Digesting gluten with oral endopeptidases to improve the management of celiac disease.

In our editorial, we want to comment on the article by Stefanolo et al titled "Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet". Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. Although avoiding gluten can permit patients to live symptom-free, ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa. As villous atrophy predisposes patients to life threatening complications, such as osteoporotic fractures or malignancies, therapeutic adjuncts to gluten-free diet become important to improve patients' quality of life and, if these adjuncts can be shown to improve villous atrophy, avoid complications. Oral administration of enzyme preparations, such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflammation, is one clinical strategy under investigation. The article is about the utility of one endopeptidase isolated from Aspergillus niger. We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

B cell academy of the gut: an update on gut associated germinal centre B cell dynamics.

BACKGROUND: The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active. MAIN BODY: The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases. CONCLUSION: B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut.

The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis.

BACKGROUND: In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations. OBJECTIVE: This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD. RESULTS: It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T-reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T-regs, a subset of T-cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T-reg function, facilitates T-reg differentiation through microbiota-mediated degradation and the kynurenine pathway. CONCLUSION: Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten-free diet.

The heart of celiac disease: understanding dilated cardiomyopathy, pathophysiology, and care-a systematic review.

BACKGROUND: Cardiac manifestations are infrequently reported in association with celiac disease, but clear link has not been established. The aim of this study was to explore the connection of dilated cardiomyopathy in celiac disease. This systematic review also provides a comprehensive overview of the association between celiac disease and various cardiac manifestations with pathophysiology and management. MAIN BODY: We searched PubMed, Cochrane Library, Google Scholar, Embase, Scopus, and Springer nature databases through June 4th 2023 for preferred studies related to our topic using MeSH and Regular keywords. After comprehensive search analysis, data extraction and quality appraisal 19 studies were included in the study. Although results varied across studies, majority of the studies revealed a positive link. Notably, some studies suggested an association between celiac disease and dilated cardiomyopathy, while others did not. These discrepancies could be attributed to differences in methodologies, study populations, and regional variations. Several studies have shown the association of various cardiac manifestations in celiac disease. CONCLUSION: Although dilated cardiomyopathy is associated with celiac disease in majority of the studies, there are also studies that conflict with the association. The complex relationship between celiac disease and cardiovascular manifestations potentiates the need for further research with standardized methodologies, larger sample sizes, and consideration of regional variations. Such insights are vital for improving clinical practice by establishing preventive strategies, active screening, early diagnosis, mitigating risks which helps in optimizing cardiovascular health in individuals with celiac disease.

Gluten-Free Diet Adherence Tools for Individuals with Celiac Disease: A Systematic Review and Meta-Analysis of Tools Compared to Laboratory Tests.

This systematic review aimed to find the tool that best predicts celiac individuals' adherence to a gluten-free diet (GFD). The Transparent Reporting of Multivariable Prediction Models for Individual Prognosis or Diagnosis (TRIPOD-SRMA) guideline was used for the construction and collection of data from eight scientific databases (PubMed, EMBASE, LILACS, Web of Science, LIVIVO, SCOPUS, Google Scholar, and Proquest) on 16 November 2023. The inclusion criteria were studies involving individuals with celiac disease (CD) who were over 18 years old and on a GFD for at least six months, using a questionnaire to predict adherence to a GFD, and comparing it with laboratory tests (serological tests, gluten immunogenic peptide-GIP, or biopsy). Review articles, book chapters, and studies without sufficient data were excluded. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) was used for data collection from the selected primary studies, and their risk of bias and quality was assessed using the Prediction Risk of Bias Assessment Tool (PROBAST). The association between the GFD adherence determined by the tool and laboratory test was assessed using the phi contingency coefficient. The studies included in this review used four different tools to evaluate GFD adherence: BIAGI score, Coeliac Dietary Adherence Test (CDAT), self-report questions, and interviews. The comparison method most often used was biopsy (n = 19; 59.3%), followed by serology (n = 14; 43.7%) and gluten immunogenic peptides (GIPs) (n = 4; 12.5%). There were no significant differences between the interview, self-report, and BIAGI tools used to evaluate GFD adherence. These tools were better associated with GFD adherence than the CDAT. Considering their cost, application time, and prediction capacity, the self-report and BIAGI were the preferred tools for evaluating GFD adherence.

Assessment of QRS duration and presence of fragmented QRS in patients with celiac disease.

