Gastrointestinal (GI) symptoms are common in patients with Williams-Beuren syndrome (WBS), but their prevalence and possible causes are not yet fully known. This study assessed GI symptoms' prevalence and their possible origin by performing a predefined set of tests in adult WBS patients. Laboratory tests and a questionnaire were administered to assess GI symptoms and dietary habits. All the patients underwent the urea breath test, H2-lactose and H2-glucose breath tests, and intestinal ultrasound (IUS) and vibration-controlled transient elastography for liver stiffness measurement (LSM) and controlled attenuation parameter (CAP, dB/m). Thirty-one patients were enrolled (72% of the whole cohort, 17 males, median age 32 years). Gastroesophageal reflux disease (GERD) symptoms were reported in 29% of the patients, abdominal pain in 26%, and altered bowel habits in 48%. Pathologic signs at (IUS) were present in 60% of the cases. Prevalence was 0.26 (95% CI 0.12-0.44) for Helicobacter pylori infection and 0.61 (95% CI 0.42-0.78) for lactose intolerance. LSM was > 6 kPa (in the range of a fibrosis score > F1) in three patients, and CAP values were > 268 dB/m (corresponding to a steatosis score > S2, e.g., moderate steatosis) in nine. The presence of altered bowel habits was significantly related to chronic abdominal pain (OR 13.1, p = 0.03). Increased BMI (> 28 kg/m2) (OR 10.8, p = 0.04) was associated with the presence of moderate-severe hepatic steatosis. After specific treatment and dietary counseling, most patients reported resolution/improvement of symptoms, whereas a few retained/developed symptoms during follow-up. Chronic abdominal pain, GERD symptoms, and unbalanced metabolic parameters were common in our WBS patients, together with an increased prevalence of lactose intolerance/colonic diverticula. Specific counseling and treatment improved symptoms for most patients.

To determine age- and sex-specific reference values for serum immunoglobulins (IgA, IgG, and IgM) in a population-based cohort of 6 to 18 years old Danish children and adolescents and investigate if immunoglobulin concentrations vary with body mass index standard deviation score (BMI SDS).

A total of 2171 school children and adolescents (median age 12.0 years) were recruited. BMI SDS was calculated, and health status was assessed by questionnaire and blood samples. Fasting serum concentrations of IgA, IgG, and IgM were determined by immunonephelometry. Sex- and age-specific percentiles were generated and partitioned following the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Multiple linear regression models were used to investigate associations betweenIgA, IgG, IgM, and BMI SDS adjusted for age and sex.

Concentrations of IgA increased with age but did not differ between boys and girls. An age-dependent increase was also detected for concentrations of IgG and IgM, although for IgG it was more pronounced in boys than girls. Girls had higher concentrations of IgG and IgM than boys at all ages. Concentrations of IgM were inversely associated with BMI SDS independent of age and sex.

We generated age- and sex-specific reference intervals for IgA, IgG, and IgM based on children and adolescents from a Danish/North-European Caucasian population-based cohort. The findings can help evaluate alterations seen in primary and secondary immunodeficiencies and autoimmune diseases.

Celiac disease (CD) is a very common immune-mediated enteropathy resulting from the interaction between dietary gluten and the immune system in genetically predisposed individuals. The immune response leads to intestinal damage, malabsorption and, ultimately, to a broad spectrum of both intestinal and extra-intestinal symptoms. According to current criteria, a proper diagnosis of CD requires an initial phase consisting of clinical case identification and serological screening that, over time, has increased in importance. In most adults and in selected children, the diagnosis is subsequently defined by histological evidence of intestinal damage as a confirmatory test, which usually returns to normal after a suitable period of a gluten-free diet (GFD). The clinical remission and disappearance of circulating antibodies after a GFD further confirm the diagnosis and represent a goal to be achieved to improve the quality of life and reduce the risk of long-term complications. However, although the diagnostic criteria for CD are well defined and described in specific guidelines, the monitoring of CD patients undergoing GFD has been less studied and, consequently, specific guidelines for this phase are still lacking. The aim of this report was to evaluate the classical tools used to monitor the adherence and response to GFD, other non-invasive biomarkers that have been proposed for CD monitoring, and the histological follow-up of CD patients in order to provide a starting point for future discussions on this specific topic.

Celiac disease (CD) is underdiagnosed and thus untreated in many cases. Untreated CD may be associated with severe health complications, increased morbidity and mortality, and considerable burdens to health care systems. Our objectives were to prospectively assess whether implementation of case finding in young children at the Dutch Preventive Youth Health Care Centers (YHCCs) is feasible and effective.

From February 2019 to January 2022, parents of all children aged 1-4 years attending the YHCCs in the Kennemerland region were invited. If there was at least 1 CD-associated symptom, a point-of-care test was performed onsite to assess the (immunoglobulin [Ig] A/IgG/IgM) celiac autoantibodies against tissue transglutaminase type 2 (TGA). If positive, the child was referred for confirmation of the diagnosis if TGA-IgA was more than 7 times the upper limit of normal or if histopathology showed Marsh 2 or 3 in addition to positive autoantibodies against endomysium.

