Demographics, clinical features and treatment of pediatric celiac disease

Sammanfattning: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy triggered by ingestion of gluten-containing food in genetically predisposed subjects. The enteropathy is presented with a wide variety of clinical manifestations, which can occur even outside the gastrointestinal tract. In the majority of cases, the diagnosis of CD is based on a small intestinal biopsy showing mucosal alterations, i.e. intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. The treatment, gluten-free diet (GFD), has recently been revised with the addition of gluten-free oats. Oats give a more diversified nutrition and increase the fibre content. The use of oats in CD is though still debated in some reports. A strict life-long adherence to the GFD can be problematic, especially for pediatric CD patients. Sweden reported of one of the highest observed CD prevalences worldwide, i.e. 3%, among 12-year-olds born during what has been described as “the Swedish celiac epidemic”, 1984−1996.The aims of this thesis were to elucidate how pediatric CD has changed during a 41-year period in Sweden, i.e. 1973−2013, in terms of clinical presentation, disease severity, incidence, and demographics. We also wanted to adress the compliance to the GFD, the use of oats in the GFD and the safety of oats inclusion in the diet by measuring urinary nitric oxide (NO) metabolites.Filed information provided data about 2856 pediatric patients  investigated for suspected CD between 1973 and 2013; of which 1030 patients were diagnosed with CD. After the data analyses the mean age of CD patients was shown to increase after the celiac epidemic period. Currently, CD shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, whereas extra-intestinal manifestations are more often displayed among adolescents.We also reported an unusually high pediatric CD incidence rate and  cumulative incidence, likely the highest reported worldwide. We hypothesised that the introduction of new antibody tests would affect the diagnostic activity and accuracy in performing small intestinal biopsies for CD investigation. However, the outcome of diagnostic activity and accuracy could not clearly be attributed to the use of antibody tests due to changes occurring in parallel during the 41-year study period, e.g. a different pattern of symptoms at presentation and improved knowledge of the disease among parents and health professionals.In a questionnaire-based study our patient group reported a high  compliance to the GFD. Long duration of the GFD may, however, influence compliance negatively. Oats have been included to the GFD of our study population in most of the cases without reporting major complications related to their well-being.The urinary measurements of NO metabolites revealed two patient groups, one with high and one with low levels. The two populations did not differ regarding sex, age, compliance to the GFD or oats consumption. Factors such as nitrate-rich foods, asthma or urinary tract infections did not affect the results. The high levels could possibly be attributed to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). The elevated levels of NO metabolites might indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD as not all of them might tolerate oats.