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The enzyme transglutaminase 2 (TG2) plays a key role in celiac disease (CeD) pathogenesis. Active TG2 is located mainly extracellularly in the lamina propria but also in the villous enterocytes of the duodenum. The TG2 inhibitor ZED1227 is a promising drug candidate for treating CeD and is designed to block the TG2-catalyzed deamidation and crosslinking of gliadin peptides. Our aim was to study the accumulation of ZED1227 after oral administration of the drug. We studied duodenal biopsies derived from a phase 2a clinical drug trial using an antibody that detects ZED1227 when bound to the catalytic center of TG2. Human epithelial organoids were studied in vitro for the effect of ZED1227 on the activity of TG2 using the 5-biotin-pentylamine assay. The ZED1227-TG2 complex was found mainly in the villous enterocytes in post-treatment biopsies. The signal of ZED1227-TG2 was strongest in the luminal epithelial brush border, while the intensity of the signal in the lamina propria was only ~20% of that in the villous enterocytes. No signal specific to ZED1227 could be detected in pretreatment biopsies or in biopsies from patients randomized to the placebo treatment arm. ZED1227-TG2 staining co-localized with total TG2 and native and deamidated gliadin peptides on the enterocyte luminal surface. Inhibition of TG2 activity by ZED1227 was demonstrated in epithelial organoids. Our findings suggest that active TG2 is present at the luminal side of the villous epithelium and that inhibition of TG2 activity by ZED1227 occurs already there before gliadin peptides enter the lamina propria. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review highlights recent research in the field of celiac disease., Recent Findings: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition., Summary: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Coeliac disease (CD) affects almost of 1% of the population, yet remains undiagnosed in the majority. Though the demonstration of enteropathy in duodenal biopsy was traditionally the essential criterion for the diagnosis of coeliac disease, the guidelines published by the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) in 2012, and revised in 2020, paved the way to a no-biopsy approach to diagnosis. In a select group of children meeting certain criteria, a definitive diagnosis of CD can now be made without the need for duodenal biopsies. This is being increasingly applied in clinical practice. It is well established that untreated coeliac disease is associated with several chronic adverse health conditions. At present, a strict gluten-free diet remains the only effective treatment for CD. The advances in our understanding of the pathogenesis of CD have led to a search for alternative treatment agents. Several investigational agents are in various phases of clinical trials at present. In this review, we outline the clinical aspects of coeliac disease and summarise various investigational treatment agents.

Coeliac disease is a common condition for which the only current treatment is a gluten-free diet. Adherence to this diet is not always easy and is associated with a reduction in quality of life for the patient and their family. Non-adherence is associated with complications of varying severity. The lack of control at the outpatient care level in a high percentage of these patients evinces the need to improve follow-up protocols and the approach to care delivery with coordination of paediatric gastroenterology units (PGU) and primary care paediatricians. With this aim in mind, the present document was developed by consensus to offer a set of recommendations adapted to our region, based on the recent recommendations published by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and with participation of the pertinent scientific societies, including those concerning the adult population, for the management and follow-up of adolescents and the transition to adult care., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Abstract: The American College of Gastroenterology revised its recommendations for diagnosing and managing celiac disease in its updated 2023 clinical guideline. Celiac disease is an autoimmune disorder causing malabsorption following exposure to gluten. A wide range of both gastrointestinal and nongastrointestinal signs and symptoms can occur. This article provides an overview of the diagnosis and management of celiac disease, aiding the NP in developing a greater awareness of the condition both to diagnose it and to refer patients as needed to gastroenterology for evaluation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fewer than 1% of patients with celiac disease (CD) will develop refractory CD (RCD). As such, most gastroenterologists might never need to manage patients with RCD. However, all gastroenterologists must be familiarized with the basic concepts of RCD and non-responsive CD (NRCD), since it can present as a severe disease with high mortality, not only due to intestinal failure, but also due to progression to enteropathy-associated T cell lymphoma (EATL) and a higher susceptibility to life-threatening infections. The diagnostic workup and differential diagnosis with other causes of gastrointestinal symptoms and villous atrophy, as well as the differentiation between type I and II RCD, are complex, and may require specialized laboratories and reference hospitals. Immunosuppression is efficient in the milder RCDI; however, the treatment of RCDII falls short, with current options probably only providing transient clinical improvement and delaying EATL development. This review summarizes the current diagnostic and therapeutic approach for patients with RCD that all doctors that manage patients with CD should know.