Background: Celiac Disease (CD) is characterized by small intestine involvement. However, cardiac manifestations may also be seen in the clinical course. The significance of the QRS prolongation and the presence of QRS fragmentation (fQRS) has been previously studied in many chronic inflammatory disorders as an independent predictor of cardiac manifestations. The study aimed to evaluate the QRS duration and presence of fQRS in patients with CD. Methods: 164 patients with CD and 162 healthy controls were included in the present study. QRS duration and presence of fQRS were calculated from the 12-lead electrocardiogram and compared between groups. The association between these parameters and disease duration was also evaluated. Results: QRS duration was found to be higher in the CD group compared to the control group (83 (76.8-93) vs. 91 (84-94), p<0.001). The presence of fQRS was demonstrated to be higher in the CD group (n=68 (41.5%) vs n=42 (25.9%), p=0.003). Notably, QRS duration was positively correlated with disease duration (Spearman's Rho= 0.47, p<0.001). In addition, disease duration was significantly higher in the fQRS (+) group (60 (23,5-144) vs. 28,5 (15-71,5), p=0.002). Conclusion: This study revealed that QRS prolongation and the presence of fQRS were higher in patients with CD. The presence of these findings may be an indicator of early subclinical cardiac involvement, especially in those with long disease duration. Thus, patients with these ECG findings can be considered for further cardiac evaluation.

A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient.

We present the case of a 62-year-old man with a history of celiac disease and IgA deficiency, following a strict gluten-free diet that was admitted to our hospital for recurrent abdominal pain, fatigue and melena. Esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A video-capsule endoscopy was performed and revealed a sub-stenosing, vegetating, and bleeding lesion in the first jejunal loop. He underwent laparotomic surgery with resection of the involved segment with loco-regional lymphadenectomy. The pathological report described a poorly differentiated adenocarcinoma of the jejunum, stage IIIA (pT3pN1). Analysis of next-generation sequencing (NGS) of DNA on the surgical sample revealed a likely pathogenetic variant in exon 15 of the DDR2 gene (c.2003G > A) and a TP53 non-frame-shift deletion (c.585_602del). Considering the risk of recurrence, he was candidate to 6 months of adjuvant chemotherapy with platinum salt and fluoropyrimidine. Thirty-eight months after the diagnosis, the patient is still disease free and in good clinical condition. This is the first described case of SBA with DDR2 mutation. Considering the limited therapeutic options beyond surgery for SBA, molecular analyses could become promising for the search for potential targetable alterations for treatments with new available drugs.

Cognitive Impairment and Insomnia in Celiac Disease: A Systematic Review and Meta-Analysis.

Emerging evidence suggests a broader spectrum of celiac disease (CeD) system involvement, including neurological manifestations. We aimed to conduct a systematic review and meta-analysis of the available evidence from studies assessing the association of cognitive impairment and insomnia with CeD. A total of 259 participants with CeD were included in the studies investigating insomnia and 179 were included in studies investigating cognitive impairment. The overall pooled odds ratio for insomnia in patients with CeD was 1.83 (95% confidence interval, 1.38 to 2.42; I2=0.00%). The present study provides valuable insights into the available evidence from studies investigating cognitive impairment in patients with CeD and our systematic review and metaanalysis revealed a significant association between CeD and insomnia.

Gluten-Free Corn Cookies Incorporated With Stinging Nettle Leaf Flour: Effect on Physical Properties, Storage Stability, and Health Benefits.

The consumption of gluten-free corn cookies is becoming very popular among nonceliac and celiac individuals. However, the absence of gluten and other nutrients in corn generally leads to cookies of lower quality in terms of nutritional value, texture, colour, and shelf life. To improve the quality characteristics of corn cookies, this study investigated the effect of incorporating an underutilised herb (Urtica dioica L. leaves) on its nutritional and physical properties. Stinging nettle leaf flour was incorporated at different levels (5%, 10%, 15%, and 20%) and compared with a control (100% corn cookies). The storage stability of the formulated corn cookies was also investigated at room and frozen (-18 ± 2°C) temperature. The incorporation of stinging nettle leaf flour increased (p < 0.05) the ash and protein content of corn cookies from 0.32% (control) to 2.56% (20% stinging nettle leaf flour incorporation) and 6.44% (control) to 21.52% (20% stinging nettle leaf flour incorporation), respectively. After in vitro starch digestion, the total phenolic content (TPC) and antioxidant activity (AA) also increased approximately 27 and seven times, respectively, and the estimated glycaemic index (GI) (eGI) decreased (p < 0.05) from 48.60% (control) to 33.18% (20% stinging nettle incorporated). Shelf life characteristics (water activity, peroxide value (PV), and microbial count) of formulated corn cookies were within acceptable limits for human consumption upon storage for 6 months. The findings indicated that stinging nettle leaves could serve as a potential food ingredient in gluten-free bakery products, particularly where low GI foods are desirable.