A total of 16 289 parents were invited for regular consultation, of whom 14 917 consented to fill in the questionnaire; 5301 (35.5%) reported symptoms. A total of 3203 tests were performed in 3103 children (58.5%; 47.8% female; median age 2.0 y) and was positive in 61 (1.9%). CD was confirmed in 56 children (1.7% [95% CI, 1.46-2.44]; median age 2.6 y). With the exception of abdominal distention (P = .036), symptoms were similarly frequent among children with and without CD. The overall crude incidence rate of CD diagnosed by case finding was 1.67 per 1000 person-years (95% CI, 1.27-2.15), significantly higher than by standard of care (0.14 per 1000 person-years; P < .001).

Case finding for CD using a point-of-care test is effective and feasible at Dutch Preventive YHCCs. Implementation of case finding into the standard of care will lead to timely diagnosis of CD in childhood.

Cow's milk protein allergy (CMPA) is a significant health issue in the pediatric age, carrying lifelong health implications. To compare the impact of different formulas on the occurrence of other atopic manifestations (AMs), autoimmune disorders (ADs) and the time of immune tolerance acquisition in a population of children with immunoglobulin E (IgE)-mediated cow CMPA.

In a 72-month prospective cohort study the occurrence of other AMs (i.e., eczema, urticaria, asthma, and rhinoconjunctivitis), ADs (i.e., celiac disease, thyroiditis, type 1 diabetes, inflammatory bowel diseases, idiopathic juvenile arthritis) and the time of immune tolerance acquisition were comparatively evaluated in IgE-mediated CMPA children treated with different formulas: extensively hydrolyzed casein formula containing the probiotic L. rhamnosus G (EHCF + LGG), rice hydrolyzed formula (RHF), soy formula (SF), extensively hydrolyzed whey formula (EHWF), or amino-acid based formula (AAF).

313 subjects were evaluated: EHCF + LGG (n = 64), RHF(n = 62), SF(n = 63), EHWF(n = 60) and AAF (n = 64). The incidence of AMs was: 0.30(Bonferroni-corrected 95%CI 0.15 to 0.44) for EHCF + LGG cohort, 0.68 (0.52-0.83) for RHF cohort, 0.73 (0.59-0.87) for SF cohort, 0.70 (0.55-0.85) for EHWF cohort and 0.83 (0.71-0.95) for AAF cohort. The corresponding risk ratios are 2.28 (1.51-3.45) for RHF vs. EHCF + LGG (p < 0.001), 2.46 (1.64-3.69) for SF vs. EHCF + LGG (p < 0.001), 2.36 (1.56-3.56) for EHWF vs. EHCF + LGG (p < 0.001), and 2.79 (1.88-4.13) for AAF vs. EHCF + LGG (p < 0.001). The 72-month immune tolerance acquisition rate was higher in the EHCF + LGG cohort. The incidence of celiac disease was 2/313 (0.006, binomial exact 95%CI 0.0007 to 0.023). No cases of other ADs were reported.

The dietary treatment with EHCF + LGG is associated with lower incidence of AMs and higher rate of immune tolerance acquisition in children with CMPA.

Celiac crisis (CC) is a rare but potentially life-threatening complication of celiac disease (CD), characterized by severe diarrhea, electrolyte imbalances, and metabolic disturbances. We report the case of a 32-year-old pregnant woman presented significant dehydration, weight loss, and steatorrheic stools. Diagnosis was confirmed by duodenal biopsy, with rapid improvement following a gluten-free diet (GFD) and corticosteroids. The diagnosis of CC was established based on the acute clinical presentation and rapid improvement following a GFD and corticosteroid therapy. This case highlights the importance of early recognition and prompt management of CC, particularly in undiagnosed or untreated CD, to prevent severe maternal and fetal complications.

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.

In pediatric patients, celiac disease (CD) may influence the health-related quality of life (HRQoL).

The study aimed to assess HRQoL and further characterise the clinical factors associated with reduced HRQoL, in a large multicenter pediatric cohort with CD.

The disease-specific questionnaire CD Dutch Questionnaire (CDDUX) and the generic questionnaire Paediatric Quality of Life Inventory (PedsQL) were used to assess the HRQoL. Clinical and sociodemographic characteristics were analyzed, univariate and multivariate analysis were conducted.

Eleven different Italian pediatric centers and 871 families were involved. Mean age at interview was 12.9 ± 2.9 years. The mean total CDDUX score of CD patients was 47.1 ± 18.8, revealing a neutral HRQoL (47.1 ± 18.8), and a good to very good HRQoL according to the PedsQL (81.4 ± 12.6), parents indicated lower scores (p = 0.03) with both questionnaires (CDDUX 45.1 ± 18.6 and PedsQL 79.9 ± 14.5). Patients with lower HRQoL were mainly female, living in Northern Italy, with lower parent's education level and non-biopsy diagnosis of CD. In multivariate analysis, the main predictor of lower CDDUX score was non-biopsy diagnosis.

