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Background and Aims There are no agreed-on endoscopic signs for the diagnosis of villous atrophy (VA) in celiac disease (CD), necessitating biopsy sampling for diagnosis. Here we evaluated the role of near-focus narrow-band imaging (NF-NBI) for the assessment of villous architecture in suspected CD with the development and further validation of a novel NF-NBI classification. Methods Patients with a clinical indication for duodenal biopsy sampling were prospectively recruited. Six paired NF white-light endoscopy (NF-WLE) and NF-NBI images with matched duodenal biopsy sampling including the bulb were obtained from each patient. Histopathology grading used the Marsh-Oberhuber classification. A modified Delphi process was performed on 498 images and video recordings by 3 endoscopists to define NF-NBI classifiers, resulting in a 3-descriptor classification: villous shape, vascularity, and crypt phenotype. Thirteen blinded endoscopists (5 expert, 8 nonexpert) then undertook a short training module on the proposed classification and evaluated paired NF-WLE–NF-NBI images. Results One hundred consecutive patients were enrolled (97 completed the study; 66 women; mean age, 51.2 ± 17.3 years). Thirteen endoscopists evaluated 50 paired NF-WLE and NF-NBI images each (24 biopsy-proven VAs). Interobserver agreement among all validators for the diagnosis of villous morphology using the NF-NBI classification was substantial (κ = .71) and moderate (κ = .46) with NF-WLE. Substantial agreement was observed between all 3 NF-NBI classification descriptors and histology (weighted κ = 0.72-.75) compared with NF-WLE to histology (κ = .34). A higher degree of confidence using NF-NBI was observed when assessing the duodenal bulb. Conclusions We developed and validated a novel NF-NBI classification to reliably diagnose VA in suspected CD. There was utility for expert and nonexpert endoscopists alike, using readily available equipment and requiring minimal training. (Clinical trial registration number: NCT04349904.)

The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.

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.

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.

INTRODUCTION Capsule endoscopy has proven its utility in diagnosing villous atrophy and lymphoma in patients with celiac disease. Recently, a novel capsule endoscopy system was introduced which enables the examination of the small and large bowel. So far, it has not been evaluated in patients with celiac disease. OBJECTIVE The primary objective of this study was to evaluate the novel panintestinal capsule endoscopy system in patients with celiac disease. METHODS Eleven patients with histologically proven celiac disease (Marsh 0-IV), who underwent a panintestinal capsule endoscopy between March 2018 and April 2019 at our institution, were included in this retrospective single-center study. All patients performed standard bowel preparation prior to the examination. Diagnostic yield, safety and therapeutic impact were analyzed. In addition, the correlation between capsule endoscopy findings and the histology of the duodenal mucosa was assessed. RESULTS Panintestinal capsule endoscopy was feasible and produced an acceptable visualization quality in all cases. Concordance of capsule endoscopy findings with the Marsh classification showed a good correlation (r = 0.8). No lymphomas were detected. Evaluation of the colon revealed diminutive polyps (median size 4 mm) in 18% of patients. CONCLUSIONS The novel panintestinal capsule endoscopy system shows a fair correlation with the Marsh classification in patients with celiac disease. It is also capable of identifying colon polyps. Therefore, the novel panintestinal capsule endoscopy system can be considered for patients with celiac disease and an indication for capsule endoscopy.

OBJECTIVES 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. MATERIAL AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Objective: To find out the underlying causes of chronic diarrhea in soldiers and how it differs from general population. Study Design: Prospective comparative study. Place and Duration of Study: Combined Military Hospital (CMH) Multan and Pak Emeritus Military Hospital (PEMH) Rawalpindi, from Dec 2017 to Jan 2020. Methodology: All soldiers in active service, having diarrhea more than 4 weeks in study and non-soldiers of the same age were included in the control group. There were inquired in details about the diarrhea symptoms and investigations carried out accordingly to find out the underlying cause. The two groups were compared to find out any differences. The data were analyzed by SPSS version 22. Results: Seventy one in study and 50 patients in control had their mean ages of 34.61 ± 8.35 and 32.42 ± 10.28 years. Mean duration of symptoms were 18 and 15 months in study and control groups respectively. Irritable Bowel Syndrome (IBS) was more common in both groups i.e. 14 (20%) and 20 (40%) in study and control groups respectively but frequency was more in second one. Seropositive celiac disease 13 (18.5%), seronegative villous atrophy 10 (14%) in study and Inflammatory Bowel Disease IBD 6 (12%) in control group were second most common conditions. Conclusions: Irritable bowel syndrome is common in this age group. Celiac and seronegative villous atrophy is second common conditions in the study group.

