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Background & Aims: In coeliac disease, the clinical role of the urinary gluten immunogenic peptide is unclear. It has been suggested it can be a non-invasive marker of villous atrophy. Therefore, we present the largest cross-sectional clinical data in patients with coeliac disease to establish the diagnostic accuracy of the urinary gluten immunogenic peptide in identifying villous atrophy. Methods: Patients providing urinary gluten immunogenic peptide were identified between September 2018 and August 2023 at the National Health Service (NHS) England National Centre for Non-Responsive and Refractory CD. In our retrospective study, the results of the urinary gluten immunogenic peptide test collected within 7 days, self-reported adherence to a gluten free diet reported within 3 months, serology collected within 7 days (immunoglobulin A - tissue transglutaminase and endomysial antibody) and histology at the time of endoscopy were compared in individuals with coeliac disease who were either asymptomatic and undergoing remission biopsies (group 1), non-responsive coeliac disease (group 2) and refractory coeliac disease on immunosuppressive therapy (group 3). Associations between dichotomous variables were calculated using chi-squared test. Results: In group 1 the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting villous atrophy were 42.9%, 83.3.%, 64.3% and 67.6% respectively. In group 2 the sensitivity, specificity, PPV and NPV for detecting villous atrophy were 36.2%, 79.0%, 39.5% and 76.6% respectively. In group 3 the sensitivity, specificity, PPV and NPV for detecting villous atrophy were 56.3%, 70.6%, 73.0% and 53.3%. More patients on immunosuppression had a positive urinary gluten immunogenic peptide than those not on immunosuppression (43.3% vs 24.1%, p<0.001). Conclusions: The urinary gluten immunogenic peptide does not have a role in identifying villous atrophy. Therefore, to assess for villous atrophy an upper gastrointestinal endoscopy is still required. [ABSTRACT FROM AUTHOR]

Infantile refractory diarrhea presents after first few days of life leading to intestinal insufficiency. It is a diagnostic challenge due to varied etiologies like food senstive enteropathy, anatomical defects and dysmotility disorders, transport and enzymatic defects, pancreatic malabsorption - cystic fibrosis (CF), primary epithelial causes like microvillus inclusion disease (MVID), tufting enteropathy and heparan sulfate deficiency, immunodeficiencies, metabolic diseases and autoimmune enteropathy. It is refractory to treatment making the patient dependent on total parenteral nutrition. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), is one of the rarest causes of intractable diarrhea. It occurs due to mutations in the FOXP3 gene, leading to dysfunction of T-regulatory cells and is characterised by diarrhoea, diabetes, and dermatitis. We aim to evaluate various causes of infantile refractory chronic diarrhea, and to present one such case of IPEX syndrome from this part of the world due to mutation not been reported in literature so far. [ABSTRACT FROM AUTHOR]

Herein, we describe a case of olmesartan-associated sprue-like enteropathy, in which improvement in villous atrophy was confirmed using small bowel capsule endoscopy. The patient was a 69-year-old woman who had persistent watery diarrhea (20 bowel movements/day) for 1 year and experienced a weight loss of 10 kg in the same period. Abdominal computed tomography revealed no abnormalities, and blood test results revealed no inflammatory reactions. Upper endoscopy and colonoscopy revealed villous atrophy in the duodenum and terminal ileum. As the patient was administered olmesartan for a long time and capsule endoscopy showed villous atrophy throughout the small bowel, she was diagnosed with olmesartan-associated sprue-like disease. Following the discontinuation of the medication, symptoms of diarrhea soon improved, and repeat capsule endoscopy indicated improvement in small intestinal villous atrophy. Olmesartan-associated sprue-like enteropathy should be considered a differential diagnosis in patients with severe chronic watery diarrhea. Our report is the first in which capsule endoscopy was performed multiple times over a long period for follow-up observation of improvements in the small intestine. In addition, our literature review regarding capsule endoscopy for olmesartan-associated enteritis might aid clinicians in the early diagnosis of the condition and the assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) is a gluten-induced enteropathy that develops in genetically susceptible individuals upon consumption of cereal gluten proteins. It is a unique and complex immune disorder to study as the driving antigen is known and the tissue targeted by the immune reaction can be interrogated. This review integrates findings gained from genetic, biochemical, and immunologic studies, which together have revealed mechanisms of gluten peptide modification and HLA binding, thereby enabling a maladapted anti-gluten immune response. Observations in human samples combined with experimental mouse models have revealed that the gluten-induced immune response involves CD4+ T cells, cytotoxic CD8+ T cells, and B cells; their cross-talks are critical for the tissue-damaging response. The emergence of high-throughput technologies is increasing our understanding of the phenotype, location, and presumably function of the gluten-specific cells, which are all required to identify novel therapeutic targets and strategies for CeD. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is an autoimmune disorder with both environmental and genetic risk factors. CD manifests itself when food containing gluten is eaten. It causes malabsorption by damaging the villi in the small intestine. This leads to the question: How do gene variants lead to the pathogenesis of Celiac disease? Other studies include genome-wide association studies to recognize more genetic risk factors associated with CD. This paper reviews how gene variants show a risk for CD and lead to the development of CD. It will show the significance of looking at how certain genes can change our body functions to alter a big part of our digestive system and how it can help us discover other genes possibly related to celiac disease. [ABSTRACT FROM AUTHOR]

