BACKGROUND & AIMS:Celiac disease (CeD) is a global issue; its burden was detailed in a systematic review almost 8 years ago. Since then, new studies have emerged, prompting an update on prevalence estimates. We also aimed to characterize clinical features and assess how diagnostic methods influence detection rates. METHODS:We conducted a systematic review and meta-analysis of CeD prevalence in the general population, searching MEDLINE, Embase, Web of Science, and Scopus from inception until April 2024. Included studies used tissue transglutaminase IgA antibodies with or without biopsy confirmation, endomysial antibodies, and deamidated gliadin peptide antibodies. Random-effects models were used to pool prevalence estimates by diagnostic methods and demographic factors. RESULTS:We included 87 articles, comprising 394,274 participants. Global seroprevalence was 1.5% (95% CI, 1.3%-1.8%; I2 = 97.1%) and biopsy-confirmed prevalence of CeD was 0.8% (95% CI, 0.6%-1.0%; I2 = 94.9%). Using multiple serologic tests increased seropositivity by 40%, reaching 2.1%. Regarding IgA deficiency, adding deamidated gliadin peptide IgG raised seroprevalence by 120% to 2.2%. Prevalence was 50% higher in females and nearly doubled in children. Although seroprevalence was highest in Oceania and North America, biopsy-confirmed CeD was highest in Europe and South America. High-income countries had the highest prevalence; 36.6% of seropositive individuals did not undergo biopsy. Among biopsied patients, 30.8% met potential CeD criteria and 41.4% of biopsy-confirmed patients were asymptomatic. CONCLUSIONS:The present evidence indicates that approximately 1 in 70 individuals globally is seropositive for CeD and 1 in 120 has biopsy-confirmed CeD. Approximately 41% are asymptomatic, highlighting the need for improved detection worldwide.

Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total antioxidant capacity (ferric-reducing ability of plasma (FRAP)), reactive species (ROS), oxidative products (advanced oxidation protein products (AOPPs) and thiobarbituric acid reactive substances (TBARSs)), and antioxidant defenses (glutathione, GSH and intracellular activity of the main antioxidant enzymes) were evaluated. Correlations between OS markers, clinical features, disease characteristics, and inflammatory indices were explored. Results: Eighty-two IBD patients (67.5% in clinical remission) and 73 healthy subjects were enrolled. IBD children showed significant FRAP reduction compared to controls and IBD adults (p < 0.0001), increased AOPPs and reduced GSH compared to controls (p < 0.0001 and p = 0.0011, respectively), higher total GSH (p = 0.020), and lower TBARSs (p = 0.023) compared to IBD adults. In the pediatric group, FRAP was significantly reduced in those with IBD and increased in older subjects and males, while AOPP levels were positively affected by increasing age. In the total IBD cohort, higher FRAP was associated with male gender, increasing age, overweight, and mesalazine therapy. The diagnosis of Ulcerative Colitis was associated with lower FRAP and AOPP levels compared to Crohn's disease. Increased fecal calprotectin significantly decreased the total antioxidant capacity. Conclusions: The antioxidant system shows significant differences in IBD compared to controls, particularly in the pediatric group. The observed pediatric-adult pattern may suggest age-related differences in oxidative balance, but these findings should be interpreted with caution, given the modest sample size. Clinical Trial Registration Number: NCT04513015.