OBJECTIVES We aimed to establish if in celiac disease (CD) with immunoglobulin A deficiency (IgAD) duodenal histopathology is influenced by human leukocyte antigen (HLA)-DQB1∗02 alleles dosage. Clinical differences between patients with CD and patients with CD and IgAD (CD-IgAD) were also evaluated. METHODS Five hundred and sixteen CD and 16 patients with CD-IgAD, enrolled over the time of 8 years, took part in this study. The severity of duodenal histopathology and frequency of CD at-risk HLA class II genes were compared in patients with CD versus patients with CD-IgAD. HLA class II genotypes were subdivided into two categories of genetic risk: high: HLA-DR3/DR7, -DR3/DR3, -DR4/DR4 -DR3/DR4 and low: HLA-DR5/DR7, -DR3/X, -DR4/X and X/X, where X means neither -DR3 nor -DR4. Then, they were compared with two types of duodenal histopathology: 0, 1, 2 and 3a of mild villous atrophy (MVA) and 3b and 3c of severe villous atrophy (SVA) according to the Marsh-Oberhuber classification. Clinical data concerning gender, number of esophagogastroduodenoscopies (EGDs) and association with other autoimmune diseases were obtained from medical records. RESULTS In comparison with CD, CD-IgAD showed an increased frequency of MVA (P

Celiac disease, a permanent, irreversible but treatable disease is an autoimmune disease triggered by gluten ingestion in genetically predisposed individuals, also known as celiac sprue and gluten sensitive enteropathy. Recent findingsIntestinal inflammation and villous atrophy in small intestines by permanent intolerance to gluten in celiac disesea leads to seveare malabsorption. About 20%-38% patients were basically nutritionally imbalance secondary malabsorption due to mucosal damage. Nutrition plays a very important role in the management of celiac disease. Gluten free diet must be balanced to cover nutrient requirements to prevent deficiencies and ensure children’s health, growth and development.Conclusion Gluten-free diet is the only accepted and available treatment in CD. It was a life-long treatment, if not carried out with attention, it may lead to nutritional imbalance which can affect children’s growth and development

Introduction A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. Methods Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. Results Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 μg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). Discussion The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

Introduction: Malabsorption occurs due to different causes and the clinical presentation varies with the underling etiology. Very few studies have been done to determine the etiological spectrum of malabsorption in northern India. Aim: To assess the etiology in patients presenting with malabsorption and to study clinical, haematological, biochemical, serological, endoscopic and histological features of these patients. Materials and Methods: Clinical assessment of 91 cases presenting with malabsorption complains in the gastro OPD was done along with vitamin B12 and fecal fat estimation. Relevant haematological, serological investigations, endoscopy was done. Duodenal biopsy was taken. Data was obtained and analysed. All patients clinically presenting with malabsorption were included in the study. The patients excluded were those, who refused for endoscopy or participation in the study. Results: The most common causes of malabsorption were non-specific duodenitis(42.8%), celiac disease (CD)(18.7%), tropical sprue (TS) (8.8%), giardiasis(3.3%), eosinophilic enteritis (2.2%), lymphangiectasia(1.1%), abetalipoproteinemia(1.1%) and 22% cases were normal histologically. The principal features differentiating celiac disease and tropical sprue were also noted. Patients with CD more often had anemia, scalloping of folds on endoscopy, moderate or severe villous atrophy and increased intraepithelial lymphocytes, in comparison to patients with TS. Conclusion: CD is commoner than TS. Though histology is gold standard for the diagnosis of CD, TS and other intestinal mucosal diseases, correlation of histological findings with clinical, hematological, endoscopic and serological findings is important as subtle histological changes may be missed depriving the patient of proper treatment. Keywords: Celiac disease, Diarrhea, Malabsorption, Tropical sprue, Villous atrophy, IELs.

Background and Aim: Autoimmune atrophic gastritis (AAG) is characterized by a variable spectrum of gastric and extra-gastric symptoms and has been associated with other autoimmune diseases. It is still unknown whether AAG patients have a higher risk of coeliac disease (CeD) or of any other particular duodenal histological damage. Our study aimed at evaluating the duodenal histological findings and the risk of CeD in patients with AAG, with and without other concurrent autoimmune diseases. Methods: We retrospectively collected all the histological findings of the adult patients undergoing upper gastrointestinal endoscopy with concurrent duodenal and gastric biopsies at our gastroenterology unit between 2015 and 2018 and who were regularly followed up at our centre. Date of endoscopy evaluation, endoscopy indication, data on previous CeD diagnosis and on other autoimmune-associated diseases, and a description of histological diagnosis were recorded. Results: Of the 2,423 evaluated endoscopies, 209 patients had an AAG diagnosis (8.6%). One hundred thirty-nine patients, aged 57.4 (standard deviation 13.2) years, were regularly followed up at our centre and were included. Of them, 4 subjects had a previous diagnosis of CeD and one had CeD diagnosis at index endoscopy. Additionally, 8 patients had an isolated increase of intraepithelial lymphocytes (IELs, 6%) and 2 villous atrophy with a normal IEL count. The risk of CeD in AAG was not modulated by the presence of other concurrent autoimmune diseases. Conclusions: We support the screening of all AAG patients with CeD autoantibodies. Findings of isolated IEL or villous atrophy are not exclusively related to CeD.

