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Background and Objective: Coeliac disease is a chronic, immune-mediated disorder for which the only treatment consists of lifelong strict adherence to gluten-free diet (GFD). However, there is a lack of evidence-based guidelines on the GFD dietary management of coeliac disease. This position paper, led by the Special Interest Group in coeliac disease of the European Society of Pediatric, Gastroenterology Hepatology, and Nutrition, supported by the Nutrition Committee and the Allied Health Professionals Committee, aims to present evidence-based recommendations on the GFD as well as how to support dietary adherence., Methods: A wide literature search was performed using the MeSH Terms: "diet, gluten free," "gluten-free diet," "diets, gluten-free," "gluten free diet," and "coeliac disease" in Pubmed until November 8th, 2022., Results: The manuscript provides an overview of the definition of the GFD, regulations as basis to define the term "gluten-free," which foods are naturally gluten-free and gluten-containing. Moreover, it provides recommendations and educational tips and infographics on suitable food substitutes, the importance of reading food labels, risk of gluten cross-contact at home and in public settings, nutritional considerations as well as factors associated to dietary adherence based on available evidence, or otherwise clinical expertise., Conclusions: This position paper provides guidance and recommendations to support children with coeliac disease to safely adhere to a GFD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The Cow's Milk-related Symptom Score (CoMISS) is an awareness tool for evaluating cow's milk-related symptoms in otherwise healthy infants <1 year of age. This study assessed whether replacing the Bristol Stool Form Scale (BSFS) with the Brussels Infants and Toddlers Stool Scale (BITSS) in non-toilet-trained infants would modify the overall CoMiSS and change the clinical approach regarding potential cow's milk allergy., Methods: Non-toilet-trained infants aged <13 months were assessed by CoMiSS using the 7 images from the BSFS (CoMiSS-BSFS) compared to the 4 images of stools from BITSS (CoMiSS-BITSS). The Wilcoxon signed-rank test and Pearson correlation coefficient were calculated. A post hoc analysis using identical tests was performed in subsets of CoMiSS-BSFS scores ≥10, ≥12, ≤5, and ≥6., Results: Eight hundred forty-four pairwise scores were collected. Applying the Wilcoxon test over the complete dataset, the difference between CoMiSS-BSFS and CoMiSS-BITSS was statistically significant ( P < 0.001). However, there was no significant difference in the subsets with CoMiSS-BSFS ≥10, ≥12, and ≥6 ( P = 0.84, P = 0.48, and P = 0.81, respectively). The significant difference remained restricted to the group with CoMiSS-BSFS ≤5, considered at low risk for CM-related symptoms ( P < 0.001)., Conclusion: Replacing BSFS with BITSS does not change the cutoff for awareness of possible CM-related symptoms and will not impact the use of CoMiSS in clinical practice. Changes in CoMiSS remained limited to the subgroup with a low risk for CM-related symptoms., (Copyright © 2023 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD)., Methods: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed., Results: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms., Conclusions: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: The authors report no conflicts of Interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain., Methods: A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected., Results: In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines., Conclusions: Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives/background: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres., Methods: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019., Results: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively., Conclusions: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety., Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN).A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes.During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors., Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease., Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Abstract: 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"., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Abstract: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed drugs in infants and children with the last decades witnessing a dramatic rise in their utilization. Although PPIs are clearly effective when used appropriately and have been regarded as safe drugs, there is growing evidence regarding their potential adverse effects. Although, largely based on adult data it is clear that many of these are also relevant to pediatrics. PPI use potentially affects gastrointestinal microbiota composition and function, decreases defence against pathogens resulting in increased risk for infections, interferes with absorption of minerals and vitamins leading to specific deficiencies and increased risk for bone fractures as well as interferes with protein digestion resulting in increased risk of sensitization to allergens and development of allergic diseases and eosinophilic esophagitis. An association with gastric, liver and pancreatic cancer has also been inferred from adult data but is tenuous and causation is not proven. Overall, evidence for these adverse events is patchy and not always compelling. Overall, the use of PPIs, for selected indications with a good evidence base, has significant potential benefit but carries more caution in infants and children. Pediatricians should be aware of the concerns regarding the potential adverse events associated with their use., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant antidiarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant antidiarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented., Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations., Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely., Conclusions: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Small bowel biopsy (SBB) is not always helpful to establish celiac disease diagnosis. Hence we have conducted a retrospective study to know the amount of SBB in our center that was not optimal for this purpose. Histological findings were not appropriate for diagnosis in 3.56% (34 out of 955). The main problem encountered was inadequate sample cutting, although this could be solved by a new recut in almost 30% of cases.

