Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.

To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.

Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.

Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.

Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado.

This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon signed-rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed.

Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence.

This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

This study aimed to determine the total prevalence of celiac disease (CeD), including undiagnosed cases, in a population-based study of adults screened for CeD.

The study used the fourth Trøndelag Health Study (HUNT4), conducted in 2017-2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analyzed for anti-transglutaminase 2 IgA and IgG. Seropositive individuals were invited for a clinical assessment, including upper endoscopy with duodenal biopsies. Previously diagnosed and seronegative CeD cases were identified through linkage to hospital records and the Norwegian Patient Registry.

The rate of CeD seropositivity was 2.0% (1107/54,505). Out of these, 724 individuals attended the clinical assessment. Additionally, the hospital records and registry identified individuals with a known CeD diagnosis, that were seronegative or without serology in HUNT4 or seropositive in HUNT4 but did not participate in the clinical assessment. In total, the study confirmed a new CeD diagnosis after participation in HUNT4 in 470 individuals and a known CeD diagnosis before participation in HUNT4 in 383 individuals. The total biopsy-confirmed prevalence of CeD was 1.5% (853/56,042), and the ratio of new, previously undiagnosed CeD cases (after HUNT4) to known, previously diagnosed CeD cases (before HUNT4) was 1.2:1 (470/383).

The total prevalence of CeD in this population-based study of adults in Norway was high and many individuals were previously undiagnosed. Detection of CeD should be improved, because early diagnosis is crucial for effective management and prevention of complications.

Given lengthy diagnosis and treatment delays existed for adult outpatients with newly diagnosed celiac disease (CD), a dietitian-led celiac disease clinic (DLCC) was implemented in 2020. Under DLCC, the dietitian removed eligible patients from the gastroenterology waitlist and ordered pathology and endoscopy for CD diagnosis, and those with CD were given timely, regular dietetic education. This pretest/posttest study aimed to compare time to CD diagnosis and treatment, and the proportion of patients were offered gastroenterologist appointments between the previous (pre-DLCC) and the DLCC expanded scope (post-DLCC) clinics.

Eligible patients were adults, referred to the gastroenterology dietitian between 2018 and 2021, with newly diagnosed CD. Demographic, medical, and appointment data were sourced from medical records. A satisfaction survey was administered to post-DLCC patients. Chi-squared and t-tests were used to compare groups.

Fifty-four patients were eligible (69%F, 43 ± 15 years, 86% had anti-TTG > 20 U/mL, n = 33 post-DLCC). Time from gastroenterologist referral triage to treatment commencement was improved by 404 days from pre- to post-DLCC (p < 0.01) in those whose CD diagnosis was not led by nursing staff, with reductions observed in both time from referral triage to CD diagnosis and CD diagnosis to treatment (p < 0.05). These improvements were conservative given COVID-19 delayed services for most (n = 29/33) post-DLCC patients. Thirty-six percent fewer post-DLCC patients were offered gastroenterologist appointments (p < 0.01). All (100%) post-DLCC respondents reported satisfaction with the clinic.

A DLCC expanded scope clinic may provide more timely diagnosis and treatment access for adult patients with newly diagnosed CD, with fewer requiring gastroenterologist appointments.

Intestinal inflammation continues in a subset of patients with celiac disease despite a gluten-free diet. Here, by applying multi-omic single-cell analysis to duodenal biopsies, we found that low-grade malignancies with lymphoma driver mutations in patients with refractory celiac disease type 2 (RCD2) are comprised by surface CD3-negative (sCD3-) lymphocytes stalled at an innate lymphoid cell (ILC)-progenitor T cell stage undergoing extensive TRA, TRB, and TRD TCR recombination. In people with refractory celiac disease type 1 (RCD1), a disease currently lacking explanation, we identified sCD3+ T cells with lymphoma driver mutations in 6 of 10 individuals with RCD1 and in one of the patients with active, recently diagnosed celiac disease. Furthermore, the mutant T cells formed large TCRαβ clones and displayed inflammatory and cytotoxic molecular profiles. Thus, accumulation of lymphoma driver-mutated T cells and sCD3- progenitors may contribute to chronic, nonresponsive celiac disease.

Celiac disease (CeD), triggered by gliadin exposure, necessitates therapeutic strategies that establish an antigen-specific immune tolerance. This study explores the therapeutic efficacy and mechanism of rapamycin-gliadin composite nanoparticles (PLN-GR) for CeD treatment. In vivo analyses demonstrated the efficient uptake of PLN-GR by antigen-presenting cells (APCs), particularly Kupffer cells and splenic dendritic cells (DCs), driving their tolerogenic phenotypic transformation. In a murine CeD model, PLN-GR administration significantly enhanced gluten tolerance and mitigated intestinal inflammation, as indicated by reduced paw edema and improved histopathological parameters. Mechanistically, PLN-GR induced macrophage metabolic reprogramming from glycolysis to oxidative phosphorylation, concomitant with elevated serum itaconate levels. This metabolic shift potentiated interorgan immunoregulatory crosstalk, expanding PD-L1+ tolerogenic splenic DCs while suppressing pathogenic Th1 cell populations. Bone marrow-derived macrophages (BMDMs) from Acod1-/- mice (deficient in itaconate synthesis) failed to induce DC tolerance upon PLN-GR treatment. However, supplementation with the itaconate derivative 4-octyl itaconate (4-OI) restored PD-L1 expression in DC2.4 cells in vitro, revealing that itaconate induces and stabilizes the tolerant DC phenotype. These findings underscore PLN-GR as a novel nanotherapeutic platform for CeD, achieving gliadin-specific tolerance through hepatic-splenic immunometabolic reprogramming and itaconate-dependent PD-L1 regulation, thereby offering a translatable strategy for autoimmune disease management.

The objective of this study was to evaluate the quality of life (QoL) of celiac patients, their predisposition to depression, and possible related factors.

