Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD).

Methods: Children with suspected CD and positive EMA (≥1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n = 133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n = 39; 59% female, mean age at the first biopsy 7.3 years, range 1.4–16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n = 94; 56% female; mean age 7.6 years at the first biopsy, range 0.70–17).

Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2–7 years (median 4.5 years).

Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.

Objective. Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats.

Material and methods. The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results.

Results. There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples.

Conclusions. Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.

Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats.

Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months.

Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized.

Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.

Background: The prevalence of coeliac disease (CD) in Swedish children has attracted considerable interest over the past few decades, and especially the influence of feeding habits on the increased incidence. A national study has reported a trend towards a decrease in incidence after a change in infant feeding recommendations was introduced in 1996. The aim of this study was to evaluate, in a geographically defined area, the change in incidence with time and the influence of the introduction of antibody analysis.

Methods: Cases of suspected paediatric CD between 1980 and 2003 were studied for prevalence, biopsy findings and antibody analyses.

Results: A total of 2029 children were investigated by small intestinal biopsy, yielding 554 CD cases. The area initially showed the same trend as the national study, but the annual incidence rate is now increasing again. Median age at diagnosis has increased significantly since 1997 from less than 2 years of age to above 5 years. Cumulative incidence at 2 years of age is much higher for the birth cohorts 1983–96 than 1980–82 or 1997–2001. Diagnostic accuracy was significantly higher after the introduction of antigliadin (AGA) analysis, and especially after antiendomysium (EMA) analysis.

Conclusions: The incidence rate of CD in small children in our region has varied widely over the 24‐year period observed. Feeding practice and methods of investigation have changed during this period. The annual incidence rate for the total child population in 2003 was almost equal to the peak value observed in 1994. There were no conclusive results on whether antibody analysis had an influence on diagnostic activity, but this seems to have increased diagnostic accuracy.

Background: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed.

Aim: To determine if children with CD tolerate oats in their GFD.

Patients and methods: In this double blind multicentre study involving eight paediatric clinics, 116 children with newly diagnosed CD were randomised to one of two groups: one group was given a standard GFD (GFD-std) and one group was given a GFD with additional wheat free oat products (GFD-oats). The study period was one year. Small bowel biopsy was performed at the beginning and end of the study. Serum IgA antigliadin, antiendomysium, and antitissue transglutaminase antibodies were monitored at 0, 3, 6, and 12 months.

Results: Ninety three patients completed the study. Median (range) daily oat intake in the GFD-oats group (n = 42) was 15 (5–40) g at the six month control and 15 (0–43) g at the end of the study. All patients were in clinical remission after the study period. The GFD-oats and GFD-std groups did not differ significantly at the end of the study regarding coeliac serology markers or small bowel mucosal architecture, including numbers of intraepithelial lymphocytes. Significantly more children in the youngest age group withdrew.

Conclusions: This is the first randomised double blind study showing that the addition of moderate amounts of oats to a GFD does not prevent clinical or small bowel mucosal healing, or humoral immunological downregulation in coeliac children. This is in accordance with the findings of studies in adult coeliacs and indicates that oats, added to the otherwise GFD, can be accepted and tolerated by the majority of children with CD.

Background: Coeliac disease is a gluten-sensitive enteropathy where pro-inflammatory cytokines and excess nitric oxide (NO) production can contribute to mucosal damage. NO urinary products are elevated in coeliac children on a gluten diet, but it is not known how rapidly this increase develops after gluten exposure.

Methods: Oral gluten challenge was performed in 25 children whose families kept a daily record of gluten intake and symptoms. Blood was analysed monthly for antigliadin (AGA) and endomysium antibodies (EMA). Urine was analysed every second week for NO products, i.e. the sum of nitrite and nitrate was measured with a colorimetric method. We performed a third biopsy when clinical symptoms indicated a relapse. Median age at the post-challenge biopsy was 3.8 (2.7-8.8) years.

Results: Signs of morphological or serological relapse were seen in all children. Mean daily gluten intake was 0.10 (range 0.02-0.26) g/kg bodyweight. Median NO level was doubled and significantly higher after 4 weeks of challenge but not after 2 weeks. EMA, but not AGA levels, correlated positively with NO. Intraepithelial lymphocyte count was significantly higher in the post-challenge biopsy, but did not correlate with the NO levels.

Conclusions: NO products in urine increased during gluten challenge. EMA levels reflected severity of mucosal damage, and NO products reflected the inflammatory response, which was doubled after 4 weeks of challenge. The NO analysis is simple and non-traumatic for the child. It can be performed repeatedly during investigation of children with suspected coeliac disease.

Background: Celiac disease (CD) is one of the most common chronic diseases in childhood in many countries. It is a small intestinal disease, caused by gluten in genetically predisposed individuals, but underlying immunological mechanisms are not exactly known. Gluten is found in wheat, rye and barley, and possibly in oats. The clinical presentation of CD varies from overt to no symptoms at all. Treatment with gluten free diet (GFD) heals the mucosa and symptoms disappear. The varying clinical presentation makes the evaluation of the "true" prevalence difficult. When screening with serum antibodies, similar prevalence is found in several countries. The reported increase of clinically detected cases among Swedish children in the mid 1980s attracted much interest and was publicly debated. Infant feeding changes was focused on, but new diagnostic tools were also introduced during this period.