INTRODUCTION:To evaluate the correlation between serum intestinal fatty acid-binding protein (IFABP) levels and quantitative duodenal morphometry in adult patients with celiac disease (CeD) at diagnosis and after long-term gluten-free diet (GFD), and to assess the role of this investigation as a noninvasive marker of mucosal injury and healing. METHODS:In this prospective cross-sectional study, adult patients with CeD on a GFD for ≥18 months (follow-up [FU]) and newly diagnosed untreated patients with CeD (ND) were enrolled. Serum IFABP levels were measured by enzyme-linked immunosorbent assay (ELISA). Duodenal biopsies from FU and ND patients underwent quantitative morphometric analysis, including villous height to crypt depth (Vh:Cd) ratio, intraepithelial lymphocyte (IEL) count, and calculation of the Vh:Cd and IEL scale index. Correlation between IFABP and histological parameters was assessed. RESULTS:IFABP levels were significantly higher in ND patients compared with FU ( P < 0.001). Across the cohort, IFABP levels correlated negatively with Vh:Cd ratio (ρ = -0.53, P < 0.001) and positively with IEL count (ρ = 0.46, P < 0.001). IFABP also showed a strong inverse correlation with the Vh:Cd and IEL scale index (ρ = -0.60, P < 0.001). In FU patients, IFABP remained significantly associated with subtle morphometric abnormalities, including reduced Vh:Cd ratio and increased IEL counts, but not with celiac serology or self-reported dietary adherence. DISCUSSION:Serum IFABP levels represent a promising, noninvasive biomarker of enterocyte damage for capturing subtle changes and current mucosal status in patients with CeD on a long-term GFD, when conventional serology and dietary questionnaires may fail.

BACKGROUND AND AIMS:The Hawthorne effect describes outcome changes driven by awareness of observation rather than active intervention. In celiac disease (CeD), improvements reported in placebo or control arms suggest that observation may influence objective outcomes. We aimed to analyze the Hawthorne and other trial-related effects in treated CeD, focusing on histological changes of the small intestinal mucosa. METHODS:We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed and ClinicalTrials.gov were searched from inception to October 2025 for studies enrolling patients with CeD on a gluten-free diet (GFD) reporting outcomes in placebo or control arms. Outcomes were synthesized qualitatively, and by a random-effects meta-analysis of pooled within-group changes in villous height-crypt depth (Vh/Cd) ratio. RESULTS:Ten studies were included in the qualitative synthesis, and three studies (168 participants) provided histological data. Placebo or control groups showed improvements in symptoms, dietary adherence markers, and mucosal morphology. Meta-analysis demonstrated a significant increase in Vh/Cd ratio (median difference +0.25; 95% CI 0.11-0.39; p < 0.001) with low heterogeneity. This improvement suggests significant gluten contamination of the pre-trial GFD. CONCLUSIONS:In treated CeD, structured monitoring is associated with meaningful histological improvement independent of active intervention, that should be considered when interpreting trial outcomes.

The Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) recognized the need to define research priorities and identify knowledge gaps to guide future investigations in pediatric digestive health. Following international examples, SIGENP aimed to provide a structured framework that aligns scientific innovation with clinical relevance and patient-centered outcomes. This narrative review represents the consensus output of SIGENP's thematic working groups (WGs) in key fields-inflammatory bowel disease (IBD), Gastrointestinal Endoscopy, Hepatology, Nutrition and Intestinal Failure, Functional and Motility Disorders, and Allergy and Immunity. Each WG conducted a focused review of recent literature, national activities, and registry data, identifying unmet needs and defining strategic objectives. Draft reports were refined through plenary discussions and finalized by consensus during dedicated SIGENP meetings. Across all areas, shared priorities emerged: advancing precision and personalized medicine, integrating multi-omics and digital tools, and promoting pediatric-specific evidence through multicenter collaboration and harmonized registries. Disease-specific gaps include early diagnosis and biomarker discovery in IBD and liver disease, standardization of pediatric endoscopy and motility diagnostics, optimization of nutritional interventions and intestinal failure management, and the exploration of organoid and immune models in celiac disease and food allergy. This review outlines a comprehensive research agenda in pediatric gastroenterology, hepatology, and nutrition developed through a structured SIGENP expert process. It provides a strategic framework to guide future research initiatives, foster collaboration, and ultimately improve outcomes for children with gastrointestinal and nutritional disorders.

The gluten-free diet (GFD) is the resolutive and safe treatment of celiac disease (CeD), i [...]