The study was planned as a case-control study and conducted between May 2023 and August 2023 at Umraniye Training and Research Hospital, Istanbul. The study included 81 patients with celiac disease (CD) aged 18-65 years who were followed up at the Gastroenterology outpatient clinic and 79 healthy controls who were admitted to the Family Medicine Outpatient Clinic. Participants were administered the Celiac Disease Questionnaire (CDQ), the World Health Organization Quality of Life Scale-Short Form (WHOQOL-BREF), and the Beck Depression Inventory (BDI). Statistical analysis was performed using SPSS 24 (Statistical Package for the Social Sciences).

The study was conducted with 160 participants, of whom 73.8 % (n = 118) were female and 26.3 % (n = 42) were male. Age and gender distributions were similar. The celiac group had significantly lower scores of the WHOQOL-BREF "Overall Health" subscale compared to healthy controls (p = 0.004, Cohen's d = 0.46). However, no significant differences were observed in other WHOQOL-BREF subscales or depression levels (p > 0.05). In the celiac group, higher education levels (undergraduate and postgraduate) were associated with better QoL scores (η2 = 0.11, p = 0.015), while lower education was linked to higher depression scores (p = 0.019). A strong negative correlation was found between CDQ scores and BDI scores (r = -0.529, p = 0.001), indicating that higher depression levels were associated with lower QoL.When controlled for confounding variables, gender and CD turned out to be independently related to overall health subscale scores.

In patients with CD, both the QoL scale CDQ and the WHOQOL-BREF scores were found to be ahead of the curve in our study. It was also observed that the WHOQOL-BREF scale "overall health" subscale score was lower in celiac patients, while other sub-parameters and depressive symptoms were comparable to healthy individuals The lower "Overall Health" subscale scores highlight the need for targeted interventions.

Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing.

Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten.

While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

The natural history of potential celiac disease is poorly defined.

To study factors predicting progression of potential celiac disease to overt celiac disease.

Medical data were collected from patients with potential celiac disease defined as positive tissue transglutaminase and/or endomysial autoantibodies without diagnostic duodenal villous atrophy.

Of 158 patients with potential celiac disease (61 % women, median age 16 years, range 1-81 years), follow-up data were available for 128. The median follow-up time in patients not receiving a diagnosis was 14.6 years, and the median time until celiac disease diagnosis was 2.1 years. Serology normalized spontaneously in 38 %, while 61 % remained seropositive and 2 % began a gluten-free diet. Seventy-three patients underwent repeat endoscopy and 63 % of them received a celiac disease diagnosis. Those with later celiac disease diagnosis reported symptoms more often (84 % vs. 62 % p = 0.020) and were less frequently screen-detected (23 % vs. 52 %, p = 0.004) at their first endoscopy. During follow-up, they experienced persistent gastrointestinal symptoms more often (54 % vs. 27 %, p = 0.006) and remained seropositive (50 % vs. 16 %, p = 0.018).

During long-term follow-up, 63 % of the patients undergoing repeat endoscopy developed celiac disease. Predictive factors included baseline symptoms and persistence of gastrointestinal symptoms and sustained seropositivity.

The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) is a global health coding system that provides a standardised language for recording, reporting and monitoring diseases. However, epidemiological studies using real-world data on clinically diagnosed coeliac disease (CD) based on the ICD-10-CM remain limited.

To evaluate in primary care: (1) the diagnostic adequacy of CD; (2) the accuracy of the ICD-10-CM code K90.0 for identifying CD; and (3) the prevalence of clinically diagnosed CD compared with the known CD seroprevalence in the same geographical area (5‰).

This was a population-based, cross-sectional study in the city of L'Hospitalet de Llobregat (269,382 inhabitants), Catalonia, from 2005 to 2020. The data retrieved with the K90.0 code from electronic medical records were cross-checked against laboratory and pathology registries. The CD diagnostic criteria were validated on a case-by-case basis. To calculate the accuracy of the K90.0 code for identifying CD, patients were classified into confirmed versus uncertain/misdiagnosed CD.

Overall, 536/737 patients (73 %) had confirmed CD, and 201/737 (27 %) were misdiagnosed. The accuracy of the K90.0 code for identifying CD was as follows: sensitivity, 91.63 %; specificity, 99.95 %; positive predictive value, 63.85 %; and negative predictive value, 99.99 %. The prevalence of clinically diagnosed CD was 1.99‰, with a decreasing age-related trend of -7.5 %.

The ICD-10-CM code K90.0 is accurate for identifying clinically diagnosed CD and is thus a great tool for epidemiological disease surveillance. The gap between CD seroprevalence and the prevalence of clinically diagnosed CD (5‰ vs. 1.99‰) calls for the implementation of case-finding programmes to reduce underdiagnosis.

Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals. It is characterized by intestinal histological damage and the production of specific autoantibodies. The latest European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2020 guidelines have excluded human leukocyte antigen (HLA) genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value, limited availability, and high cost in some countries. However, HLA genetic testing remains valuable in certain clinical contexts. This study provided practical indications for when to request and how to interpret HLA genotyping, emphasizing its continued relevance for CD diagnosis in specific cases. We also proposed a strategy for monitoring the risk of developing type 1 diabetes (T1D) in patients with CD, based on the risk stratification carried by different HLA genotypes. A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in 2012, when HLA genotyping became mandatory for the diagnosis of CD. We identified key clinical scenarios where HLA testing remains useful. Several high risk HLA-DQ genotypes strongly associated with CD were highlighted, including HLA-DQ2.5/HLA-DQ2.2 and HLA-DQ2.5/HLA-DQ2.5. Notably, while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD, it appears to confer protection against T1D. To support clinical practice, we presented a table clarifying commonly used HLA terminology, and another summarized the main clinical situations in which HLA genotyping should still be considered. These findings underscore the dual role of HLA testing: Not only can it help rule out CD in selected cases, but it also identifies patients with CD at risk for T1D, guiding personalized monitoring strategies.

Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in genetically susceptible individuals. The characteristic histologic features of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a subset of individuals with elevated concentrations of serum tissue transglutaminase (TTG) antibodies have intact duodenal villous architecture at initial endoscopy and biopsy but then progress to CeD over time while on gluten-containing foods. We hypothesized that these rare potential CeD cases with progression can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD and to study the final cascade into the overt lesions of CeD. We retrospectively identified 16 children over a 10-year period with elevated serum TTG antibody concentrations but without significant villous atrophy at index duodenal biopsies, in whom subsequent biopsies confirmed CeD while consuming gluten-containing foods. Their clinical and histologic features were compared with age-, race-, and gender-matched controls including active CeD (n = 28) and non-CeD children (negative TTG antibody, normal histology, n = 35). Transcriptomic analysis was performed on a subset of the index biopsies of potential CeD cases with progression and controls. None of the 16 children with potential CeD with progression had a family history of CeD or presented with poor growth or anemia or had commenced a gluten-free diet at the time of index biopsy. The index biopsies of children with potential CeD with progression had significantly greater prevalence of intraepithelial lymphocytes (81% vs 12%, P = .002) and mild villous atrophy (94% vs 22%, P = .006) compared with non-CeD biopsies; none had severe villous atrophy (P = .002). Transcriptomic analysis demonstrated upregulated type I interferon signaling, Janus kinase (JAK)/signal transducer and activator (STAT) pathway of transcription activation and innate and adaptive immunity in duodenum of potential CeD with progression was comparable to non-CeD but preserved signaling in brush border absorption, transporter functions, and epithelial metabolic functions, compared with active CeD. Our results show for the first time that mild mucosal injury in the duodenum of children with potential CeD with progression is accompanied by upregulation of pathways also activated in CeD. Mild mucosal injury and type I interferon signaling may be the initiating cellular and molecular biomarkers in identifying the subset of potential CeD individuals who would progress to CeD while consuming gluten-containing foods.

Comprehensive screening of the general population is the only approach capable of identifying the majority of cases with celiac disease. In 2023, the Italian Parliament enacted a law to implement nationwide screening for celiac disease and type 1 diabetes. However, critical decisions regarding the target population, optimal timing, and screening methods remain unresolved. Previous observational studies on birth cohorts of children with genetic risk for these conditions have demonstrated that the incidence peaks early in life and is influenced by HLA risk genotypes. This mini-review explores different aspects of screening for celiac disease, presenting the advantages and challenges of identifying children before onset of symptoms. In addition, we summarize the current knowledge and gaps in understanding related to screening programs for celiac disease in children and adolescents and discuss health benefits, psychosocial aspects and cost-effectiveness, and their potential implications for future public health strategies.

The correlation between clinical, serological, and endoscopic findings and histological response after a gluten-free diet (GFD) is limited in adult celiac (CD) patients. This study aims to evaluate the effects of GFD on intraepithelial lymphocyte (IEL) localization by comparing the histopathological, clinical, serological, and endoscopic findings of adult CD patients. The patients (n = 131) were divided into three groups: those with good (CDgc) (n = 23) and poor (CDpc) (n = 21) GFD compliance and newly diagnosed ones (nCD) (n = 87). Total and supranuclear IELs were counted per 100 enterocytes and divided into three groups: apical, mixed, and basal, according to ROC (Receiver operating characteristic) analysis. The roles of clinicopathological parameters in predicting good dietary compliance were calculated using the multivariable logistic regression model. CDgc group predominantly (78.3 %) exhibited a basal pattern, and none exhibited an apical. Conversely, most CDpc and nCD patients showed mixed (66.7 % and 73.6 %, respectively) and apical (9.5 % and 25.3 %) patterns. Non-atrophic Marsh types (p = 0.040) and basal pattern (p = 0.043) were independent parameters predicting good dietary compliance. This study first showed that IEL localizations can indicate GFD compliance in samples from CD patients. Localization-based examination of IELs can be an additional histological indicator in monitoring GFD compliance and signs of recovery, especially in adult CD patients.

Coeliac disease (CD) is an autoimmune disorder treated with a gluten-free diet (GFD), requiring substantial changes in food choices and eating habits. This study explores the challenges faced by adults living with CD focusing on the theme of food literacy (FL), namely functional, relational, and system FL competencies.

A secondary analysis of data obtained through an online questionnaire was conducted. Adults living with CD in Québec, Canada and subscribed to Coeliaque Québec's newsletter were invited to complete a questionnaire. Using the critical incident method, respondents described a negative experience in their journey living with CD. Content analysis was done in a deductive and inductive manner, based on the 2022 Slater Food Literacy framework adapted to CD.

A total of 743 patients were included in the analysis. The qualitative analysis resulted in 11 codes under the three themes of FL. Patients reported challenges in finding reliable nutrition and medical information, managing a GFD in social settings, explaining CD and preventing gluten contamination, preparing balanced gluten-free (GF) meals, and making informed food choices. Patients reported on the negative impact of the GFD on their relationship with food, and how CD inhibits conviviality. Finally, patients addressed the need to advocate for GF food access in grocery stores and restaurants.

This study highlights the broad impacts of effectively managing CD and the GFD on patients' functional, relational and system FL competencies. Future research should explore how social and economic factors further interact with FL competencies of adults living with CD.

