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.

Dietary habits in Italian children with inflammatory bowel disease: A case-control multicenter study.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) tend to self-modify their dietary habits according to disease activity and symptoms. This study aimed to assess the adequacy of the usual diet in Italian children with IBD in comparison to a control group and to the recommended dietary allowances (RDA). METHODS: Dietary habits of IBD children and age- and gender-matched healthy controls were investigated using a validated Food Frequency Questionnaire in five Italian pediatric IBD centers. Adherence to the Mediterranean diet (MD) was assessed using the KID-MED test. Energy (EI), macro, and micronutrients intakes were compared between the two groups, to the RDA and the predicted total energy expenditure (EI/total energy expenditure [TEE]%). RESULTS: IBD subjects (n = 110) reported a lower EI, EI/RDA%, and EI/TEE% compared to controls (n = 110) (p = 0.012, p < 0.0002, and p = 0.014), lower total protein and fat intakes (p = 0.017, p < 0.0001) and lower minerals/RDA, vitamins/RDA and micronutrients/RDA ratio (%). Poor adherence to the MD was more frequent in IBD children compared to controls (p = 0.013). The total EI and carbohydrate intake were inversely correlated with higher disease activity. CONCLUSIONS: Italian children with IBD report an inadequate diet in terms of energy, macro, and micronutrients and have a low adherence to a high-quality MD pattern.

Unauthentic Information About Celiac Disease on Social Networking Pages: Is It a Matter of Concern in Celiac Disease Management?

BACKGROUND: Facebook (FB) is the most popular online networking platform. Many celiac disease Facebook (CD-FB) pages spread awareness about celiac disease (CD). To get the latest information, patients with CD frequently follow such pages. However, little is known about whether such pages provide authentic and reliable information. AIMS: This study aims to investigate whether CD-FB pages spread misleading information to patients with CD. METHODS: On the Facebook social networking platform, CD-FB pages created in three celiac-prevalent countries (Italy, the USA, and India) were explored using different combinations of keywords. The type/category of the CD-FB page, country of origin, purpose, page web link, and number of followers/members were documented in a Microsoft spreadsheet. All posts distributed on selected CD-FB pages in the last 3 years were thoroughly screened. RESULTS: From August 2022 to March 2023, a total of 200 CD-FB pages from Italy, the USA, and India were explored. Out of these 200 pages, 155 CD-FB (Italy 70; the USA 46; India 39) were found eligible. Of them, 20 (13%) CD-FB pages (Italy 4; the USA 5; India 11) shared misleading information about CD. Surprisingly, 11 (8%) of these 20 pages (Italy 0; the USA 2; India 9) supported alternative treatment options for CD. CONCLUSIONS: CD-FB pages are useful for disseminating celiac-disease-related information. While most such pages provide useful information, 13% of CD-FB pages allow misleading information. Patients with CD should consult their treating unit before following any uncertain information posted on CD-FB pages.

Coeliac disease.

Coeliac disease is an autoimmune disorder that primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. Prevalence in the general population ranges from 0·5% to 2%, with an average of about 1%. The development of the coeliac enteropathy depends on a complex immune response to gluten proteins, including both adaptive and innate mechanisms. Clinical presentation of coeliac disease is highly variable and includes classical and non-classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical cases. The disease is associated with a risk of complications, such as osteoporosis and intestinal lymphoma. Diagnosis of coeliac disease requires a positive serology (IgA anti-transglutaminase 2 and anti-endomysial antibodies) and villous atrophy on small-intestinal biopsy. Treatment involves a gluten-free diet; however, owing to the high psychosocial burden of such a diet, research into alternative pharmacological treatments is currently very active.

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.

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.

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.

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.

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.

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.

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.

OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Lower Level of Plasma 25-Hydroxyvitamin D in Children at Diagnosis of Celiac Disease Compared with Healthy Subjects: A Case-Control Study.

OBJECTIVE: To evaluate the vitamin D status of children with a new diagnosis of celiac disease compared with healthy controls. STUDY DESIGN: This was a case-control study. Cases were consecutive children with newly diagnosed celiac disease. Controls were healthy children matched for age, sex, ethnicity, and month of blood testing. Plasma 25-hydroxyvitamin D (25-OHD) was measured as the index of vitamin D nutritional status. The Student t test was used for comparisons. Differences in frequencies were evaluated with the χ2 test. Associations between variables were estimated by calculating Pearson correlation coefficients. RESULTS: There were 131 children with celiac disease enrolled (62% females; mean age 8.1 ± 1.1 years). The control group included 131 healthy children (62% females; mean age 8.2 ± 1.2). All were of European origin. Plasma 25-OHD levels were significantly lower in patients than in controls (25.3 ± 8.0 and 31.6 ± 13.7 ng/mL; P < .0001). The percentage of children with vitamin D deficiency (<20 ng/mL) was significantly higher in children with celiac diseaseas compared with controls (31% vs 12%; P < .0001). The concentration of 25-OHD was significantly lower in patients than in controls during summer (P < .01) and autumn (P < .0001). CONCLUSIONS: In this case-control study, at diagnosis, children with celiac disease showed lower levels of plasma 25-OHD compared with healthy subjects. Vitamin D status should be checked at diagnosis of celiac disease, particularly during summer and fall months.

