Risk of Morbidity in Contemporary Celiac Disease

Nina R Lewis; Geoffrey KT Holmes


Expert Rev Gastroenterol Hepatol. 2010;4(6):767-780. 

In This Article

Abstract and Introduction


Celiac disease is one of the most common chronic diseases encountered in the Western world with a serological prevalence of approximately 1%. Since it is so common, much comorbidity will occur either as associations or simply by chance, or as complications of the disorder. Many of the published studies purporting to establish the frequency of these occurrences have been limited by factors such as the source and number of patients considered, choice of control groups and ascertainment bias. Recent epidemiological studies have attempted to minimize these sources of error and provide more reliable information. Autoimmune diseases constitute clinically important associations, of which Type 1 diabetes mellitus and thyroid disorders are the most important. Several liver disorders, including primary biliary cirrhosis and primary sclerosing cholangitis, are also associated. The frequency of malignant complications of celiac disease is much lower than earlier studies have indicated, with lymphoma increased by approximately fivefold and the absolute number of tumors is small. The increase in fracture risk in celiac disease is only modest. Although neurological and psychiatric conditions affect celiac patients, no disorder specifically associated with celiac disease has been identified. Reproductive problems have been overexaggerated. It is important that these co-morbidities are recognized because if not, symptoms will be falsely attributed to deliberate or inadvertent ingestion of gluten, rather than prompt a search for a second diagnosis. Furthermore, in a patient with an established diagnosis that is considered falsely to account for the whole clinical picture, celiac disease is likely to remain undetected.


Previously regarded as a rare disorder, it is now appreciated that celiac disease is a major healthcare problem affecting 1% of the general population.[1] Recent population-based studies have provided more robust estimates of risks traditionally associated with clinically diagnosed celiac disease. They have also demonstrated other morbidity factors and, indeed, some benefits from having celiac disease, such as reduced risk of breast cancer in female celiacs[2–7] and lower total cholesterol[1,8] in comparison with the general population.

Before the morbidity associated with celiac disease can be described, the limitations of the studies on which this article is based need to be acknowledged. First, the distinction between clinically diagnosed and undetected celiac disease needs to be reiterated. Despite the development of highly sensitive and specific serological tests allowing noninvasive and large-scale screening of the general population in order to identify individuals with celiac disease,[9] an increased awareness of the condition, and an active case-finding strategy adopted by some centers, there remains a substantial gap between the number of adults with clinically diagnosed celiac disease and those with undetected celiac disease. Currently, the ratio of undetected celiac disease to diagnosed disease is approximately 8:1 in England[10] and 3:1 in Finland.[11,12] In the literature, reported morbidity associated with celiac disease is based on clinically diagnosed disease that only accounts for the minority, or tip of the celiac iceberg.[13] It is unknown if people with undetected celiac disease, lying below the waterline of the celiac iceberg and accounting for the majority of cases of the condition, share similar risks of morbidity to that of clinically diagnosed celiac disease. Second, because celiac disease is common, it follows that many diseases will occur in association. For the purposes of this article, some of the comorbidities will be regarded as complications of celiac disease. Others will be regarded as associations, or simply as occurring by chance.

Further limitations to the published studies include:

  • Selection biases, such as choice and nature of the population studied, continued participation in the study and nonparticipation in the study;

  • Information biases, such as the recalling of events, collection of data by the study investigators and the measurement of the outcomes of interest;

  • Ascertainment biases, such as incidental detection of celiac disease whilst undergoing tests for another condition and vice versa;

  • Confounding factors, such as the apparent reduced risk of lung cancer in celiac disease due to celiacs being less likely to smoke in comparison with people without celiac disease.


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