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety., Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed.A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes.During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors., Results: A total of 33 recommendations were voted on using the nominal voting technique., Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care.

Objectives: The Bristol Stool Form Scale (BSFS) is inadequate for non-toilet trained children. The Brussels Infant and Toddler Stool Scale (BITSS) was developed, consisting of 7 photographs of diapers containing stools of infants and toddlers. We aimed to evaluate interobserver reliability of stool consistency assessment among parents, nurses, and medical doctors (MDs) using the BITSS., Methods: In this multicenter cross-sectional study (2016-2017), BITSS photographs were rated according to the BSFS. The reliability of the BITSS was evaluated using the overall proportion of perfect agreement and the linearly weighted κ statistic., Results: A total of 2462 observers participated: 1181 parents (48.0%), 624 nurses (25.3%), and 657 MDs (26.7%). The best-performing BITSS photographs corresponded with BSFS type 7 (87.5%) and type 4 (87.6%), followed by the BITSS photographs representing BSFS type 6 (75.0%), BSFS type 5 (68.0%), BSFS type 1 (64.8%), and BSFS type 3 (64.6%). The weakest performing BITSS photograph corresponded with BSFS type 2 (49.7%). The overall weighted κ-value was 0.72 (95% CI 0.59-0.85; good agreement). Based on these results, photographs were categorized per stool group as hard (BSFS type 1-3), formed (BSFS type 4), loose (BSFS types 5 and 6), or watery (BSFS type 7) stools. According to this new categorization system, correct allocation for each photograph ranged from 83 to 96% (average: 90%). The overall proportion of correct allocations was 72.8%., Conclusions: BITSS showed good agreement with BSFS. Using the newly categorized BITSS photographs, the BITSS is reliable for the assessment of stools of non-toilet trained children in clinical practice and research. A multilanguage translated version of the BITSS can be downloaded at https://bitss-stoolscale.com/.

Objectives: In young children, the use of fecal calprotectin (fCP) as a biomarker is limited because reference values have not been widely accepted up to now. Moreover, reference values for fecal eosinophil-derived neurotoxin (fEDN) in children have not been established. The aim of the present study was to investigate fCP and fEDN levels in young healthy children to establish reference values., Methods: Stool samples were obtained from healthy children ages 0 to 12 years. fCP and fEDN levels were analyzed using the EliA Calprotectin 2 assay (Phadia AB) and a novel research assay (on the ImmunoCAP platform), respectively., Results: In the 174 included children (87 boys), 95th Percentile values ranged from 1519 mg/kg at 0 months to 54.4 mg/kg at 144 months for fCP and from 9.9 mg/kg at 0 months to 0.2 mg/kg at 144 months for fEDN. There was a statistically significant association between age and fCP concentrations (P < 0.001) and age and fEDN concentrations (P < 0.001). We also found a statistically significant association between fEDN and fCP concentrations (rho = 0.52, P < 0.001). According to our results, we provide a nomogram and we suggest 3 different age groups for evaluation of fCP and fEDN concentrations, the 95th percentile being respectively 910.3 and 7.4 mg/kg for 0-12 months, 285.9 and 2.9 mg/kg for >1 to 4 years, and 54.4 and 0.2 mg/kg for >4 to 12 years., Discussion: By using an improved analytical method, we have confirmed that young healthy children have higher fCP concentrations than healthy adults. We, for the first time, report reference values for fEDN concentrations in a pediatric population. The proposed nomograms and reference values for fCP and fEDN are aimed at facilitating the applicability of biomarkers for both neutrophil- and eosinophil-mediated intestinal inflammation in children in clinical practice.