Navigating celiac disease and the gluten-free diet in China.

BACKGROUND: Little is known about celiac disease (CeD) diagnosis and management in China. AIM: This pilot aimed to be the first study to describe, quantitatively and qualitatively, how individuals living in China navigate CeD and the gluten-free diet (GFD). METHODS: Participants were 13 adults and four parents of children with reported CeD, recruited from 11 mainland China cities via an online GFD support group. CeD-specific quality of life (CD-QOL and CD-PQOL) and diet adherence (CDAT) were assessed. In-depth interviews addressed experiences with CeD and the GFD. RESULTS: Six of 17 participants reported biopsy- or serology-confirmed CeD. The mean (SD) adult CDAT score was 15.2 (3.6), > 13 indicating inadequate GFD adherence. The mean adult CD-QOL score was 62.1 (24.1) out of 100, in the "medium" to "good" range. Results were similar in children. Major interview themes included: (1) a challenging journey to obtain diagnosis; (2) social and structural barriers to maintaining the GFD; and (3) reliance on self in management of CeD. CONCLUSION: Obtaining a diagnosis, maintaining a GFD, and living with CeD can be extremely challenging in mainland China. Results suggest an urgent need for CeD-specific education and Asian-adapted GFD guidance for both healthcare practitioners and patients.

Increased Prevalence of Celiac Disease in School-age Children in Italy.

BACKGROUND & AIMS: Celiac disease is one of the most common diseases worldwide, with an apparent trend of increasing prevalence. We investigated the prevalence of celiac disease in children in Italy in 2015-2016 and compared that with data from 25 years ago. METHODS: We screened 4570 children (5-11 years old, 80.1% of the eligible population) from metropolitan areas of Ancona and Verona for HLA genes associated with increased risk of celiac disease, and for total serum levels of IgA and IgA class anti-tissue transglutaminase in HLA positives. Diagnoses of celiac disease were confirmed by detection of anti-endomysial antibody and analysis of intestinal biopsies. The prevalence of celiac autoimmunity and celiac disease were calculated and compared with values from the same geographical area during the years 1993-1995, after adjustment for the different diagnostic algorithm. RESULTS: We identified 1960 children with celiac disease-associated haplotypes (43% of children screened; 95% CI, 40.8%-45.2%). The prevalence of celiac disease autoimmunity in the HLA-positive subjects was 96/1706 (5.62%; 95% CI, 4.53%-6.71%) and 54 of these children satisfied the diagnostic criteria for celiac disease. In the eligible population there were other 23 known cases of celiac disease. The overall estimated prevalence of celiac disease was 1.58% (95% CI, 1.26%-1.90%); this value is significantly higher than the 1993-1995 adjusted prevalence (0.88%; 95% CI, 0.74%-1.02%). CONCLUSIONS: We found the prevalence of celiac disease in children in Italy to be greater than 1.5%; this value has increased significantly over the past 25 years. Studies are needed to determine the causes of this large increase.

Celiac disease: a comprehensive current review.

BACKGROUND: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.

Contribution of Oral Hygiene and Cosmetics on Contamination of Gluten-free Diet: Do Celiac Customers Need to Worry About?

OBJECTIVES: The only available treatment for celiac disease (CD) is the gluten-free diet. It is unclear whether the presence of gluten in oral hygiene products and cosmetics that are applied on the mouth is a reason of concern for CD patients. The aim of this study was to test the level of gluten contamination in oral hygiene and cosmetic products available in the Italian market. METHODS: A total of 66 products (toothpastes = 37; dental tablets = 2; mouthwashes = 5; lip-balms = 10; lipsticks = 12) labelled gluten-free or with unknown gluten content were randomly collected from different supermarkets and pharmacies. The gluten quantification was determined by the R5 ELISA method approved by EU regulations. RESULTS: Out of 66 oral hygiene and cosmetics, 62 products (94%) were found to be gluten-free (gluten level <20 ppm), while 4 (6%) (toothpastes = 3; lipsticks = 1) showed a gluten level >20 ppm (toothpastes: 20.7, 31.4, and 35 ppm; lipstick: 27.4 ppm). None of the selected products had ingredient derived from wheat, barley, or rye. CONCLUSIONS: Gluten contamination is currently not an issue in a wide array of cosmetic and oral hygiene products that are commonly in the market.