Celiac disease (CeD), an autoimmune disorder triggered by gluten, affects around 1% of the global population. Standard treatment is a strict gluten-free diet (GFD), which poses significant challenges due to dietary restrictions, cross-contamination and subsequent persistent intestinal inflammation. This underscores the need for new treatment options addressing the complex pathophysiology of CeD. Recent research focuses on developing drugs that target intestinal barrier regeneration, gluten peptide modification, immune response alteration, and gut microbial ecosystem modulation. These approaches offer potential for more effective management of CeD beyond GFD. Gluten-independent treatments may be particularly relevant under the FDA's draft guidance for CeD, which emphasizes drug development as an adjunct to GFD for patients with ongoing signs and symptoms of CeD despite strict GFD., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The enzyme transglutaminase 2 (TG2) plays a key role in celiac disease (CeD) pathogenesis. Active TG2 is located mainly extracellularly in the lamina propria but also in the villous enterocytes of the duodenum. The TG2 inhibitor ZED1227 is a promising drug candidate for treating CeD and is designed to block the TG2-catalyzed deamidation and crosslinking of gliadin peptides. Our aim was to study the accumulation of ZED1227 after oral administration of the drug. We studied duodenal biopsies derived from a phase 2a clinical drug trial using an antibody that detects ZED1227 when bound to the catalytic center of TG2. Human epithelial organoids were studied in vitro for the effect of ZED1227 on the activity of TG2 using the 5-biotin-pentylamine assay. The ZED1227-TG2 complex was found mainly in the villous enterocytes in post-treatment biopsies. The signal of ZED1227-TG2 was strongest in the luminal epithelial brush border, while the intensity of the signal in the lamina propria was only ~20% of that in the villous enterocytes. No signal specific to ZED1227 could be detected in pretreatment biopsies or in biopsies from patients randomized to the placebo treatment arm. ZED1227-TG2 staining co-localized with total TG2 and native and deamidated gliadin peptides on the enterocyte luminal surface. Inhibition of TG2 activity by ZED1227 was demonstrated in epithelial organoids. Our findings suggest that active TG2 is present at the luminal side of the villous epithelium and that inhibition of TG2 activity by ZED1227 occurs already there before gliadin peptides enter the lamina propria.

