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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]

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]

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 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D‐xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests. [ABSTRACT FROM AUTHOR]

Aim of the current study was to evaluate the inter‐observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the “PreventCD” study, a multinational‐ prospective‐ randomized study in children with at least one‐first‐degree relative with CD and positive for HLA‐DQ2/HLA‐DQ8. Ninety‐eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza‐Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh‐Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well‐controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist. [ABSTRACT FROM AUTHOR]

Background and purpose: Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow‐up biopsy. The objective of this study was to determine whether persistent VA on follow‐up biopsy affected long‐term epilepsy risk and epilepsy‐related hospital emergency admissions. Methods: This was a nationwide cohort study. We identified all people in Sweden with histological evidence of CD who underwent a follow‐up small intestinal biopsy (1969–2008). We compared those with persistent VA with those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant International Classification of Diseases codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures. Results: Villous atrophy was present in 43% of 7590 people with CD who had a follow‐up biopsy. The presence of persistent VA was significantly associated with a reduced risk of developing newly‐diagnosed epilepsy (hazard ratio, 0.61; 95% confidence interval, 0.38–0.98). On stratified analysis, this effect was primarily amongst males (hazard ratio, 0.35; 95% confidence interval, 0.15–0.80). Among the 58 patients with CD with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (hazard ratio, 0.37; 95% confidence interval, 0.09–1.09). Conclusions: In a population‐based study of individuals with CD, persisting VA on follow‐up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy‐related hospital admissions. The mechanism as to why persistent VA confers this benefit requires further exploration. [ABSTRACT FROM AUTHOR]

Aim: Screening children with type 1 diabetes for coeliac disease is controversial, because they often appear asymptomatic. Our aim was to establish whether active screening should be recommended.Methods: This study focused on 22 children whose coeliac disease was detected by serological screening during diabetes surveillance and 498 children diagnosed because of a clinical suspicion. We compared the clinical and histological data at diagnosis and the children's adherence and responses to a gluten-free diet.Results: The serological screening group suffered less from decreased growth (p = 0.016) and clinical symptoms (p < 0.001) at diagnosis than the clinical group. The groups did not differ in terms of age at diagnosis (p = 0.903), gender (p = 0.353), anaemia (p = 0.886), endomysial antibody titres (p = 0.789) and the severity of small-bowel mucosal atrophy (p = 0.104). They also showed equal adherence (p = 0.086) and clinical responses (p = 0.542) to a gluten-free diet after a median follow-up of 13 months.Conclusion: Coeliac patients detected during diabetes surveillance had signs of malabsorption and advanced mucosal damage that was similar to those diagnosed on a clinical basis. They often suffered from unrecognised gluten-dependent symptoms and showed excellent adherence and responses to a gluten-free diet. Our findings support active screening for coeliac disease in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To describe the clinical and pathological features of a series of patients with biopsy findings of a coeliac disease-like enteropathy in the setting of an acute illness. Methods and results: Eighteen cases of an abrupt-onset, self-limited illness with coeliac-like enteropathy (SLCE) were collected prospectively. Medication reaction, immune disorder, food allergy and parasitic infection were excluded. Coeliac disease was excluded by the transient nature of the illness and absence of tissue transglutaminase (TTG) elevation (nine of nine) or human leucocyte antigen (HLA)- DQ2/DQ8 haplotype (eight of nine). Clinical symptoms were recorded and histopathological findings in all gastrointestinal sites were quantified. Findings in the duodenum were compared to a coeliac disease control group. In 12 cases the clinical diagnosis was infective enteritis, probably viral in type. In six cases, a definite diagnosis was not established. Histological differences from coeliac disease included intra-epithelial neutrophil infiltration (P < 0.001), fewer intra-epithelial lymphocytes (P = 0.038) and uniform or crypt predominant intra-epithelial lymphocytosis in SCLE. One case displayed pan-gastrointestinal tract lymphocytosis. All resolved within 6 months. Conclusions: Histopathologists need to be aware that a coeliac disease-like enteropathy may occur in the setting of an acute gastrointestinal illness and resolve without sequelae. [ABSTRACT FROM AUTHOR]

Background and Aim Celiac disease ( CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance ( NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy. Methods Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum test was used. Partial least squares-discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software. Results Partial least squares-discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy. Conclusions NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine the characteristics of patients with celiac disease and differences between those who presented during adolescence or adulthood. Methods We retrospectively reviewed the case records of 233 consecutive patients with celiac disease who were diagnosed at 12-18 years or >18 years of age. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition criteria. Results The diagnosis of celiac disease was made after 18 years of age in 153 (65.7%) patients. Median duration of symptoms at the diagnosis was 54 months (range 1 month to 29 years). In all, 103 (44.2%) patients with atypical manifestations were referred by other departments for evaluation. Chronic diarrhea (48.5%), short stature (27.0%) and chronic anemia (9.0%) were the common modes of presentation. Elevated level of aminotransaminase were present in 50 (24.3%) patients. Chronic diarrhea, hypocalcemia and hypoalbuminemia were present in significantly higher number of adult than adolescent patients. In all, 227 (97.4%) patients responded to a 6-month gluten-free diet and six non-responders were non-compliant. Conclusions More than 40% of the patients with celiac disease present to clinicians other than gastroenterologists or internists with atypical manifestations. A high index of suspicion is required for diagnosing its variant forms. [ABSTRACT FROM AUTHOR]