Few data are available on flow cytometry (FC) for monitoring intraepithelial lymphocytes (IELs) in refractory celiac disease (RCD), non-responsive celiac disease (NRCD), and non-celiac enteropathies (NCEs). AIMS.1) To investigate the significance of monitoring IELs immunophenotype with FC in patients with NRCD, RCD and NCEs; 2) to evaluate FC concordance with immunohistochemistry (IHC) and γ-TCR clonality analysis. Patients investigated between January-2012 and February-2023 were divided into two groups: 1)confirmed RCD or NRCD being investigated for persistent symptoms and suspected complications of celiac disease (CD); 2)NCEs lacking clinical/histological response. Clinical/molecular features and outcomes were retrospectively collected and analysed according to presence/absence of aberrant IELs on FC (cut-off≥20 % CD103+sCD3-CD8-iCD3+ IELs). 52 patients (18 RCD,21 NRCD,13 NCEs; 38F, 55±13 years; median follow-up 30 months, IQR 2-58) underwent 100 FC IELs determinations. 22/52 had ≥2 FC determinations and IEL phenotype remained unchanged over time in all them (κ=1.00). Aberrant IEL phenotype in CD was associated with increased mortality (HR 4.2, 95 % CI 1.5–11.9, p < 0.01). No patients with NCEs had an aberrant IEL phenotype at FC, although 3/13 developed lymphoma and 4/13 died. Concordance of FC was fair with both IHC (κ=0.40) and γ-TCR clonality analysis (κ=0.22). FC is accurate for assessing and monitoring IEL phenotype and providing important prognostic information in celiac patients. Further study is needed on its role in NCEs. [ABSTRACT FROM AUTHOR]

Coeliac Disease (CD) and Sjogren’s Syndrome (SS), both autoimmune disorders, are gaining attention for their complex interaction when occurring together. CD involves gluten intolerance and can present with gastrointestinal symptoms, while SS affects various organs, primarily causing dryness of the eyes and mouth. Diagnosis for each relies on specific criteria including serologic testing and histopathology. When these conditions overlap, they create unique clinical challenges, highlighting the need for a thorough understanding of their combined effects on health. This exploration aimed to uncover the intricacies of their relationship, including clinical manifestations and implications for diagnosis and management when dealing with both simultaneously. In both cases (58-year-old female and 47-year-old female), there was gastrointestinal villous atrophy as a manifestation of CD, which improved with simple dietary modification.

Background and Aim: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. Methods: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold‐rise in anti‐tissue transglutaminase antibody (IgA anti‐tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. Results: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12–60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non‐gastrointestinal complaints and had a longer delay in the diagnosis of CeD. Conclusions: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings. [ABSTRACT FROM AUTHOR]

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Coeliac Disease (CD) and Sjogren's Syndrome (SS), both autoimmune disorders, are gaining attention for their complex interaction when occurring together. CD involves gluten intolerance and can present with gastrointestinal symptoms, while SS affects various organs, primarily causing dryness of the eyes and mouth. Diagnosis for each relies on specific criteria including serologic testing and histopathology. When these conditions overlap, they create unique clinical challenges, highlighting the need for a thorough understanding of their combined effects on health. This exploration aimed to uncover the intricacies of their relationship, including clinical manifestations and implications for diagnosis and management when dealing with both simultaneously. In both cases (58-year-old female and 47-year-old female), there was gastrointestinal villous atrophy as a manifestation of CD, which improved with simple dietary modification. [ABSTRACT FROM AUTHOR]