Background & Aims: Celiac disease (CD) is a chronic inflammatory disease of the small intestine induced and maintained by gluten ingestion in susceptible individuals. Current treatment consists of strict adherence to a lifelong gluten-free diet (GFD) which is considered safe and effective in the large majority of patients. However, since adherence to a GFD is difficult and has a negative impact on quality of life, an increasing interest in other treatment options has emerged. Moreover, in some individuals a GFD is not sufficiently effective, necessitating alternative treatments., Methods: By performing a systematic search, we constructed a detailed narrative review. Only treatment options considered relevant and conducted in a phase I, II or III clinical trial were included., Results: Based on the pathophysiology of CD, four major therapeutic approaches can be distinguished: firstly, by focusing on intraluminal gluten detoxification before absorption occurs, secondly, by modulating intestinal permeability and preventing paracellular uptake, thirdly, by enhancing immunological tolerance to gluten and finally, by regulating gluten auto-immunity., Conclusions: Despite significant efforts, no treatment has yet completed a phase III clinical trial. Future studies will likely focus on the use of supplemental drugs in conjunction to a GFD, with ALV003 and ZED-1227 currently being the most promising therapeutic options., Competing Interests: Conflict of interest None to declare., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nonresponsive celiac disease (CeD) is relatively common. It is generally attributed to persistent gluten exposure and resolves after correction of diet errors. However, other complications of CeD and disorders clinically mimicking CeD need to be excluded. Novel therapies are being evaluated to facilitate mucosal recovery, which might benefit patients with nonresponsive CeD. Refractory CeD (RCeD) is rare and is divided into 2 types. The etiology of type I RCeD is unclear. A switch to gluten-independent autoimmunity is suspected in some patients. In contrast, type II RCeD represents a low-grade intraepithelial lymphoma. Type I RCeD remains a diagnosis of exclusion, requiring ruling out gluten intake and other nonmalignant causes of villous atrophy. Diagnosis of type II RCeD relies on the demonstration of a clonal population of neoplastic intraepithelial lymphocytes with an atypical immunophenotype. Type I RCeD and type II RCeD generally respond to open-capsule budesonide, but the latter has a dismal prognosis due to severe malnutrition and frequent progression to enteropathy-associated T-cell lymphoma; more efficient therapy is needed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to treatment with a gluten-free diet and the ensuing clinical and histologic recovery. Traditionally, this has been accomplished by means of regular on-site attendance at specialist health care facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited health care resources challenge the current centralized and nonindividualized follow-up strategies. The improved noninvasive surveillance tools and online health care services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population., (© 2024. The Author(s).)

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coeliac disease is an autoinflammatory condition caused by immune reactions to cereal gluten proteins. Currently, the only available treatment for the condition is a lifelong avoidance of gluten proteins in the diet. There is an unmet need for alternative therapies. Coeliac disease has a strong association with certain HLA-DQ allotypes (DQ2.5, DQ2.2 and DQ8), and these disease-associated HLA-DQ molecules present deamidated gluten peptides to gluten-specific CD4 + T cells. The gluten-specific CD4 + T cells are the drivers of the immune reactions leading to coeliac disease. Once established, the clonotypes of gluten-specific CD4 + T cells persist for decades, explaining why patients must adhere to a gluten-free diet for life. Given the key pathogenic role of gluten-specific CD4 + T cells, tolerance-inducing therapies that target these T cells are attractive for treatment of the disorder. Lessons learned from coeliac disease might provide clues for treatment of other HLA-associated diseases for which the disease-driving antigens are unknown. Thus, intensive efforts have been and are currently implemented to bring an effective tolerance-inducing therapy for coeliac disease. This Review discusses mechanisms of the various approaches taken, summarizing the progress made, and highlights future directions in this field., (© 2024. Springer Nature Limited.)

Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Patients who come to clinical consultation for chronic diarrhoea (i.e., diarrhoea lasting for more than four weeks) may suffer from a wide range of clinical conditions. The possible diagnoses range from a misunderstanding of what can be considered normal and what pathological in terms of daily bowel movements, to a severe malabsorption syndrome. Since the list of possible causes of chronic diarrhoea can be puzzling, the physician's approach needs to be systematic and structured in order to allow the correct diagnosis and treatment. This article proposes an algorithm for the diagnosis of chronic diarrhoea and discusses in detail the key clinical aspects of celiac disease, which is considered a paradigmatic disease as regards chronic malabsorptive diarrhoea., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.

Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an inflammatory response is triggered in the small intestine, and this reaction can be alleviated by the elimination of gluten from the diet. The clinical manifestations of CD vary greatly from person to person and begin at a young age or in adulthood. Influence of genetic factors on CD development is evident in carriers of the DQ2 and/or DQ8 allele. HLA genotypes are associated with gut colonization by bacteria, particularly in individuals suffering from CD. In addition, beneficial gut microbes are crucial for the production of DPP-4, which plays a key role in immune function, as well as metabolic and intestinal health. Therefore, probiotics have been recommended as a complementary food supplement in CD.

Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Celiac disease (CeD) is a widespread, gluten-induced, autoimmune disorder that lacks any medicinal therapy. Towards the goal of developing non-dietary treatments for CeD, research has focused on elucidating its molecular and cellular etiology. A model of pathogenesis has emerged centered on interactions between three molecular families: specific class II MHC proteins on antigen-presenting cells (APCs), deamidated gluten-derived peptides, and T cell receptors (TCRs) on inflammatory CD4 + T cells. Growing evidence suggests that this pathogenic axis can be pharmacologically targeted to protect patients from some of the adverse effects of dietary gluten. Further studies have revealed the existence of additional host and environmental contributors to disease initiation and tissue damage. This review summarizes our current understanding of CeD pathogenesis and how it is being harnessed for therapeutic design and development., Competing Interests: Declaration of interests C.K. serves as a director of ImmunogenX. H.A.B. declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Celiac disease is a chronic genetically based gluten-sensitive immune-mediated enteropathic process primarily affecting the small intestinal mucosa. The disorder classically presents with diarrhea and weight loss; however, more recently, it has been characterized by subclinical occult or latent disease associated with few or no intestinal symptoms. Diagnosis depends on the detection of typical histopathological biopsy changes followed by a gluten-free diet response. A broad range of clinical disorders may mimic celiac disease, along with a wide range of drugs and other therapeutic agents. Recent and intriguing archeological data, largely from the Gobleki Tepe region of the Fertile Crescent, indicate that celiac disease probably emerged as humans transitioned from hunter-gatherer groups to societies dependent on agriculture to secure a stable food supply. Longitudinal studies performed over several decades have suggested that changes in the prevalence of the disease, even apparent epidemic disease, may be due to superimposed or novel environmental factors that may precipitate its appearance. Recent therapeutic approaches are being explored that may supplement, rather than replace, gluten-free diet therapy and permit more nutritional options for future management.