BACKGROUND AND AIM There is a lack of uniformity of reporting on features of celiac disease (CD) on small bowel capsule endoscopy (SBCE). This makes determining extent of disease and comparison of severity of disease challenging. METHODS De-identified SBCEs of 300 patients (78 CD [26%], 18 serology negative villous atrophy [6%], and 204 controls with normal duodenal histology [68%]) were included. Videos were reviewed by two experts. All patients had duodenal histology taken within 2 weeks of SBCE. The degree of agreement in CD features and extent of disease was then determined. The resulting score for each factor was used to determine overall severity of disease. RESULTS There was substantial agreement in the kappa coefficient for the detection of CD features between reviewers (0.67). Agreement for extent of affected small bowel (SB) mucosa was high (0.97). On multiple regression analysis, several features of CD correlated with extent of affected SB mucosa for both reviewers. The odds ratios derived from this analysis were then used to score features of CD, enabling scores of severity to be calculated for each patient. The median overall scores for patients increased significantly according to the independent classification of severity by the capsule reviewers: mild (20, 0-79), moderate (45, 25-123), and severe (89, 65-130) (P = 0.0001). CONCLUSION The good correlation of CD scores between expert reviewers confirms the validity of features of CD on SBCE. An objective score of CD features in the SB is useful in the follow up of patients with CD and serology negative villous atrophy.

BACKGROUND Celiac disease (CD) is a systemic, chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals, with a prevalence of 1% worldwide. Sjogren's syndrome (SS) is also a systemic autoimmune disease, mainly characterized by ocular and oral sicca symptoms and signs. Sharing a common genetic background, CD and SS are known associated autoimmune diseases, but currently available guidelines are not reporting it. CASE SUMMARY We report the case of a 39-year-old woman, who was in the care of her rheumatologist for 2 years with SS. On routine follow-up she was found to have iron deficiency, without anemia. She had no gastrointestinal complaints and denied any obvious source of blood loss. IgA tissue transglutaminase antibodies were positive and endoscopy with duodenal biopsies revealed crypt hyperplasia and villous atrophy. A diagnosis of CD was set and gluten-free diet was recommended. CONCLUSION We present a review of existing data in the literature regarding the association of the two diseases, summarizing prevalence studies of CD in SS patients and the other way around. Screening recommendations and future research perspectives are also discussed, highlighting clinically relevant unanswered questions with respect to the association of CD with SS. publishedVersion

Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse effect suspected to be related to its use. The author presents a case of a 63-year-old female with refractory gastrointestinal (GI) symptoms including diarrhea with associated weight loss and severe electrolyte abnormalities necessitating hospitalization. An extensive inpatient evaluation ensued and was initially unremarkable. Esophagogastroduodenoscopy (EGD) discovered an endoscopically normal duodenum that was biopsied and notably revealed villous atrophy and intraepithelial lymphocytosis. Colonoscopy was normal appearing though biopsy findings were significant for nonspecific colitis. The endoscopy findings in the setting of the clinical presentation confirmed the diagnosis of olmesartan-associated enteropathy (OAE). Clinical improvement was noted after cessation of olmesartan and histological resolution was confirmed with repeat EGD post-discharge.

BACKGROUND Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking. AIM To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology. METHODS Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction. RESULTS Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values. CONCLUSION The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Non-responsive celiac disease (NRCD) has many aetiologies, including gluten exposure. Budesonide may be used for refractory celiac disease (RCD) and celiac crisis. We reviewed the effectiveness of budesonide to induce clinical and histologic response in NRCD with villous atrophy (VA). Case series of adult cases with NRCD and VA prescribed budesonide at two celiac centers. Clinical variables and mucosal recovery (i.e., normal villous architecture within 1 year of treatment) were evaluated. Forty-two cases [77% female, median age 45.0 (IQR 28.3–60.0) years] were included. Most common symptoms were diarrhea (64%) and abdominal pain (62%). Budesonide was initiated at 9 mg (83%) for a median duration of 16.0 weeks (IQR 6.8–25.0 weeks). In total, 57% exhibited a clinical response, positively associated with diarrhea (adjusted OR 6.08 95% CI 1.04–35.47) and negatively with fatigue (adjusted OR 0.18 95% CI 0.03–0.98). Clinical response was higher among those with dietitian counseling prior to budesonide (n = 29, 70 vs. 23%, p

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

Aim. The aim of the study was to determine the usefulness of HLA DQ2/DQ8 genotyping in children with T1D in various clinical situations: as a screening test at the diabetes onset, as a verification of the diagnosis in doubtful situations, and as a test estimating the risk of CD in the future. Materials and methods. Three groups of patients with T1D were included: newly diagnosed (n=92), with CD and villous atrophy (n=30), and with potential CD (n=23). Genetic tests were performed (commercial test, PCR, and REX), and clinical data were collected. Results. The results of genetic tests confirmed the presence of DQ2/DQ8 in 94% of children with diabetes (group I) and in 100% of children with diabetes and CD (groups II and III, respectively). Comparative analysis of the HLA DQ2/DQ8 distribution did not show any differences. Allele DRB1∗04 (linked with HLA DQ8) was significantly less common in children with diabetes and CD (group I versus groups II and III, 56.5% vs. 24.5%; p=0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p=0.001). DRB1∗04 was significantly less frequent in children with villous atrophy compared to potential CD (13% vs. 39%; p=0.03). Conclusions. Genotyping HLA DQ2/DQ8 as a negative screening has limited use in assessing the risk of CD at the diabetes onset and does not allow to verify the diagnosis of CD in doubtful situations. The presence of the DRB1∗04 allele modulates the risk of CD and significantly reduces it and can predict a potential form.

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).