BACKGROUND:The D1Ce Screen pilot study stems from the Italian Republic Law 130/2023 introducing the screening based on autoantibody measurement on capillary blood for the identification of people in pre-symptomatic, early phase of type 1 diabetes (T1D) and/or having silent celiac disease (CD) in the general paediatric population to reduce the impact of the two more frequent and severe chronic diseases of childhood. AIM:Primary aim is to assess, on a smaller scale, the organizational feasibility, acceptability and sustainability by the National Health Service of the screening program to be conducted nationwide in Italy according to the law. METHODS AND ANALYSIS:This is an observational multicenter study, planning to screen 5,363 children from four Italian regions (Lombardy, Marche, Campania, Sardinia), proportionally distributed according to population of the single Regions, representative of the North, Centre, South and Islands of Italy. Participants are screened by autoantibodies within three classes of age 2-2.9, 6-6.9, and 10-10.9 years, corresponding to reported peaks of seroconversion, in order to maximize the identification of future cases of disease. HLA typing for HLA DQ2 and DQ8 is also performed for CD risk in dry blood spots (DBS). Screening procedures are conducted by primary care paediatricians (PCPs), responsible for: direct contact with families; information about the study; administration of written informed consent, privacy statement and questionnaires; execution of blood drawing by finger prick; capillary blood collection for autoantibody and HLA testing and shipment to the central laboratory. Feasibility, acceptability and sustainability will be estimated by number of participating paediatricians; screened children in the four Regions and within the classes of age; feedback questionnaires; number of fingerpicks to obtain sufficient capillary blood for assays; any adverse events; costs evaluation in relation to assigned budget. Secondary objectives include frequency of T1D and CD specific autoantibodies to assess the prevalence of pre-symptomatic (Stage 1 and Stage 2) TD1 and undiagnosed CD in the three classes of age of general paediatric population. STUDY REGISTRATION:D1Ce Screen is not registered to any International Study Registry, as it is a pilot observational study requested by the Italian law 130/2023.

OBJECTIVES:Patient travel accounts for around 10% of healthcare-related greenhouse gas emissions. Telemedicine (TM) may contribute to reducing emissions. This study aimed to compare CO2 emissions, costs, and satisfaction associated with TM versus face-to-face (FTF) visits for follow-up of pediatric patients with celiac disease (CeD). METHODS:CeD patients (2-16 years), attending follow-up visits, were invited to choose between FTF or TM visits via Google Meet. Data on carbon footprint, cost, usability, and satisfaction (telehealth usability questionnaire [TUQ]), and dietary adherence (celiac dietary adherence test [CDAT]) were collected using Google Forms. RESULTS:Between March 2023 and November 2024, 300 patients were invited and 131 included (58 TM, 73 FTF). Baseline characteristics were similar (gender, age, and respondent). CDAT scores were comparable (p = 0.9). Compared to FTF, TM visits were shorter (30 vs. 75 min), with lower CO₂ emissions (0.08 vs. 24.00 kg), fewer lost workdays (18.9% vs. 81.1%), and reduced costs (€0.55 vs. €15.7; all p < 0.001); satisfaction was high except for "reliability" (median score: 16). CONCLUSIONS:TM is a sustainable alternative for CeD follow-up, reducing CO₂ emissions, costs, and time. High satisfaction supports broader TM implementation in line with environmental goals.

Background and aim:The prevalence and clinical spectrum of symptoms due to inadvertent gluten exposure in children with celiac disease (CeD) on a gluten-free diet (GFD) are not well defined. This study aimed to assess these acute reactions through an online survey. Methods:Parents of children with CeD treated with a GFD for at least 12 months completed an online questionnaire. The survey focused on symptoms occurring within 24 h of gluten-contaminated food ingestion. Results:Data were collected for 296 children. Acute reactions after unintentional gluten ingestion were reported in 98 cases (33.1%). The most common symptoms were abdominal pain (57.1%), diarrhea (42.9%), vomiting (31.6%), headache (12.2%), and fatigue (14.3%). Less frequent symptoms included nausea, constipation, urticaria, aphthous stomatitis, and arthropathy (each ∼5%-7%). In 86% of cases, symptoms appeared within 2-3 h. Gluten exposure most often occurred while dining out, especially in restaurants and school cafeterias. Conclusions:One-third of children with CeD on a GFD experience acute reactions to accidental gluten ingestion. These reactions typically arise rapidly and are dominated by gastrointestinal symptoms, aligning with reports from existing literature, where vomiting and nausea have been observed in 3%-46% of patients at the time of CeD diagnosis and in 13%-61% during gluten challenge.