The HRQoL in a large cohort of Italian children is reported as neutral-good. This indicates a high level of adaptive behaviors in response to the daily challenges of CD. Parents tend to underestimate their children's HRQoL. Specific clinical factors, including non-biopsy diagnosis, may be associated to lower HRQoL.

Lifelong adherence to a gluten-free diet (GFD) is the primary treatment of celiac disease (CeD), a gluten-driven enteropathy. Concerns have been raised about increased exposure to arsenic from a GFD because rice, which naturally bioaccumulates arsenic, is commonly used as a substitute for gluten-containing grains such as wheat. We hypothesize that arsenic exposure increases in newly diagnosed children with CeD after they adopt a GFD.

This is a single-center prospective longitudinal cohort study of children (age 2-18 years) with elevated celiac serology who underwent a diagnostic endoscopy before initiation of a GFD between January and May 2022. The primary outcome was change in urinary arsenic concentration between endoscopy and after 6 months on a GFD.

Of the 67 recruited participants, 50 had a biopsy diagnostic of CeD and were invited to continue the study. Thirty-five participants completed sample collection. Participants were from a middle-class, well-educated population that was predominantly White with presenting symptoms of abdominal pain (51%) and diarrhea (29%). After 6 months on a GFD, there was a significant increase in the median urinary arsenic concentration (3.3 µg/L vs 13.6 µg/L, P = 0.000004). In regression models, family history of CeD and Hispanic ethnicity were associated with having a higher urinary arsenic concentration after 6 months on a GFD.

Children with newly diagnosed CeD have increased arsenic exposure shortly after transitioning to a GFD. While the arsenic levels were well below acutely toxic concentrations, the clinical impact of chronic exposure to mildly elevated arsenic levels is unknown.

Early-life use of acid-suppressive therapy has increased over the past 2 decades. Although these medications are widely used, recent studies showed an association between early-life use of acid-suppressive therapy and various long-term outcomes, including celiac disease.

To assess the association between early-life use of acid-suppressive therapy and the risk of celiac disease autoimmunity using 2 observational approaches on a large population-based database.

The cohort study took place in Israel using Maccabi Healthcare Services data. The data were collected on December 8, 2023, and were initially analyzed from January to May 2024. Analysis of the data continued during the revision rounds that took place from October 2024 to February 2025. Children born between January 1, 2005, and December 31, 2020, were included, grouped based on their exposure to acid-suppressive therapy within the first 6 months after birth and subsequently followed up for outcome development until the age of 10 years or December 8, 2023. A retrospective matched cohort design (N = 79 820) and retrospective matched test-negative case-control design (n = 24 684), including only the population tested for celiac disease autoimmunity, were used separately and compared.

Prescription purchase of acid-suppressive therapy, either proton-pump inhibitors or histamine-2 receptor antagonists, during the first 6 months of life.

Celiac disease autoimmunity was defined as a positive anti-transglutaminase 2 enzyme-linked immunosorbent assay test result according to the thresholds of the commercial kits used. Time to first positive result for celiac disease autoimmunity was defined as the outcome in the cohort design, and acid-suppressive therapy use was defined as the outcome in the test-negative design.

The cohort design included 79 820 children (41 319 boys with no acid-suppressive therapy use [51.8%]; median birth year, 2015 [IQR, 2011-2018]), of whom 19 955 (25.0%) used acid-suppressive therapy. The rate of celiac disease autoimmunity was significantly higher among children using acid-suppressive therapy than among those not using acid-suppressive therapy (1.6% [310 of 19 955] vs 1.0% [610 of 59 865]; P < .001). The adjusted hazard ratio of acid-suppressive therapy use for development of celiac disease autoimmunity was 1.52 (95% CI, 1.33-1.74). In the test-negative case-control design, a total of 24 684 children were included (62.2% girls; median birth year, 2012 [IQR, 2009-2016]), of whom 6176 (25.0%) were celiac disease autoimmunity positive. The rate of acid-suppressive therapy users among those who tested positive for celiac disease autoimmunity was not significant compared with those who tested negative (5.0% [309 of 6176] vs 4.6% [858 of 18 508]; P = .25). The adjusted odds ratio of a positive celiac disease autoimmunity test for acid-suppressive therapy use was 1.07 (95% CI, 0.94-1.23), which was nonsignificant compared with the population that tested negative.

This retrospective study included both cohort and test-negative case-control designs. In the cohort design, acid-suppressive therapy was significantly associated with celiac disease autoimmunity. In the test-negative case-control design, this association was not significant. These results suggest a residual confounding by health care utilization in cohort designs studying celiac disease and suggest a noncausal association between acid-suppressive therapy and celiac disease autoimmunity.

In uncertain cases of coeliac disease (CD), gluten challenge (GC) may be necessary to confirm or exclude the diagnosis. However, data on diagnostic outcomes after GC are limited.

We aimed to evaluate outcomes after GC in patients with unconfirmed CD who had already started a gluten-free diet (GFD), and identify predictors of a confirmed diagnosis.

Patients with unconfirmed CD already on a GFD, who underwent GC and subsequent testing with endomysial antibodies (EmA) and duodenal biopsy between 06/2000-06/2021 were included. Clinical data, prior test results, and final diagnoses were retrospectively collected and analysed.