The impact of diet on psoriasis is not well studied but it is of interest to many patients. A hypocaloric diet with corresponding weight loss can reduce psoriasis severity in overweight or obese patients and should be considered an important supplement to conventional therapy, as argued in this review. Gluten-free diet might improve severity of psoriasis in patients with coeliac disease or merely presence of coeliac-specific antibodies. Mediterranean diet might also be beneficial. Overall, studies do not support a beneficial effect of micronutrient supplements (i.e., vitamin D, selenium, vitamin B12) in patients with normal serum levels., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Objectives: The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL)., Methods: We invited 243 randomly selected children diagnosed with CD in 2013-2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment., Results: The mean age at study enrolment was 12.7 (range 7.8-18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3-8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%-100%] of children without follow-up versus 91% (95% CI: 85%-95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%-86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%-80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL., Conclusions: In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Celiac disease (CD) is a gluten related disorder which affects all age-groups and occurs in genetically susceptible population after introduction of gluten in diet. The worldwide prevalence of CD is ~1% and it is higher in certain "at-risk groups". The clinical features are variable, ranging from classical diarrhea to an asymptomatic state. Diagnosis requires serology and duodenal histology although a non-biopsy diagnosis is recommended by European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for a select group of children. Treatment of CD is with a life-long strict gluten free diet (GFD) along with correction of nutritional deficiencies. Regular follow-up to assess compliance and efficacy of GFD is mandatory. Non-responsive CD needs evaluation by a specialist as it can be due to incorrect diagnosis, poor dietary compliance, coexisting conditions like small bowel bacterial overgrowth, pancreatic insufficiency etc. and lastly, refractory CD. Most patients diagnosed as CD in childhood receive no medical or dietary supervision after transition to adulthood and nearly a third are non-compliant to GFD. No requirement of medications, patient's perception of understanding GFD and absence of symptoms with intermittent non-compliance leads to neglect of care after transition. Poor dietary adherence leads to nutritional deficiencies, osteoporosis, fertility issues and risk of malignancy. It is mandatory that the patients know about CD, need of strict GFD, regular follow-up, disease complications, and are capable of communicating with the health-care personnel before transition. Formulating a phased transition care program with joint pediatric and adult clinics is required for a successful transition and improving the long-term outcome., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose of Review: Proteases constitute a group of enzymes that hydrolyze peptide bonds. Intestinal proteases are an integral part of gut homeostasis and digestion. This review discusses the broader classification of proteases, regulation of proteolytic activity (PA) in the intestinal tract, and how dysregulation of intestinal proteases contributes to the pathophysiology of conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease. We also discuss recent advancements in therapeutic modulation that directly or indirectly target intestinal proteases and can be utilized to treat these illnesses., Recent Findings: Host and microbiota derived proteases have been associated with symptoms in subsets of patients with IBS, IBD and celiac disease. Elevated PA mediates barrier dysfunction, visceral hypersensitivity as well as immune activation and inflammation. Recent mechanistic studies have revealed the nature of disease-associated proteases and mechanisms regulating their activity, particularly those driven by the microbiota. Advancements in activity-based probes have allowed novel ways of in vivo imaging of PA. Newer strategies targeting proteases include monoclonal antibodies, engineered microbiota as well as specific protease inhibitors., Summary: Significant progresses made in the detection as well as regulation of PA is likely to provide therapeutic advancements for gastrointestinal diseases., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Gluten-free diet (GFD) is the most effective method to manage celiac disease (CD). Many patients do not reach the complete symptom alleviation, even by strict GFD. Recent studies have reported inconsistent results regarding the beneficial benefits of taking probiotics. Therefore, we aimed to evaluate the effects of probiotics on gastrointestinal (GI) symptoms and the possible underlying causes in CD and celiac disease autoimmunity (CDA) patients. Databases, including PubMed, Scopus, Embase, Web of Science and Google Scholar, were searched for clinical trials published until July 2022 about assessing the effects of probiotics or synbiotics on CD or CDA patients. We collected data on GI symptoms, CD markers, inflammatory and immune responses, adverse events, and gut microbiota. A random effect meta-analysis was used to estimate the pooled standardized mean difference (SMD) and confidence interval (CI). We screened 7234 articles, of which 14 were included in the qualitative analysis and 5 in the quantitative analysis. Probiotics might alleviate GI symptoms, especially in the highly symptomatic patients, and improve immune response in CD and CDA patients. Results of the meta-analysis showed that probiotics increased the abundance of Bifidobacterium (SMD: 0.72, 95%CI (0.13, 1.30) and Lactobacillus (SMD: 0.49, 95%CI (0.18, 0.80) as compared with placebo. Probiotics did not increase the adverse events compared to the placebo. Probiotics might alleviate GI symptoms and immune response and improve dysbiosis in CD and CDA patients. However, high-quality clinical trials are needed to increase the level of evidence. Also, the most suitable combination of probiotics is yet to find., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Celiac disease (CD) is an organ-specific autoimmune disorder that occurs in genetically predisposed individuals when exposed to exogenous dietary gluten. This exposure to wheat gluten and related proteins from rye and barley triggers an immune response which leads to the development of enteropathy associated with symptoms of bloating, diarrhea, or malabsorption. The sole current treatment is to follow a gluten-free diet for the rest of one's life. Intestinal barriers are enriched with Unconventional T cells such as iNKT, MAIT, and γδ T cells, which lack or express only a limited range of rearranged antigen receptors. Unconventional T cells play a crucial role in regulating mucosal barrier function and microbial colonization. Unconventional T cell populations are widely represented in diseased conditions, where changes in disease activity related to iNKT and MAIT cell reduction, as well as γδ T cell expansion, are demonstrated. In this review, we discuss the role and potential employment of Unconventional T cells as a therapeutic target in the pathophysiology of celiac disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.

