A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Awareness of gluten-free diet among the general public in Saudi Arabia

Introduction: Gluten is the combination of gliadin and glutenin within a fraction of wheat. Its fraction is used in food because of its unique structure-building attributes. The gluten in wheat flour forms a three-dimensional protein network when mixed and hydrated properly. Even those with-out a diagnosis of an illness linked to gluten are beginning to follow a GFD. Methodology: This study aimed to examine the knowledge and use of the gluten-free diet among the general population of Saudi Arabia. This cross-sectional study included participants 18 years and older. Frequencies and percentages were used for descriptive data. Results: A total of 793 were included in the study. Morethan half of the participants knew what gluten and gluten-free diet are. Females demonstrated a greater awareness of gluten-free diet and their use (%). Other questions on the prevalence of gluten-free diet use showed that 5% follow itrigorously, while 10.3% follow it with lapses. Conclusion: The majority of the respondents were aware ofthe gluten diet; mostly, the gluten-free diet was followed due to health-related lifestyles. Future research on a broader scale in SA is highly needed to better understand the Saudi population (AU)

Lactose Malabsorption and Presumed Related Disorders: A Review of Current Evidence.

BACKGROUND: Lactose malabsorption (LM) is a frequent clinical problem associated with several digestive and extra-digestive diseases. The aim of this manuscript was to clarify the real clinical impact of LM on these disorders. METHODS: A literature search for digestive and extra-digestive disorders related to LM was carried out using PubMed, Medline and Cochrane. RESULTS: A transient lactase deficiency is present in celiac disease (CD) on a normal diet. The persistence of symptoms in CD on a gluten-free diet may be instead, in part, attributed to a primary LM. Similar circumstances are present in inflammatory bowel diseases (IBD), in which LM can be responsible for a part of persistent symptoms in IBD on clinical remission. LM and irritable bowel syndrome (IBS) are instead independent conditions. On the other hand, a lactose-restricted diet may be useful for some IBS patients. A reduced lactose intake can lead to low bone mass and limited risk of fragility fractures. Finally, the absorption of levothyroxine could be conditioned by LM. CONCLUSIONS: LM can be responsible for persistent symptoms in CD and IBD. The association with IBS seems to be casual. Bone mass and levothyroxine absorption can be affected by LM.

Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Anti-SARS-CoV-2 immunoglobulin profile in patients with celiac disease living in a high incidence area.

BACKGROUND AND AIM: How symptoms and antibodies related to SARS-CoV-2 infection develop in patients with celiac disease (CD) is unclear. We aimed to investigate the impact of SARS-CoV-2 infection in CD patients. METHODS: CD patients were interviewed about the development of COVID-19 symptoms, compliance with anti-virus measures and adherence to a gluten-free diet (GFD). The presence of anti-SARS-CoV-2 IgG and IgA (anti-RBD and N proteins) was compared to that in non-CD subjects. Expression of the duodenal ACE2 receptor was investigated. When available, data on duodenal histology, anti-tissue transglutaminase IgA (tTGA), comorbidities and GFD adherence were analyzed. RESULTS: Of 362 CD patients, 42 (12%) reported COVID-19 symptoms and 21% of these symptomatic patients presented anti-SARS-CoV-2 Ig. Overall, 18% of CD patients showed anti-SARS-CoV-2 Ig versus 25% of controls (p = 0.18). CD patients had significantly lower levels of anti-N IgA. tTGA, duodenal atrophy, GFD adherence or other comorbidities did not influence symptoms and/or antibodies. The ACE2 receptor was detected in the non-atrophic duodenal mucosa of patients; atrophy was associated with lower expression of the ACE2 receptor. CONCLUSION: CD patients have an anti-SARS-CoV-2 Ig profile similar to non-celiac controls, except for anti-N IgA. No risk factors were identified among CD parameters and GFD adherence.

Antitissue transglutaminase antibodies' normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience.

INTRODUCTION: Few data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors. MATERIAL AND METHODS: We retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD. RESULTS: TGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7-12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization. CONCLUSIONS: Our population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7-12 years for a proper management and follow-up.

The GLU-10: a validated ten-point score to identify poorly instructed celiac patients in need of dietary interventions.

BACKGROUND: A standard tool to assess patients' knowledge about gluten and the gluten-free diet (GFD) is lacking. METHODS: We aimed to develop and validate a questionnaire to assess GFD knowledge. A 10-point questionnaire (GLU10) covering different aspects of knowledge about gluten content in food/non-food products and the gluten-free living was developed. To validate this questionnaire, it was administered to adult celiac patients already instructed on gluten and the GFD and non-celiac controls. Patients were prospectively recruited at our Gastroenterology Outpatient Clinic between August 2020 and February 2021. RESULTS: One hundred and six patients (52 celiac patients and 54 controls) participated in the validation phase. Celiac patients scored significantly higher than controls on the GLU10 Questionnaire (median 6 points vs. 2 points, P<0.001). Higher self-reported knowledge of the GFD was related to a higher score (P<0.001). ROC curve confirmed the ability of the GLU10 Questionnaire to discriminate between subjects with good and poor GFD knowledge (AUC=0.94, 95% CI: 0.90-0.98). A score of 5 was identified as the best cut-off (sensitivity 80.8%, specificity 94.4%). On multivariable logistic regression analysis, being a celiac patient (P<0.001) and having a university degree (P=0.04) were associated to a high GLU10 Score (≥5). CONCLUSIONS: GLU10 is the first validated questionnaire for assessing knowledge of a GFD in celiac patients and the general population.

