Short summary

Celiac disease was previously thought to be a rare disease, primarily occurring in children and with a narrow range of gastrointestinal symptoms, but the understanding of the disease has developed over the last decades and it is now recognized as a common disease of all ages, and with a wider range of symptoms, both gastrointestinal and extra-intestinal.

The aim of this study is to describe the prevalence and changes over time of the clinical presentation and diagnosis of celiac disease in Danish children, contributing to an updated picture of the clinical presentation of celiac disease.

Rationale

Celiac disease is a chronic inflammatory disease elicited by gluten in genetically susceptible individuals. It is characterized by a variable combination of gluten-dependent symptoms, celiac disease-specific antibodies, human leukocyte antigens (HLA) DQ2/DQ8 and enteropathy.

The prevalence of diagnosed celiac disease is 0.15 % in Denmark, which is lower than in comparable countries such as Sweden and Norway. It is unknown whether this difference is caused by a true difference in prevalence or by a higher proportion of undiagnosed cases due to differences in awareness or clinical presentation.

The prevalence of celiac disease is increasing. The incidence of diagnosed celiac disease in Denmark increased fourfold from 1996 to 2010. The increasing prevalence might be due to better diagnostics and knowledge about the disease as well as to a true increase in the prevalence, as it is seen in other immune-mediated diseases. Most likely the increase is due to a combination of effects. It is unknown whether the prevalence has increased further since 2010.

Celiac disease can present at any age. The clinical manifestations vary from asymptomatic to severely affected cases and include gastrointestinal as well as extraintestinal symptoms, that are triggered by the intake of gluten. Studies have suggested a shift in symptoms towards a milder presentation, but other studies have not confirmed this finding. The clinical presentation of celiac disease and the changes over time in Danish children and adolescents are not described.

Celiac disease is associated with other autoimmune diseases such as type I diabetes mellitus, juvenile rheumatoid arthritis, autoimmune thyroid disease and IgA-nephropathy, and screening for celiac disease in patients with these diseases is recommended. The association is partly explained by sharing of predisposing genes; however, it is speculated if onset of one autoimmune disease may trigger onset of others, suggesting that early diagnosis and treatment of celiac disease may prevent development of other autoimmune diseases.

The diagnosis of celiac disease was previously based on histological evaluation of duodenal biopsies with demonstration of villous atrophy and crypt hyperplasia with increased levels of intraepithelial lymphocytes (1990 guidelines from the European Society of Gastroenterology, Hepatology and Nutrition (ESPGHAN)). The duodenal biopsy requires an upper endoscopy in general anesthesia.

In 2012 ESPGHAN published new guidelines for the diagnosis of celiac disease in children that are based on serological and genetic testing. In children with gastrointestinal symptoms of celiac disease, high levels of celiac disease-specific antibodies (tissue transglutaminase 2 IgA and endomysial antibodies IgA) and HLA DQ2/DQ8 genotype, the diagnosis can be made without duodenal biopsies. It is unknown how many diagnosed children omit the biopsy.

We will describe the prevalence of celiac disease in children and adolescents as well as changes over time of symptoms, clinical findings and laboratory test results. Furthermore, we will describe co-morbidity and the timely relation with celiac disease diagnosis. And finally, we will describe the consequences of the ESPGHAN 2012 diagnostic guidelines for children at Hans Christian Andersen Children's Hospital.

The study will contribute to an updated picture of the clinical presentation of celiac disease and possibly provide us with new information on the detection of the disease. Furthermore it will investigate whether the 2012 ESPGHAN guidelines has lead to fewer biopsies in the diagnosis of celiac disease.

Description of the cohort

The cohort is composed of children and adolescents (<18 years of age) with celiac disease, diagnosed at HC Andersen Children's Hospital in the period 2007 to 2017.

Data and biological material

The medical records include information on symptoms, clinical findings and co-morbidity at time of diagnosis; celiac disease specific antibodies, HLA typing and other laboratory test results as well as pathologist description of duodenal biopsies.

Collaborating researchers and departments

HCA Research, HC Andersen Childrens Hospital, Odense University Hospital

• Professor Steffen Husby, DMSc
• PhD student Stine Dydensborg Sander
• PhD student Cæcilie Crawley Larsen