Competing Interests: MK received the PDF award from the Farncombe Family Digestive Health Research Institute. EFV is secretary of the International Society for the Study of Celiac Disease; is a member of the Advisory Board of the Biocodex Foundation; is a Tier 1 Canada Research Chair in Microbial Therapeutics and Nutrition in Gastroenterology; and is funded by a Kallyope grant and holds a PJT CIHR grant (number 168840) unrelated to this study. MIPS received consulting honoraria from Takeda and research funding from ProventBio and an AFP Gastroenterology Division and HAHSO AFP Innovation grant project (number HAH-22-002).

Background: Celiac disease is a major public health problem in many countries, including Iran. Considering the disease's exponential spread throughout the world and its risk factors, identifying the educational priorities and minimum data required to control and treat the disease is of great significance., Methods: The present study was conducted in two phases in 2022. In the first phase, a questionnaire was developed based on the information obtained from a review of the literature. Later, the questionnaire was administered to 12 pundits in the fields of nutrition (n = 5), internal medicine (n = 4), and gastroenterology (n = 3). As a result, the necessary and important educational content was determined for developing the Celiac Self-Care System., Results: According to the experts' viewpoints, the educational needs of patients were classified into nine categories of demographic information, clinical information, long-term complications, comorbidity, tests, medications, dietary recommendations, general recommendations, technical capabilities as well as 105 subcategories., Conclusions: Due to the increased prevalence of Celiac disease and the lack of an established minimum set of data, determining the required educational information is of great importance at the national level. Such information could be useful in implementing educational health programs to raise the public level of awareness. In the field of education, such contents can be employed in planning new technology based on mobile phones (mobile health), preparing registries, and producing widely used content., (© 2023. The Author(s).)

Coeliac disease is a common autoimmune disorder induced by ingesting gluten, the protein component of wheat, barley, and rye. It is estimated that one-in-hundred people worldwide have coeliac disease, of whom the majority remain undiagnosed. Coeliac disease is characterized by a wide range of gastrointestinal and extraintestinal symptoms but can also present asymptomatically. Diagnosing coeliac disease depends on the concordance of clinical, serological and histopathological data. However, the diagnosis can be challenging and frequently overlooked. Undiagnosed coeliac disease is associated with an increased risk of complications and detrimental effects on quality of life. Early diagnosis and treatment of coeliac disease are necessary to reduce the risk of long-term complications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.

Background: Celiac disease has an increasing incidence worldwide and is treated with lifelong adherence to a gluten-free diet. We aimed to describe gluten-free diet adherence rates in children with screening-identified celiac disease, determine adherence-related factors, and compare adherence to food records in a multinational prospective birth cohort study., Methods: Children in The Environmental Determinants of Diabetes in the Young study with celiac disease were included. Subjects had at least annual measurement of adherence (parent-report) and completed 3-day food records. Descriptive statistics, t-tests, Kruskal-Wallis tests and multivariable logistic and linear regression were employed., Results: Two hundred ninety (73%) and 199 (67%) of subjects were always adherent to a gluten-free diet at 2 and 5 years post celiac disease diagnosis respectively. The percentage of children with variable adherence increased from 1% at 2 years to 15% at 5 years. Children with a first-degree relative with celiac disease were more likely to be adherent to the gluten-free diet. Gluten intake on food records could not differentiate adherent from nonadherent subjects. Adherent children from the United States had more gluten intake based on food records than European children (P < .001 and P = .007 at 2 and 5 years respectively)., Conclusion: Approximately three-quarters of children with screening-identified celiac disease remain strictly adherent to a gluten-free diet over time. There are no identifiable features associated with adherence aside from having a first-degree relative with celiac disease. Despite good parent-reported adherence, children from the United States have more gluten intake when assessed by food records. Studies on markers of gluten-free diet adherence, sources of gluten exposure (particularly in the United States), and effects of adherence on mucosal healing are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mehta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This manuscript reports the recent advances in idiopathic pulmonary hemosiderosis (IPH), a rare cause of diffuse alveolar hemorrhage in children and adults. This narrative review of the literature summarizes different aspects of IPH, including proposed pathogenesis, patient demographics, clinical and radiological characteristics, treatment, and prognosis. Additionally, the association between Celiac Disease (CD) and IPH is carefully evaluated. IPH is a frequently misdiagnosed disease. The delay in the diagnosis of IPH is often significant but fortunately, appears to have decreased in recent years. IPH in adults and children have distinct demographic preferences. The autoantibodies are common in IPH but with a definite difference between the adult and pediatric populations. The definitive diagnosis of IPH requires lung biopsy and careful exclusion of all competing diagnoses, even with lung biopsy showing bland pulmonary hemorrhage. The presence of nonspecific inflammatory cells or lymphoid aggregates may suggest a secondary immunologic phenomenon and needs careful evaluation and follow-up. A substantial number of patients suffer from coexisting CD, also known as Lane-Hamilton syndrome (LHS), and all patients with IPH need to be evaluated for LHS by serology. Although strict gluten free diet can manage the majority of patients with LHS, other patients generally require immunosuppressive therapy. The corticosteroids are the backbone of IPH therapy. Recently utilized experimental treatment options include mesenchymal stem cell transplant, liposteroid and bronchial artery embolization. The immunosuppression should be adjusted to achieve optimal disease control. Patients may progress to end-stage lung disease despite all measures, and lung transplantation may be the only viable option., (© 2022 Wiley Periodicals LLC.)