Frequency of seropositive celiac disease and hypothyroidism among children and adolescents with congenital heart disease: A case-control study.

BACKGROUND: The prevalence of celiac disease (CD) and hypothyroidism exhibit significant variation in different studies among patients with congenital heart disease (CHD). This study evaluated the frequency of laboratory test abnormalities in children and adolescents with CHD in Shiraz, Iran. METHODS: This prospective case-control study was conducted on 223 children and adolescents with CHD and healthy individuals referred to the heart clinic affiliated with Shiraz University of Medical Sciences between February 2019 and December 2021. They were classified into case and control groups. Blood tests were performed for total IgA antibody, anti-tissue transglutaminase IgA antibody (anti-TTG Ab), T4, and thyroid stimulating hormone (TSH) and anti-thyroid peroxidase antibodies in serum, along with transthoracic echocardiography. Likewise, demographic characteristics of patients, including age, sex, weight, height, and body mass index (BMI), were recorded. Also, anti-TTG Ab levels were compared among CHD patients according to cyanosis status, gender, age (above and below five years), and BMI (under and over 18.5). RESULTS: Ninety-eight CHD patients and 100 healthy individuals with an average age of 5.32 ± 4.05 years (1-18 years) were examined. In children with CHD, atrial septal defect (27%), ventricular septal defect (20%), and tetralogy of Fallot (13%) were the most prevalent disorders. Only one CHD patient had an anti-TTG Ab level of 16.6 unit/mL, considered borderline for seropositive CD diagnosis. There was no difference in anti-TTG Ab levels between age (above and below five years), BMI (under and over 18.5), cyanosis status, and gender groups. Seven CHD patients had high TSH levels, three had cyanotic CHD, and one had Down syndrome. The TSH levels and non-autoimmune hypothyroidism were significantly higher in CHD patients than in normal subjects (p < 0.05). CONCLUSIONS: According to the results of this study, the serum level of TSH and prevalence of non-autoimmune hypothyroidism were higher in patients with CHD than in normal subjects, but the serum level of anti-TTG Ab was not different between the two groups.

Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview.

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described.

Importance of an Ongoing Nutritional Counselling Intervention on Eating Habits of Newly Diagnosed Children with Celiac Disease.

A strict lifelong gluten-free diet (GFD) is the current treatment for the management of celiac disease (CD). Several studies have demonstrated that without proper dietary assessment, this diet leads to nutritional deficiencies and/or imbalances. The present study aimed to improve the dietary habits of newly diagnosed children with CD through ongoing and face-to-face dietary counseling. Forty-three participants were followed during the first year after CD diagnosis. Dietary data were collected at diagnosis (Vt0), after 3 months on a GFD (Vt3), and after 1 year following a GFD (Vt12). Participants completed a 3-day 24-h food recall, a food frequency questionnaire, and the KIDMED index. After each data collection, participants received dietary assessment and nutritional education. Participants consumed more plant-origin foods after the intervention, with most of them reaching the daily recommendations. Fresh food intake increased and that of ultra-processed foods decreased. Compliance with the Mediterranean diet also improved. Personalized dietary assessment and ongoing follow-up improved the dietary patterns of children recently diagnosed with CD, highlighting the importance of dietitian involvement in the management of CD.

Compliance and Attitudes towards the Gluten-Free Diet in Celiac Patients in Italy: What Has Changed after a Decade?