Background and Aim: Celiac disease (CeD) is mainly reported from the northern and western parts of India. In central India, it is believed to be a disease of children, with limited data among adults diagnosed for the first time after the age of 18 years. Hence, we aimed to describe CeD's clinical and demographic features among adults and children/adolescents in central India. Methods: This is a retrospective analysis of a prospectively maintained database of all patients diagnosed for CeD from 2010 to 2019. The disease in adults was confirmed when symptoms developed for the first time after 18 years and had positive anti‐transglutaminase antibodies with villous atrophy on duodenal biopsy. It was compared with pediatric patients with CeD diagnosed during the same time period. Results: Of the 170 patients diagnosed with CeD, 118 were adults and 52 were children or adolescents. The mean age of presentation of adult CeD was 37.3 ± 11.93 years, while in the pediatric and adolescent group it was 9.19 ± 5.4 years. Classical presentation with chronic, painless, small‐bowel‐type diarrhea was seen in 44.1% of adults compared to 57.7% in the pediatric age group. Among the adult patients, 55.9% presented with nonclassical symptoms, which included abdominal pain (40.7%) and weight loss (36.4%). The common presenting symptom in children other than diarrhea was weight loss (50%) and abdominal pain (34.6%). Conclusion: CeD is common in central India, with an increasing number of patients being diagnosed for the first time after 18 years of age and presenting more often with nonclassical symptoms. [ABSTRACT FROM AUTHOR]

Astrovirus infection is an enteric viral disease, which leads to economic losses in the poultry industry worldwide. This study aimed to detect Chicken Astrovirus (CAstV) infection in broiler chicks in Sulaymaniyah province. Tissue samples were collected from 100 chicks from Sulaymaniyah broiler farms between July 2021 and February 2022 and were separated into 3 groups according to their age; 1-week-old chicks, group B; (n=33), was 2 weeks old chicks, and group C; (n=34) for 3 weeks old chicks. The tissue samples (intestine, liver, and kidney) were analyzed by PCR and suspected samples were passed for the histological techniques and preparation of H&E stain. Samples in groups B and C had characteristic gross and histologic lesions, specifically, the histopathologic sections revealed atrophied hepatocytes, the presence of urate crystals in the kidneys and ureters, also villous atrophy with cryptitis and crypt abscess in the duodenum. RT-PCR for detection and amplification of the 362 bps-ORF-1b (partial) region of the virus genome revealed, that 5 of the 100 samples were positive for CAstV; group B (2 samples) and group C (3 samples), while group A was negative for CAstV. Isolated CAstV strain IQ/CAstv/suly/2022 with (ON093075) was closely related to four Iranian ones.

Drug-induced enteropathy is a common cause of non-coeliac villous atrophy. It should be considered in seronegative villous atrophy including those that are nonresponsive to a gluten-free diet. Olmesartan is associated with a severe form of spruelike enteropathy. Enteropathy associated with other sartans seems to be very rare. Mycophenolate mofetil is the most common cause of villous atrophy after solid-organ transplantation, with histologic lesions mimicking inflammatory bowel disease or graft versus host disease. Immune-checkpoints inhibitors are responsible for immune-mediated colitis mimicking inflammatory bowel disease, or microscopic colitis. Cases of villous atrophy, either related or unrelated to coeliac disease, have also been reported. [ABSTRACT FROM AUTHOR]

The differential diagnosis of non-coeliac enteropathies (NCEs) is challenging and includes a wide range of aetiologies. Drug-induced NCEs are relatively common and characterized by duodenal villous atrophy, which resolves upon suspension of the offending drug. Immune-checkpoint inhibitors (ICIs), targeting molecules involved in the activation of cytotoxic T cells by targeting, for example, PD-1, PD-L1 and CTLA4, are increasingly used for many types of cancers. Adverse events occurring in the gastrointestinal tract have been described, predominantly in the form of immune-mediated colitis mimicking inflammatory bowel disease. Small bowel involvement whilst on ICI therapy is also possible, though less well described. Herein, we describe two cases of enteropathy with villous atrophy and negative coeliac serology due to ICIs: a 65-year-old man affected by stage IV pulmonary adenocarcinoma under treatment with pembrolizumab and an 18-year-old woman affected by stage IV auricular melanoma who was treated with nivolumab. We also provide a review of the current literature describing small bowel involvement during therapy with ICIs, alone or in combination, for different types of solid tumours. Implications for clinical practice include considering the possibility of small bowel involvement in oncological patients treated with ICIs and the inclusion of ICIs amongst the iatrogenic causes of NCE with villous atrophy. Enteropathies due to ICIs may also represent a pathogenetic model for the understanding of the molecular mechanisms leading to villous atrophy in NCE.