According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

Background: The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended in 2008, based on observational data, to avoid both early (<4 months) and late (≥7 months) introduction of gluten and to introduce gluten while the infant is still being breast-fed. New evidence prompted ESPGHAN to revise these recommendations., Objective: To provide updated recommendations regarding gluten introduction in infants and the risk of developing coeliac disease (CD) during childhood., Summary: The risk of inducing CD through a gluten-containing diet exclusively applies to persons carrying at least one of the CD risk alleles. Because genetic risk alleles are generally not known in an infant at the time of solid food introduction, the following recommendations apply to all infants, although they are derived from studying families with first-degree relatives with CD. Although breast-feeding should be promoted for its other well-established health benefits, neither any breast-feeding nor breast-feeding during gluten introduction has been shown to reduce the risk of CD. Gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Based on observational data pointing to the association between the amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. The optimal amounts of gluten to be introduced at weaning, however, have not been established.

Objectives: A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD)., Methods: The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy., Results: CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse., Conclusions: Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

Objectives: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children., Methods: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age., Results: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years., Conclusions: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.

Background: The need for an early and accurate diagnosis in celiac disease (CD) has focused attention on new diagnostic approaches, based on the efficiency of serological markers and the high negative predictive value of human leukocyte antigen (HLA) non-DQ2/8., Methods: We performed a retrospective review of all of the patients suspected of having CD who had undergone a small bowel biopsy in our gastroenterology unit. All symptomatic children with serological marker at time of biopsy (immunoglobulin A-tissue transglutaminase antibody, endomysial antibody, and HLA genotype) were included. The triple test (TT) was positive if immunoglobulin A-tissue transglutaminase antibody was 10 times the upper limit of normal, plus positive endomysial antibody plus human leukocyte antigen-DQ2/DQ8., Results: A total of 150 patients met the inclusion criteria and were enrolled in the study. One hundred sixteen were positive for the TT; 113 of 116 (97.4%) had a Marsh 2/3 histological lesion and had been considered to have CD. Thus, positive predictive value of the TT was 97.4%. The other 3 cases (2.6%) had Marsh 0/1 lesion, so we consider them to be false-positives for the TT; however, on follow-up, all 3 children developed histological damage after a gluten challenge. Finally, the positive predictive value of the TT was 100%. Thirty-four patients were negative for the TT: 22 patients are celiac, 3 are celiac but challenge gluten diet is pending, and the 9 patients left have other gastrointestinal disorder., Conclusions: Our study supports the view that in selected children who are symptomatic and positive for the TT, CD diagnosis could be established independent of histological findings.

Background and Objectives: A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis., Patients and Methods: Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet., Results: Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear., Conclusions: Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.

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.

Objective: Selective granulocyte-monocyte adsorption (GMA) apheresis is a safe technique that has shown efficacy in inflammatory bowel disease (IBD), especially in adult steroid-dependent and steroid-refractory ulcerative colitis. GMA apheresis is performed with Adacolumn, a direct blood perfusion system that selectively adsorbs circulating granulocytes and monocytes. Studies on efficacy of GMA apheresis in paediatric IBD are scarce. Our aim was to evaluate efficacy, safety, and tolerability of GMA apheresis in paediatric IBD patients followed for 1 year., Patients and Methods: Nine patients with a mild to moderate flare-up (6 boys, 3 girls; 5 ulcerative colitis [UC], 4 Crohn disease [CD]) were included. Mean age at inclusion was 13 years and 9 months, and mean disease duration before inclusion was 28 months. All of our patients with UC were steroid-dependent; patients with CD had been unsuccessfully treated with other therapies. GMA apheresis consisted of 5 consecutive weekly sessions lasting 60 minutes each., Results: After the 5 sessions, 4 of 5 patients with UC and 1 of 4 patients with CD achieved remission. This remission was maintained in 2 of 4 patients with UC and in the single patients with CD. Patients taking steroids could begin to taper their daily doses after the second apheresis, and 3 of 5 of these patients reached the end of the study steroid-free. GMA apheresis was well tolerated and no severe side effects related to the technique were observed., Conclusions: GMA apheresis is a safe, well-tolerated technique in paediatric IBD. As previously reported, we have observed a better efficacy in promoting and maintaining remission, and reducing conventional drugs in patients with UC than in patients with CD.