Problemática nutricional en pacientes celíacos. Dificultades para conseguir una situación nutricional adecuada / Nutritional problems in celiac patients. Difficulties in achieving an adequate nutritional status

La enfermedad celíaca es la enfermedad crónica intestinal más frecuente que existe. Afecta aproximadamente al 1 % de la población mundial, a todos los grupos de edad y tiene síntomas de presentación tanto digestivos como extradigestivos.El tratamiento de la enfermedad celíaca se basa en la retirada estricta del gluten de la dieta. Este tratamiento supone la mejora de los síntomas y de la histología y la disminución de comorbilidades a largo plazo.Las personas con enfermedad celíaca realizan con frecuencia dietas alejadas del ideal teórico, por lo que deben ser supervisadas y orientadas para lograr dietas sin gluten y también variadas y equilibradas.En estos pacientes es importante evitar el consumo de gluten, pero también lograr un aporte adecuado de nutrientes y su problemática sanitaria, junto con las limitaciones que deben introducir en la dieta, hacen más difícil lograr una alimentación correcta, por lo que el colectivo merece una vigilancia y un control nutricional especiales. (AU)

Celiac disease is the most common chronic intestinal disease. It affects approximately 1 % of the world population, affects all age groups and has symptoms both digestive and extra-digestive.The treatment of celiac disease is based on the strict withdrawal of gluten from the diet. This treatment supposes the improvement of symptoms and histology and the reduction of long-term comorbidities.People with celiac disease often follow diets that are far from the theoretical ideal, so they must be supervised and guided to achieve gluten-free diets that are also varied and balanced.In these patients it is important to avoid gluten consumption, but also to achieve an adequate supply of nutrients. However, their health problems, together with the limitations they must introduce in the diet make it more difficult to achieve a correct diet, so the group deserves special nutritional monitoring and surveillance. (AU)

Compliance to a Gluten-Free Diet in Swedish Children with Type 1 Diabetes and Celiac Disease.

Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.

Nutritional Deficiencies in Celiac Disease: Current Perspectives.

Gluten-induced T-cell-mediated immune response damages the villous structure that significantly affects the functioning of the small intestinal mucosa [...].

Factors Associated with Maladaptive Eating Behaviors, Social Anxiety, and Quality of Life in Adults with Celiac Disease.

A gluten-free diet (GFD), which is the only treatment for celiac disease (CeD), is challenging and associated with higher levels of anxiety, disordered eating, and lower quality of life (QOL). We examined various demographic and health factors associated with social anxiety, eating attitudes and behaviors, and QOL. Demographics and health characteristics, QOL, eating attitudes and behaviors, and social anxiety of adults with CeD were acquired using validated measures. The mean scores for QOL, SAQ, and CDFAB were compared across various demographic groups using the Z statistical test. The mean QOL score was 57.8, which is in the moderate range. The social anxiety mean scores were high: 78.82, with 9% meeting the clinical cutoff for social anxiety disorder. Those on a GFD for a short duration had significantly higher SAQ scores (worse anxiety), higher CDFAB scores (worse eating attitudes and behavior), and lower QOL scores. Those aged 23-35 years had lower QOL scores (p < 0.003) and higher SAQ scores (p < 0.003). Being single (p < 0.001) and female (p = 0.026) were associated with higher SAQ scores. These findings suggest that the development of targeted interventions to maximize QOL and healthy eating behaviors as well as to minimize anxiety is imperative for some adults with CeD.

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease.

BACKGROUND: Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. METHODS: Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. RESULTS: The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. CONCLUSIONS: Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called "gluten encephalopathy", which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

Changes in Diet and Anthropometric Parameters in Children and Adolescents with Celiac Disease-One Year of Follow-Up.

Celiac disease (CD) may cause numerous nutrient deficiencies that a proper gluten-free diet (GFD) should compensate for. The study group consists of 40 children, aged 8.43 years (SD 3.5), on average, in whom CD was diagnosed on the basis of clinical symptoms, immunological and histopathological results. The patients' height, weight, diet and biochemical tests were assessed three times: before diagnosis, after six months, and following one year of GFD. After one year, the patients' weight and height increased but nutritional status (body mass index, BMI percentile) did not change significantly. The children's diet before diagnosis was similar to that of the general Polish population: insufficient implementation of the dietary norm for energy, fiber, calcium, iodine, iron as well as folic acid, vitamins D, K, and E was observed. Over the year, the GFD of the children with CD did not change significantly for most of the above nutrients, or the changes were not significant for the overall assessment of the diet. Celiac patients following GFD may have a higher risk of iron, calcium and folate deficiencies. These results confirm the need for personalized nutritional education aimed at excluding gluten from the diet, as well as balancing the diet properly, in patients with CD.

Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

Celiac Disease in Children.

Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. In patients with suspected celiac disease, measurement of serum IgA antibodies to tissue transglutaminase-2 has a high sensitivity and specificity and is the first screening test that should be ordered. The diagnosis of celiac disease is based on the presence of mucosal damage in small intestinal biopsies in patients having circulating celiac disease-specific antibodies. Celiac disease management includes lifelong adherence to a gluten-free diet and continuous long-term follow-up.

The Gluten-Free Diet for Celiac Disease and Beyond.

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.