Aims: To describe epidemiological changes in the county of Östergötland from 1980 to 2001. To analyse the possible influence of diagnostic activity and accuracy and the possible influence of certain infant feeding patterns on disease occurrence. To study gluten intake, clinical, histological and immunological parameters during gluten challenge. To evaluate the practical usefulness of the nitric oxide (NO) analysis in CD.

Material and methods: All children (0-17.9 years) investigated for suspected CD in the county of Östergötland 1980-2001 were studied regarding disease occurrence, diagnostic activity and accuracy. Data on infant feeding were analysed in 72 CD children and 288 agematched referents. During gluten challenge 25 children were studied regarding gluten intake, serum antibodies, NO products in the urine, clinical symptoms and mucosal histology. NO products were also measured at different stages of CD investigation in !37 children.

Results: The incidence rate of CD in small children has fluctuated over the study period. How, or whether, infant feeding and/or diagnostic tools have influenced this is not known.

CD children were significantly shorter breastfed, more seldom breastfed at gluten introduction, and started more often with follow-up formula than porridge. This could be interpreted in two ways. Breastfeeding per se could protect against CD, but it is also known that a breastfed baby consumes lower amounts of gluten at the time of introduction. The lower exposure can make symptoms more vague in early childhood and thus postpone the diagnosis.

Gluten intake during challenge varied a lot. Some CD children reacted to minute amounts of gluten. Despite the small amounts given, all children showed signs of relapse at a clinical, serological, or histological level.

CD children on a gluten containing diet have significantly higher levels of NO products in the urine, compared to reference children and to CD children on a GFD. NO products increased during gluten challenge, and doubled within four weeks of challenge. This is probably caused by iNOS activation and increased NO production in the diseased intestinal mucosa.

Conclusions: How, or whether, changes in infant feeding and/or new diagnostic tools influenced the fluctuating incidence of the disease is not known. Very small amounts of gluten caused relapse in CD children. NO products in the urine were elevated in CD children on a gluten diet, and doubled within four weeks of gluten challenge. NO analysis is simple and non-traumatic for the child, and could be of value as a diagnostic tool in celiac disease.

Bakgrund: Celiaki (glutenintolerans) är en av de vanligaste kroniska sjukdomarna hos barn, både i Sverige och i andra länder. Celiaki är en tunntarmssjukdom som orsakas av gluten hos personer med ärftlig benägenhet. Gluten finns i vete, råg, korn och kanske också i havre. Den bakomliggande immunologiska mekanismen är fortfarande inte helt känd. Celiaki kan ge varierande symptom, alltifrån kraftiga magtarmsymtom tiH nästan inga symtom alls. Om patienten håller glutenfri diet (GFD) läker tarmen och symtomen försvinner. Livslång GFD innebär fördelaktiga hälsoeffekter både på kort och på lång sikt.

Sjukdomens varierande symtomatologi gör det svårt att uppskatta den "sanna" förekomsten. Vid screening med serumantikroppar hittas ungefar samma förekomst av sjukdomen i olika länder. I mitten av 1980-talet ökade antalet kliniskt upptäckta fall bland svenska barn kraftigt. Detta rönte stort intresse och debatterades livligt, även i pressen. Förändringar i spädbarnsuppfödningen diskuterades som orsak, men nya diagnostiska metoder infördes också under perioden.

Mål: Att beskriva förändringar i förekomst av celiaki hos barn i Östergötland under åren 1980 till 2001. Att analysera eventuellt inflytande av träffsäkerhet och intensitet i diagnostiken samt spädbarnsuppfödning på sjukdomens förekomst. Att studera glutenintag, kliniska, immunologiska och histologiska parametrar under glutenprovokationen. Att utvärdera den praktiska nyttan av att mäta kvävemonoxid (NO)-metaboliter i urinen hos celiakibarn,

Material och metod: Alla barn (0-17 .9 år) som undersökts för misstänkt celiaki i Östergötland under åren1980-2001 registrerades. De studerades med avseende på sjukdomsförekomst samt träffsäkerhet och intensitet i diagnostiken. Uppfödningsdata från 72 celiakibam och deras 288 åldersmatchade kontroller analyserades. Under glutenprovokationen studerades glutenintag, kliniska symtom, NO-metaboliter i urinen, tarmslemhinnans histologi och serumantikroppar. På 137 bam under olika skeden i celiakiutredningen mättes också NO-metaboliter.

Resultat: Antalet nyinsjuknade småbarn varierade mycket kraftigt under de 22 år vi studerat. Huruvida förändrad spädbarnsuppfådning, och/eller fårbättrade diagnostiska metoder har påverkat sjukdomens förekomst går ej att avgöra.

