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Objectives: An increased frequency of celiac disease (CeD) has been reported in severe Immunoglobulin E (IgE) -mediated food allergy (FA). This observation requires confirmation, and whether CeD affects FA severity and resolution is unknown. The study aims to estimate the prevalence of CeD in patients with FA and to investigate whether CeD affects FA severity and oral tolerance., Methods: Consecutive patients with FA referred for allergen reintroduction, either to evaluate allergy resolution or to start oral immunotherapy (OIT), were evaluated for CeD and for FA severity. The primary outcome was the prevalence of CeD. Secondary outcomes were the frequency of severe FA and the level of clinical tolerance at study entry and at last follow-up in patients with isolated FA versus patients with FA + CeD., Results: Two hundred twenty-eight patients were included. CeD was confirmed in 15 patients (6.6%) of whom, 8 patients had a previously established diagnosis of CeD and were on a gluten-free diet. Severe FA was observed in 12 patients with FA + CeD (80%) versus 88 patients with FA (42%) ( P = 0.006). At baseline, patients with FA + CeD had significantly higher median allergen-specific IgE levels [61.8 kU/L; interquartile range (IQR) 11.6-279.0] compared to patients with FA (20.3 kU/L; IQR 2.9-72.7) ( P < 0.001). Complete clinical tolerance was observed in 1 of 15 patients (7%) with FA + CeD versus 98 of 205 patients (48%) with FA ( P = 0.002)., Conclusions: CeD is highly prevalent in patients with FA and could affect FA severity and response to OIT. CeD screening should be considered in patients with severe or persistent FA., 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: To investigate the compliance to the gluten-free diet in a cohort of adult celiac patients 20 years after the diagnosis, received in childhood through a mass screening., Methods: This is an observational historic cohort follow-up study. It was carried out at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Two matched cohorts of adult celiac patients, diagnosed in childhood through a mass screening or for symptoms were enrolled. Adherence to the gluten free-diet and development of autoimmune diseases were investigated through a questionnaire administrated in the course of a phone interview.The primary study outcome was the adherence to the gluten-free diet, measured through the Biagi questionnaire, in the two cohorts of celiac patients., Results: We contacted 25 patients (mean age 28 years, 19 females) diagnosed with screening and 34 patients (mean age 25 years, 26 females) diagnosed in the same period for symptoms. After 20 years, in the cohort diagnosed with screening and in the cohort diagnosed for symptoms the adherence to the gluten-free diet was optimal in 14 (56%) and 26 (81%), improvable in 5 (20%) and 3 (9%), inadequate in 6 (24%) and 3 (9%), respectively. In the two cohorts, four patients (16%) and six patients (18%) developed other autoimmune diseases., Conclusions: Twenty years after the diagnosis, near half of the patients diagnosed in a mass screening, does not have an optimal adherence to the gluten-free diet and a remarkable proportion of them have developed another autoimmune disease., 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.)