Background: ELISA methods for the measurement of IgA antigliadin antibodies (AGA), both home-made and commercial systems, routinely employ wheat gliadin fractions as coating antigens. We investigate the sensitivity and specificity for CD diagnosis of a new ELISA method using a highly immunoreactive beta-turn rich gamma3-avenin peptide as an alternative coating antigen., Methods: The assay was standardized with antihuman IgA peroxidase-conjugated as the second antibody. Alternatively, an ELISA based on the use of protein A-peroxidase was assayed to measure both IgG plus IgA antibodies. Sixty-three sera from healthy controls were analyzed to establish the system's cut-off point. Sera from 103 coeliac and from 65 noncoeliac children were tested; for diagnosis purposes, a small intestinal biopsy had been performed in all of them., Results: For the IgA class antibodies assay a high sensitivity and specificity of 90.3% and 98.5%, respectively, was obtained, comparable to those achieved for IgA antiendomysium antibodies (EmA) with the same sera., Conclusions: In view of the high sensitivity and specificity obtained together with water solubility of the peptide and easiness for large-scale reproducible synthesis, the new AGA IgA avenin peptide ELISA represents a significant improvement in CD diagnosis in comparison with conventional established AGA IgA ELISA using crude gliadins as coating antigens.

Background: To date, the most commonly accepted techniques for the screening of coeliac disease are indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA), which reveal antiendomysium and antigliadin antibodies respectively. We report the use of a simple visual system for coeliac disease screening based on the use of Staphylococcus aureus protein A, which binds to both IgG and IgA, thus avoiding the need for two parallel immunoassays., Materials and Methods: Opaque polystyrene microwell strips coated with a wheat gliadin extract were incubated with sera followed by incubation with protein A-colloidal gold conjugate. The resulting colour was compared with that of positive and negative control sera. The procedure took less than an hour., Results: One hundred and forty-five biopsy-proven sera, 94 from active coeliac patients and 51 from non-coeliac patients with diverse gastrointestinal pathologies or diabetes mellitus, were assayed. Ninety of the 94 sera from the active coeliac patients were positive, whereas only 3 of the 51 non-coeliac control subjects were positive. The technique has a sensitivity of 95.7% and a specificity of 94.1%., Conclusions: The sensitivity and specificity of the visual system are greater than those of most ELISA systems and are similar to those observed with IgA antiendomysium antibodies when tested in the same population. Moreover, it is inexpensive, quick, simple to perform and easy to interpret, i.e. it requires no qualified personnel. It is for these features, together with the outstanding sensitivity and specificity, that we propose this immunoassay as a new test for reliable coeliac disease screening.

One hundred forty-one children with insulin-dependent diabetes mellitus were screened for serum immunoglobulin A (IgA) antigliadin antibodies by means of an enzyme-linked immunosorbent assay (ELISA) method. None of them had gastrointestinal symptoms, and no major nutritional disturbances were detected except for a girl with moderate growth delay. Twelve patients with positive IgA antigliadin antibodies on two or more consecutive measurements underwent a small intestinal biopsy; four of them had a subtotal villous atrophy, and celiac disease was diagnosed; in another patient, a partial villous atrophy was observed. Children suffering from both diabetes and celiac disease showed an onset of diabetes at a younger age than did nonceliac patients. Prevalence of celiac disease in the screened population is 2.85%, which is higher than in the general population of the Comunidad Valenciana (one in 2,500 live births).

An 11-year-old girl with a history of insulin-dependent diabetes mellitus had erythema elevatum diutinum (EED) associated with a celiac disease related to a possible kidney disease. Dapsone did not improve the skin manifestations. However, the lesions disappeared after a gluten-free diet was begun. To our knowledge, this report describes the first case of EED in a patient with celiac disease.