Coeliac disease is the most common immune-mediated enteropathy, affecting approximately 1 % of the population worldwide. Currently, the vast majority of individuals remain undiagnosed. Coeliac disease is triggered by gluten ingestion in genetically predisposed individuals carrying the human leukocyte antigen (HLA) genes; HLA-DQ2 and HLA-DQ8. Patients with coeliac disease present with a wide spectrum of gastrointestinal and extraintestinal manifestations and, in some cases, without any symptoms. The diagnosis of coeliac disease in adults is based on a combination of clinical suspicion, positive serological markers and histological evidence of small intestinal atrophy on duodenal biopsies. The only effective treatment is a strict, lifelong gluten-free diet. However, up to 20 % of patients report persistent or recurrent symptoms. In this review, we provide a comprehensive update on coeliac disease, focusing on its relevance to the different medical specialities and highlighting the need for a multidisciplinary approach to its diagnosis and management. Clinicians practicing internal medicine have a unique opportunity to diagnose this multisystem autoimmune disease. By doing so, they would avoid delays in diagnosis for these patients. A low threshold for serological testing is recommended.

Coeliac disease (CD) is an autoimmune disease affecting 1.4% of the population worldwide. The only treatment for this condition is a strict, lifelong gluten-free diet (GFD). Although the complexity of this condition is recognised, the definitive follow-up strategy and long-term management have still not been developed in the United Kingdom (UK) and Australia. This meta-synthesis aimed to explore the experiences of patients living with CD who follow the GFD in the UK and Australia.

A systematic search for primary qualitative literature related to experiences of patients with CD on a GFD and a meta-synthesis of the results were conducted. Healthcare-relevant online databases were screened: Academic Search Complete, CINAHL, MEDLINE, and Scopus, followed by reference list searching. A defined inclusion criteria were used to identify relevant studies. The data synthesis from the literature followed the thematic synthesis approach. A clear description of the methodology and peer review were applied to ensure transparency.

A total of 286 studies were screened for eligibility. Of those, six studies met the inclusion criteria. The experiences of 198 patients living with CD were analysed and reported. Five analytical themes emerged through the thematic synthesis process: acceptance and adaptation, dietary burden, cost burden, socialising, and importance of support. All themes were found to impact patients' quality of life (QoL). The overall quality of the reviewed studies was described as good.

This meta-synthesis revealed insights into the daily experiences of patients with CD in adhering to a GFD in the UK and Australia, being the first secondary qualitative study to explore this phenomenon. It highlighted the need for the development of defined strategies for patient follow-up to provide holistic care, considering the complexities of this condition and its impact on both physical and psychological domains.

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure. Moreover, there are a variety of potential complications and comorbidities of coeliac disease that might be related to malabsorption and/or chronic immune activation. Overall, individuals with coeliac disease have increased mortality compared with the general population, underscoring the severity of this common disease. Comorbidities and complications that have been associated with coeliac disease include poor growth, reproductive complications, kidney and liver diseases, respiratory disease (such as pneumonia) and infections (including sepsis). Furthermore, coeliac disease has been linked to other autoimmune disease and psychiatric disease, as well as certain cancers. Data suggest that mucosal healing on a gluten-free diet might protect against some, but not all, of these complications. In this Review, we present absolute and relative risks of coeliac-associated disorders. We discuss underlying mechanisms, the role of the gluten-free diet and mucosal healing, as well as implications for follow-up and non-dietary treatment of coeliac disease.

Celiac disease (CD) is an immune-mediated enteropathy of the small intestine triggered by gluten ingestion. Although the small bowel is the main organ affected, peripheral blood cell alterations have also been described in CD. We aimed to investigate immunological cell patterns in the blood of treated CD patients and in response to a 3-day gluten challenge (GC). Blood samples were collected from 10 patients with CD and 8 healthy controls on a gluten-free diet at baseline and 6 days after initiating the GC. All the samples were analyzed by spectral flow cytometry using a 34-marker panel. We found that patients with CD displayed a lower proportion of memory B cells compared to healthy controls, both at baseline and post-GC. Additionally, we observed the previously reported activated gut-homing CD4+, CD8+, and TCRγδ+ T lymphocytes on day 6 post-GC, and found the CD8+ subpopulation to be the most readily identifiable by flow cytometry. Importantly, the CCR9 marker proved effective in enhancing the selection of these gluten-responsive T cells, offering the potential for increased diagnostic accuracy. Spectral flow cytometry involves a complex data analysis, but it offers valuable insights into previously unexplored immunological responses and enables in-depth cell characterization.

Due to the need to reorganize the care network for the national screening mandated by law, a new healthcare model was required for the management of coeliac disease. The hub-and-spoke model is a new healthcare organizational system, here we describe its application (supported by telehealth), in the management of pediatric coeliac disease (CD) in Liguria. The results of the pilot phase are presented and the system's strengths and weaknesses discussed.

A mixed-methods survey followed by an observational pilot study was performed. A multiphase approach was used including preparation setting, operative planning and application. The pilot phase involves a single primary center. The reduction of families' expenditure and environmental impact was assessed using the Viamichelin calculator.

A regional meeting followed by a survey (specifically developed for this study) and a needs analysis highlighted the priority to have an efficient, up to date and homogeneous model of care assistance throughout the network. A diagnostic and therapeutic care pathway (PDTC) was developed by the regional working group. The project involved 986 Ligurian families and allowed a 90% reduction in the distance traveled by families residing within the pilot center's catchment area, saving €177 and 113 kg of CO2 on average per family per year.

The Gaslini Diffuso hub-and-spoke system for managing CD in Liguria exemplifies a commitment to enhancing healthcare efficiency and patient care, reducing environmental impact and cost for both family and healthcare system.

