterol. 2007;102(4):864-870. 

In This Article

Discussion

The increase of long-term mortality, i.e., greater than 5 yr after diagnosis, we have found with childhood-diagnosed celiac disease was fairly unexpected and is in marked contrast to the pattern seen with adult diagnosed disease in our study. All the deaths in children occurred more than 5 yr after diagnosis with the main cause of the increase being deaths from accidents, suicide, and violence, which accounted for about one-third of the 13 excess deaths. An increase of mortality from malignant disease accounted for about a quarter of the excess deaths in childhood-diagnosed disease. In adults the small but persistent long-term increase of mortality was partly attributable to an increased mortality from malignant disease, predominantly gastrointestinal cancer and lymphoma.

Particular strengths of our study are that the cohort is population based and that there has been little loss to follow-up for mortality, with only 5% having been lost or having emigrated. We have been able to estimate the relative increases in mortality rates by comparing the experience of this cohort with regional data and for the first time make long-term comparisons between those people diagnosed with celiac disease in childhood versus those diagnosed as adults. In addition the long-term follow-up has allowed a detailed cause-specific mortality analysis by time since diagnosis, which was not available previously. Potential limitations are that of necessity that the cohort was assembled some time ago and it is possible therefore that because of recent changes in the mode of the diagnosis of celiac disease any excess mortality related to severity of disease at present may be overestimated. Nonetheless, we found no evidence of this when we stratified by decade of diagnosis. In addition, we have made the assumption that dietary restriction was reasonably well adhered to in this group, yet we have no objective evidence to confirm this. It is conceivable that the increased mortality from some malignancies may be restricted to those people who were either not compliant or, perhaps, did not respond to dietary treatment.

Reasons why children diagnosed with celiac disease should be at increased risk of external causes of death are speculative. Some case reports and case series have reported that untreated celiac disease is associated with psychiatric morbidity.[10,11,12] Hallert et al. have reported that adult patients established on a gluten-free diet have a tendency toward a poorer quality of life than the general population or other people with chronic diseases.[13,14] Diagnosing celiac disease early in life has been considered desirable to avoid possible complications of long-term gluten exposure. However, the actual process of labeling a child with celiac disease and requiring them to adhere to a gluten-free diet may be, in some way, detrimental. Some surveys of behavior in children have reported that those with chronic diseases are more likely to be "risk takers" compared with healthy children.[15,16] Children with insulin-dependent diabetes mellitus, for example, do appear to have a slightly increased risk of external causes of death.[17] In contrast, survivors of childhood cancer are not at any excess risk of external cause of death yet they, in general, are not required to take life-long therapy.[18,19,20] Poor adherence to a gluten-free diet and depression or other psychiatric morbidity are likely to be associated. As with other chronic illness we suspect the psychiatric morbidity is likely to result in reduced compliance. However, we cannot exclude the converse, namely, that better dietary adherence might improve any depression or other psychiatric morbidity and make self-harm less likely.

Our findings for those people diagnosed as adults are similar to recent studies from both the United Kingdom and Sweden in which a 30-40% mortality increase was found.[3,4] Indeed, the decline in mortality risk over time from diagnosis in these studies is remarkably similar to our findings. In these two studies most of the long-term follow-up (i.e., greater than 10 yr) was mainly in people diagnosed as adults, so comparisons between childhood-diagnosed disease and adulthood-diagnosed disease are difficult to interpret. Despite an average follow-up of only 8.1 yr in their cohort Peters et al. did find that those people diagnosed between the ages of 2 and 10 yr had an all-cause SMR of 2.2 (based on 11 deaths), which is not inconsistent with our findings.[3] Compared with other studies our mortality estimates for adults are in general lower,[6,7,8] but the absence of deaths from breast cancer in women is consistent with other studies that have found a substantially reduced incidence of this malignancy in women with celiac disease.[4,21,22] The finding of an increased risk of cerebrovascular disease has also been observed previously.[3,23]

In summary, adults diagnosed with celiac disease had only a reassuringly small increase of long-term mortality, which is, for comparison, only about half that seen in Crohn's disease.[24] In contrast, children diagnosed with celiac disease had an increase of long-term mortality, most of which was difficult to attribute directly to the disease itself. While the absolute mortality increase was small the excess of deaths from accidents, suicides, and violence is cause for concern.


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