Background The causes of seronegative villous atrophy can be grouped as coeliac or noncoeliac related. There is no consensus on how to approach subjects with seronegative coeliac disease. Aim To evaluate the accuracy of both an increase in CD3+ T-cell receptor gamma delta+ (TCRγδ+ ) intraepithelial lymphocytes and coeliac lymphogram for the diagnosis of coeliac disease in patients with seronegative villous atrophy. Methods Sixty-seven consecutive patients with seronegative villous atrophy were included. Duodenal biopsies to assess TCRγδ+ and CD3- by flow cytometry were performed at the index endoscopy. Coeliac lymphogram was defined as an increase in TCRγδ+ plus a decrease in CD3- intraepithelial lymphocytes. Sensitivity, specificity and Fagan's nomogram were calculated. Results Coeliac disease was diagnosed in 37 patients and noncoeliac villous atrophy in 30. Coeliac patients were younger (39 ± 3 vs 55 ± 3 years; P = 0.001), more often showed HLA-DQ2/8 (97.6% vs 61%; P = 0.002) and had a more severe histology (61% vs 32% Marsh 3b-c; P = 0.055), as compared to noncoeliac ones. Coeliac lymphogram was associated with a sensitivity of 87% (CI, 73.7-95) and specificity of 96.7% (82.7-99.9), whereas evaluating only TCRγδ+ yielded a sensitivity of 91.3% (79.2-97.6) and specificity of 83.3% (65.3-94.3). Among patients with a pre-test coeliac disease probability of 30%, post-test probabilities were 92% and 5% for positive and negative coeliac lymphogram, and 70% and 4% for positive and negative TCRγδ+ . Conclusions Coeliac lymphogram was associated with a high level of diagnostic evidence either against or in favour of coeliac disease in patients with seronegative villous atrophy.

A 43-yr old female with two prior renal transplants for renal failure associated with diabetes, retinopathy and coronary artery disease developed diarrhea. Her medications included mycophenolate mofetil, an immunosuppressive medication documented to cause sprue-like mucosal changes in the small intestine. Later studies revealed a small intestinal mucosal lesion characterized by marked crypt hyperplasia, villous atrophy and increased intra-epithelial lymphocytes. Serological studies for celiac disease were negative and repeated biopsies despite a strict gluten-free diet, revealed histopathological persistence of a severely abnormal sprue-like enteropathy. Eventually, further biopsies of her small intestine revealed superimposed changes characterized by dense sub-epithelial collagen deposits histochemically staining positive for trichrome, typical of collagenous sprue and representing an expansion of published pathological features of mycophenolate-associated small intestinal mucosal disease.

Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure with electrolyte imbalances and impaired growth. CTE is typically diagnosed by its characteristic histological features, including villous atrophy, crypt hyperplasia and focal epithelial tufts consisting of densely packed enterocytes. Mutations in the EPCAM and SPINT2 genes have been identified as the etiology for this disease. The significant morbidity and mortality and lack of direct treatments for CTE patients demand a better understanding of disease pathophysiology. Here, the latest knowledge of CTE biology is systematically reviewed, including clinical aspects, disease genetics, and research model systems. Particular focus is paid to the pathogenesis of CTE and predicted mechanisms of the disease as these would provide insight for future therapeutic options. The contribution of intestinal homeostasis, including the role of intestinal cell differentiation, defective enterocytes, disrupted barrier and cell–cell junction, and cell-matrix adhesion, is vividly described here (see Graphical Abstract). Moreover, based on the known dynamics of EpCAM signaling, potential mechanistic pathways are highlighted that may contribute to the pathogenesis of CTE due to either loss of EpCAM function or EpCAM mutation. Although not fully elucidated, these pathways provide an improved understanding of this devastating disease.

Background and Objective: Pediatric guidelines on celiac disease (CD) state that children with anti-transglutaminase antibodies (TGAs) &gt, ×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 &gt, 18 years. TGAs were expressed as xULN. Duodenal lesions were classified as atrophic or non-atrophic 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 &gt, ×10 ULN, and 93 (76.8%) had villous atrophy. The cut-off of &gt, ×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 &gt, ×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.

Adherence to a gluten-free diet in celiac disease remains challenging. Clinicians may view mucosal healing as crucial. From the patient's perspective, avoidance of an invasive upper endoscopy may be desirable. A fundamental misconception is that noninvasive tools including symptoms, serology, dietary adherence questionnaires, and novel gluten immunogenic peptides may detect ongoing villous atrophy rather than assess adherence. Duodenal biopsies are the only reliable method for assessment of mucosal healing-however, we as clinicians should provide patients with the uncertainties of this approach allowing them to make an informed decision on an individual basis.

The differential diagnosis and treatment of seronegative enteropathy, also termed seronegative villous atrophy (SNVA), is a clinical challenge. Although seronegative coeliac disease (CD) is a frequent cause of SNVA, the aetiology can include immune-mediated, inflammatory, infectious, and drug-related forms. As a misdiagnosis of SNVA can result in patients being unnecessarily placed on a lifelong strict gluten-free diet or even given incorrect immunosuppressive therapy, the aim of this paper is to provide an evidence-based and practical approach for the workup and management of SNVA.