Pediatric Celiac Disease in Central and East Asia: Current Knowledge and Prevalence.

The current prevalence of pediatric Celiac Disease (CD) is estimated to be around 1% in the general population, worldwide. However, according to the geographic area, a great variability of CD prevalence has been described. Whereas a number of studies are available from Europe, North and South America, Australia, South-West Asia, and North Africa, the knowledge and awareness of CD in large parts of the remaining world areas is definitively poor. In several countries of Central and East Asia, the consumption of wheat is consistent and/or has significantly increased in recent decades, and CD is supposed to be underdiagnosed in children. In this mini-review, we aimed to summarize the current knowledge about the prevalence of pediatric CD in Central and East Asia, paying attention to the HLA-DQ immunogenetic background as well. Indeed, CD is likely not to be as uncommon as previously or currently thought in countries like Russia, Kazakhstan, and China, in addition to India, where pediatric CD has been clearly showed to be quite prevalent. Therefore, there is an urgent need for population-based studies on the prevalence of CD in those countries, especially in children, in order to increase the awareness of this disease and to improve the diagnostic strategy in these areas.

Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Celiac disease is a major public health problem worldwide. Although initially it was reported from countries with predominant Caucasian populations, it now has been reported from other parts of the world. The exact global prevalence of celiac disease is not known. We conducted a systematic review and meta-analysis to estimate the global prevalence of celiac disease. METHODS: We searched Medline, PubMed, and EMBASE for the keywords celiac disease, celiac, celiac disease, tissue transglutaminase antibody, anti-endomysium antibody, endomysial antibody, and prevalence for studies published from January 1991 through March 2016. Each article was cross-referenced with the words Asia, Europe, Africa, South America, North America, and Australia. The diagnosis of celiac disease was based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. Of 3843 articles, 96 articles were included in the final analysis. RESULTS: The pooled global prevalence of celiac disease was 1.4% (95% confidence interval, 1.1%-1.7%) in 275,818 individuals, based on positive results from tests for anti-tissue transglutaminase and/or anti-endomysial antibodies (called seroprevalence). The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% (95% confidence interval, 0.5%-0.9%) in 138,792 individuals. The prevalence values for celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was higher in female vs male individuals (0.6% vs 0.4%; P < .001). The prevalence of celiac disease was significantly greater in children than adults (0.9% vs 0.5%; P < .001). CONCLUSIONS: In a systematic review and meta-analysis, we found celiac disease to be reported worldwide. The prevalence of celiac disease based on serologic test results is 1.4% and based on biopsy results is 0.7%. The prevalence of celiac disease varies with sex, age, and location. There is a need for population-based prevalence studies in many countries.

Safety of Oats in Children with Celiac Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease. STUDY DESIGN: This noninferiority clinical trial used a double-blind, placebo-controlled, crossover design extended over 15 months. Three hundred six children with a biopsy-proven diagnosis of celiac disease on a gluten-free diet for ≥2 years were randomly assigned to eat specifically prepared gluten-free food containing an age-dependent amount (15-40 g) of either placebo or purified nonreactive varieties of oats for 2 consecutive 6-month periods separated by washout standard gluten-free diet for 3 months. Clinical (body mass index, Gastrointestinal Symptoms Rating Scale score), serologic (IgA antitransglutaminase antibodies, and IgA anti-avenin antibodies), and intestinal permeability data were measured at baseline, and after 6, 9, and 15 months. Direct treatment effect was evaluated by a nonparametric approach using medians (95% CI) as summary statistic. RESULTS: After the exclusion of 129 patients who dropped out, the cohort included 177 children (79 in the oats-placebo and 98 in the placebo-oats group; median, 0.004; 95% CI, -0.0002 to 0.0089). Direct treatment effect was not statistically significant for clinical, serologic, and intestinal permeability variables (body mass index: median, -0.5; 95% CI, -0.12 to 0.00; Gastrointestinal Symptoms Rating Scale score: median, 0; 95% CI, -2.5 to 0.00; IgA antitransglutaminase antibodies: median, -0.02; 95% CI, -0.25 to 0.23; IgA anti-avenin antibodies: median, -0.0002; 95% CI, -0.0007 to 0.0003; intestinal permeability test: median, 0.004; 95% CI, -0.0002 to 0.0089). CONCLUSIONS: Pure nonreactive oat products are a safe dietary choice in the treatment of children with celiac disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00808301.