Health-Related Quality of Life in Children and Adolescents with Celiac Disease: From the Perspectives of Children and Parents

Aim. To examine how celiac children and adolescents on gluten-free diet valued their health-related quality of life, and if age and severity of the disease at onset affected the children's self-valuation later in life. We also assessed the parents' valuation of their child's quality of life. Methods. The DISABKIDS Chronic generic measure, short versions for both children and parents, was used on 160 families with celiac disease. A paediatric gastroenterologist classified manifestations of the disease at onset retrospectively. Results. Age or sex did not influence the outcome. Children diagnosed before the age of five scored higher than children diagnosed later. Children diagnosed more than eight years ago scored higher than more recently diagnosed children, and children who had the classical symptoms of the disease at onset scored higher than those who had atypical symptoms or were asymptomatic. The parents valuated their children's quality of life as lower than the children did. Conclusion. Health-related quality of life in treated celiac children and adolescents was influenced by age at diagnosis, disease severity at onset, and years on gluten-free diet. The disagreement between child-parent valuations highlights the importance of letting the children themselves be heard about their perceived quality of life

Роль кафедры акушерства и гинекологии ФПК и ПК в подготовке врачей-интернов

ИНТЕРНАТУРА И РЕЗИДЕНТУРААКУШЕРСТВОГИНЕКОЛОГИЯМЕДИЦИНСКОЙ ПРАКТИКИ МЕНЕДЖМЕНТОБРАЗОВАНИЕ МЕДИЦИНСКО

Coeliac Disease in Childhood : On the Intestinal Mucosa and the Use of Oats

Celiaki, eller glutenintolerans, är en av våra vanligaste kroniska sjukdomar i barnaåren. Sjukdomen orsakar en kraftig inflammation i tunntarmens slemhinna efter intag av glutenhaltig föda hos personer med ärftlig benägenhet att utveckla celiaki. En frisk tarm är kraftigt veckad för att öka ytan för upptag av näringsämnen. Ytan består dessutom av åtskilliga fingerliknande utskott, s.k. villi, och mellan villi finns kryptorna där celldelning och celldifferentiering sker. Villi och kryptor kantas av epitelceller, enterocyter, vilkas uppgift är att ta upp näring från tarminnehållet samt att utgöra en selektiv barriär mellan den yttre och inre miljön i tarmen. Den typiska tarmskadan vid celiaki karakteriseras av avsaknad av villi och kraftigt förlängda kryptor, och både näringsupptaget och barriärfunktionen är dessutom störda. Den enda behandling som finns att tillgå vid celiaki är en livslång glutenfri diet. De skadliga proteinerna i vetegluten kallas gliadin, och det finns liknande proteiner i råg, korn, och havre. I havre kallas proteinet avenin. Möjligheten att använda havre vid celiaki har diskuterats flitigt, men numera anses det riskfritt för majoriteten av både barn och vuxna att använda havre i den glutenfria dieten. Målet med den här avhandlingen var att undersöka hur barn med celiaki reagerar på havre i kosten. Detta studerades med avseende på antikroppar mot avenin samt med en metod som mäter halten av kväveoxid- (NO-) produkter i urinen. Ett andra mål var att studera tunntarmens struktur vid olika stadier av celiaki. I den första studien undersökte vi om celiakibarn har antikroppar i serum mot avenin. Vi fann att så var fallet och att nivåerna var signifikant högre än hos friska kontrollbarn. När barnen sattes på glutenfri kost sjönk antikroppsnivåerna, för att öka igen när gluten återinfördes i kosten. Blodproverna till den här studien togs innan debatten om havre kom igång, vilket gör att vi tror att de olika dieterna även speglar ett sant intag av havre. Studien visade också att det inte var någon korsreaktion mellan antikroppar mot avenin och gliadin. Vi använde sedan vår metod för att mäta antikroppar mot avenin i en randomiserad studie där havre gavs till barn med nydiagnostiserad celiaki. Barnen fick antingen en vanlig glutenfri diet eller en med tillsats av specialhavre. Antikroppsnivåerna sjönk markant redan efter tre månader i båda grupperna, och vid studietidens slut, efter ca ett år, hade alla utom ett par patienter återfått normala nivåer. Samma barn studerades även med avseende på NO-produkter i urinen. NO är en kortlivad molekyl som fungerar som budbärare i och mellan celler, och produktionen av den ökar markant vid en inflammation. Tidigare studier har visat att barn med obehandlad celiaki har extremt höga halter av NO-produkter i urinen. I vår studie sjönk även dessa värden signifikant efter tre månader, och det var ingen skillnad mellan grupperna. Efter ett år hade dock fyra barn i havregruppen och ett barn i den grupp som fick vanlig glutenfri kost, fortfarande extremt höga nivåer av NO-produkter. Dessa båda studier styrker den kliniska uppfattningen att de flesta barn med celiaki kan tåla havre, men de visar också att man bör följa upp de celiakibarn som kompletterar sin glutenfria kost med havre eftersom vissa barn verkar ha kvarstående tecken på inflammation i tarmen. I tarmbiopsier från barn med olika stadier av celiaki studerades förekomst och lokalisering av occludin och claudiner, proteiner som är viktiga för att upprätthålla barriärfunktionen i tarmen. Vi fann ett ökat uttryck av occludin vid obehandlad celiaki, vilket vi tror speglar den ökade celldelning och de förändrade barriäregenskaper som man ser vid aktiv celiaki. Resultaten tyder även på att uttrycket av claudin 1-5 inte tycks påverkas av kosten hos barn med celiaki.Coeliac disease (CD) is one of our most common chronic diseases in childhood. The disease causes an intense inflammation in the small intestinal mucosa after ingestion of gluten-containing cereals in genetically predisposed individuals. The mucosal lesion in CD is characterised by villous atrophy and crypt hyperplasia, and both the absorptive and the barrier functions of the enterocytes are disturbed. The treatment of CD is a life-long adherence to a gluten-free diet (GFD). The toxic fraction of wheat gluten is gliadin, and there are similar proteins in rye, barley and oats. In oats this protein is called avenin, and it is proposed to be less toxic than the others. The use of oats in CD has been debated, but it is now considered safe for the majority of both children and adults with CD. The aims of this thesis were to investigate the humoral and inflammatory reactions to oats in children with CD, and also to study the intestinal mucosa at different stages of the disease. In a retrospective study we found that children with CD had antibodies to oats avenin, and that the levels were significantly higher than in controls. The levels attenuated during GFD, and we also showed that there was no crossreactivity between antibodies to oats and gliadin. We then used our method for measuring antibodies to avenin in a randomised, double-blind trial of oats given to children with newly diagnosed CD. The children were given either a traditional GFD or a GFD supplemented with oats. There was a rapid decrease in antibody levels in both groups already after three months on diet, and at the end of the study period all but a few had normalised their levels. The same children were also studied using urinary nitric oxide (NO) products as markers for intestinal inflammation. Likewise, these values decreased significantly after three months. At the end of the study four children in the GFD-oats group and one in the standard GFD group still had extremely high concentrations of urinary NO metabolites. Taken together, these studies strengthen the clinical impression that oats can be tolerated by the majority of children with CD, but they also warrant a caution, since there seem to be children that do not tolerate oats in their diet. The structure and distribution of occludin and claudins 1-5, tight junction proteins known to play a crucial role in maintaining the barrier function, was studied in biopsy specimens from children at different stages of CD. There was an increased expression of occludin in untreated CD, which reflects the characteristics of crypt cell hyperplasia and altered barrier properties seen in active CD. The findings also indicate that gluten intake does not significantly influence the expression and distribution of claudins 1-5 in coeliac children

