Differences in Plasma 25-Hydroxyvitamin D Levels at Diagnosis of Celiac Disease and Type 1 Diabetes.

AIM: The aim of this work is to assess the vitamin D levels, evaluated as plasma 25-hydroxyvitamin D of children with a new diagnosis of celiac disease (CD), of children with a new onset of type 1 diabetes (T1D) and in children with CD at diagnosis of T1D (T1D&CD). METHODS: In this single-center observational study, we collected data for four groups of children and adolescents: T1D, CD, T1D&CD, and a control group (CG). The CG included schoolchildren who had negative results during a mass screening campaign for CD and were not diagnosed for T1D, according to RIDI Marche registry data, were considered for the purposes of this study. Plasma 25-hydroxyvitamin D, 25(OH)D2, and 25(OH)D3 were considered as the parameters for evaluating vitamin D nutritional status, and the date of measurement was recorded to analyze vitamin D level seasonality. Vitamin D nutritional status was categorized as follows: severe deficiency (<10 ng/mL), deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or sufficiency/adequacy (≥30 ng/mL). The Kruskal-Wallis test was used to compare the groups. The association of 25(OH)D levels with health conditions and seasonal differences of 25(OH)D levels was analyzed using a multiple linear regression model. RESULTS: The number of children enrolled for the present study was 393: 131 in the CG, 131 CD, 109 T1D, and 22 T1D&CD. Significantly lower levels of vitamin D were displayed for children with CD, T1D, or both the diseases. Interestingly, severe vitamin D deficiency was detected in no children with CD, 1.5% of children in the CG, in 24.4% with T1D, and 31.8% with T1D&CD (p < 0.001). As expected, the CG children vitamin D levels were significantly influenced by seasonality. Contrarily, no seasonal differences were reported in children with CD, T1D, and T1D&CD. Multiple regression analysis showed that children with T1D and T1D&CD had lower 25(OH)D levels of 9.9 ng/mL (95% CI: 5.4; 14.5) and 14.4 ng/mL (95% CI: 6.2-22.7) compared to CG children (p < 0.001). CONCLUSIONS: Our results showed low levels of vitamin D diagnosis of T1D, CD, and T1D&CD; however, severe deficiency was only reported in children with T1D and T1D&CD. More studies are needed to better understand the role of this deficiency in children newly diagnosed with CD and T1D.

Performance assessment of a new G12/A1 antibody-based rapid ELISA using commercially available and gluten-spiked food samples.

OBJECTIVE: Food products with <20 mg/kg gluten can be labeled 'gluten-free' according to international regulations. Several antibodies-based ELISAs have been develop to track gluten traces in food products. Among them, R5 and G12 antibody-based ELISAs are the frequently used methods. However, these antibodies have certain limitations. We evaluated the accuracy of G12/A1 antibody-based 'Glutentox ELISA Rapid G12' and compared the results with the current reference method i.e., R5 antibody-based 'Ridascreen R5 ELISA'. METHODS: In the first step, the performance of Glutentox ELISA Rapid G12 kit was inspected by determination of the threshold value i.e., > or <20 mg/kg gluten in different food products. In the second step, quantification accuracy was assessed by quantification of gluten in gluten-free food products spiked with gliadin reference material. RESULTS: In total 47 food products (naturally and labeled gluten-free, and food with traces of gluten) were included. Of them, 29 products were quantified with <20 mg/kg, and 18 with a low level of gluten by both the kits. Six out of 29 gluten-free products were used for the recovery test at different spike levels. Gluten concentration and mean recovery rates of individual kits showed consistency. CONCLUSION: GlutenTox Rapid G12 ELISA could be an appropriate choice for detecting gluten in food products but needs more in-house validation and collaborative tests.

Patient and Community Health Global Burden in a World With More Celiac Disease.

Celiac disease is one of the most common life-long disorders worldwide, with a prevalence mostly ranging between 0.7% and 2.9% in the general population and a higher frequency in females and well-defined at-risk groups, such as relatives of affected individuals and patients with autoimmune comorbidities. Increasing clinical detection is facilitated by improving awareness, implementation of a case-finding approach, and serology availability for screening at-risk patients, among other factors. Nevertheless, due to huge clinical variability, many celiac disease cases still escape diagnosis in most countries, unless actively searched by proactive policies. The burden of celiac disease is increasing, as is the need for better longitudinal care. Pediatric screening of the general population could represent the road ahead for an efficient intervention of secondary prevention aimed to reduce the social and health burden of celiac disease. This review analyses the epidemiology of celiac disease continent by continent, discusses current strategies to improve the detection of celiac disease, and highlights challenges related to the burden of celiac disease globally.

