Malignancy and mortality in a population-based cohort of patients with coeliac disease or ‘gluten sensitivity’

AIM: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin an- tibody test in Northern Ireland. METHODS: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortal- ity statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. RESULTS: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 pa- tients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin anti- bodies and they were defined as gluten sensitive. Ma- lignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was signifi- cantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin’s lym- phoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortal-ity, mortality from malignant neoplasms, non-Hodgkin’s lymphoma and digestive system disorders were signifi- cantly higher in gluten sensitive patients compared to the Northern Ireland population. CONCLUSION: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly re- duced in the cohort of patients with gluten sensitivity.

Non-celiac gluten sensitivity: All wheat attack is not celiac

Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,"non-celiac gluten sensitivity"(NCGS)has been suggested to affect up to 6%of the United States public.While reliable clinical tests for CD exist,diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten.NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins.At present,an enormous food industry has developed to supply gluten-free products(GFP)with GFP sales in 2014 approaching$1 billion,with estimations projecting sales to reach$2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice.Features of NCGS and other gluten related disorders(e.g.,irritable bowel syndrome)call for a review of current distinctive diagnostic criteria that distinguish each,and identification of biomarkers selective or specific for NCGS.The aim of this paper is to review our current understanding of NCGS,highlighting the remaining challenges and questions which may improve its diagnosis and treatment.

Non-celiac gluten sensitivity： questions still to be answered despite increasing awareness

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, inctuding tow-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

The Impact of Gluten-Free Diet on Hormonal Balance

This study investigated how a gluten-free diet affects hormones, with particular emphasis on cortisol, thyroid, insulin, and sex hormones. Background: For medical diseases such as non-celiac gluten sensitivity, wheat allergy, and celiac disease, a gluten-free diet is important. The main area of concern for research is how a gluten-free diet can affect hormone levels and related health consequences. A review of the body of research on this topic, including studies on hormone regulation and the impact of dietary modifications, is a part of the methodology. These findings imply that a gluten-free diet may have an impact on hormone levels, which may affect metabolism, weight, and general health. These implications include the need for additional studies, particularly in those with autoimmune illnesses, to completely comprehend the relationship between a gluten-free diet and hormone regulation.

May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis?

AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS.RESULTS After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels(6.1 ± 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD 88 levels similarly to non gluten-related causes of DL(7.8 ± 4.9 and 6.7 ± 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count(15-25 and more than 25/100 enterocytes) strongly correlated with mR NA levels of all tested molecules(P < 0.0001).CONCLUSION Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of t TG and IFNγ m RNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. My D88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value.

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin

AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

Current guidelines for the management of celiac disease:A systematic review with comparative analysis

BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

AIMTo analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE).METHODSThis is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 &#x000b1; 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed.RESULTSThe overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn&#x02019;s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P &#x0003c; 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.CONCLUSIONCE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.