158 patients underwent GC (median duration 3 months, IQR 3-6) and CD was confirmed in 47/158 (29.7 %) (41 conventional CD, 1 CD + IgAdeficiency, 5 potential CD), non-coeliac enteropathies (NCEs) were diagnosed in 3 patients, and enteropathy was ruled out in 108. Prior positive serology strongly predicted CD diagnosis after GC (OR 36.8, 95 %CI 13.8-100.0, p < 0.001), whereas prior reported villous atrophy did not (p = 0.83), as this was frequently (35 %) due to incorrect sampling/interpretation of poorly oriented specimens. Duration of GC was also not associated with diagnostic outcomes (p = 0.37).

Prior positive serology strongly predicted CD diagnosis after GC, while histological results without positive serology should be interpreted cautiously. Clinicians should consider NCEs in older patients with severe symptoms.

To determine the utility of anti-tissue transglutaminase IgA antibodies (tTG-IgA) and anti-deaminated gliadin peptide IgG antibodies (DGP-IgG) in detecting coeliac disease (CD) and whether DGP-IgG can replace anti-endomysial IgA antibody in the European Society for Paediatric Gastroenterology Hepatology and Nutrition no-biopsy approach in diagnosing CD.

Children aged < 19 years who had paired tTG-IgA and DGP-IgG performed and had a gastroscopy with biopsies between 1 March 2016 and 31 October 2020 were retrospectively reviewed.

Of 1206 patients who fulfilled the study criteria, 298 (24.7%) patients were diagnosed with CD. Fifteen patients with IgA deficiency were excluded from any tTG-IgA analysis. tTG-IgA had sensitivity and specificity of 93.5% and 92.0%, respectively, in detecting CD, while DGP-IgG had sensitivity of 97.0% and specificity of 86.7%. tTG-IgA ≥ 10x upper limit of normal (ULN) alone had a specificity of 99.3% and a positive predictive value (PPV) of 96.8%. An optimal DGP-IgG threshold was identified to be 70 U/mL (3.5x ULN) based on > 99% specificity in detecting CD. When tTG-IgA ≥ 10x ULN was combined with DGP-IgG ≥ 3.5 ULN, the PPV in diagnosing CD was 98.5%. DGP-IgG performed well in detecting CD in 126 children aged < 3 years, with all patients with CD having an elevated DGP-IgG (sensitivity 100%).

Combined tTG-IgA ≥ 10x ULN and DGP-IgG ≥ 3.5x ULN provided a high PPV (98.5%) in diagnosing CD. DGP-IgG testing can potentially replace EMA testing in those children with tTG-IgA ≥ 10x ULN. Future studies should evaluate DGP-IgG testing as a sequential test.

Celiac disease (CeD) has been associated with a low response to hepatitis B (HBV) vaccination, but guidelines for testing and revaccination among individuals with CeD are sparse. We examined the risk of future HBV among individuals with CeD in a population-based Swedish cohort. Furthermore, we examined the rate of prior HBV infection in CeD patients.

All individuals in Sweden diagnosed with biopsy-verified CeD between 1990 and 2017 were identified through the ESPRESSO cohort. Each individual with CeD was matched by age, sex, calendar year, and birth country (Nordic vs. other) with up to 5 reference individuals.

We identified 44,721 CeD and 222,238 reference individuals. The incidence rates of diagnosed HBV were 2.3 and 2.9 per 100,000 person-years, respectively. This represented no association with CeD (HR 0.77 (0.45-1.30)). This null association was similar for those with a Nordic (HR 0.80 (0.40-1.60)) and non-Nordic ((HR 0.31 (0.09-1.08)) country of birth. Rates of prior HBV infection were low (CeD 0.08%, controls 0.06%). This corresponded to a small but insignificant increase among individuals with CeD (odds ratio, OR 1.41 (0.97-2.05).

In a population-based Swedish cohort, there was no increased risk of developing HBV in individuals with CeD. This finding does not support current practices of testing and revaccination for HBV. Additional studies should be completed in areas with higher endemic rates of HBV. Slightly higher rates of prior HBV infection in CeD may be secondary to increased testing in those seeking medical care for another disease process.

Autoimmune thyroid diseases (ATD) are the most prevalent autoimmune disorders associated with celiac disease (CD). Both conditions can often be detected through serological screening in asymptomatic patients over several years. Various guidelines for screening thyroid disease (TD) are available in children with CD and vice versa.

We conducted a systematic review to identify the most recent and relevant guidelines, comparing their recommendations to analyze key differences and suggesting a practical clinical approach.

Out of 1,294 articles reviewed, we identified 20 guidelines published between January 2013 and January 2024. These guidelines, primarily from gastroenterological organizations in Europe and North America, recommend different timings and methods for screening the co-occurrence of these diseases, both at diagnosis and during follow up. Some guidelines recommend only clinical follow-up without routine serological screening. There is limited consensus on screening for TD [using thyroid-stimulating hormone test (TSH)] in asymptomatic children newly diagnosed with CD, and even less agreement on screening for CD [using anti-transglutaminase antibodies (tTG) immunoglobulin A (IgA) test and total IgA] in children newly diagnosed with TD. No standardized procedures exist for managing patients with isolated low tTG and human leukocyte antigen (HLA) genotyping is rarely recommended as a first- line screening method.