Objectives: Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up., Methods: We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients., Results: Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality., Conclusions: Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. All co-authors have seen and agreed with the content of the manuscript. There are no financial interests to report., (Copyright © 2022. Published by Elsevier Ltd.)

Celiac disease (CD) is an immunoallergic enteropathy affecting genetically susceptible individuals upon dietary exposure to gluten. In current clinical practice, the diagnosis of CD is based on a combination of clinical, serologic, and histologic factors with the possible exception of pediatric patients. Histopathologic evaluation of small intestinal tissue plays a critical role in the disease diagnosis and management, despite many practical challenges. Recently published best practice guidelines help to standardize biopsy sample procurement, tissue preparation, histology interpretation, and reporting, to optimize patient care. In addition, an increasing demand for monitoring the disease course, particularly demonstrating the efficacy of dietary and nondietary interventions for disease management, calls for the use of quantitative histology. With the advent of a gradual transition toward digital pathology in routine diagnostic practice, quantitative histopathologic evaluation in CD shows a promising future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The pattern of practice regarding the diagnosis, dietary counselling and follow-up of patients with celiac disease (CeD) varies between practice to practice., Methods: A web-based questionnaire based on review of literature, group discussions and expert group meetings was developed to understand the practice of CeD in India. The questionnaire was administered through social media (WhatsApp) to 18 Indian celiac support groups comprising 2980 patients with CeD., Results: Overall, 970 (32.5%) patients responded to the questionnaire (median age: 21 years; females 63.9%). While 679 (71.1%) patients were diagnosed based on a combination of serology and biopsy, 214 (22.4%) were diagnosed based on serology alone. After diagnosis, 875 (91%) patients were counselled initially by physician and only 585 (61%) were referred to a dietician for dietary counselling. In a majority of cases, the time spent by doctors and dietitians during first counselling was between 10 and 20 minutes only. After first counselling, 191 (20%) and 355 (37.3%) patients did not re-visit the physician and the dietitian, respectively. Among those who followed up, structured follow-up was conducted in only 515 (53.8%) patients. Overall, 232 (24.3%) patients were self-monitoring their serological parameters, while 495 (51.8%) patients did not receive a formal assessment of dietary adherence during follow-up., Conclusion: The practice of diagnosis, dietary counselling and follow-up of patients with CeD in India is not as per standard guidelines. Most of the patients are not referred to a dietitian. There is a need for reinforcement of guidelines for proper care and management of patients with CeD., (© 2023. Indian Society of Gastroenterology.)