Celiac disease (CeD) is one the commonest life-long diseases on a worldwide scale. The incidence today ranges from sporadic cases up to around 50 cases per 100,000 person-years and is generally increasing. The prevalence is much higher than previously thought, mostly 1% to 2% in the general population in countries where wheat is the staple food. Most cases of CeD remain undiagnosed if not proactively searched for by mass screening. Epidemiology of CeD can be positioned in 1 of 4 stages: emergence, acceleration in incidence, compound prevalence, and prevalence equilibrium. Each of these stages has its clinical challenges.

ObjectivesDiagnosis of celiac disease (CeD), an immune-mediated disorder, is based on clinical presentation, a panel of serological markers, and the histopathological findings in duodenal biopsies. Commonly, pediatric CeD patients fulfill these criteria for diagnosis. However, lack of correlation between serology tests and histology, or no accessible biopsies because of clinical conditions or during the COVID pandemic, are conditions that led to inconclusive diagnoses. Since the majority of CeD patients carry HLA-DQ2 and/or DQ8 alleles, HLA testing is used as a complementary tool in diagnosis though is costly and not broadly available for gastroenterology centers.MethodsWe performed a retrospective study to assess the performance of HLA testing when applied to selected groups of patients who could not be definitely diagnosed following the common algorithm. Eighty patients underwent testing for CeD-related HLA-DQ2 and DQ8 alleles.ResultsHLA typing contributed to diagnosis in 34 patients with positive serology but normal mucosa or those who presented negative serology or slightly positive serology (less than 3 times ULN) and duodenal histopathological changes. In patients with normal histology and negative or slightly positive serology, or those who did not undergo intestinal biopsy (39 in total), HLA typing contributed to CeD diagnosis in 23 cases, only 16 patients were admitted for a clinical follow-up program.ConclusionHLA-DQ typing supported the diagnosis in 57 of 80 children (71.2%) with previously inconclusive results, providing a beneficial approach for diagnosing celiac disease (CeD) in selected cases.

Nonceliac wheat sensitivity is a recently characterized disorder. Pathogenesis is still unclear, but it is known that not only gluten but also other wheat components, such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols and amylase-trypsin inhibitors, could activate patient's immunity and cause the onset of symptoms. This review illustrates the progress made over the last few decades and clinical/histologic features, as well as controversies. The lack of a biomarker makes the diagnosis still difficult. It is currently a diagnosis of exclusion, confirmed by a double-blind challenge with wheat. Further studies are needed to improve the diagnostic and therapeutic approach to this disease.

Background/Objectives. Rules for gluten-free (GF) food varies throughout the world. A maximum gluten level of 20 parts per million (ppm) in GF items is allowed in countries adopting the Codex Alimentarius recommendation, e.g. USA, Canada, UK, and the EU. More stringent criteria (no detectable gluten) are requested in other countries, e.g. Australia. However, only few data are available on the toxicity/safety of gluten traces in the diet of patients with celiac disease (CeD). The aim of this review was to review the scientific background of the gluten threshold in GF food. Methods. Studies on the dose-effect relationship between the amount of low gluten and detectable damage in CeD patients were examined and critically reviewed within the context of the current Codex Alimentarius rules. Results. A gluten dose higher than 10 mg per day, corresponding to 500 g of daily GF products at 20 ppm, may be harmful for most CeD patients. There is wide inter-patient variability in the response to a gluten intake of 10 mg. The potential toxicity of gluten traces < 10 mg/day of gluten remains unclear. Conclusions. The 20 ppm gluten threshold is safe for most patients, however further randomized controlled trials are required to evaluate the effects of 0-10 mg/day of gluten intake and, consequently, the safety of the current threshold at 20 ppm for “hypersensitive” CeD patients. New techniques, e.g. IL-2 measurement after a single-dose gluten challenge, may facilitate the investigation of the gluten dose-response curve, particularly in the low range of gluten intake.