Over the past decade, there has been a growing recognition of the importance of identifying children with co-occurrence of CD and TD who could benefit from early treatment, even in the absence of symptoms. However, international guidelines still show a lack of consensus regarding screening for these frequently associated autoimmune diseases, with notable differences in the use of HLA testing and follow-up protocols.

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Association of CD and aplastic anemia (AA) has been reported in the literature, yet this association remains rare in children. The authors report a case of a previously healthy 4-year-old boy with 1-month history of diarrhea, asthenia, loss of appetite, and weight loss. Laboratory evaluation showed bicytopenia with very severe aregenerative anemia and neutropenia. Bone marrow aspirate and biopsy were performed with findings suggestive of bone marrow aplasia. Further etiological research showed IgA deficiency and increased plasma concentrations of anti-tissue transglutaminase IgG antibodies (anti-tTG IgG 336 U/mL). Patient underwent upper digestive endoscopy confirming diagnosis of CD. The child started a gluten-free diet (GFD) with subsequent clinical and serological improvement. At 12-month post-hospitalization follow-up, the child was asymptomatic, with normal growth rate, resolution of bicytopenia, and anti-tTG IgG lower but still positive (151 U/ml) due to partial adhesion to GFD. To the best of author's knowledge, this is the eighth published pediatric case describing the association of CD with AA. The pathogenesis of this association is not yet fully understood. The authors suggest that CD screening should be considered in patients with unexplained hematological abnormalities.

The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) allows a no-biopsy diagnostic of celiac disease under certain conditions. We assessed the impact of the diagnostic algorithm on the patient's long-term outcome by comparing the serology-based diagnosed patients to biopsy-proven ones.

We reviewed the charts of children presenting with antitransglutaminase IgA titers above ten times upper limit of normal and consecutively diagnosed with celiac disease between 2010 and 2014, a time-period overlapping with ESPGHAN diagnostic guideline change in 2012. Outcome measures for no-biopsy vs. biopsy-proven diagnosed patients were clinical and laboratory findings, compliance to gluten-free diet and to regular visits after one, two and 8-10 years of follow-up.

Clinical and laboratory, i.e., serum chemistry and autoantibody outcome measures on gluten-free diet clearly showed worse patient healing in the 33 serology-based diagnosed children compared to the 30 biopsy-proven ones. The attendance of the follow-up visits was also higher in the biopsy group.

Our results indicate that dietary transgressions are common in childhood celiac disease resulting in slow healing. Therefore, there is a need of improvement of the management, with special attention regarding the ESPGHAN no-biopsy criteria diagnosed patients. Our study also indicates that novel treatments adjunctive to diet are warranted in children.

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.

The role of immune cell profiles at birth in determining the risk of celiac disease (CD) development is currently unestablished. This study aimed to determine the associations between T- and B-cell profiles at birth and pediatric CD.

This regional cohort study analyzed prospectively collected dried blood spots from 158 children with CD (median 7 years old at CD diagnosis) and two matched comparators each (n = 316). We quantified T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) as measures of thymic and bone marrow output at birth. Moreover, we used epigenetic cell counting to estimate the percentages of lymphocyte subsets: CD3+, CD4+, CD8 + T cells, CD4 + memory T, regulatory T, B, and NK cells.

No associations were found between measured immune cell markers at birth and CD development (all p values > 0.26). The median number of copies was 120 for TRECs (IQR = 92-168) and 136 (IQR = 91-183) for CD patients and comparators, respectively, and for KRECs, it was 69 (IQR = 45-100) for CD patients and 66 for comparators (IQR = 44-93). Across the groups, there were similar median percentages of T cells (CD, 32.6% [IQR = 27.0-43.8%] vs. comparators, 33.9% [IQR = 26.3-45.7%]) and B cells (CD, 25.4% [IQR = 20.3-30.6%] vs. comparators, 24.7% [IQR = 19.9-30.8%]). The ratio of the lymphocyte subset estimates between CD patients and comparators approximated one; all p values were > 0.26. The results were consistent across strata defined by sex, HLA type, and age at diagnosis.

Genetic and epigenetic markers for B cells and T cells in immune cell profiles at birth did not impact susceptibility to childhood-onset CD.

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.

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.

Among the possible adverse reactions to gluten, celiac disease, non-celiac gluten sensitivity, and IgE-mediated wheat allergy have been classically described. A non-IgE-mediated reaction similar to food protein-induced enterocolitis syndrome (FPIES) after inadvertent gluten ingestion in a celiac patient was recently reported. We present three children affected by celiac disease with exquisite control, including appropriate adherence to an exclusion diet, who suffered a severe adverse food reaction after unappreciated outdoor ingestion of gluten, meeting the criteria for a definitive diagnosis of FPIES. The strict and prolonged exclusion of gluten from the diet is postulated as the possible trigger for this serious entity after an involuntary transgression. Although the first published cases are recent, we might be witnessing an increase in the frequency of presentation. Therefore, we believe emergency services must be alert to the possibility of diagnosis of FPIES in celiac patients due to involuntary transgressions. The determination of gluten glycoimmunopeptides in urine or stool samples may be useful for certifying the inadvertent consumption of wheat as the cause of FPIES.