In celiac disease (CeD), dietary gluten serves as the driver for a comparatively well characterized small bowel mucosal immune response that generally results in small bowel mucosal villous atrophy and crypt hyperplasia along with a disease-specific transglutaminase 2 (TG2) targeting autoantibody response. Individuals with positive TG2 autoantibodies but normal small intestinal mucosal morphology are regarded at increased risk of developing CeD and represent patients with potential CeD. The removal of gluten from the diet leads to disappearance of the autoantibodies and normalization of the mucosal architecture in most cases. However, refractory CeD patients deviate from this dogma as they present with abnormal T cell compartment, persistent symptoms and villous atrophy despite a strict gluten-free diet. The heterogeneity of CeD presentation is further diversified by varying symptomatology. Gastrointestinal symptoms are the most canonical signs of CeD, and they include for instance diarrhea, vomiting, constipation and abdominal pain. Yet, a great portion of the patients manifest the disease at extraintestinal sites such as skin, musculoskeletal system or neuronal tissues. Beyond the involvement of various transglutaminase autoantibodies, the detailed immune mechanisms contributing to the development of these manifestations remains elusive, though. This review highlights the current understanding of the immunological differences in various manifestations of CeD. As the immunological basis of the different CeD phenotypes is at present insufficiently understood, more research on the subject is warranted before such data could be maximally applied to clinical practice.

Celiac disease is defined as a systemic immunological disorder caused by gluten (gliadin and other prolamin) in genetically predisposed individuals, who present with a variety of gluten-dependent symptoms, specific antibodies, the presence of the HLA DQ2 and DQ8 histocompatibility antigen, and enteropathy. Its prevalence, depending on the studied population and methodology, is estimated at 0.75-1.6% of the general population. During the complex immune reaction it induces, most cells involved in inflammatory processes are activated, which leads to the gradual atrophy of intestinal villi and the proliferation of enterocytes within intestinal crypts. The pathogenesis of celiac disease is extremely complicated and is still the subject of research. According to the current diagnostic guidelines, the following criteria should be taken into account: clinical symptoms (intestinal and extraintestinal), the presence of antibodies against tissue transglutaminase in the IgA class, the level of total IgA, and the presence of typical histological changes in duodenal biopsies. Diet-resistant celiac disease is one of the most important clinical challenges, causing serious complications. Currently, the basic method for treating celiac disease is an elimination diet (i.e., the exclusion of products that may contain gluten from the diet), however, new therapeutic strategies are still being sought, mainly based on supplementation with exogenous endopeptidases, modification of the immune response, and the use of zonulin inhibitors and transglutaminase 2 inhibitors. Clinical trials of new drugs are ongoing. The gradually expanding knowledge about the pathogenesis of celiac disease may allow for the development of new therapeutic strategies for both patients with a mild disease course, as well as those that are diet-resistant.

The main treatment for Celiac Disease (CD) is the gluten-free diet (GFD). However, in some CD patients, iron deficiency anemia can be persistent despite a GFD.

In this study, we aim to evaluate the prevalence of anemia in both adults and children with CD at the diagnosis and during the GFD.

In this cross-sectional study including both adults and children with CD, the demographic characteristics and hemoglobin, iron, folate and vitamin B12 levels were retrospectively retrieved from patients' medical records at the time of diagnosis (T0); after 3-5 years (T1) and after 8-10 years (T2) of GFD.

311 CD patients (184 adults and 127 pediatric patients) were included in the study. No difference was observed in the prevalence of anemia in the overall population after 3-5 years of GFD in both adult and pediatric patients compared to the diagnosis. At 8-10 years, in the adult patient's group, a significant reduction in the prevalence of anemia was observed (24% vs. 17.8% p = 0.043).

Despite the GFD and a very long observational period the diagnosis of anemia persists in 17.8% and 4.4% of adult and pediatric patients, respectively. The diagnostic delay (longer in adult patients) and a more pronounced ultrastructural mucosal injury could play a role in the persistence of anemia despite the GFD.

coeliac disease (CD) is an inflammatory condition of the small intestine caused by immunological intolerance towards dietary gluten. Associations between CD and other autoimmune disorders have been extensively reported. However, the risk in CD patients of developing immune-mediated renal diseases (IMRDs) as a function of the duration of exposure to gluten remains uncharacterized.

we used data from the Swedish national patient register to retrospectively construct two subcohorts of CD patients by either years before or after CD diagnosis, matched by sex and age to reference individuals (ratio 1:6). Adopting cox regressions, we assessed the risk in CD to develop IMRDs.

we found that unrecognized CD patients had a higher risk to develop the majority of the IMRDs here investigated compared with matched reference individuals. Following a CD diagnosis, the risk was reduced in eight of the twelve IMRDs. Furthermore, if patients were diagnosed with CD earlier in childhood they showed less or no increased risk to develop IMRDs compared with reference individuals. CD patients diagnosed by the age of 15 had an overall 12% increased risk of developing any IMRD, (HR: 1.12; CI = 1.02, 1.24; p < 0.02), as those with a CD diagnosis between 16 and 30 years of age had a 60% increased risk of developing IMRD (HR: 1.61; CI = 1.36, 1.91; p < 0.001).

Our data show that individuals diagnosed with CD at an earlier age have a lower risk of developing immune-mediated kidney conditions.

In recent years, wheat- and gluten-free diets have increased in demand due to reported increases in various conditions reported to be driven by ingredients of these food products. Celiac disease, wheat allergy and non-celiac wheat sensitivity constitute the three main categories of wheat-related disorders. Celiac disease is a well-characterized immune-mediated disease caused by immune reaction against specific gliadin epitopes, the main protein in wheat. Screening studies of samples collected over time bring evidence that there is a true increase in prevalence not only driven by increased testing activity. Clinical presentation of CeD is diverse and there is an increased risk of autoimmune co-morbidities. Wheat allergy consists of IgE- and non-IgE-mediated reactions, driven by Th2-cells directing eosinophil and basophil responses. Rapid IgE-mediated reactions are characterized by specific IgE antibodies in conjunction with symptoms originating especially from the respiratory and gastrointestinal tract. There is an increased risk of other allergies and the majority recover during adolescence. Non-IgE-mediated wheat allergy is a less-well defined condition, which is often diagnostically challenging due to a longer interval between exposure and symptoms and lack of non-invasive biomarkers. In this condition, wheat as a trigger needs to be established by exclusion followed by dietary challenge. Non-celiac wheat sensitivity, despite being the most recently recognized, has the highest reported prevalence among the three wheat-related entities. It remains, however, particularly poorly characterized due to unclear pathophysiology and lack of diagnostic markers. This narrative review will scrutinize the shared and distinct clinical features of the three wheat-related conditions, focusing on epidemiology, clinical presentation, co-morbidities, diagnosis, treatment and prognosis.