Purpose: About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute. Methods: Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNA-sequencing, and RT-qPCR of genes of interest. Results: VA development was connected to the lack of intestinal (IgA+) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzyme+CD8+ T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type I/III and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA+) PCs. Chronic NV infection exacerbated this signature when compared to stage-matched NV-negative samples. Conclusions: Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination. [ABSTRACT FROM AUTHOR]

Introduction: Celiac disease (CD) is an autoimmune enteropathy characterized by atrophy of the intestinal mucosa triggered by the ingestion of gluten in individuals with a genetic predisposition. CD manifests with heterogeneous array of symptoms, including a wide range of intestinal and extraintestinal symptoms and manifestations (EIMs). The mechanisms involved in the pathogenesis of EIMs in CD are not only related to intestinal mucosal damage and associated malabsorption but also to systemic inflammation. To date, the only effective treatment for CD is a lifelong gluten-free diet (GFD). Proper adherence to the GFD leads in most cases to a gradual resolution of intestinal atrophy and results in an improvement of the clinical manifestations associated with intestinal damage., Areas Covered: This review, based on a Pubmed literature search, describes the extraintestinal complications associated with CD, emphasizing strategies for therapeutic management and responsiveness to the GFD., Expert Opinion: CD is associated with different EIMs which can affect different organs. The main clinical interest is if these complications respond to the GFD, which occur at variable rate and not for all disorders associated with CD. Therefore, often complementary additional therapies are needed to achieve optimal symptoms resolution.

Abstract Background Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. Case presentation We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved. Conclusions This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis.

Celiac crisis (CC) is a rare life-threatening course of celiac disease, observed mainly in children. In adults, CK can be the first manifestation of the disease and, very rarely, a relapse that occurs in patients who do not follow the gluten-free diet (AGD). Triggers can be stress, surgery, childbirth, etc. A clinical observation of CC developed in a 49-year-old patient with previously established latent celiac disease with subtotal villous atrophy, stage Marsh III C is presented. The patient did not comply with AHD. After severe angina, she developed anorexia, diarrhea, emaciation, coagulopathy, bilateral pulmonary embolism, infarction pneumonia, and enterogenic sepsis. As a result of intensive therapy with prednisolone, Fraxiparine, antibiotics, fresh frozen plasma and strict adherence to hypertension, remission of the disease was achieved.

Celiac disease is a chronic autoimmune enteropathy affecting about 1% of the population. Gluten ingestion triggers an immune response in genetically susceptible patients, resulting in intestinal and extraintestinal disease manifestations. Current recommendations for diagnosis include serology for celiac-specific antibodies to transglutaminase, endomysium, and deamidated gliadin, and IgA serology. New highly accurate point-of-care tests can efficiently screen for celiac disease and improve the diagnostic timeframe. Definitive diagnosis is most commonly made via biopsy of the small bowel showing villous atrophy. A gluten-free diet with micronutrient supplementation is the only recommended treatment for celiac disease. Primary care providers must be able to recognize screening indications, refer patients appropriately, and provide proper patient education and follow-up. [ABSTRACT FROM AUTHOR]

Collagenous sprue (CS) is a rare autoimmune gastrointestinal disorder characterized by specific histologic changes in the small intestine. It often presents with more severe symptoms and a worse prognosis compared to celiac disease, including significant malabsorption, weight loss, and nutrient deficiencies. Despite treatment with a gluten-free diet, symptom improvement is limited, with only a small fraction of patients responding positively. This case report highlights the diagnostic challenges and clinical features of CS in a 74-year-old woman, whose symptoms resolved following cessation of olmesartan. The case emphasizes the importance of recognizing medication-induced forms of the disease and outlines the need for targeted management strategies to improve patient outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Goshgarian et al.)

From April 2014 to September 2015, 153 piglets from 52 farms in Jeju were diagnosed with porcine epidemic diarrhea (PED). The major PED cases were focused on suckling piglets (144 piglets, 94.1%), particularly in 1-7-day-old piglets. Histopathologically, severe villous atrophy was observed in the small intestine, especially in the jejunum and ileum. The mean villous height to crypt depth ratios of the jejunum and ileum were 1.4:1 and 1.5:1, respectively. The major histopathologic findings of the small intestine were cytoplasmic vacuolation, cuboidalization, squamation, and exfoliation of the mucosal enterocytes in the villi. The cytoplasmic vacuolations in the enterocytes were the most prevalent lesions in the small intestine and were more severe in the ileum than in the jejunum. According to immunohistochemistry methods, the PED virus (PEDV) antigens were presented in the cytoplasms of the enterocytes, and were distributed more prevalently in the ileum than in the jejunum. PEDV antigens were also detected in the colon of 26 piglets (19.5%). Sequence comparison and phylogenetic analysis indicated that 12 PEDV had more than a 98.9% homology with each other. These PEDV strains were highly homologous with the genogroup 2 North American group. [ABSTRACT FROM AUTHOR]

Sprue-like enteropathy associated with olmesartan is characterized by villous atrophy in the duodenum. We report the case of an 81-year-old woman diagnosed with olmesartan-associated sprue-like enteropathy with no villous atrophy in the duodenum. The patient had been taking olmesartan for 10 years and complained of diarrhea and weight loss. Despite undergoing general treatment for 2 months, her symptoms showed no improvement. Gastrointestinal endoscopy and pathological findings showed no villous atrophy in the duodenum. However, villous atrophy was observed in the small intestine by capsule endoscopy. Pathological biopsy with double balloon endoscopy provided a definitive diagnosis. Diarrhea improved with the discontinuation of olmesartan and weight increased within a week of withdrawal. After the improvement of clinical symptoms, both endoscopic and pathological findings of villous atrophy in small intestine showed improvement. [ABSTRACT FROM AUTHOR]