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).

Diagnosis 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.

We 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.

HLA 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.

HLA-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.

There is high variability in the follow-up of paediatric patients with coeliac disease (CD) in Europe. The aim of this study was to know the current reality of paediatric CD follow-up in Spain through professionals and the patients themselves and their families.

A cross-sectional descriptive study was conducted using 2 anonymous web surveys, one aimed at paediatric gastroenterologists, and the other at members of CD patients' associations.

A total of 96 responses from paediatricians and 4745 from patients (1362<15 years) were analysed. Among the professionals, 84.4% carry out follow-up only at the hospital level. A percentage of 80.2 lack a joint follow-up protocol with primary health care. The transition after the paediatric age is made to adult gastroenterologists by 56.2% of professionals (only 8.3% in a protocolized manner). A percentage of 58.3 do not have a dietitian and 64.6% do not use quality of life questionnaires. The patients stated that they mainly performed follow-up visits in the hospital (68.8%). Only 15.7% ever consult a dietitian. Scheduled visits were more frequent in paediatric patients than in adults (95.1% vs. 63.5%, p<0.001). The variable most associated with attendance at follow-up visits was that the survey had been answered by the patient's parents (odds ratio 2.6, p<0.001).

In Spain, there is a lack of follow-up protocols for paediatric CD patients integrating hospitals and primary care, as well as protocols for the transition to adult professionals. The participation of dietitians is very low. Adult patients adhere less to follow-up visits.

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.

To characterize the frequency and predictors of follow-up endoscopic biopsy in patients with celiac disease.

The utility of routine follow-up biopsy in patients after a diagnosis of celiac disease is uncertain, especially in patients whose symptoms resolve on the gluten-free diet.

Using the Merative MarketScan U.S. commercial insurance and Medicare databases, we identified 30,737 patients with biopsy-diagnosed celiac disease. We followed them until they had a second duodenal biopsy (our primary outcome) or insurance coverage ended.

Among the patients with celiac disease we identified, 5976 (19.4%) underwent a follow-up biopsy. The median time between initial and follow-up biopsies was 16.8 months. Compared with younger patients, those aged 20 years or older had an increased likelihood of undergoing a follow-up biopsy (cumulative incidence rate at 5 y for patients age ≥20 y was 36.0%, 95% CI: 35.0%-37.1% vs 21.9%, 95% CI: 20.5%-23.4% in patients age ≤19 y). Follow-up biopsies occurred less frequently in more recent calendar years. Follow-up biopsy was more common among patients with an Elixhauser Comorbidity Index of 1 (hazard ratio: 1.09; 95% CI: 1.01-1.17) or ≥2 (hazard ratio: 1.28; 95% CI: 1.20-1.37) compared with patients with an index of zero. Among patients who had a follow-up biopsy, 57% had a celiac disease-related symptom recorded in the 30 days before the procedure.

Follow-up duodenal biopsy is performed in a substantial minority of U.S. patients with celiac disease. Adult age and increased comorbidity burden were associated with a greater likelihood of follow-up biopsy. Just under half of follow-up biopsies are performed for routine surveillance, in the absence of persistent symptoms.

Celiac disease (CeD), also known as gluten enteropathy, is an immune-mediated inflammatory enteropathy triggered by intolerance to gluten. It presents with a spectrum of symptoms, including both gastrointestinal and extraintestinal manifestations, as well as neurological symptoms. A review of the literature indicates that 10-22% of patients with CeD present with neurological symptoms. The objective of this study is to assess the influence of a gluten-free diet (GFD) on brain bioelectrical activity and neurological symptoms in children with CeD. Methods: The study was conducted using a multidisciplinary approach, encompassing a comprehensive array of clinical data gathered alongside laboratory test results, questionnaires, and electroencephalogram (EEG) assessments. The study population included 85 children: 18 newly diagnosed cases of CeD patients (NDC), subsequently reassessed after 6 months on a GFD as a celiac disease on diet (CDD); 27 CeD patients on a GFD for over 12 months (CDD2); and 40 healthy individuals in the comparison group (CG). Results: It was observed that over half of the NDC group exhibited neurological symptoms, particularly headaches. Following a six-month period on a GFD, there was a notable reduction in symptom severity. In comparison to the CG, the NDC patient group exhibited a higher prevalence of abnormalities in EEG recordings (p = 0.032), including focal sharp waves or slow waves. Conclusions: The results demonstrate that a GFD has a positive impact on the neurological condition of children with CeD. The clinical improvements correspond with EEG normalization, which supports the hypothesis that dietary intervention plays a role in mitigating CeD-associated neurological dysfunction.

Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

We aimed to explore the potential effect of ritlecitinib on CeD serology levels before and after ritlecitinib treatment in research participants of clinical trials.