Living with celiac disease (CD), a chronic autoimmune condition, leads to a variety of challenges in daily life for the affected individual. The aim of this study was to describe perceptions of CD from the perspective of persons living with the condition. A total of 157 free text comments from a questionnaire sent to persons in a Celiac Disease Member Association was analyzed using qualitative content analysis. The findings are presented in two categories. "Personal explanations of causes" describes the respondents' thoughts about different medical aspects of the disease and thoughts about their diagnosis and the onset of the disease. "My everyday life with the condition" describes how respondents perceive how the disease affects life on many levels: emotionally, socially, and physically. Living with CD impacts lives, and early diagnosis seems to have a calming effect and improve everyday life. Follow-up reception after the diagnosis was expressed as valuable, as questions arise during the disease trajectory. Counseling by health care personnel with specific knowledge regarding CD from diagnosis onwards seems vital, as the only available treatment is a gluten-free diet.

Celiac disease (CeD) may be associated with elevated liver enzymes. However, little is known about the risk of chronic liver disease (CLD) of various etiologies or major adverse liver outcomes (MALO) in CeD. We aimed to investigate the long-term risk of CLD in patients with CeD.

Swedish nationwide cohort study. We identified 48,027 patients with biopsy-confirmed CeD between 1969 and 2017. Each patient was exactly matched with ≤5 general population reference individuals (n = 231,909) and followed through 2021. Flexible parametric survival models estimated adjusted hazard ratios (aHRs) of any and specific CLD (i.e., viral hepatitis, metabolic dysfunction-associated steatotic liver disease [MASLD], alcohol-related liver disease, and autoimmune liver disease) and MALO (compensated/decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death).

During a median follow-up of 16.0 years, 649 patients with CeD and 1571 reference individuals developed any CLD (incidence rate: 79.4 vs. 39.5/100,000 person-years). CeD patients had a higher risk of developing any CLD than reference individuals (aHR = 2.01, 95%CI:1.82-2.22). This risk remained elevated ≥25 years after diagnosis, giving one extra CLD case per 110 CeD patients until then. Positive associations were present for autoimmune liver disease (aHR = 4.86), MASLD (aHR = 2.54), and alcohol-related liver disease (aHR = 1.51). Individuals with CeD were at significantly higher risk of incident MALO (aHR = 1.54). Sibling comparisons and sensitivity analyses confirmed the main findings.

CeD is associated with a persistently increased risk of any incident CLD, although the absolute risk is low. Physicians should be vigilant to early signs of liver dysfunction in patients with CeD.

European Crohn's and Colitis Organisation, the Swedish Society for Medical Research (project#: PG-23-0315-H-02), FORTE (project#: 2016-00424), Takeda, and the Swiss National Science Foundation (project#: P500PM_210866).

A large proportion of individuals with coeliac disease (CeD) remain undiagnosed.

The aim of this study was to assess serological screening for CeD in the adult general population.

The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017-2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found.

Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals.

The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.

In celiac disease (CeD), interleukin 15 (IL-15) affects the epithelial barrier by acting on intraepithelial lymphocytes, promoting interferon γ (IFN-γ) production and inducing strong cytotoxic activity as well as eliciting apoptotic death of enterocytes by the Fas/Fas ligand system. This study investigates the effects of a monoclonal antibody neutralizing the effects of IL-15 (aIL-15) on tissue-damaging immune response in untreated CeD patients by using an organ culture system. Jejunal biopsies from 10 untreated CeD patients were cultured ex vivo with or without aIL-15. Epithelial expressions of CD95/Fas, HLA-E and perforin were analyzed by immunohistochemistry. Apoptosis was detected in the epithelium by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Additionally, the surface epithelium compartment of ex vivo cultured biopsy samples was isolated by laser capture microdissection (LCM). RNA from each LCM sample was extracted and the relative expression of IFN-γ was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). Biopsies cultured with the aIL-15 antibody showed a reduction in Fas, HLA-E and perforin epithelial expression, as well as a decrease in epithelial TUNEL+ cells compared to biopsies cultured without the aIL-15 antibody. Moreover, downregulation of epithelial IFN-γ expression was recorded in biopsies incubated with aIL-15, compared to those cultured without aIL-15. Our findings suggest that neutralizing the effects of IL-15 in ex vivo cultured untreated CeD intestinal mucosa could block apoptosis by downregulating Fas and HLA-E expression and the release of cytotoxic proteins, such as perforin. Furthermore, it can dampen the hyperactive immune response by reducing IFN-γ expression. More generally, our study provides new evidence for the effects of anti-IL-15 neutralizing monoclonal antibodies in preventing or repairing epithelial damage and further supports the concept that IL-15 is a meaningful therapeutic target in CeD, or inflammatory diseases associated with the upregulation of IL-15.

Gastroenterologists still raise concerns about adopting a non-biopsy strategy for diagnosing celiac disease (CeD) in adults.

To assess the performance of the concurrent detection of two autoantibodies targeting two independent antigens, tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP).

This prospective, multicenter, binational study collected consecutive patients with a high pre-test probability for CeD. Between 2018 and 2020, adults were enrolled at four Italian and one Argentinian center. Serology was also blindly analyzed by a central laboratory (Werfen, San Diego, USA) for tTG IgA and DGP IgG by Aptiva Particle-based multi-analyte technology (PMAT) assays. CeD diagnosis required histological confirmation of Marsh 3 damage.