Background and Objective: Pediatric guidelines on celiac disease (CD) state that children with anti-transglutaminase antibodies (TGAs) >×10 upper limit of normal (ULN) may avoid endoscopy and biopsy. We aimed to evaluate whether these criteria may be suitable for villous atrophy diagnosis in CD adults. Materials and Methods: We retrospectively enrolled patients with CD aged >18 years. TGAs were expressed as xULN. Duodenal lesions were classified as atrophic or nonatrophic according to Marsh-Oberhuber. Fisher’s exact and t-test were used for variables comparison. Receiver operating characteristics (ROC) curve analysis was performed with estimation of area under the curve (AUC), sensitivity, specificity, and positive and negative predictive value (PPV/NPV). Results: One hundred and twenty-one patients were recruited. Sixty patients (49.6%) had TGA >×10 ULN, and 93 (76.8%) had villous atrophy. The cut-off of >×10 ULN had sensitivity = 53.7%, specificity = 64.3%, PPV = 83.3%, and NPV = 29.5% to predict atrophy. Therefore, considering pediatric criteria, in 50 (41.3%) patients, biopsy could have been avoided. Patient subgroup with atrophy had higher TGA levels despite being not significant (37.2 ± 15.3 vs. 8.0 ± 1.3 ULN, p = 0.06). In adults, a slightly better diagnostic performance was obtained using a cut-off of TGA >×6.2 ULN (sensitivity = 57.1%, specificity = 65.6%, and AUC = 0.62). Conclusions: Despite our confirmation that villous atrophy is linked to high TGA levels, CD and atrophy diagnosis based only on serology is not reliable in adults. [ABSTRACT FROM AUTHOR]

Clinical elements differentiating enteropathy due to angiotensin II-receptor-blockers (ARBs-E) from coeliac disease (CD) are poorly defined. The histopathological features on duodenal and gastric biopsies in these patients still need to be investigated. To describe the clinical phenotype of ARBs-E in comparison to CD, and the histological findings of gastric and duodenal biopsies in ARBs-E. Clinical data of patients with ARBs-E and CD diagnosed between 2013 and 2020 were retrospectively reviewed. Baseline presenting symptoms and demographics were compared (Fisher's exact test and t -test). Gastric and duodenal histology in ARBs-E were revised by two independent pathologists. 14 ARBs-E and 112 CD patients were enroled. Weight loss (p < 0.01), acute onset of diarrhoea (p < 0.01), hospitalization (p < 0.01), and older age at diagnosis (p < 0.01) were more common in ARBs-E. Duodenal histology in ARBs-E showed intraepithelial lymphocytosis in 71%, increased mucosal eosinophilic count in 57%, with preserved neuroendocrine, Paneth and goblet cells in all patients. Gastric histologic lesions at baseline, including lymphocytic gastritis, eosinophilic gastritis, chronic active gastritis, and metaplastic atrophic gastritis patterns were observed in 73% of patients, without Helicobacter pylori infection. ARBs-E showed a severe clinical phenotype, often requiring hospital admission. Gastric involvement at diagnosis is very common, and this could further support this diagnosis. [ABSTRACT FROM AUTHOR]

Background: Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up.Case Presentation: We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved.Conclusions: This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis. [ABSTRACT FROM AUTHOR]

Chronic diarrhea, villous atrophy and/or increased intraepithelial T-lymphocytes (IEL) occur in many inflammatory disorders including celiac disease (CD). However, a definite diagnosis is difficult to make in some patients despite an extensive diagnostic work-up. Clinical outcomes and histological phenotypes of such patients we refer to as unclassifiable enteropathy (UEP) remain unclear. We performed a retrospective single-center analysis of patients with chronic diarrhea, weight loss and increased IEL. Patients with defined etiologies including infections, CD, drugs, immunodeficiencies or neoplasms were excluded. Clinical and histologic/immunophenotypic parameters were analyzed. Nine patients with UEP were identified. Small intestinal damage ranged from minor villous abnormalities to complete atrophy while all patients displayed high numbers of CD103+ CD8+ IELs. In contrast to CD, these CD8+ T cells were not confined to the surface epithelium, but also infiltrated the crypts. Additional histological features included apoptotic crypt epithelial cells and mixed inflammatory infiltrates in the tunica propria. Involvement of other segments of the gastrointestinal tract was observed in 7/9 patients. A clonal intestinal T-cell lymphoproliferative disorder developed in 2 patients, one of which had a fatal disease course. The majority of patients responded to corticosteroids, while response to immunosuppressive medications yielded heterogeneous results. We report a patient population with 'difficult-to-classify' enteropathies characterized by various degrees of villous atrophy and strongly increased intraepithelial CD103+ CD8+ T cells in the small intestine which harbor an increased risk for T-cell lymphoproliferative disorders. Clinical course, histology, and response to immunosuppressive therapy all suggest an autoimmune pathogenesis. [ABSTRACT FROM AUTHOR]