This study aims were (i) to describe Italian celiac patients who agreed to participate in the latest web survey and their attitudes toward the GF diet (compliance, perceived limitations, and worries) and (ii) to compare the answers given by the 2011 and 2022 responders. The self-administered questionnaire was distributed through the Italian Coeliac Association channels (link on social media, websites, and newsletters) to all of the celiac patients willing to participate in 2011 and 2022 (2427 and 3529 responders who answered the same questions, respectively). Descriptive analyses and the Pearson's chi-squared test were performed. The responders were 1 to 84 years old and mainly female. The prevalence of adherent patients in 2022 was 91%, with the highest value (94%) in children (≤10 years old) and adolescents (15-17 years old). Overall, young adults were the most worried group. About a decade after the first survey, we observed a decreasing prevalence of transgression events (-5%) and (at least) occasional temptation (-17%), a decreasing prevalence of health-related and general worries, but an increasing prevalence of social life withdrawal. In conclusion, it is important to periodically monitor celiac patients' compliance and attitudes towards the gluten-free diet. As also highlighted in international guidelines, a reorganization of the diagnosis/follow-up visits, including an expert dietary consultation, is needed.

The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases.

Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.

Gluten dependent activation of CD4+ T cells by MHC class II-expressing epithelium.

BACKGROUND AND AIMS: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T cell interactions in organoid monolayers expressing human MHC class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. METHODS: Epithelial MHC class II (MHCII) was determined in active and treated CeD, and in non-immunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without IFN-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T cell co-cultures were incubated with gluten, pre-digested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. RESULTS: Active CeD patients and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer-T cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T cell activation markers, and the release of IL-2, IFN-γ, and IL-15 in co-culture supernatants. Gluten metabolized by P. aeruginosa, but not the lasB mutant, enhanced CD4+ T cell proliferation and activation. CONCLUSIONS: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten pre-digestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in CeD patients.

The emerging role of biotechnological advances and artificial intelligence in tackling gluten sensitivity.

Gluten comprises an intricate network of hundreds of related but distinct proteins, mainly "gliadins" and "glutenins," which play a vital role in determining the rheological properties of wheat dough. However, ingesting gluten can trigger severe conditions in susceptible individuals, including celiac disease, wheat allergy, or non-celiac gluten sensitivity, collectively known as gluten-related disorders. This review provides a panoramic view, delving into the various aspects of gluten-triggered disorders, including symptoms, diagnosis, mechanism, and management. Though a gluten-free diet remains the primary option to manage gluten-related disorders, the emerging microbial and plant biotechnology tools are playing a transformative role in reducing the immunotoxicity of gluten. The enzymatic hydrolysis of gluten and the development of gluten-reduced/free wheat lines using RNAi and CRISPR/Cas technology are laying the foundation for creating safer wheat products. In addition to biotechnological interventions, the emerging artificial intelligence technologies are also bringing about a paradigm shift in the diagnosis and management of gluten-related disorders. Here, we provide a comprehensive overview of the latest developments and the potential these technologies hold for tackling gluten sensitivity.

Diagnostic Accuracy of IgA Anti-Transglutaminase Assessed by Chemiluminescence: A Systematic Review and Meta-Analysis.

A new chemiluminescence immunoassay method (CLIA) for detecting IgA anti-transglutaminase (atTG IgA) in celiac disease (CD) has prompted inquiries into its diagnostic performance. We conducted a systematic review and meta-analysis comparing CLIA with traditional enzyme-linked immunosorbent assay (ELISA) and fluorescence enzyme immunoassay (FEIA). We searched PubMed, Medline, and Embase databases up to March 2024. The diagnostic references were intestinal biopsy and ESPGHAN guidelines. We calculated the sensitivity and specificity of atTG IgA assessed by CLIA and the odds ratio (OR) between the assays. Eleven articles were eligible for the systematic review and seven for the meta-analysis. Sensitivity and specificity of atTG IgA CLIA-assay were 0.98 (95% CI, 0.95-0.99) and 0.97 (95% CI, 0.94-0.99), respectively. The sensitivity of atTG IgA antibody detection did not significantly vary across the three assay modalities examined (CLIA vs. ELISA OR: 1.08 (95% CI, 0.56-2.11; p = 0.8); CLIA vs. FEIA OR: 6.97 (95% CI, 0.60-81.03; p = 0.1). The specificity of atTG IgA assessed by FEIA was higher than for CLIA (OR 0.17 (95% CI, 0.05-0.62); p < 0.007). According to the systematic review, normalization of atTG IgA levels in CD patients following a gluten-free diet was delayed when using CLIA compared to ELISA and FEIA methods. Conflicting findings were reported on the antibody threshold to use in order to avoid biopsy confirmation.

Bronchiectasis combined with chronic sinusitis following Celiac disease: a case report.