Objectives: During the past decades, there has been a shift in the clinical presentation of coeliac disease (CD) to nonclassical, oligosymptomatic, and asymptomatic forms. We assessed clinical presentation of CD in children and adolescents in Central Europe., Methods: Paediatric gastroenterologists in 5 countries retrospectively reported data of their patients diagnosed with CD. Clinical presentation was analyzed and the differences among very young (<3 years) and older children and adolescents were studied., Results: Data from 653 children and adolescents (median age 7 years 2 months; 63.9% girls) from Croatia, Germany, Hungary, Italy, and Slovenia were available for the analysis. One fifth (N = 134) of all children were asymptomatic. In symptomatic children, the most common leading symptom was abdominal pain (33.3%), followed by growth retardation (13.7%) and diarrhoea (13.3%). The majority of symptomatic children (47.6%; N = 247) were polysymptomatic. Abdominal pain was the most common symptom in polysymptomatic (66.4%) as well as in monosymptomatic children (29.7%). Comparing clinical presentation of CD in very young children (younger than 3 years) with older children (3 years or older), we found that symptoms and signs of malabsorption were significantly more common in younger (P < 0.001), whereas abdominal pain and asymptomatic presentation were more common in older children and adolescents (both P < 0.001)., Conclusion: In children with CD, abdominal pain has become the most common symptom. However, in younger children, symptoms of malabsorption are still seen frequently. This raises a question about the underlying mechanism of observed change in clinical presentation in favour of nonclassical presentation and asymptomatic disease at certain age., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Celiac disease (CD) remains undiagnosed for a long time in many adult and pediatric patients. We assessed the knowledge about CD among healthcare professionals (HCPs) and CD patients in Central Europe (CE)., Methods: HCPs and CD patients from 5 CE countries were asked to complete the web-based questionnaire about CD. The questions were divided into subsections on epidemiology, clinical presentation, diagnostics, treatment, and follow-up. Achieved scores of different specialists managing patients with CD were compared and regional differences in patients' knowledge were analyzed., Results: Questionnaire was completed by 1381 HCPs and 2262 CD patients or their caregivers from Croatia, Hungary, Germany, Italy, and Slovenia. Mean score achieved by HCPs was 50.9%, and by CD patients 56.4%. Pediatric gastroenterologists scored the highest (69.4%; P < 0.001). There were significant differences in knowledge of patients from different CE regions with German participants scoring the highest (58.3%). Members of CD societies scored higher compared with nonmembers (mean score 58% vs 53.2%; P < 0.001) and patients diagnosed less than 5 years ago scored higher compared with those diagnosed more than 10 years ago (mean score 57.3% vs 54.6%; P < 0.001)., Conclusions: The knowledge about CD among HCPs and CD patients is not satisfactory. Further awareness-raising and learning activities are needed to improve HCPs' knowledge and to minimize the number of unrecognized patients and unnecessary diagnostic delays. Patients should be better informed about their disease to reach higher compliance with the gluten-free diet., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The current European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines introduced the option to diagnose coeliac disease (CD) in children and adolescents without upper endoscopy if the defined criteria are met. The aim of our study was to evaluate how frequently paediatric gastroenterologists in Central Europe used the "no-biopsy" approach and how often the duodenal biopsy could have been omitted., Methods: Medical records of patients aged < 19 years diagnosed with CD in 2016 from five European countries were analysed, focusing on levels of transglutaminase antibodies (TGA) at the time of diagnosis and on whether the diagnosis was confirmed using duodenal biopsy or "no-biopsy" approach. Clinical presentation and delays until final diagnosis were analysed according to diagnostic approach., Results: Data from 653 children (63.9% female, median age: 7 years, range: 7 months-18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. One fifth ( n = 134) of included children were asymptomatic at diagnosis. Of 519 symptomatic children, 107 (20.6%) were diagnosed by the "no-biopsy" approach. Out of the remaining 412 children who underwent duodenal biopsies, 214 (51.9%) had TGA ≥ 10 times upper level of normal (ULN) and would have been eligible for the "no-biopsy" approach. Signs and symptoms of malabsorption were more frequent in children diagnosed without duodenal biopsies. There were no differences in diagnostic delays with respect to the diagnostic approach., Conclusion: In this cohort, about 60% of symptomatic CD patients could have been diagnosed without duodenal biopsies. The aim of the "no-biopsy" approach was to make the diagnostic procedure less challenging without compromising its reliability. However, this option was applied only in 20%, in spite of fewer burdens to the family and reduced costs. The reasons for this discrepancy are unknown. Physicians should be made more aware about the reliability of CD diagnosis without biopsies when the ESPGHAN guidelines for CD diagnosis are followed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 Petra Riznik et al.)