Background and Aim Systemic sclerosis (SSc) is known to involve the gastrointestinal (GI) tract, resulting in dysmotility, gastroesophageal reflux disease, and mucosal changes causing significant morbidity. The study aimed to assess esophageal motility and duodenal mucosal changes in SSc. Methods This is a prospective, cross‐sectional, single‐center study of 23 patients with SSc diagnosed on the basis of standard criteria. Clinical details including the GI symptoms were recorded. All of them underwent esophagogastroduodenoscopy with duodenal biopsy, and 21 underwent esophageal manometry. Results Regurgitation, heartburn, and dysphagia were seen in 19 (82%), 16 (69%), and 10 (43%) patients, respectively. On endoscopy, 19 patients (83%) showed changes of reflux esophagitis (4 had grade C esophagitis), and 3 had esophageal candidiasis. Of the 21 patients who underwent esophageal manometry, 13 (62%) had absent peristalsis, 6 (28%) had ineffective peristalsis, and 10 (48%) had hypotensive lower esophageal sphincter (LES). Duodenal biopsy showed partial villous atrophy in 9 (39%) patients, increased intraepithelial lymphocytes in 18 (78%), and excess of mononuclear inflammatory cells in lamina propria in 21 (91%). Partial villous atrophy was seen more commonly in those with abnormal esophageal peristalsis and a hypotensive LES. Conclusion Most of the patients with SSc had esophageal dysmotility in the form of absent peristalsis, ineffective esophageal peristalsis, and hypotensive LES. Histology of descending duodenum demonstrated partial villous atrophy and chronic inflammatory infiltrates in most of the patients with SSc.

Several environmental, genetic, and immune factors create a “perfect storm” for the development of coeliac disease: the antigen gluten, the strong association of coeliac disease with HLA, the deamidation of gluten peptides by the enzyme transglutaminase 2 (TG2) generating peptides that bind strongly to the predisposing HLA-DQ2 or HLA-DQ8 molecules, and the ensuing unrestrained T cell response. T cell immunity is at the center of the disease contributing to the inflammatory process through the loss of tolerance to gluten and the differentiation of HLA-DQ2 or HLA-DQ8-restricted anti-gluten inflammatory CD4+ T cells secreting pro-inflammatory cytokines and to the killing of intestinal epithelial cells by cytotoxic intraepithelial CD8+ lymphocytes. However, recent studies emphasize that the individual contribution of each of these cell subsets is not sufficient and that interactions between these different populations of T cells and the simultaneous activation of innate and adaptive immune pathways in distinct gut compartments are required to promote disease immunopathology. In this review, we will discuss how tissue destruction in the context of coeliac disease results from the complex interactions between gluten, HLA molecules, TG2, and multiple innate and adaptive immune components.

Coeliac disease, an autoimmune disease, is caused by ingestion of gluten in genetically susceptible individuals. The currently used modified-Marsh grading, used to assess mucosal injury, is fraught with interobserver and intraobserver variability. The aim is to reduce this variability by villous length morphometry. Our prospective study was conducted on newly diagnosed cases of coeliac disease that were assessed by serohaematological profile, and duodenal biopsies were evaluated by modified Marsh grading. Villous length was measured in Grades 2, 3a and 3b using an eyepiece graticule lens calibrated with a stage micrometer. Severity of mucosal injury in different Marsh grades was significantly correlated to mean villous length, elevation of mean IgA tTG and drop in haemoglobin. [ABSTRACT FROM AUTHOR]

Several environmental, genetic, and immune factors create a "perfect storm" for the development of coeliac disease: the antigen gluten, the strong association of coeliac disease with HLA, the deamidation of gluten peptides by the enzyme transglutaminase 2 (TG2) generating peptides that bind strongly to the predisposing HLA-DQ2 or HLA-DQ8 molecules, and the ensuing unrestrained T cell response. T cell immunity is at the center of the disease contributing to the inflammatory process through the loss of tolerance to gluten and the differentiation of HLA-DQ2 or HLA-DQ8-restricted anti-gluten inflammatory CD4+ T cells secreting pro-inflammatory cytokines and to the killing of intestinal epithelial cells by cytotoxic intraepithelial CD8+ lymphocytes. However, recent studies emphasize that the individual contribution of each of these cell subsets is not sufficient and that interactions between these different populations of T cells and the simultaneous activation of innate and adaptive immune pathways in distinct gut compartments are required to promote disease immunopathology. In this review, we will discuss how tissue destruction in the context of coeliac disease results from the complex interactions between gluten, HLA molecules, TG2, and multiple innate and adaptive immune components. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment.