181 adult patients with suspected CeD were enrolled (134 with histological diagnosis of CeD and 47 not histologically confirmed as CeD). Patients positive for both tTG IgA and DGP IgG (double positive) were predictive of CeD in 92.5 % of patients at >1x upper limit of normal (ULN). Double positivity for tTG IgA and DGP IgG, both at >10x ULN, had a 100 % positive predictive value for the presence of Marsh 3 histology.

Incorporating DGP IgG alongside tTG IgA in a single-step approach can be considered a valid confirmatory strategy for definitive non-biopsy diagnosis of CeD.

Background: The clinical presentation of coeliac disease (CD) is various and may influence disease course. We aimed to investigate the associations of clinical presentation with comorbidities and disease complications in a cohort of Hungarian coeliac patients. Methods: In this retrospective study, data of consecutive CD patients were analysed. Clinical presentation (classical vs. non-classical), extraintestinal manifestations and comorbidities (anaemia, metabolic bone disease, dermatitis herpetiformis, IgA deficiency, chromosomal abnormalities, autoimmune diseases and malignancy) were assessed. Student's t-test (for age at diagnosis) and the Chi-squared test or Fisher's exact test (for categorical variables) were applied as analyses. Results: A total of 738 patients were included. In classical vs. non-classical comparisons, classical presentation was significantly associated with metabolic bone disease (59 vs. 36%, respectively, p < 0.001), anaemia (47 vs. 38%, respectively, p = 0.027) and malignancy (6 vs. 2%, respectively, p = 0.006); however, autoimmune diseases and dermatitis herpetiformis were more common with non-classical presentation (23 vs. 31%, p = 0.02, and 5 vs. 16%, p = 0.014, respectively). Conclusions: Our findings confirm that clinical presentation is associated with certain comorbidities and complications in CD. More personalised follow-up may be recommended based on clinical presentation.

Bread wheat serves as an important staple crop in the human diet, largely because of the physicochemical properties of its dough and its protein content. Gluten is the main and complex component of wheat proteins. Despite the significant importance in breadmaking properties, wheat gluten contains some immunogenic peptides capable of triggering a T cell reaction in celiac disease (CD) patients, leading to inflammation in the small intestine. Among gluten proteins, α-gliadins are the most immunogenic components because they possess the primary T-cell stimulating epitopes (DQ2.5-Glia-α1, DQ2.5-Glia-α2, and DQ2.5-Glia-α3), which are primarily located on the D subgenome. Developing new wheat varieties by integrating the D subgenome from various sources is not only useful for introducing low immunogenic gluten, but it can also circumvent the challenging policies arising from the manipulation of wheat genome through transgenic approaches. Here, we performed RNA amplicon sequencing of the most toxic region of alpha-gliadins to analyze the content and composition of CD-related alpha-gliadin epitopes across eight synthetic wheat lines developed from crosses between durum wheat and different Aegilops species containing the D-genome (Ae. tauschii, Ae. crassa, and Ae. ventricosa). By searching the previously identified 121 epitopes and those with one mismatch in our amplicons, we found 54 different α-gliadins epitopes across our genotypes, four of which were new variants. The canonical epitopes were present in all lines, although their expression patterns varied. The occurrence of DQ2.5-Glia-α1a and DQ2.5-Glia-α3 was higher than that of DQ2.5-Glia-α2 and DQ2.5-Glia-α1b across all genotypes. Since a higher quantity of toxic alpha-gliadin epitopes is associated with increased immunogenicity in individuals susceptible to celiac disease, we measured the frequency of the most toxic alpha-gliadin epitopes among different synthetic lines to estimate the overall immunogenic load of our lines. Generally, the immunogenic load of lines with the D-genome originating from Ae. crassa was much lower than those with the D-genome from Ae. tauschii. In this way, the Ae. tauschii derived lines 5 and 6 contained higher levels of toxic alpha-gliadin epitopes, while lines 3, 4, and 7 (derived from Ae. crassa) contained the lowest levels of toxic peptides. We conclude that replacing the bread wheat D-genome with that of the Ae. crassa may help lower the gluten immunogenicity in the deriving synthetic wheat lines.

Celiac disease is attributable to a combination of genetic predisposition and exposure to dietary gluten, with immune system involvement. The incidence is increasing globally, and the societal economic burden of celiac disease stretches beyond the cost of gluten-free food. This enteropathy that affects the small intestine has been related to different disorders and comorbidities. Thus, the implications of suffering from this disease are multidimensional and need further consideration. Celiac disease is a serious condition that remains under-recognized, resulting in an increased need for programs for better management. This review aims to summarize the current evidence regarding celiac diseases, with special emphasis on clinical implications, diagnosis, dietary management, socioeconomical aspects, and future perspectives.

The reported prevalence of coeliac disease (CD) in rheumatoid arthritis (RA) is variable.

To evaluate the prevalence and incidence of CD in RA and controls.

Case-control study on administrative data.

The RECord linkage On Rheumatic Disease database (administrative data, 2004-2013) was used to retrieve patients with RA and age and sex-matched controls. Prevalence and incidence of CD were calculated and stratified according to age, gender, and calendar year.

The cohort included 346,956 subjects (mean age 59.9 (14.5), 70.7% females), of which 70,061 RA and 276,895 controls. Median follow-up was 9 years (IQR 9-9). The prevalence of CD was higher in RA (171/70,061 = 0.24% (0.2-0.3%) vs 398/276895 = 0.14% (0.1-0.2%), p < 0.001). The prevalence of CD among females with RA was increased compared to controls (0.3% vs 0.08%, p < 0.001), but was not increased in males with RA. The incidence was higher in RA and remained stable throughout the observation period.