Objectives: Coeliac disease (CD) is a systemic autoimmune disorder affecting about 1% of the population. Many patients remain undiagnosed or are diagnosed with substantial delay. We assessed diagnostic delays in symptomatic CD children in Central Europe (CE)., Methods: Paediatric gastroenterologists in 5 CE countries retrospectively reported data of their patients diagnosed in 2016. Age at first CD-related symptom(s), first visit to paediatric gastroenterologist and confirmed diagnosis were used to determine diagnostic delays., Results: Data from 393 children (65% girls, median age 7 years, range 7 months to 18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. Median duration from first symptom(s) to visit to paediatric gastroenterologist was 5 months (range 0-10 years; preschool 4 months, school-aged 5 months), and further duration until final diagnosis was 1 month (range 0-5 years) with significant regional differences (P < 0.001). Median diagnostic delay was 6 months (range 0-10 years; preschool 5 months, school-aged 7 months). Type of clinical presentation had little, however, significant effect on delays. Reduced body mass in delays longer than 3 years compared with delays shorter than 1 year was found (z score -0.93 vs -0.39, P < 0.05)., Conclusions: Time from first symptoms to CD diagnosis in children in 5 CE countries is slightly shorter compared with few other small paediatric studies, and significantly shorter than reported for adults. Nevertheless, delays of more than 3 years in 6.6% of children are worrisome. Raising awareness about the variable symptoms and implementation of reliable diagnostic tools will further reduce diagnostic delays.

Objectives: Available data indicate that liver involvement is present in a significant proportion of children with celiac disease (CD) at the diagnosis (elevated transaminases 15%-57%, autoimmune liver disease 1%-2%). We sought to evaluate prevalence, clinical course, and risk factors for liver involvement in a large cohort of children with CD., Methods: Children (age 0-18 years) diagnosed with CD from March 2010 to April 2016 were enrolled. Liver involvement was considered to be present when alanine transaminase (ALT) levels were >40 U/L (hypertransaminasemia [HTS]). Patients with HTS were re-evaluated after at least 12 months of a gluten-free diet., Results: CD was diagnosed in 806 patients during the study period; of these, ALT levels were available for 700 patients (86.9%), and were elevated in 27 (3.9%, HTS group); median ALT and aspartate transaminase levels in the HTS group were 57 U/L (interquartile range 49-80 U/L) and 67 U/L (interquartile range 53-85 U/L), respectively. Younger age, malabsorption symptoms, and low hemoglobin or ferritin were significantly more common in the HTS group at univariate analysis. At multivariate analysis, only age ≤4.27 years correlated with risk of liver involvement (odds ratio 3.73; 95% confidence interval: 1.61-8.66). When retested on a gluten-free diet, all but 3 patients normalized ALT levels; of these, 1 was diagnosed with sclerosing cholangitis., Conclusions: Liver involvement in celiac children is now less frequent than previously reported, possibly due to changing CD epidemiology. Younger age is the only risk factor. Associated autoimmune liver disease is rare.

Objectives: Antibodies against transglutaminase 6 (anti-TG6) have been implicated in neurological manifestations in adult patients with genetic gluten intolerance, and it is unclear whether autoimmunity to TG6 develops following prolonged gluten exposure. We measured the anti-TG6 in children with celiac disease (CD) at the diagnosis time to establish a correlation between these autoantibodies and the duration of gluten exposure. We investigated a correlation between anti-TG6 and the presence of neurological disorders., Methods: Anti-TG6 (IgA/IgG) were measured by ELISA in sera of children with biopsy-proven CD and of children experiencing gastrointestinal disorders. CD patients positive for anti-TG6 were retested after 2 years of gluten-free diet (GFD)., Results: We analyzed the sera of 274 CD children and of 121 controls. Anti-TG6 were detected in 68/274 (25%) CD patients and in 19/121 (16%) controls, with significant difference between the 2 groups (P = 0.04). None of the CD patients and of the controls testing positive for anti-TG6 were experiencing neurological disorders. Eleven of 18 (61%) CD patients with other autoimmune diseases were positive for anti-TG6. In CD patients, a significant correlation between the gluten exposure before the CD diagnosis and anti-TG6 concentration was found (P = 0.006 for IgA; P < 0.0001 for IgG). After GFD anti-TG6 concentrations were significantly reduced (P < 0.001). No significant correlation was observed between anti-TG6 and anti-TG2 serum concentrations., Conclusions: Anti-TG6 are more prevalent in children with untreated CD in the absence of overt neurological disorders. The synthesis of the anti-TG6 is related to a longer exposure to gluten before the CD diagnosis, and the autoimmunity against TG6 is gluten dependent and disappeared during GFD.