Linköping University Medical Dissertations No. 965 Coeliac Disease in Childhood On the Intestinal Mucosa and the

nce upon a time there was a little baby girl who had troubles with her stomach. Her cheeks were glowing, her belly was swollen, and her arms and legs were so very thin. The baby girl’s parents were worried and they took their daughter to see the doctor. The doctor examined her small intestine and he finally gave the diagnosis: the baby had coeliac disease and she could not eat anything that contained wheat, rye, barley, or oats. The parents felt relieved knowing what was wrong with their little girl and they learned how to cook gluten-free food. Very soon the little baby girl began to grow, smile

Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 - 2013.

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.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.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 during the epidemic 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 "post-epidemic" period (p<0.001).The incidence rate and cumulative incidence of coeliac disease 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

Diagnostic activity and accuracy among Swedish children investigated for CD with biopsy between 1973 and 2013.

<p>Arrows indicate when AGA, EMA, t-TGA tests were used in >50% of the cases investigated for CD, and also the introduction of the 2012 ESPGHAN guidelines for CD diagnosis into clinical practice. Diagnostic activity was considered as the number of subjects biopsied per 1,000 children in the study population. Diagnostic accuracy was specified as the number of CD cases per total number of children with suspected CD who underwent biopsy. The diagnostic activity and accuracy are described as ratios. The purple line represents the incidence rate of CD in the pediatric population during the same time period.</p

Evaluation of Multiple Diagnostic Indicators in Comparison to the Intestinal Biopsy as the Golden Standard in Diagnosing Celiac Disease in Children

Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the disease. The criteria for diagnosing CD were previously based primarily on histologic evaluation of small intestinal biopsies, but nowadays are often based only on blood tests and symptoms. In this context, we elucidated the accuracy of three diagnostic indicators for CD, alone or in combination. Genetic analyses of HLA-type and nine single nucleotide polymorphisms (SNPs) known to be associated with CD were performed in 177 children previously investigated for the suspicion of CD. CD was confirmed in 109 children, while 68 were considered non-celiacs. The antibodies and urinary nitrite/nitrate concentrations of all of them were measured. The combinations of all the variables used in the study would classify 93% of the study population in the correct diagnostic group. The single best predictors were antibodies (i.e., anti-endomysium immunoglobulin A (IgA) (EMA) and transglutaminase IgA (TGA)), followed by HLA-type and nitric oxide (NO)-metabolites. The nine SNPs used did not contribute to the right diagnoses. Although our control group consisted of children with mostly gastrointestinal symptoms, the presented methodology predicted a correct classification in more than 90% of the cases

Flowchart of investigation.

<p>Flowchart of investigation.</p

Annual incidence rate of CD in different age groups from 1973 to 2013.

<p>Annual incidence rate of CD in different age groups from 1973 to 2013.</p

Cumulative incidence of CD by age for the birth cohorts 1973−1983, 1984−1996, and 1997−2013.

<p>Cumulative incidence of CD by age for the birth cohorts 1973−1983, 1984−1996, and 1997−2013.</p