ABSTRACT
Objective:
Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the ...autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)‐DQ2 and HLA‐DQ8; and CD‐specific antibody tests have improved.
Methods:
A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence‐based recommendations on CD‐specific antibody testing.
Results:
In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti‐tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA‐DQ2 and HLA‐DQ8 testing is valuable because CD is unlikely if both haplotypes are negative.
Conclusions:
The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.
Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte ...antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD.
As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR.
Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium).
The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.
In this trial involving infants at high risk for celiac disease, the introduction of gluten at 4 months of age, as compared with delayed exposure to gluten until 6 months of age, did not reduce the ...risk of celiac disease at 3 years of age.
Celiac disease, an immune-mediated systemic disorder elicited by gluten in genetically susceptible persons, is characterized by anti–transglutaminase type 2 antibodies (TG2A) and enteropathy.
1
The prevalence of celiac disease is 1 to 3% in the general population and approximately 10% among first-degree family members of patients with celiac disease.
2
–
10
Celiac disease is treated with a gluten-free diet. More than 95% of patients have the HLA-DQ2 heterodimer, either in the
cis
or
trans
configuration. Most of the remaining patients have the HLA-DQ8 heterodimer or half of the HLA-DQ2 heterodimer (DQB1*02).
1
,
8
,
11
–
14
However, more than 25% of the general population . . .
Summary
Background
New evidence emerged on early feeding practices and the risk of coeliac disease.
Aim
To systematically update evidence on these practices to find out whether there is a need to ...revise current recommendations.
Methods
MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease‐related autoimmunity.
Results
We identified 21 publications, including two, new, large, randomised controlled trials performed in high‐risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development.
Conclusions
Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.
Excluding oligo‐, di‐, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review ...the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered. Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low‐FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low‐FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low‐FODMAP diet is considered in children.
Abstract
Background and Aims
Inflammatory bowel disease IBD is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives ...here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states.
Methods
We undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018.
Results
Incidence rates for both paediatric Crohn’s disease CD and ulcerative colitis UC were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30.
Conclusions
The incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north–south than an east–west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.
To identify specific gut bacteria associated with coeliac disease (CD) at diagnosis and after treatment with a gluten-free diet (GFD) in a paediatric population.
30 and 18 faecal samples from ...untreated and treated CD patients and 25 and 8 biopsy samples from untreated and treated CD patients, respectively, were analysed. In addition, 30 faecal and 8 biopsy samples from control children were evaluated for comparative purposes. Gut bacterial groups were quantified by real-time PCR.
Bacteroides and Clostridium leptum groups were more abundant in faeces and biopsies of CD patients than in controls regardless of the stage of the disease. E coli and Staphylococcus counts were also higher in faeces and biopsies of non-treated CD patients than in those of controls, but their levels were normalised after treatment with a GFD. Bifidobacterium levels were lower in faeces of both groups of CD patients and in biopsies of untreated CD patients compared to controls. Similar bacterial groups were related to CD in biopsies and faeces, indicating that faecal microbiota partly reflects that of the small intestine in CD patients, and could constitute a convenient biological index of this disorder.
Duodenal and faecal microbiota is unbalanced in children with untreated CD and only partially restored after long-term treatment with a GFD, constituting a novel factor linked to this disorder.
Octreotide, a somatostatin analogue, has been used for more than 20 years in children with gastrointestinal bleeding, chylothorax or chylous ascites, intestinal lymphangiectasia, pancreatitis, ...intestinal dysmotility, and severe diarrhoea; however, until now, there is a lack of randomised clinical trials evaluating the efficacy of this compound in childhood. Hence, we aimed to review the literature in order to determine the evidence of its use and safety in children, using PubMed from 2000 to 2021 with the search terms "octreotide" and "children" and "bleeding or chylous ascites or chylothorax or acute pancreatitis or lymphangiectasia or diarrhoea or intestinal dysmotility".
1 Instituto de Agroquímica y Tecnología de Alimentos (Consejo Superior de Investigaciones Cientificas), Apartado 73, 46100 Burjassot, Valencia, Spain
2 Hospital Universitario La Fe, Avenida Campanar ...21, 40009 Valencia, Spain
3 Hospital General Universitario, Avenida Tres Cruces s/n, 46014 Valencia, Spain
Correspondence Yolanda Sanz yolsanz{at}iata.csic.es
Received 22 May 2007
Accepted 8 August 2007
Coeliac disease (CD) is the most common immune-mediated enteropathy characterized by chronic inflammation of the small intestinal mucosa. The ingestion of gluten is responsible for the symptoms of CD, but other environmental factors are also thought to play a role in this disorder. In this study, the composition of the duodenal microbiota of coeliac children with active disease, symptom-free CD patients on a gluten-free diet and control children was determined. Bacteriological analyses of duodenal biopsy specimens were carried out by fluorescent in situ hybridization coupled with flow cytometry. The proportions of total bacteria and Gram-negative bacteria were significantly higher in CD patients with active disease than in symptom-free CD patients and controls. Bacteroides and Escherichia coli groups were significantly more abundant in CD patients with active disease than in controls, whilst these bacterial deviations were normalized in symptom-free CD patients. The ratio of Lactobacillus–Bifidobacterium to Bacteroides–E. coli was significantly reduced in coeliac patients with either active or inactive disease compared with controls. The differences in Atopobium , Eubacterium rectale–Clostridium coccoides , Clostridium histolyticum , Clostridium lituseburense , sulphate-reducing bacteria and Faecalibacterium prausnitzii populations among the three groups of children were less relevant. Overall, the higher incidence of Gram-negative and potentially pro-inflammatory bacteria in the duodenal microbiota of coeliac children was linked to the symptomatic presentation of the disease and could favour the pathological process of the disorder.
Abbreviations: CD, coeliac disease; DGGE, denaturing gradient gel electrophoresis; FISH, fluorescent in situ hybridization; IBD, inflammatory bowel disease.
Summary
In coeliac disease (CD), anti‐tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti‐TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European ...multi‐centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti‐TG2 deposits in very early intestinal biopsies from at‐risk infants and their predictive value for villous atrophy. Sixty‐five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti‐TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD‐associated antibodies and/or symptoms suggesting disease. Deposits of anti‐TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti‐TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti‐TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti‐TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti‐TG2 are a constant presence and appear very early in the natural history of disease.
In Coeliac Disease anti‐tissue transglutaminase2 IgA antibodies (anti‐TG2) are produced and deposited in the intestine. In our study, we aimed to investigate in very early intestinal biopsies from children at risk for Celiac Disease their appearance and their predictive value for villous atrophy.
We demonstrated that in Celiac Disease the intestinal deposits of anti‐TG2 are constant presence.
They appear very early in the natural history of disease.
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