Celiakibam hade ammats kortare tid, ammades mer sällan vid glutenintroduktionen och fick oftare börja med välling än med gröt. Det kan tolkas antingen som att amning i sig skyddar mot celiaki, men det är också känt att ett barn som ammas får i sig mindre mängder gluten vid introduktionen. Denna lägre exponering skulle kunna ge lindrigare symtom, och på så sätt försvåra och fårsena diagnosen.

Mängden gluten som barnen åt under provokationen varierade kraftigt. Vissa barn reagerade på ytterst små mängder. Trots de små mängder barnen fick i sig visade alla tecken på återfall i sjukdomen, antingen kliniskt, serologiskt eller histologiskt.

Hos celiakibam som åt g!uten uppmättes signifikant högre värden av NO-metaboliter i urinen än hos kontrollbarn och celiakibarn som inte åt gluten. Det beror antagligen på enzymaktivcring med ökad NO-produktion i den sjuka tarmslemhinnan. Under glutenprovokationen fördubblas NO-mctabolitema inom fyra veckor.

Sammanfattning: Huruvida fårändringar i spädbarnsuppfödningen och/eller förbättrade diagnostiska metoder har påverkat den varierande förekomsten av celiaki hos småbarn i Sverige går ej att avgöra. Mycket små glutenmängder var tillräckliga för att orsaka återfall under provokationen. NO-metaboliter i urinen var signifikant högre hos celiakibarn som åt gluten, än hos kontrollbarn och celiakibarn som åt glutenfritt Under provokationen stiger värdena till det dubbla inom f)rra veckor. NO-analysen är enkel, billig och dessutom skonsam för barnet. Den skulle därfår kunna utgöra ett värdefullt tillskott i den diagnostiska arsenalen.

Background: Previously, a gluten challenge was customary to establish the diagnosis of celiac disease in children. There are no clear recommendations on how to perform this challenge or what markers to rely on for timing the biopsy after the challenge. The authors' aim was to monitor gluten intake, clinical symptoms, and antibody kinetics to evaluate the influence of gluten exposure during the challenge.

Methods: Twenty-five children under investigation for suspected celiac disease were challenged. One child was excluded because blood samples, food records, or biopsy was lacking. Median age at the postchallenge biopsy was 3.8 (2.7-8.8) years. The families kept daily records of the children's gluten intake and of symptoms that occurred. Blood samples were taken monthly for analysis of antigliadin and endomysium antibodies and total immunoglobulin A (IgA). A third biopsy was performed when clinical symptoms suggested a relapse.

Results: All 24 children showed deterioration of the mucosa or elevated antibodies during gluten challenge. Median duration of the challenge was 13 (5-51) weeks, and mean gluten intake was 1.7 (0.2-4.3) g/d and 0.1 (0.02-0.26) g/kg daily.

Conclusions: Gluten intake during the challenge varied widely, and the parents were unable to give their children the recommended amount. Despite the small amounts given, all children showed signs of relapse at a clinical, laboratory, or histologic level. Much smaller amounts of gluten than previously suggested seem sufficient to cause relapse during gluten challenge in children.

Background: Celiac disease is characterized by morphologic and functional aberrations of the small intestinal mucosa, i.e. crypt hyperplasia, villous atrophy, infiltration of intraepithelial lymphocytes, and alteration of permeability. Nitric oxide has been shown to affect mucosal permeability after ischemia-reperfusion, but little is known about the regulatory role of nitric oxide in celiac disease. The purpose of this study was to assess nitric oxide production in children with celiac disease and in control subjects.

Methods: The sum of nitrite and nitrate in the urine was measured with a colorimetric method in 137 children with a median age of 3 years, 84 patients and 53 reference children, all of whom underwent a small intestinal biopsy to confirm or overrule suspicion of celiac disease.

Results: Median urinary nitrite-nitrate concentration in celiac children was 3323µM (4147 ± 1102; mean ± SEM) at first clinical examination and 2501 µM (2939 ± 386) after gluten challenge, which was significantly higher than concentrations in reference children(1029 µM; 1174 ± 116) and in children with celiac disease on a gluten-free diet (882 µM; 1369 ± 360) (p< 0.0001).

Conclusions: A gluten-containing diet is associated with an increased nitrite-nitrate secretion in the urine in children with celiac disease, presumably as a result of nitric oxide synthase activation and nitric oxide production in the diseased small intestinal mucosa.

Infant feeding history was investigated in 72 celiac and 288 age-matched reference children in a retrospective questionnaire study. The reply rate was 100% in celiac and 91. 6% in reference children. The celiac children were breast-fed for a significantly shorter time than reference children, and they were less often breast-fed at the introduction of gluten. The age of the children at gluten introduction was similar, but the cellac children were significantly more often introduced by a gluten-containing follow-up formula, while the reference children more often started on a gluten-containing porridge. The results can be interpreted in two ways. First, it could be argued that breast milk per se protects against symptoms of celiac disease in childhood. It could, however, also be claimed that breast-feeding merely modulates the gluten introduction, causing a less abrupt introduction of gluten in the baby diet and thereby fewer overt symptoms of the disease.