Coeliac disease is the most well-known cause of villous atrophy in duodenal biopsies. Other well recognised causes of villous atrophy include infection with Giardia duodenalis and HIV, peptic duodenitis, drug-induced enteropathy, common variable immunodeficiency, Crohn’s disease, Whipple’s disease, small intestinal bacterial overgrowth, eosinophilic gastroenteritis, tropical or collagenous sprue and autoimmune enteropathy. While mucosal adaptation due to malnutrition, leading to villous atrophy, has been reported in paediatric populations in Africa and South America, in hibernating animals and animal models of experimental starvation, there is very little literature on adult human subjects. We report a case of a 76-year-old gentleman, presenting with chronic metabolic acidosis and anorexia who was found to have villous atrophy on duodenal biopsy, in the absence of any evidence of coeliac disease or other non-coeliac enteropathy. The nutritional state improved with correction of the underlying metabolic abnormality, and serial endoscopic assessment showed improvement in the villous atrophy. We discuss the relationship between malnutrition and villous atrophy, and suggest a potential workup for non-coeliac villous atrophy.

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.

ObjectiveThe differential diagnosis and management of seronegative enteropathies is challenging due to the rarity of these conditions, the overlap of clinical and histopathological features and the current lack of an international consensus on their nomenclature.DesignThis is a narrative review providing pragmatic guide on the investigation and clinical management of seronegative enteropathies in adults based on the available literature and our clinical experience.ConclusionsSeronegative coeliac disease is the most frequent cause among the heterogeneous group of seronegative enteropathies and its diagnosis is confirmed by the clinical and histological response to a gluten-free diet after the exclusion of other causes of villous atrophy. Correct identification and targeted management of seronegative enteropathies is mandatory because of the variation in terms of clinical outcomes and prognosis.

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.Целиачный криз (ЦК) редкое жизнеугрожающее течение целиакии, наблюдается преимущественно у детей. У взрослых ЦК может быть первым проявлением болезни и крайне редко рецидивом, возникающим у пациентов, не соблюдающих аглютеновую диету (АГД). Триггерами могут служить стрессы, оперативные вмешательства, роды и др. Представлено клиническое наблюдение ЦК, развившегося у больной 49 лет с установленной ранее латентной формой целиакии с субтотальной атрофией ворсинок, стадии Marsh III С. Пациентка не соблюдала АГД. После тяжелой ангины у нее появились анорексия, диарея, истощение, коагулопатия, двухсторонняя тромбоэмболия ветвей легочной артерии, инфарктная пневмония и энтерогенный сепсис. В результате интенсивной терапии преднизолоном, Фраксипарином, антибиотиками, свежезамороженной плазмой и строгого соблюдения АГД достигнута ремиссия заболевания.

Olmesartan is an angiotensin II receptor blocker, approved in 2002 by the Food and Drug Administration for the treatment of hypertension. During chronic therapy with olmesartan, sprue-like enteropathy can occur, being mainly characterised by non-bloody diarrhoea, weight loss and variable degrees of duodenal mucosal damage, which resolved after withdrawal of olmesartan. We hereby report the case of a 77-year-old, poli-treated male patient with a 3-month history of diarrhoea, vomiting and weight loss, associated with severe intestinal villous atrophy and lymphocytic infiltration of gastric and colonic mucosa. After extensive investigations aimed at excluding other possible causes of chronic diarrhoea, a diagnosis of olmesartan-associated enteropathy was made, which was later confirmed by clinical improvement after the discontinuation of the drug. Repeated endoscopy 8 months later showed complete healing of duodenal mucosa with normal villous architecture. Villous atrophy and lymphocytic infiltration of duodenal mucosa are the most described pathologic finding, but several cases of gastric and colonic involvement have also been reported. We, therefore, reviewed the available literature, focussing on the extent of mucosal damage throughout the whole intestine and on its possible causative factors.

Duodenal villous atrophy with olmesartan was described in 2012, 10 years following registration of olmesartan. Clinical features are severe watery diarrhoea, usually occurring in association with weight loss. Onset is delayed, with a mean duration of prior exposure to olmesartan of 3 years. Diagnosis may be delayed. Symptoms resolve over weeks following cessation of olmesartan. Epidemiological studies suggest increased risk with olmesartan, rather than a class effect of all angiotensin receptor blockers. Post-marketing surveillance for drug safety remains important.

Introduction Narrow-band imaging with magnification endoscopy (NBI-ME) allows real-time visual assessment of the mucosal surface and vasculature of the gastrointestinal tract. This study aimed to determine the performance of NBI-ME combined with the water immersion technique (NBI-ME-WIT) in detecting villous atrophy. Methods All patients who underwent gastroscopy were included. The duodenum was further examined with NBI-ME-WIT only after examination with white light endoscopy did not reveal a cause of anaemia or dyspepsia. Targeted biopsies were taken of visualised areas. NBI-ME-WIT findings were compared with the final histopathological analysis. We calculated the sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of NBI-ME-WIT in detecting villous atrophy and the hypothetical cost saved by using a biopsy-avoiding approach. Results 124 patients (83 female) with a mean age of 46 (range 18-82) years were included. The most common indication for gastroscopy was abdominal pain (39%), followed by anaemia (35%), chronic diarrhoea/altered bowel habits (19%) and dyspepsia (6%). NBI-ME-WIT was able to detect all nine patients with villous atrophy - eight patchy and one total villous atrophy. The Sn, Sp, PPV and NPV of NBI-ME-WIT in detecting villous atrophy were 100.0%, 99.1%, 90.0% and 100.0%, respectively. Taking into account the cost of biopsy forceps (AUD 17) and pathology (AUD 140), this biopsy-avoidance strategy could have saved AUD 18,055 in these patients. Conclusion NBI-ME-WIT is a specific and sensitive tool to recognise and accurately diagnose villous atrophy. Biopsies can be avoided in patients with normal-sized villi, which may decrease the overall cost of the procedure.