While celiac disease is estimated to affect about 1% of the world's population, it is thought to be uncommon not only in India but in Asia also. There is a lack of studies on the prevalence of celiac disease from Asian nations. The aim of the present study was to estimate the prevalence of celiac disease in the community. In a cross sectional study, we estimated the prevalence of celiac disease in urban and rural populations in the National Capital Region, Delhi, India. A structured questionnaire was administered, by door-to-door visits, to all participants to collect socio-demographic data and to screen for features of celiac disease, namely chronic or recurrent diarrhea and, anemia. In children, additional features, namely short stature (linear height below 5th percentile for age) and failure to thrive/gain weight were also used. All respondents who were screen positive (any one of above) and 10% of screen negative individuals were called for serological testing, which is anti-tissue transglutaminase antibody. All serologically positive respondents were invited to undergo further evaluation including endoscopic biopsy. Celiac disease was diagnosed on the basis of a positive serology, the presence of villous atrophy and/or response to gluten free diet. Among 12 573 contacted, 10 488 (83.4%) (50.6% male) agreed to participate. Based on screening, 5622 (53.6%) participants were screen positive. Of all those screen positive, 2167 (38.5%) agreed for serological testing; additionally 712 (14%) negatives were also tested. The overall sero-prevalence of celiac disease was 1.44% (95% confidence interval [CI] 1.22 1.69) and the overall prevalence of celiac disease was 1.04% (95% CI 0.85 1.25). The prevalence of celiac disease in this north Indian community is 1 in 96. Celiac disease is more common than is recognized in India. [ABSTRACT FROM AUTHOR]

Background: Cyclophosphamide (CYP) and methotrexate (MTX) have been used as immunosuppressants in induction or maintenance protocols in a large variety of xenotransplantation models. Combining the use of transgenic porcine organs expressing human decay-accelerating factor (hDAF) with immunosuppressive therapy that included the use of CYP or MTX, survival of primate recipients of life-supporting renal xenografts has been prolonged. However, both drugs can cause significant systemic toxicity and, in particular, gastrointestinal (GI) toxicity. To date only limited data have been reported on the histopathological features deriving from the use of such agents in non-human primates. Methods: Cyclophosphamide or MTX was used as part of the immunosuppressive regimen in 15 bilaterally nephrectomized non-human primate ( Macaca fascicularis) recipients of a life-supporting hDAF porcine kidney. At post-mortem, a detailed analysis of the GI tract in animals receiving either CYP or MTX was performed. Paraffin-embedded sections of each portion of the GI tract were prepared and stained with hematoxylin and eosin (H&E). In some animals, additional investigations by immunohistochemistry (CD3, CD5, CD20, CD79 αcy, lambda, and kappa light chains) and by in situ hybridization for EBV encoded RNA (EBER) were undertaken. Results: The xenografted animals from the CYP group had a mean survival of 31 days (range: 0 to 90 days); animals from the MTX group survived a median of 14 days (range: 0 to 39 days). GI complications were the most frequent cause of euthanasia after renal failure. In CYP-treated animals GI-tract lesions were primarily characterized by diffuse, severe lymphoplasmocytic mucosal inflammatory infiltrate. Variable degrees of villi atrophy and fusion, gut-associated lymphoid tissue (GALT) and goblet cell hyperplasia were also observed. In MTX-treated primates, findings were consistent with severe villi atrophy associated with mild-to-moderate disseminated lymphoplasmocytic infiltration. Conclusions: In conclusion, GI tract lesions are an early and consistent finding when CYP or MTX are used as induction agents in this model. The two compounds induce different types of GI tract damage, however, in agreement with their different mechanisms of action. Whilst CYP primarily determines inflammatory lesions, MTX leads to a degenerative type of damage. This study indicates that immunosuppressive drugs can cause severe GI tract damage in primate recipients of renal xenografts and may be responsible for life-threatening lesions. [ABSTRACT FROM AUTHOR]

Provides information on the relation of coeliac disease (CD) and villous atrophy. Effect of food allergy and food-sensitive enteropathies on the injuries sustained by the small intestine; Relation of insulin-like growth factor level in the incidence of CD; Immunohistochemical markers and symptoms of CD.

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first-degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at-risk populations. [ABSTRACT FROM AUTHOR]

Toscano E. Historical views on celiac disease: the contribution of Adolf Baginsky (1843-1918). Acta Paediatr 2004; 93: 417-418. Stockholm. ISSN 0803-5253. [ABSTRACT FROM AUTHOR]