The use of urine peptidomics to define dietary gluten peptides from patients with celiac disease and the clinical relevance.

INTRODUCTION: Determination of urinary gluten immunogenic peptides (GIP) has emerged as one of the most attractive test to monitor the adherence to the gluten-free diet (GFD) of patients with celiac disease (CD), being a simple, noninvasive and direct method to detect gluten contamination of the GFD. AREAS COVERED: We conducted a scoping review in Medline (PubMed) of articles published up to April 2023 that analyzed any aspect of the clinical relevance of the use of urinary GIP measurement in patients with CD. A total of 17 articles reporting the clinical use of urinary peptidomics for the follow-up of CD patients were finally included. EXPERT OPINION: Available data suggest that a negative urinary GIP result is a reliable noninvasive predictor of intestinal mucosa healing in CD patients treated with the GFD, especially if testing three urine samples on different days including the weekend. Due to conflicting results about the sensitivity and the specificity of the urinary GIP determination, additional in-depth information is needed, particularly related to (1) the relationship between the amount of ingested gluten and the quantity of urinary GIP excreted in treated CD patients, (2) the GIP kinetics and best timing for sample collection.

Cross-Cultural Participation in Food-Related Activities and Quality of Life among Children with Celiac Disease.

Children with celiac disease may face challenges in managing a gluten-free diet during their daily interactions and activities. The objective of this study was to compare how children with celiac disease manage their gluten-free diet and participate in food-related activities in Italy and Israel and to assess their quality of life. The previously validated Children's Activities Report (CD-Chart) and the Disease-specific Health-Related Quality of Life Questionnaire for Children with Celiac Disease (CDDUX) were administered in Italy to children aged 8-16 diagnosed with CD (n = 39). The results were compared to data that had been previously gathered from Israeli children with CD (n = 106). The CD-Chart demonstrated satisfactory internal reliability within each cultural group (Italy: α = 0.82; Israel: α = 0.76). Mann-Whitney U-tests indicated significant differences between the two groups. The Italian children exhibited a significantly higher preference for participating in the activities compared to the Israelis (U = 3283.50, p < 0.001). Nonetheless, the Italian children displayed a notable decrease in their level of involvement in the preparation required before engaging in different activities (U = 760.50, p < 0.001). Moreover, they exhibited significantly lower self-determination in this preparatory process compared to the Israeli children (U = 726.00, p < 0.001). Significant group differences were found between the CDDUX children's self-reports and parents' proxy reports in the Israeli group but not in the Italian group. The CD-Chart revealed both shared and distinct participation characteristics in daily food-related activities across different cultural contexts. By incorporating the CD-Chart and the CDDUX, healthcare professionals can emphasize crucial aspects of day-to-day health management and guide them in establishing suitable intervention objectives to enhance effective health self-management.

Very early onset of coronary artery aneurysm in a 3-month infant with Kawasaki disease: a case report and literature review.

BACKGROUND: Kawasaki disease (KD) is a medium vessel vasculitis, of unknown etiology, typically presenting in children younger than 5 years of age. Prolonged fever (at least five days) is a major clinical criterion of KD, while cardiac involvement may occur in up to 25% of patients, generally in the second week of the disease. CASE PRESENTATION: We describe the case of KD developing in a 3-month infant, with an early occurrence of coronary artery aneurysm after only 3 days of fever, complicated by thrombosis, requiring aggressive treatments. CONCLUSIONS: Time of development of cardiac complications can be different in young infants with KD and both diagnostic criteria and treatment indications should be individualized in this class of age.