Background Celiac disease (CD) is characterized histologically by inflammation and villous atrophy. Villous atrophy is thought to result from a disruption of epithelial cellular proliferation and death. Epithelial cells in intestinal mucosa normally proliferate in the crypts and migrate towards the lumen, eventually dying. Apoptotic bodies in crypts are usually abnormal and are associated with certain disease states. The presence of crypt apoptosis in celiac disease has not been thoroughly examined by routine histologic assessment of crypt apoptotic body count (ABC). Methods We quantified the ABC in duodenal biopsies from celiac patients before and after initiation of a gluten-free diet (GFD). We examined twenty-three duodenal biopsies from adult patients with celiac disease at diagnosis and following GFD and determined the maximum ABC in 10 consecutive crypts. Fourteen biopsies from heartburn patients served as controls. Results Mean duration between paired biopsies was 2.9 (0.5–8.5) years. Mean maximum ABC in active celiac disease was 5.44 per crypt and decreased to 2.60 with GFD (p =

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive type of intestinal lymphoma which affects individuals without evidence of enteropathy. In this single-centre case series, we describe the first two cases of MEITL in Caucasian patients suffering from histologically-proven coeliac disease (CD). Original medical records were retrieved and anonymised. All biopsy and surgical MEITL specimens were reviewed by three haematopathologists. Two patients aged 63- and 55-year old at CD diagnosis, subsequently developed a MEITL. MEITL always involved the ileum and was multifocal. Both patients died from complications after surgery, including gastrointestinal bleeding, septic shock and multiorgan failure, with a mean survival since MEITL diagnosis of 15.5 ± 16.3 months. In one case, array-CGH revealed a large deletion on chromosome nine between 9p13.1 and 9p24.1, and a recurrent chromosome gain at 9q33-q34. Our cases indicate that a subset of MEITL may arise in Caucasian patients suffering from CD. The clinical, pathological and molecular features of these cases show a partial overlap with enteropathy-associated T-cell lymphoma.

A 45-year-old Japanese male patient who was diagnosed with celiac disease (CeD) developed type I enteropathy-associated T-cell lymphoma (EATL). In 2013, the patient was admitted to our hospital with worsening of diarrhea and weight loss. Pathological examination of biopsy specimens from the duodenum and ileum led to a diagnosis of suspected EATL. A previous total colonoscopy (TCS) indicated villous atrophy in the terminal ileum. The patient was changed to a gluten-free diet, and the nutritional status gradually improved. In September 2014, he experienced acute right lower abdominal pain. He underwent urgent surgery, and a perforation was identified in the ileum. A diagnosis of type I EATL was made following histopathological examination. After eight courses of CHOP therapy, the patient entered complete remission. TCS and esophagogastroduodenoscopy with magnifying narrow-band imaging performed in 2015 identified villous regrowth in the distal ileum and duodenum. Capsule endoscopy also found villous regrowth in the entire small intestine. To our knowledge, this is the first case of type I EATL following CeD with villous atrophy before EATL occurrence in a Japanese HLA-DQ2 carrier. The possibility of type I EATL occurring after CeD should be recognized, although CeD is quite rare in Japan.

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.

Olmesartan induced enteropathy was first described in 2012. It is a rare adverse effect of this antihypertensive drug. The clinical presentation commonly includes severe chronic diarrhea leading to weight loss and a variable degree of dehydration. Histological findings are most commonly observed in the duodenum and consist of partial or total villous atrophy, increased intraepithelial lymphocytes and inflammation in the lamina propria. Involvement of gastric and colic mucosa has also been described. We report on the case of a 63-year-old man, treated by olmesartan, who presented with severe chronic diarrhea. Biopsies from different levels of the gastrointestinal tract revealed a pandigestive intraepithelial lymphocytosis.

Common variable immunodeficiency (CVID) causes a chronic debilitating syndrome in affected patients and often leads to high morbidity and mortality. Among its several presentations, chronic enteropathy leading to malabsorption syndrome continues to offer a major diagnostic dilemma. Lately, higher testing for norovirus infection in patients with CVID enteropathy has correlated its presence to chronic diarrhoeas, severe villous atrophy and malabsorption syndromes. There have been no such reports of its clinical and histopathological manifestations in CVID from India. Here, we demonstrate the significance of testing for norovirus in the gut with multiplex PCRs in an adult patient with a chronic undiagnosed CVID enteropathy and its response to monthly intravenous immunoglobulin (IVIG) therapy. Our patient responded after three cycles of monthly IVIG with a complete clinical recovery of his bowel functions, leading to a significant improvement in his quality of life and performance status.