The effect of ritlecitinib on CeD serology (tTG-IgA, DGP-IgA/IgG) levels was retrospectively evaluated in participants from three phase 2 and one phase 3 ritlecitinib clinical trials including participants with active AA, rheumatoid arthritis (RA) and vitiligo, whose serum samples at baseline and post-treatment were available. All statistical comparisons of the changes between initial and follow-up samples used the Wilcoxon matched pairs exact test.

Of 1146 research participants, 21 individuals had a positive tTG-IgA in their baseline samples (positivity rate, 0.018, 95% CI = 0.011-0.028). Among these 21 individuals, follow-up samples were available in 15 participants from the ritlecitinib group and in 3 from the placebo group. In follow-up samples, the values of tTG-IgA in the 15 participants treated with ritlecitinib significantly decreased from baseline (p < 0.01), while in the placebo group the tTGA-IgA levels remained close to the baseline values.

A decrease in CeD serology levels with ritlecitinib treatment suggests that ritlecitinib may provide beneficial effect in CeD.

Celiac disease (CD) is a chronic, permanent, gluten-dependent disease that manifests itself with inflammation of the small intestine and malabsorption in genetically predisposed individuals with HLA-DQ2 and -DQ8 (human leukocyte antigen) histocompatibility antigens.

The diagnostic criteria for celiac disease have undergone numerous modifications over the years. The aim of the study is to evaluate the frequency of HLA-DQ2/DQ8 genes in a group of patients with celiac disease diagnosed in 1980-2010 in order to verify the primary diagnosis of CD.

The study group included 50 patients, 13 men and 37 women, who had been diagnosed with celiac disease many years ago based on histopathological criteria and improvement of health condition after receiving a gluten-free diet. The control group consisted of 31 healthy volunteers, 18 women and 13 men. All subjects underwent a genetic analysis assessing the presence of histocompatibility antigens HLA-DQ2.2, -DQ2.5, and -DQ8, along with the assessment of alleles encoding the α and β subunits of the antigens, according to European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines from 2020, using the EUROarray technique at EUROIMMUNE®.

In the study group, 12 (24%) patients did not meet the genetic criteria. Among the remaining patients (Group 1) with celiac disease, the presence of HLA-DQ2.5 (50.0% vs. 9.68%; p < 0.01) and the co-occurrence of both alleles of HLA-DQ2 (31.6% vs. 6.45%; p < 0.05) were detected significantly more frequently than in the control group. Among patients with celiac disease, the prevalence of HLA-DQ8 was also slightly more frequent (13.2% vs. 3.23%; p > 0.05). Patients who did not meet the genetic criteria for celiac disease (Group 2) had a single string α-HLA-DQ2.5 significantly more often than control subjects (66.67% vs. 38.71%; p < 0.05).

Among patients with celiac disease diagnosed before 2010, based on the 2020 ESPGHAN criteria, it is advisable to verify the previous diagnosis, taking into account genetic criteria.

A novel electrochemical detection method utilizing a cost-effective hybrid-modified electrode has been established. A glassy carbon (GC) modified electrode was tested for its ability to measure electrochemical tTG antibody levels, which are essential for diagnosing and monitoring Celiac disease (CD). Tissue transglutaminase protein biomolecules are immobilized on a quantum dots-polypyrrole nanocomposite in the improved electrode. Initial, quantum dots (QDs) were obtained from Bombyx mori silk fibroin and embedded in polypyrrole film. Using carbodiimide coupling, a polyamidoamine (PAMAM) dendrimer was linked with GQDs-polypyrrole film to improve sensor sensitivity. The tissue transglutaminase (tTG) antigen was cross-linked onto PAMAM using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)-N-hydroxy succinimide (NHS) chemistry to develop a nanoprobe that can detect human serum anti-tTG antibodies. The physicochemical characteristics of the synthesized nanocomposite were examined by FTIR, UV-visible, FE-SEM, EDX, and electrochemical studies. The novel electrode measures anti-tissue antibody levels in real time using human blood serum samples. The modified electrode has great repeatability and an 8.7 U/mL detection limit. Serum samples from healthy people and CD patients were compared to standard ELISA kit assays. SPSS and Excel were used for statistical analysis. The improved electrode and detection system can identify anti-tissue antibodies up to 80 U/mL.

The association between celiac disease (CD) and autism spectrum disorder (ASD) remains inconclusive. Reports from different observational studies have become controversial, necessitating exploration of the causal relationship between CD and ASD. To assess true causality, this study used a two-sample Mendelian randomization (MR) analysis to determine the causal association between CD and ASD. Summary-level data from a genome-wide association study (GWAS) of the European population were used to select instrument variables (IVs) at genome-wide significance (p < 5 × 10-8). The strength of IVs was also evaluated with F-statistics. The inverse variance weighted method (IVW) was the primary MR analysis, supported by other MR tests such as the weighted median method and weighted mode. The presence of horizontal pleiotropy was tested with MR-Egger and MR-PRESSO while other sensitivity analyses such as heterogeneity, leave-one-out analysis, and scatterplot were used to assess the validity of our MR results. Our study did not show an association between CD and ASD (OR, 0.994; 95% CI, 0.935-1.057; p = 0.859). There was also no evidence of horizontal pleiotropy (MR-Egger intercept = 0.015; p-value = 0.223) and heterogeneity (Q = 14.029; p-value = 0.051). These results were also complemented by the leave-one-out analyses, forest plot, and scatter plot, which showed that none of the SNPs influenced the result. The result of this study shows that CD is not causally associated with ASD.