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis (DH) is an autoimmune skin disease that causes itchy, blistering rash, typically on the elbows, knees and buttocks. DH and coeliac disease share the same genetic background, gluten-dependent enteropathy and antibody response against tissue transglutaminase. DH is currently considered a cutaneous manifestation of coeliac disease, and the prevailing hypothesis is that DH develops as a late manifestation of subclinical coeliac disease. The incidence of DH is decreasing contemporarily with the increasing incidence of coeliac disease. The IgA immune response in DH skin is directed against epidermal transglutaminase, while the autoantigen in the gut is tissue transglutaminase. Granular IgA deposition in the papillary dermis is pathognomonic for DH, and is a finding used to confirm the diagnosis. The treatment of choice for DH is a life-long gluten-free diet, which resolves the rash and enteropathy, increases quality of life, and offers a good long-term prognosis.

Abstract Background The diagnosis of Coeliac disease (CD) requires a combination of sign/symptoms, positivity of specific antibodies and duodenal histological evidence of villous atrophy. Duodenal villous atrophy, despite representing the CD landmark, is not specific since it is found in many gastrointestinal disorders. Giardiasis is one of the most common human intestinal protozoan infestations in industrialized countries whose histological duodenal mucosa damage could mimic that of CD. The present report shows how a wise clinical and laboratory assessment led us shortly to a correct diagnosis. Case presentation A 42-year-old outpatient woman without previous significant gastrointestinal diseases, was referred with dyspeptic symptoms, fatigue and mild diarrhea from 4 months. Her first investigations including immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (anti-tTG) and stool parasitological and cultural analysis were negative. An esophagogastroduodenoscopy (EGDS) showed no mucosal alteration. But histology demonstrated a Helicobacter Pylori (HP) pan-gastritis while duodenal mucosa showed villous atrophy consistent with a diagnosis of CD Marsh type 3b. While on gluten-free diet (GFD) the patient didn’t experience any improvement of symptoms. Duodenal biopsies were then reviewed showing the presence of trophozoites of Giardia on the luminal surface of the duodenal wall and at the same time, a second stool examination revealed the presence of trophozoites and cysts of Giardia. Treated with metronidazole, 500 mg twice daily for 6 days the patient reduced diarrhea after few days. After about 2 months of GFD she was invited to discontinue it. At the same time stool examination was repeated with negative results. She subsequently performed eradication for Hp with triple therapy (Pylera®). Around 6 months later, the patient did not complain any gastrointestinal symptoms. Serological tests were normal and at a follow-up EGDS, duodenal mucosa had normal histology with normal finger-like villi and absence of Giardia trophozoites. Conclusion This case report shows how CD diagnosis can sometimes be manifold. Intestinal villous atrophy alone may not automatically establish a diagnosis of CD. In the present case the clinical scenario could be fully explained by giardiasis. Indeed, different diagnostic tools and a multi-step approaches have been used to determine the final correct diagnosis.

Most absorption of nutrients takes place in the proximal small intestine, and the most common disorders leading to malabsorption are associated with a morphological abnormality in the duodenal mucosa that is appreciable in histological sections of biopsy specimens. Coeliac disease is the most well‐known example, causing intraepithelial lymphocytosis, inflammation and villous atrophy in the duodenum. Remarkably similar inflammatory changes can be induced by other processes, including medications, e.g. angiotensin II receptor blockers and immune checkpoint inhibitors, immune dysregulation disorders, e.g. common variable immunodeficiency and autoimmune enteropathy, infections, collagenous sprue, and tropical sprue. However, there are often subtle histological differences from coeliac disease in the type of inflammatory infiltrate, the presence of crypt apoptosis, and the extent and type of inflammation beyond the duodenum. The clinical setting and serological investigation usually allow diagnostic separation, but some cases remain challenging. Histopathology is also important in assessing the response to treatment, such as the change in villous architecture caused by a gluten‐free diet, or the response to cessation of a potentially causative medication. This review examines the practical role that histopathology of duodenal biopsy specimens plays in the assessment and management of inflammatory malabsorptive processes of the proximal small intestine, with a particular emphasis on coeliac disease. [ABSTRACT FROM AUTHOR]