Aim The objective of the study was to observe the association of villous atrophy with anti-tissue transglutaminase levels in the identified subjects that met our addressed inclusion criteria. Methods A case series study was conducted among 40 patients presenting with dyspepsia along with signs and symptoms of celiac disease at the Bolan Medical Complex Hospital, Quetta over a period of five months from 25/5/17 to 25/10/17. The patients were referred to undergo tissue transglutaminase antibody serum test. The positive ones underwent biopsies to assess pathological entities including villous atrophy, blunting (focal or total), crypts, Intestinal layers and the number of Intraepithelial lymphocytes. The results collected were analyzed by using IBM SPSS version 20 (IBM Corp., Armonk, NY). Results There was a weak, negative correlation between tTGA and focal villous blunting (r = -0.345, p = 0.029) showing that high levels of tTGA are associated with lower risk of focal villous blunting. Correlation of tTGA and total villous blunting was a weak positive correlation (r = 0.282, p = 0.07) showing that high levels of tTGA are associated with increased risk of total villous blunting. There was a weak, negative correlation between tTGG and focal villous blunting (r = 0.409, p = 0.009) showing thathigh levels of tTGG are associated with a greater risk of focal villous blunting (p < 0.01) while tTGG and total villous blunting was a weak negative correlation (r = -0.330, p = 0.03) showing that high levels of tTGG are associated with lower risk of total villous blunting. Conclusion The study concludes by providing evidence of the absence of tissue transglutaminase antibodies in patients with histology-proven celiac disease. It implies that serology tests may be negative in some of the patients with typical chronic symptoms. Therefore, in such cases, histopathology may be conclusive in defining the status of celiac disease.

Background and Aims: Methods of assessing gluten-free diet (GFD) adherence in adults with coeliac disease (CD) include serological testing, dietitian evaluation, questionnaires and repeat duodenal biopsies. Persisting villous atrophy (VA) is associated with CD complications, however gastroscopy with biopsies is expensive and invasive. This study aimed to assess the abilities of a duodenal bulb (D1) biopsy and the Celiac Dietary Adherence Test (CDAT) to detect persisting VA in adults with CD. Methods: A prospective observational study of adult CD patients referred for follow-up duodenal biopsies was performed. Quadrantic biopsies were taken from the second part of the duodenum (D2), in addition to a D1 biopsy. Patients underwent follow-up serological testing, and completed the CDAT and Biagi Score. These non-invasive adherence markers were compared against duodenal histology. Results: 368 patients (mean age 51.0 years, 70.1% female) had D1 and D2 biopsies taken at follow-up gastroscopy. Compared to D2 biopsies alone, additional D1 biopsies increased detection of VA by 10.4% (p

Microvillous inclusion disease (MVID), also known as congenital microvillus atrophy remains an important differential diagnosis of intractable secretory diarrhea in neonatal period. The condition is inherited as an autosomal recessive disorder with no sex predilection and more commonly reported in those tribes with consanguineous marriages. The pathognomonic electron microscopic findings includes villous atrophy with the formation of intracellular microvillous inclusions. Definite treatment includes either isolated small bowel or combined small bowel and liver transplantation. Herein, we are describing a case of intractable diarrhea in a preterm neonate with MVID phenotype presented on second day of life with intractable diarrhea. The diagnosis was established by classical electron microscopic findings in the intestinal biopsy sample.

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.

Celiac disease is an immune-mediated process against gluten, resulting in inflammation and villous atrophy of the duodenum. Symptoms of malabsorption characterize the classic presentation; however, abdominal pain, constipation, and nutritional deficiencies can also be seen. We present a case of a 4-year-old boy who was found to have celiac disease after presenting with diarrhea, abdominal pain, weight loss, and new-onset pancytopenia. Symptoms resolved, and laboratory values normalized after the initiation of a gluten-free diet, indicating the bone marrow suppression was due to celiac disease, which needs to be considered when hematologic abnormalities are present, even in the absence of gastrointestinal symptoms.

Background and Aims: There is little agreement on the nomenclature and description of Crohn's disease (CD) lesions that can be found in the small and large bowel using capsule endoscopy (CE). We performed a systematic review to identify mucosal lesions that have been described using CE in CD, in both the small bowel and colon, with the aim to make propositions to homogenize such descriptions.Methods: A systematic literature search was conducted using Embase, Medline (OvidSP), and Cochrane Central on August 6, 2019. Clinical studies providing nomenclature and descriptions for small bowel and colonic inflammatory lesions using CE in CD were selected for data collection.Results: In total, 851 articles were included for abstract screening out of which 219 were analyzed for full-text review. Twenty-two articles were selected for data extraction. Seven items, accompanied by clear descriptions, were found for the small bowel: i.e., ulcer, erosion, aphthoid lesion, edema, fissure, cobblestone appearance, and villous atrophy. No studies were found describing inflammatory items using CE in colonic CD.Conclusions: The most frequently described CD lesions using CE were ulcers and erosions. Subjective interpretation of CE inflammatory findings plays an important role. Based on our findings, a range of suggestions regarding items and descriptions is made that might form the basis of a pan-enteric CE activity index.

