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Demographics, clinical features and treatment of pediatric celiac disease
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 76 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1473
National Category
Pediatrics Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-122371DOI: 10.3384/diss.diva-122371ISBN: 978-91-7685-977-3 (print)OAI: oai:DiVA.org:liu-122371DiVA: diva2:865981
Public defence
2015-11-19, Linden, ing 65 pl 9, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Funder
Region ÖstergötlandMedical Research Council of Southeast Sweden (FORSS)Region ÖstergötlandSwedish Research Council
Available from: 2015-10-30 Created: 2015-10-30 Last updated: 2015-10-30Bibliographically approved
List of papers
1. The clinical presentation of celiac disease in 1030 Swedish children: changing features over the past 41 years: a long-term follow-up study
Open this publication in new window or tab >>The clinical presentation of celiac disease in 1030 Swedish children: changing features over the past 41 years: a long-term follow-up study
2016 (English)In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 1, 16-22 p.Article in journal (Refereed) Published
Abstract [en]

Background- Aims

The features of pediatric celiac disease have changed in recent decades. We hypothesized that the age at diagnosis continued to increase, whereas the severity of symptoms should decrease.

Methods

In the present study, filed data about 1030 pediatric patients diagnosed with celiac disease between 1973 and 2013 were analysed. Available information covered 99.8% of the small bowel biopsies, and included information on sex, age, and clinical symptoms.

Results

The age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years the current years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterized by severe pathology. In recent years, the monosymptomatic form of celiac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased.

Conclusions

The mean age of newly diagnosed patients increased the last 15 years. Currently celiac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

Place, publisher, year, edition, pages
Elsevier, 2016
National Category
Clinical Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-122369 (URN)10.1016/j.dld.2015.09.018 (DOI)000368761300004 ()
Note

Funding agencies: Medical Research Council of Southeast Sweden; County Council of Ostergotland; Swedish Research Council

Available from: 2015-10-30 Created: 2015-10-30 Last updated: 2017-12-01Bibliographically approved
2. Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 – 2013: a long-term follow-up study
Open this publication in new window or tab >>Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 – 2013: a long-term follow-up study
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12Article in journal (Refereed) Published
Abstract [en]

Objective

The prevalence of coeliac disease in Sweden during the “epidemic period” (1984−1996) was one of the highest in the world. The aim of this study was to assess the coeliac disease incidence in our region over the 41-year period, and how diagnostic activity and diagnostic accuracy were affected by the introduction of antibody testing. We also looked into how patients with mild enteropathy were evaluated.

Methods

In the county of Östergötland in Sweden, 2790 paediatric patients were investigated for suspected coeliac disease between 1973 and 2013. Notes were scrutinised for data on sex, age, histopathological reports and final diagnosis. For comparative purposes this period was divided into three sub-periods (1973−1983, 1984−1996 and 1997−2013) named pre-epidemic, epidemic and post-epidemic.

Results

Coeliac disease diagnosis was received by 1,030 patients. The peak incidence rate, 301 cases/100,000 in 1994 for the age group 0−1.9 years is the highest figure ever reported. The other age groups, 2−4.9, 5−14.9, and 15−17.9 years, also had high incidence rates. After the 1984−1996 “epidemic period” the incidence decreased for the youngest group but continued to increase for the other groups. The cumulative incidence at 18 years-of-age for children born 1994 reached 14 cases/1000 births, the highest figure hitherto reported. Diagnostic activity differed significantly between the three sub-periods (p<0.001) increasing gradually from 1984 and reaching a peak value of 0.87 in 2012. Cases of mild enteropathy were more frequently regarded as non-coeliac disease cases, decreasing significantly in the “postepidemic” period (p<0.001).

Conclusions

The incidence rate and cumulative incidence of coeliac disease among children were possibly the highest ever reported. Changes in diagnostic activity and accuracy could not be attributed to the introduction of new antibody tests, possibly because of other changes e.g. variations in the symptoms at presentation and improved knowledge of the disease among parents and health professionals.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2015
National Category
Clinical Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-122370 (URN)10.1371/journal.pone.0144346 (DOI)000366903600037 ()
Note

Funding agencies: Medical Research Council of Southeast Sweden; County Council of Ostergotland; Swedish Research Council

Vid tidpunkten för disputation förelåg publikation som manuskript

Available from: 2015-10-30 Created: 2015-10-30 Last updated: 2017-12-01Bibliographically approved
3. Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study
Open this publication in new window or tab >>Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study
Show others...
2014 (English)In: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 34, no 5, 436-441 p.Article in journal (Refereed) Published
Abstract [en]

The only known treatment for celiac disease is a gluten-free diet (GFD), which initially meant abstention from wheat, rye, barley, and oats. Recently, oats free from contamination with wheat have been accepted in the GFD. Yet, reports indicate that all celiac disease patients may not tolerate oats. We hypothesized that celiac children comply well with a GFD and that most have included oats in their diet. A food questionnaire was used to check our patients; 316 questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of the children reported that they were trying to keep a strict GFD. However, accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases, mistakes took place when the patients were not at home. Symptoms after incidental gluten intake were experienced by 162(61.6%) patients, mostly (87.5%) from the gastrointestinal tract. Small amounts of gluten (less than4 g) caused symptoms in 38% of the cases, and 68% reported symptoms during the first 3 hours after gluten consumption. Oats were included in the diet of 89.4% of the children for a mean of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than once a week. Among those who did not consume oats, only 5.9% refrained because of symptoms. General compliance with the GFD was good. Only the duration of the GFD appeared to influence adherence to the diet. Most patients did not report adverse effects after long-term consumption of oats.

Place, publisher, year, edition, pages
Elsevier, 2014
Keyword
Celiac disease; GFD compliance; Oats; Children; Food questionnaire
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109147 (URN)10.1016/j.nutres.2014.04.006 (DOI)000337715700008 ()24916557 (PubMedID)
Available from: 2014-08-13 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
4. Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet
Open this publication in new window or tab >>Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet
Show others...
2014 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 11, 1311-1317 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 mu M. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, less than 1400 mu M, while 29.8% demonstrated high levels, that is, greater than 1400 mu M. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keyword
celiac disease; gluten-free diet; oats; urinary nitrite/nitrate
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113064 (URN)10.3109/00365521.2014.946081 (DOI)000345603400006 ()25263796 (PubMedID)
Note

Funding Agencies|Medical Research Council of Southeast Sweden; County Council of Ostergotland; Swedish Research Council

Available from: 2015-01-09 Created: 2015-01-08 Last updated: 2017-12-05

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