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Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease.
Myléus, A, Stenhammar, L, Högberg, L, Browaldh, L, Daniels, IM, Fagerberg, UL, Gudjónsdóttir, AH, Malmquist, M, Sandström, O, Ivarsson, A
Acta paediatrica (Oslo, Norway : 1992). 2019;(6):1140-1143
Abstract
AIM: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction. METHODS In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies. RESULTS All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia. CONCLUSION The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.
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Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.
Norström, F, van der Pals, M, Myléus, A, Hammarroth, S, Högberg, L, Isaksson, A, Ivarsson, A, Carlsson, A
Journal of pediatric gastroenterology and nutrition. 2018;(1):64-68
Abstract
OBJECTIVES Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. Data are, however, lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. METHODS A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid-stimulating hormone and free thyroxine. RESULTS TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). CONCLUSIONS The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicates that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.
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Oral immunoglobulin treatment improved intestinal permeability in children with active Crohn's disease.
Sundqvist, T, Stenhammar, L, Tjellström, B, Magnusson, KE, Forslund, T, Högberg, L
Acta paediatrica (Oslo, Norway : 1992). 2017;(4):647-653
Abstract
AIM: Crohn's disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohn's disease. METHODS The study was performed at the Department of Paediatrics, Norrköping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age- and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. RESULTS OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. CONCLUSION Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.
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Exclusive Enteral Nutrition Does Not Normalize Gut Microflora Function in Pediatric Perianal Crohn Disease.
Tjellström, B, Stenhammar, L, Magnusson, KE, Midtvedt, T, Norin, E, Sundqvist, T, Högberg, L
Journal of pediatric gastroenterology and nutrition. 2015;(1):e4
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High adherence to a gluten-free diet in adolescents with screening-detected celiac disease.
Webb, C, Myléus, A, Norström, F, Hammarroth, S, Högberg, L, Lagerqvist, C, Rosén, A, Sandström, O, Stenhammar, L, Ivarsson, A, et al
Journal of pediatric gastroenterology and nutrition. 2015;(1):54-9
Abstract
OBJECTIVES The aim of the study was to evaluate the gluten-free diet (GFD) adherence after 1 year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS A total of 18,325 twelve-year-olds were invited to participate in a population-based CD screening (Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This substudy included 210 children with TG2-IgA, evaluated both at the initial biopsy occasion and at 1-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS After 1 year, 85% (179/210) had normalized TG2-IgA levels (<5 U/mL). Among those who had >50 U/mL at diagnosis, 25% (16/63) still had elevated TG2-IgA, but for the majority their initial values were more than halved. Most reported a high level of GFD adherence ("always" 82% [158/193] and "often" 16% [30/193]), and 75% [145/193] reported always adhering combined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely; however, a majority of these initially had the highest TG2-IgA levels. CONCLUSIONS GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12-year-olds. Almost all of them had normalized serology and reported GFD adherence at the 1-year follow-up. A few adolescents who reported GFD adherence, however, had elevated TG2-IgA levels, suggesting more severe disease and/or nonadherence.
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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.
Tapsas, D, Fälth-Magnusson, K, Högberg, L, Hammersjö, JÅ, Hollén, E
Nutrition research (New York, N.Y.). 2014;(5):436-41
Abstract
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 (<4 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.
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Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet.
Tapsas, D, Fälth-Magnusson, K, Högberg, L, Forslund, T, Sundqvist, T, Hollén, E
Scandinavian journal of gastroenterology. 2014;(11):1311-7
Abstract
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 μM. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, <1400 μM, while 29.8% demonstrated high levels, that is, >1400 μM. 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.
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Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease.
Sjöberg, V, Hollén, E, Pietz, G, Magnusson, KE, Fälth-Magnusson, K, Sundström, M, Holmgren Peterson, K, Sandström, O, Hernell, O, Hammarström, S, et al
Clinical and translational gastroenterology. 2014;(6):e58
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Abstract
OBJECTIVES Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa. METHODS Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR. RESULTS The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04). CONCLUSIONS A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.
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The effects of oats on the function of gut microflora in children with coeliac disease.
Tjellström, B, Stenhammar, L, Sundqvist, T, Fälth-Magnusson, K, Hollén, E, Magnusson, KE, Norin, E, Midtvedt, T, Högberg, L
Alimentary pharmacology & therapeutics. 2014;39(10):1156-60
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Plain language summary
Oats have been allowed in the gluten-free diet of patients with coeliac disease (CD), however concerns have been raised that they may not be safe to eat in a subset of these patients. Short chain fatty acids (SFCAs) have been identified as a marker of inflammation and gut metabolism. Recent studies have found that children with CD often have elevated SCFA levels, indicating a disturbance in the gut microflora. The aim of this study was to identify the effect of consuming oats in children recently diagnosed with CD by examining faecal SCFAs. 116 children were treated with or without oats in their gluten-free diet for one year to see if oats affect the gut microflora. The findings of this study indicate that the children consuming oats had higher faecal SCFA concentration after one year than those not consuming oats. Based on this study, the authors’ conclude that oats do affect the gut microflora metabolism and that some coeliac children consuming oats may develop gut mucosal inflammation, leading to further future complications.
Abstract
BACKGROUND Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
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Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease.
Lahdenperä, AI, Fälth-Magnusson, K, Högberg, L, Ludvigsson, J, Vaarala, O
Scandinavian journal of gastroenterology. 2014;(2):145-56
Abstract
OBJECTIVE The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. MATERIAL AND METHODS Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. RESULTS The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. CONCLUSION Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.