Abstract

Celiac disease is markedly underdiagnosed in Denmark: is it time for screening?

In our study of 16,776 participants from eight population-based cohort studies examined during 1976–2012 and followed in nation-wide registries, the prevalence of undiagnosed celiac disease was 1.0%.

Introduction

Celiac disease is a lifelong autoimmune disease caused by an abnormal immune response triggered by the ingestion of gluten proteins from wheat, rye and barley, in genetically susceptible individuals. Celiac disease is common worldwide and affects around 1% of the population, but data from Denmark has been lacking. The treatment of celiac disease is life-long gluten-free diet. Celiac disease has been described by an iceberg metaphor, where only the clinical detectable cases can be seen above waterline. Still today, regardless of increased attention and improved diagnostic tests, many cases of celiac disease remain undiagnosed. Yet, screening for celiac disease in the general population remains a controversial issue. We screened a Danish adult population for celiac disease and human lymphocyte antigen (HLA) DQ2 and HLA DQ8, with the overall objective to increase our knowledge about the epidemiology of celiac disease and the potential of screening for celiac disease among adults in Denmark. Furthermore, in a new study of eight population-based cohort studies comprising 16,776 participants examined during 1976–2012 and followed in nation-wide registries we investigated long-term consequences of undiagnosed celiac disease with regard to mortality and incidence of cancer and other chronic diseases.

Methods

In the first study (The Health2006 study), we screened 2,297 individuals from the populationfor celiac disease antibodies, HLA DQ2 and HLA DQ8. Celiac disease antibody positive participants (IgA/IgG tissue transglutaminase (TTG) ≥ 7 U/ml and/or IgA/IgG deamidated glaidin peptide (DGP) ≥ 10 U/ml) were invited to a clinical examination by a gastroenterologist including duodenal-biopsies. Furthermore, the participants underwent allergy tests, physical examination and questionnaires.

In the biobank study, serum samples from 16,776 individuals from eight population-based cohort studies were screened for IgA and IgG TTG and IgG DGP. Undiagnosed celiac disease was defined as celiac disease antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/ml and/or IgG-DGP ≥ 10 U/ml) in individuals without a diagnosis of celiac disease recorded in the national patient register. Participants were individually linked to, and followed in, the Danish nation-wide registries with regard to vital status and incidence of diseases.

Results

The prevalence of biopsy-proven screen-detected celiac disease in the Health2006 study was 0.5%, which was almost ten times higher than the known prevalence in the National Patient Registrer. 47.7% were HLA DQ2 and HLA DQ8 positive and thus genetically at risk of celiac disease. We found no differences in symptoms before screening between the participants with and without screen-detected celiac disease. The participants were generally satisfied with their participation in the screening program, and most of the diagnosed individuals experienced improved self-reported well-being on gluten-free diet.

In the biobank study comprising 16,776 individuals, we found that undiagnosed celiac disease, defined as celiac disease antibody positivity without a known register-based diagnosis of celiac disease, was associated with increased incidence of gastrointestinal cancer, breast cancer, cancer of the uterus, head and neck cancer, and cardiovascular disease, but we found no significant association with mortality. The prevalence of undiagnosed celiac disease was 1.0 % with no statistically significant increase over time (1976–2012).

Conclusion

We found evidence that celiac disease is markedly underdiagnosed in Denmark. Surprisingly, almost half of the Danish general population screened for HLA DQ2 and DQ8 were HLA DQ2/DQ8 positive, illustrating that HLA screening only would exclude about half of the population if used in screening and that HLA DQ2 and HLA DQ8 distribution is probably not the reason for why the prevalence of celiac disease is low in Denmark.

In our study of 16,776 participants from eight population-based cohort studies examined during 1976–2012 and followed in nation-wide registries, the prevalence of undiagnosed celiac disease was 1.0%. Undiagnosed celiac disease was associated with increased risk of cardiovascular disease and cancer suggesting that untreated celiac disease has serious long-term health consequences.

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