Social media has become a popular tool for patients with Celiac Disease (CD) to find information about their disease. However, limited research has been conducted to evaluate the impact of information shared on social media, specifically regarding CD.

This study aimed to assess the effectiveness of a nutrition education program on CD and gluten-free diet (GFD) delivered through social networks by experts in the field.

The program, called GLUTLEARN, was delivered over six weeks via Instagram to individuals with CD and their supporters (people involved in the care of individuals with CD). Pre and post-intervention questionnaires were used to evaluate the program's effectiveness.

A total of 93 participants (63 with CD, 30 supporters), predominantly female (92.5 %) and European (93.5 %), took part in the program. GLUTLEARN has been found to be effective in improving the knowledge of people with CD and their supporters and improving attitudes among individuals. Furthermore, they showed a high level of concern about the disease and an interest in continuous learning.

Social networks give advantages for promoting nutrition education. Nevertheless, it is important to feed these nets with reliable information. The GLUTLEARN program is a valuable method for delivering reliable and current education about CD and the GFD, which leads to better disease control. It would be beneficial for more interventions to focus not only on individuals with CD but also on those who are avoiding gluten for various reasons or are involved in their care.

Non-responsive celiac disease (NRCD) is defined as ongoing symptoms despite 6-12 months of gluten-free diet (GFD), the only known treatment for celiac disease (CeD). There is inconsistency in studies describing the proportion of patients having NRCD and its various causes among patients with CeD. We therefore conducted a systematic review and meta-analysis to determine the prevalence and causes of NRCD.

The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched for original studies reporting the proportion of patients with persistent symptoms after ≥ 6 months of GFD. Studies reporting the etiologies of NRCD were also identified. The systematic review was conducted as per the Meta-analysis of Observational Studies in Epidemiology guidelines. Statistical analysis was performed in STATA.

Of 2965 search results, nine studies met the inclusion and exclusion criteria. Five studies (n = 4414) reported data on prevalence, and seven studies (n = 790) reported the causes of NRCD. The pooled prevalence of NRCD was 22% (95% confidence interval, 11-35%). Among patients with NRCD, inadvertent exposure to gluten was the most common cause (33%), followed by functional gastrointestinal disorders including irritable bowel syndrome in 16%. Refractory CeD type II along with its premalignant and malignant sequelae was observed in 7% of patients with NRCD.

One in five patients with CeD may not respond to GFD and would likely be classified as NRCD. Inadvertent gluten exposure was the cause of ongoing symptoms in one-third of patients with NRCD. Improving adherence to GFD along with developing novel therapeutics to mitigate symptoms due to ongoing gluten exposure is critical.

The no-biopsy approach to diagnose celiac disease (CD), introduced in the 2012 European Society for Gastroenterology and Hepatology and Nutrition guidelines, requires an anti-endomysial antibody (EMA) confirmatory serology test following a high-positive immunoglobulin A anti-tissue transglutaminase-2 (anti-TG2) antibody ≥10 times the upper limit of normal (ULN). The aim of this retrospective study is to compare EMA positivity and high-positive anti-TG2 in patients who had their confirmatory test within 2 months of their first high-positive anti-TG2 test. Among 933 patients who had high-positive anti-TG2 serology more than 10 times the ULN in their first sample, all had both high-positive anti-TG2 and positive EMA, most of them with very high EMA titers (99.6%) in their confirmatory test. In conclusion, we suggest that a repeated anti-TG2 test can replace the EMA test as the confirmatory serology test for the confirmation of the diagnosis of CD in the no-biopsy approach.

Celiac disease is one of the most common chronic immune-mediated gastrointestinal conditions, characterized by the presence of disease-specific serum antibodies against self-antigen transglutaminase 2. Even though modern serological assays can identify most untreated celiac disease patients and are also increasingly being used to establish a diagnosis, several challenges are associated with the tests, including a lack of standardization, the variable sensitivity and specificity of commercial assays, and inadequate sensitivity for monitoring adherence to a gluten-free diet.

This narrative review outlines the current use of serological tests in case-finding and screening, as well as in the follow-up of dietary treatment. Additionally, the possible challenges and pitfalls of serological tests, along with future directions, are addressed.

The excellent accuracy of modern autoantibody tests, especially for greatly elevated levels of transglutaminase 2 antibodies and positive endomysial antibodies, enables using serological testing in establishing a diagnosis. However, better international standardization of the assays is required, the necessity of endomysial antibody testing needs to be further scrutinized, and additional research is needed to improve noninvasive tools for follow-up and to further expand the no-biopsy criteria for celiac disease.