INTRODUCTION: Celiac disease is a disease triggered by a protein called gluten. Celiac disease has intestinal and extraintestinal manifestations. Bronchiectasis is a permanent dilation of the bronchi that causes symptoms, such as cough producing a large amount of sputum, recurrent respiratory infections, and breathlessness. In addition, bronchiectasis can present in 60% of cases with chronic rhinosinusitis. CASE PRESENTATION: A 40-year-old Arab woman presented with a worsening old cough with an increased amount of sputum; the patient was diagnosed with Celiac disease 7 months prior. Investigations started with laboratory tests followed by a computed tomography scan for the head and chest, bronchoscopy, bronchoalveolar lavage, and spirometry; the final diagnosis was bronchiectasis with chronic rhinosinusitis. She was advised to commit to the gluten-free diet, in addition to the medications prescribed for her bronchiectasis and chronic rhinosinusitis. CONCLUSION: Celiac disease and bronchiectasis might share an immunologic disturbance that caused both entities, so Celiac disease should be kept in mind as an etiology for pulmonary diseases.

Impact of celiac disease in Behçet's syndrome patients: a study based on the database of Türkiye.

Background/aim: Our primary aim was to investigate the effects of concomitant celiac disease (CD) on the clinical characteristics of Behçet's syndrome (BS) patients. Materials and method: The study was a retrospective, nationwide, multicenter study. Turkish Ministry of Health National Electronic Database (e-Nabiz) is used under Health Ministry's supervision to extract the subject's data. Statistical analysis: Statistical analyses were made by the Statistical Package for Social Sciences (SPSS) software version 20 (IBM Corp., Armonk, New York). Continuous variables were presented by mean ± standard derivation (SD) or median (min-max) according to normality and compared by student-t test. A binary logistic regression analysis was performed to further investigating the relation between having a concomitant CD with each BD manifestation and comorbidity, frequencies of which were detected to be significantly different in the student-test. Results: A total of 84,241 patients diagnosed with BS were analyzed, and CD was identified in 175 (0.21 %) patients. The group with CD had a mean age of 41.30 ± 13.69 which was significantly younger. the prevalence of females was significantly higher (71.4%). The mean age of first admission for BS was also significantly younger in the group with CD (36.64 ± 13.28). BS patients with CD had a significantly higher prevalence of inflammatory bowel disease (27.2% vs. 7.3%, p < 0.001). When comorbid conditions were investigated depression (35.4% vs. 23.3%, p < 0.001), migraine (7.4 % vs. 2.6%, p < 0.001), fibromyalgia (10.9% vs. 4.5%, p < 0.001) and osteoporosis (12.6% vs. 6.6%, p = 0.001) were significantly more frequent in BS patients with CD. Conclusion: Our results suggest coexistence of CD in BS patients is related to female dominance and probably to an earlier disease onset. Several CD-related comorbidities as well as inflammatory bowel disease were more frequent in the CD group which implied an increased overall disease burden.

Decreasing incidence of celiac disease in Southern Sweden.

BACKGROUND: The incidence of celiac disease (CD) has increased rapidly in the late 20th and early 21st centuries, but there are recent reports of rates levelling off in countries with a high prevalence. The aim of this study was to investigate current trends in CD in southern Sweden. PATIENTS AND METHODS: Children and adults diagnosed with CD by biopsy or serology in the region of Skåne, southern Sweden, from 2010-2022 were included. The home address was identified through registers to analyze temporal and geographical trends. RESULTS: A total of 3218 CD-patients were identified (52.2% children), the vast majority detected in clinical care but a few children by screening studies. The age-standardized incidence rate was 18.6 cases/105. The incidence decreased at a rate of -0.75 cases/105 (95% CI -1.14 to -0.35, p 0.002). The incidence among girls under 18 years almost halved throughout the study period, decreasing by -2.94 cases/105 (95% CI -4.59 to -1.29, p 0.002), while there only were small changes among men. The most common age of onset was 3-9 years. CD incidence varied by place of living and was more common in small towns than urban or rural areas. CONCLUSIONS: The incidence of CD in southern Sweden is decreasing, primarily in children and women who traditionally have had the highest risk of CD. CD was diagnosed most frequently in children 3-9 years old. There were regional variations in incidence. CD was most common in small towns, pointing to the importance of environmental factors in CD etiology.