Background: Celiac disease is characterized by small intestinal malabsorption of nutrients after the ingestion of wheat gluten or related proteins from rye and barley, villus atrophy of the small intestinal mucosa, prompt clinical and histologic improvement following strict adherence to a gluten-free diet, and relapse when gluten is retaken. Aim of the Study: Evaluation of patients seeking gastroenterology and hepatology teaching hospital/medical city/Baghdad with suspected celiac disease regarding serological investigation, histological findings and genetic testing, to determine sensitivity, specificity, positive predictive value and negative predictive value for every test. Patients and Method: The study is a cross sectional descriptive analytic study conducted at the teaching hospital of gastroenterology and hepatology/Baghdad/Iraq during a period from the 1st of February 2018 to the 1st of April 2019. After thorough history and Clinical examination patients with suspected celiac disease were sent for serological investigation (TTG IgA and IgG), (antigliadin IgA and IgG), all patients were sent for endoscopic examination for duodenal biopsies with subsequent histological assessment. Patients who failed to be confirmed (positive serology and negative histology or vice versa) were sent either for HLA genotyping or for IgG Deaminated gliadin peptide. Sensitivity & specificity were measured for each test. Results: A total of 140 suspected celiac disease patients involved in this study. Mean age was 18.9 years and ranged from 2 years to 60 years. Male represented 36.4% of the cases while female represented 63.6%. Only 19 patients show positive family history of celiac disease (13.6%). Regarding associated autoimmune diseases, the majority (111 patients) have no associated diseases (79.3%) while the other patients who have associations most of them show positive association with type 1 DM (16.4%). Fifty patients (35.7%) presented with short stature, (25.7%) came with diarrhea. The other symptoms vary between bloating and distention, unexplained anemia and weight loss. Constipation was seen in one patient. tTG IgA and tTG IgG showed high sensitivity, specificity, positive predictive value and negative predictive value while antigliadin antibody failed to show these significant results. Conclusion: The use of serologic markers in celiac is easy, direct, noninvasive and reliable and could be benefit in the diagnosis and monitoring of the disease. More specifically, both the tTG-IgA/IgG are very good markers in the diagnosis of CD. This study confirmed the high specificity and sensitivity of tTG, and the low results of AGA, but celiac serology does not replace the biopsy in the diagnosis but is useful as an assistant for diagnosis. [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) is a widespread autoimmune enteropathy caused by dietary gluten peptides in genetically susceptible individuals, which includes a range of intestinal and extraintestinal manifestations. Currently, there is no effective treatment for CeD other than strict adherence to a gluten-free diet (GFD). However, persistent or frequent symptoms and also partial villus atrophy were observed in some patients with CeD due to intentional or inadvertent gluten exposure during the use of GFD. It means that GFD alone is not enough to control CeD symptoms and long-term complications. Accordingly, new therapeutic approaches for CeD treatment such as gluten proteolysis, removing gluten from the digestive tract, promoting tight junction assembly, inhibiting intestinal tissue transglutaminase 2, using probiotics, and developing immunotherapeutic methods have been proposed through different strategies. This review focused on discussing the novel therapeutic strategies for CeD management. [ABSTRACT FROM AUTHOR]

Background: Narrow band imaging (NBI) with magnification better visualizes the duodenal microsurface and mucosal vascularity. NBI delineates villous atrophy better than conventional white light endoscopy. Aims: This study was conducted to evaluate the diagnostic accuracy of narrow band imaging with magnification (NBI-ME) in celiac disease (CD). Methods: In this prospective study, consecutive patients of suspected CD and controls were subjected to tissue transglutaminase antibody test and endoscopic evaluation initially with white light followed by NBI-ME, and biopsies were taken from duodenum. Duodenal villous patterns on NBI were interpreted as normal, blunted distorted, and absent. Severity of villous atrophy was reported according to the modified Marsh criteria. Results: One hundred and twenty-two patients (mean age of 27.53 ± 13.37 years and a male to female ratio of 1:1.26) and 40 controls were studied. The sensitivity and specificity of NBI-ME in predicting villous atrophy were found to be 95.54% and 90%, respectively. The specificity and negative predictive value of NBI-ME in predicting villous atrophy amongst controls was 100% and 97.5%, respectively. Abnormal findings (blunted and absent villous patterns) combined with elevated transglutaminase antibody (> 5-fold) were found to have high accuracy in predicting villous atrophy. Conclusion: NBI with magnification has high sensitivity and specificity in predicting villous atrophy in patients with celiac disease. [ABSTRACT FROM AUTHOR]

Aim:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease.Methods:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated.Results:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum.Conclusion:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD. [ABSTRACT FROM AUTHOR]

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Intestinal graft-vs.-host disease (GVHD) is a serious complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter- and intra-observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter- and intra-observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo-HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo-HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non-pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter-observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra-observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390). [ABSTRACT FROM AUTHOR]