Introduction Duodenal bulb biopsies have been demonstrated to increase the diagnostic rate of newly diagnosed coeliac disease (CD) by 10%. The aim of this study was to assess the utility of duodenal bulb biopsies for the assessment of established CD. Methods A prospective study of 375 established CD patients (mean age 51.0 years; 69.9% female) who underwent endoscopy for assessment of persisting symptoms or remission at Sheffield Teaching Hospitals was performed, between 2013–2019. Quadrantic biopsies were taken from D2 in addition to duodenal bulb biopsies. Results 63.2% (n=237) of patients had ongoing villous atrophy (VA). Table 1 outlines the histological appearance of D1 and D2 biopsies. Among those with VA (n=237), this was confined to D1 in 10.2% (n=14) and to D2 in 8.0% (n=11). There was no significant difference in number of patients with VA confined to D1 versus D2 (p=0.69). There was no difference in age (p=0.18) or gender (p=0.10) between patients with VA confined to D1 compared to the remaining cohort. As time from diagnosis increased, the proportion of individuals with complete duodenal mucosal healing (defined as Marsh 0 in both D1 and D2 biopsies) also increased. Two years after diagnosis 4.9% (n=11) of patients had complete healing, increasing to 10.7% (n=24) after 4 years, 17.3% (n=39) after 6 years, 20.9% (n=49) after 8 years and 24.0% (n=54) after 10 years. A further 11.1% (n=25) of patients achieved complete healing after more than 10 years since diagnosis. Conclusions Duodenal bulb biopsies increased the detection of VA by 10% in established CD, highlighting the importance of bulbar biopsies in established CD for the first time in the literature. Complete mucosal healing can occur in established CD after a significant delay, suggesting development of immune tolerance in these individuals.

Intestinal Villous atrophy is part of the diagnostic challenge for both pathologists and gastroenterologists, given its infrequent and the presence of multiple differential diagnosis. Here is a case of a patient with chronic diarrhea and endoscopic documentation of loss of villous architecture and histologic atrophy of the villi, ruling out autoimmune etiologies and immunodeficiencies, documenting an autoimmune enteropathy with a favorable response after the use of immunosuppressive therapy.

Celiac disease (CD) is a chronic intestinal inflammation caused by gluten ingestion in genetically predisposed individuals. Overt-CD and potential-CD are the two main forms of gluten intolerance in pediatric patients with different grades of intestinal mucosa lesion and clinical management. For overt-CD patients the gluten-free diet is mandatory, while for potential-CD the dietary therapy is recommended only for those subjects becoming clinically symptomatic overtime. To date, specific early biomarkers of evolution to villous atrophy in potential-CD are lacking. We recently observed an expansion of TCRγδ+ T cells and a concomitant disappearance of IL4-producing T cells in the intestinal mucosa of overt-CD patients compared to potential-CD children, suggesting the involvement of these two cells subsets in the transition from potential-CD to overt-CD. In this study, we demonstrated that the intestinal densities of IL4+ T cells inversely correlated with TCRγδ+ T cell expansion (p &lt, 0.005) and with the serum levels of anti-tissue transglutaminase antibodies (p &lt, 0.01). The changes of these two cell subsets strongly correlated with mucosal lesions, according to the histological Marsh classification, as the transition from M0 to M3 lesions was associated with a significant reduction of IL4+ T cells (M0 vs. M1 p &lt, 0.04, M0 vs. M3 p &lt, 0.007) and an increase of TCRγδ+ T cells (M0 vs. M1 p &lt, 0.05, M0 vs. M3 p &lt, 0.0006). These findings strongly suggest that the detection of TCRγδ+ and IL4+ T cells could serve as cellular biomarkers of mucosal lesion and targets of novel immunomodulatory therapies for CD.

Objectives Use of deamidated gliadin peptide (DGP) test kits as adjunctive to Tissue-transglutaminase IgA (TTG-IgA) for the diagnosis of celiac disease (CD) has been a controversial issue. The objectives of our study were to evaluate the diagnostic performance of DGP antibodies compared to TTG-IgA and to evaluate the correlation between DGP-antibodies titers and degree of enteropathy. Methods We included children who underwent endoscopy and biopsies because of positivity of any of the serology tests in the "celiac profile" (TTG-IgA, DGP-IgA, and DGP-IgG), from 2012 to 2019. We divided children into clinically suspected cases of CD (Group 1) and asymptomatic cases screened because they were from a high risk-group (Group 2). Results Group 1 constituted 52 children and group 2 included 81 children [76 type1-diabetes (T1D)]. The sensitivity and positive predictive value (PPV) of DGP-IgG in group 1 (90%, 98%) and group 2 (91%, 85.5%) were comparable to TTG-IgA (98%, 92% in group 1; 100%, 80% in group 2). By adding DGP-IgG to TTG-IgA, the performance of TTG-IgA has improved marginally in group 1 (sensitivity 100%, PPV 92.3%). All cases with DGP-IgG titer 2 times ULN in group 1, and > 4 times ULN in group 2 had villous atrophy. All T1D patients with TTG IgA > 10 times ULN had villous atrophy. Conclusion DGP-IgG assay did not add to the performance of TTG-IgA. DGP-IgG titer correlated with enteropathy. The diagnosis of CD can be made in asymptomatic T1D child with TTG-IgA titer > 10 times ULN and positive endomyseal antibodies.