Effects of the supplementation with a multispecies probiotic on clinical and laboratory recovery of children with newly diagnosed celiac disease: A randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of a multispecies probiotic on clinical and laboratory recovery of children with celiac disease (CeD) at diagnosis. METHODS: Children with newly diagnosed CeD entered a randomized double-blind placebo-controlled trial. A gluten-free diet (GFD) plus a multispecies probiotic or placebo were administered for 12 weeks. Growth, laboratory, and clinical parameters were recorded at enrollment, after 3 and 6 months of follow-up. RESULTS: Overall, 96 children completed the study: 49 in group A (placebo) and 47 in group B (probiotic). A significant increase of BMI-Z score was found in both groups after 3 and 6 months of treatment (p < 0.001), however the increase of BMI-Z score was significantly higher and faster in Group B than in Group A. Other clinical and laboratory parameters improved in both groups after 3 and 6 months (p<0.001), but no difference was found between the groups and a comparable time trend was observed in both groups. CONCLUSIONS: Treatment with a multispecies probiotic induced a higher and faster increase of BMI in children with newly diagnosed CeD. The mechanism of this positive effect remains to be elucidated.

First experience of combined enzyme replacement therapy and hematopoietic stem cell transplantation in alpha-mannosidosis.

We describe the first case of bridge therapy in alpha-mannosidosis (AM) in an infant diagnosed at only 5 months of life who underwent enzyme replacement therapy (ERT) in the pre- and peri-transplant phases. Eight ERT infusions were administered before hematopoietic stem cell transplantation (HSCT) and continued for additional 90 days until complete engraftment. The clinical and laboratory data after 3 years post-HSCT show that the early combined intervention may reduce the disease progression and the urine and plasma content of mannosyl-oligosaccharides (OS) monitored by liquid chromatography tandem mass spectrometry (LC-MS/MS). This report highlights that early diagnosis and prompt initiation of such treatments in AM are the best chance to minimize the progression of symptoms.

Nonceliac gluten sensitivity.

PURPOSE OF REVIEW: To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations. RECENT FINDINGS: The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better 'umbrella' terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS. SUMMARY: Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Vitamin D status in healthy Italian school-age children: a single-center cross-sectional study.

BACKGROUND: Vitamin D is involved in calcium homeostasis and bone metabolism, although its extra-skeletal actions are also well-known. Low serum 25(OH)D levels are common both in adults and children worldwide. METHODS: The purpose of this cross-sectional study was to determine the distribution of 25(OH)D levels in a cohort of healthy Italian school-age children, aged 5-10 years, in relationship to determinants of vitamin D deficiency such as season, BMI, gender, age and ethnicity. RESULTS: The mean serum 25(OH) D level was 28.2 ng/mL; the prevalence of 25(OH)D sufficiency (> 30 ng/mL), insufficiency (20-30 ng/mL), deficiency (10-20 ng/mL) and severe deficiency (< 10 ng/mL) was 36%, 37%, 21% and 6% of the study-group population, respectively. The lower serum 25(OH)D values were observed during winter (21.6 ng/mL) and spring (22.9 ng/mL), as compared to summer (46.7 ng/mL) (p < 0.001). Higher BMI z-scores were associated with lower 25(OH)D level while no statistical difference was observed as related to gender and age groups. CONCLUSIONS: Healthy Italian schoolchildren show low 25(OH)D levels, particularly during winter and spring time. Seasonality, ethnicity and overweight/obesity were confirmed to influence the vitamin D status, thus indicating the need for effective initiatives to support adequate vitamin D status in this population group.

Hypertrophic Pyloric Stenosis in an Adolescent Girl: An Atypical Presentation of an Unexpected Disease.

Hypertrophic pyloric stenosis is a common cause of vomiting in the first few weeks of life, but in rare cases, it may occur in older subjects with a major risk of delayed diagnosis and complications. We describe the case of a 12-year-and-8-month-old girl who presented to our department for epigastric pain, coffee-ground emesis, and melena, which arose after taking ketoprofen. An abdomen ultrasound showed thickening (1 cm) of the gastric pyloric antrum, while upper-GI endoscopy documented esophagitis and antral gastritis with a non-bleeding pyloric ulcer. During her hospital stay, she had no further episodes of vomiting and was therefore discharged with a diagnosis of "NSAIDs-induced acute upper gastrointestinal tract bleeding". After 14 days, following recurrence of abdominal pain and vomiting, she was hospitalized again. At endoscopy, pyloric sub-stenosis was found, abdominal CT showed thickening of large gastric curvature and pyloric walls, and an Rx barium study documented delayed gastric emptying. On suspicion of idiopathic hypertrophic pyloric stenosis, she underwent Heineke-Mikulicz pyloroplasty with resolution of symptoms and restoration of a regular caliber of the pylorus. Hypertrophic pyloric stenosis, although occurring rarely in older children, should be taken into account in the differential diagnosis of recurrent vomiting at any age.

Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children.

BACKGROUND: Celiac disease is a common lifelong disorder. Recent studies indicate that the number of clinically detected cases has increased over the last decades, however little is known about changes in the prevalence and the detection rate of celiac disease. AIM: To evaluate the current prevalence and detection rate of celiac disease in Italy by a multicenter, mass screening study on a large sample of school-age children. METHODS: children aged 5-11 years were screened at school by HLA-DQ2 and -DQ8 determination on a drop of blood in six Italian cities; total serum IgA and IgA anti-transglutaminase were determined in children showing HLA-DQ2 and/or -DQ8 positivity. Diagnosis of celiac disease was confirmed according to the European guidelines. RESULTS: 5994 children were eligible, 4438 participated and 1873 showed predisposing haplotypes (42.2%, 95% CI=40.7-43.7). The overall prevalence of celiac disease was 1.65% (95% CI, 1.34%-2.01%). Only 40% of celiac children had been diagnosed prior to the school screening. Symptoms evoking celiac disease were as common in celiac children as in controls. CONCLUSION: In this multicenter study the prevalence of celiac disease in school-age Italian children was one of the highest in the world. Determination of HLA predisposing genotypes is an easy and fast first-level screening test for celiac disease. Without a mass screening strategy, 60% of celiac patients remain currently undiagnosed in Italy.

18-year follow-up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long-term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme-replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I.

Wheat consumption and prevalence of celiac disease: Correlation from a multilevel analysis.

Celiac disease (CD) is triggered by both genetic and environmental factors. More than 1% of the world's population is affected by CD. In recent years, studies have confirmed a worldwide rising trend in CD prevalence. "Westernized diet" is one of the main factors of this increasing prevalence. However, the relationship between wheat consumption, its dynamics, and CD has not been adequately investigated on a global scale. This study aimed to perform a multilevel analysis of the association between wheat consumption and CD. Wheat consumption data from countries and continents were obtained from the database. The relative increase/decrease in wheat consumption over a long period (since 1961) and a short period (since 2004) were calculated using various statistical tools. The relationship between wheat consumption and celiac frequency was determined using the R-commander R package version 2.6-2. Pearson's correlation coefficient (r = 0.88) confirmed a high positive correlation between wheat consumption and the prevalence of biopsy-proven CD by estimating continent-wide wheat consumption data, but an insignificant correlation was found when the data were compared country-wide.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Distribution of celiac disease predisposing genes HLA-DQ2 and HLA-DQ8 in the native population of southern India.

BACKGROUND: Celiac disease (CD) is an intestinal inflammatory condition caused by the ingestion of gluten peptides in wheat and related grains in individuals carrying HLA-DQ2 and/or HLA-DQ8 genes. In comparison to HLA-DQ8, a higher HLA-DQ2 prevalence is reported in European population where wheat has been the staple food for thousands of years. In non-European population, this pattern of HLA-DQ CD-predisposing gene distribution has not always been found. The aim of this study was to evaluate the HLA-DQ2 and HLA-DQ8 distribution in the native low-gluten consuming southern Indian population. METHODS: Overall, 211 dried blood spots (DBS) were collected from native southern Indian individuals. HLA-DQ characterization and the determination of homozygous/heterozygous status were performed using commercially available HLA-DQ typing kits. RESULTS: Of 211 collected DBS, 88 (42%, 95% CI: 36-48) were positive for HLA-DQ2 and/or HLA-DQ8 heterodimers. Overall, 40 (19%, 95% CI: 14-24) samples typed positive for HLA-DQ2 and 48 (23%, 95% CI: 18-28) typed positive for HLA-DQ8 genotypes. Of 40 HLA-DQ2-positive individuals, only one subject tested homozygous for the DQB1*02 allele. CONCLUSIONS: In the southern Indian native general population, the prevalence of HLA-DQ8 is higher in comparison to HLA-DQ2 prevalence. This finding could be related to the delayed introduction of wheat in the diet of the southern Indian population.