The prevalence and incidence of CD were increased in RA, particularly in females.

IMU-856 is an orally available and systemically acting small molecule modulator of sirtuin 6 (SIRT6), a protein that serves as a transcriptional regulator of bowel epithelium regeneration. We aimed to evaluate the safety, clinical activity, pharmacodynamics, and pharmacokinetics of IMU-856 in healthy participants and in patients with coeliac disease.

This study reports the results from a completed first-in-human, three-part, double-blind, randomised, placebo-controlled, clinical trial of IMU-856 in healthy participants and patients with coeliac disease done in Australia and New Zealand. In part A, healthy participants were enrolled in six cohorts and randomly assigned (3:1) using a block randomisation algorithm to receive single ascending doses of IMU-856 ranging from 10 mg to 160 mg or matching placebo. Based on the results from part A, three doses were selected for part B to evaluate the safety, tolerability, and pharmacokinetics of IMU-856 once daily for 14 days using the same randomisation algorithm. Part C enrolled patients with well controlled coeliac disease. Participants were centrally randomised 1:1:1 using an interactive web response system to receive either low dose or high dose of IMU-856 or placebo once daily for 28 days that included a 15-day gluten challenge starting on day 14. The primary objective was safety and tolerability of IMU-856. Safety analyses were done on all patients who received at least one dose of the study drug. The trial is registered with the ANZCTR registry (ACTRN12620000901909).

Between July 27, 2020, and Oct 28, 2022, 71 healthy participants were enrolled in part A and B and assigned to either placebo (n=19) or IMU-856 (n=52). In part A and B, the IMU-856 doses were 10 mg (n=6), 20 mg (n=6), 40 mg (n=13), 80 mg (n=12), 120 mg (n=4), 160 mg (n=11). 43 patients with coeliac disease were enrolled in part C and assigned to either placebo (n=14), IMU-856 80 mg (n=14), or IMU-856 160 mg (n=15). Treatment-emergent adverse events (TEAEs) occurred in 24 (73%) of 33 participants in part A and 15 (79%) of 19 participants in part B receiving any dose of IMU-856 compared with six (50%) of 12 participants in part A and five (71%) of seven participants in part B with placebo. TEAEs were mainly mild in severity. In part C, TEAEs occured in 26 (90%) of 29 patients on any dose of IMU-856 and ten (71%) of 14 receiving placebo; the most common TEAEs with any dose of IMU-856 by preferred term were headache (13 [45%] of 29), nausea (nine [31%]), diarrhoea (eight [28%]), and abdominal distension (seven [24%]). Two serious adverse events occurred with IMU-856 treatment (one in part B [bacterial myocarditis] and one in part C [biliary colic]), both of which were unrelated to IMU-856. No dose-limiting toxicities, systematic safety laboratory changes, or deaths occurred during the study. In part C, mean decrease in villous height was -20·9 μm (SD 34·8) among patients who received IMU-856 80 mg, -22·5 μm (51·1) among those who received IMU-856 160 mg, and -60·3 μm (52·2) among those who received placebo.

The favourable safety profile, along with preliminary activity, suggests that IMU-856 should be studied in future trials of coeliac disease.

Immunic Australia.

Celiac disease (CD) is a systemic, immune-mediated enteropathy that occurs following dietary consumption of gluten in genetically susceptible individuals. The global prevalence of celiac disease is estimated to be approximately 1.4%, with variation based on age, sex, and geographic location. CD typically presents early in life with diarrhea, abdominal pain, abdominal distention, weight loss, and impaired growth. In severe cases, patients with CD can present in a state of celiac crisis (CC), classically characterized with profuse diarrhea and life-threatening metabolic derangements.

In this report, we discuss a 23-month-old girl in a state of CC who presented atypically with hypoalbuminemia, generalized edema, and constipation.

Even in the presence of atypical symptoms, such as edema or constipation, CD should be considered as a differential diagnosis in pediatric patients with severe gastrointestinal disturbances. Additionally, we propose a revised definition of CC that is specific to the pediatric population.

Celiac disease (CeD) is increasingly diagnosed but significant disparities exist in awareness, practices, resources, and legislation worldwide. We conducted a global online survey with CeD experts to assess this disparity internationally.

A 55 questions survey encompassing nine domains relevant to CeD care (awareness, gluten-free [GF] foods availability/cost/quality, GF labeling, CeD dietician availability, insurance for CeD patients, medical training, research funding, patient support groups, and unmet needs) was generated and sent to CeD experts worldwide electronically. Countries were stratified based on per capita income as high-income (HIC) and lower-income countries (LIC) (including upper-middle-, lower-middle-, and low-income countries). Survey responses were summarized as a single score using principal component analysis.

Valid responses were obtained from 131(37.4%) [HIC: 71; LIC: 60] of contacted CeD experts from 63 countries. Compared with HIC, LIC experts perceived worse availability (HIC:80% vs LIC: 47%; P < 0.001), quality (52% vs 20%; P < 0.001), and legislation for labeling of GF foods (82% vs 37%; P < 0.001), with unfavorable reimbursement policies (27% vs 12%; P = 0.002), subsidies (32% vs 13%; P < 0.001), and insurance (76% vs 43%; P < 0.001) for CeD patients. LIC also lacked awareness about CeD among general physicians (69% vs 32%; P < 0.001), trained celiac dieticians (39% vs 12%; P = 0.002), and active CeD patient support groups (93% vs 50%; P < 0.001). All experts believed that GF foods were costly (94% vs 87%), frequently contaminated (27% vs 32%), and unfavorably taxed (97% and 93%). The experts agreed on key unmet needs and better research funding. Overall CeD preparedness score (median 58.3 vs 33.0; P < 0.001) was also associated with income.

The present survey highlights the opinion of global experts on the challenges, opportunities, and preparedness related to CeD and differences worldwide by income.