Celiac Disease Without Villous Atrophy

Current diagnostic criteria of celiac disease require small bowel villous atrophy, although the damage develops gradually. We therefore searched for evidence of disease in 10 adults suspected to have celiac disease, but evincing only minor mucosal inflammation and increase in ⁺ cells without villous atrophy. Twenty untreated celiac and 27 nonceliac patients served as biopsy controls. CD3⁺, ⁺, and ⁺ cells were increased in patients with only minor mucosal lesions, but less than in celiac patients. The inflammation resolved on gluten-free diet, and abdominal symptoms were alleviated. Eight of 10 had positive endomysial, seven gliadin, and nine tissue transglutaminase antibodies; all normalized on diet. Eight patients had osteopenia; HLA DQ2 was found in all. Minor mucosal lesions with an increase in ⁺ intraepithelial lymphocytes were suggestive of celiac disease. Our patients showed a clinical, histological, and serological recovery on diet; risk of osteopenia speaks in favor of dietary treatment.     

Celiac Disease and Increased Risk of Pneumococcal Infection: A Systematic Review and Meta-Analysis

Background

Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease.

Prevalence of Silent Celiac Disease in Patients with Dyspepsia

Celiac disease (CD) has become more common than in the past, although it frequently remains undetected for long periods of time. One reason for this is failure by health care professionals to recognize the variable clinical manifestations of CD and to perform the appropriate tests to make the diagnosis. Although dyspepsia may be part of a clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD. We aimed to determine the prevalence of CD in otherwise healthy dyspeptic patients by means of serologic screening followed by endoscopic biopsies if appropriate. Anti-endomysium antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged from 19–52 years (mean ± SD age, 36±16 years). Duodenal biopsies were compatible with CD in all, whereas abnormal endoscopic findings were noted in 2. Therefore, a 1.5% prevalence of CD was observed in this study group. The odds ratio for CD was 2.57 (95% confidence interval) in comparison with the general population. CD should be kept in mind as a cause of dyspepsia during clinical activities. The association between these 2 conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD. During endoscopic examination for dyspepsia, if indicated, endoscopists should carefully inspect the duodenum for CD findings. Although routine serologic screening can not be recommended, it may be appropriate for the patients with refractory dyspepsia, especially females.     

Intestinal Diffuse Large B-Cell Lymphoma Associated with Celiac Disease: A Japanese Case

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.     

Diagnostic Approach to a Patient with Suspected Celiac Disease: A Cost Analysis

Serological testing is an important tool in the diagnostic work-up of suspected celiac disease. Our aim was to apply a decision analysis model to compare the costs of serological testing versus small bowel biopsy in the diagnostic work-up of celiac disease. A cost-minimization approach was employed. A decision analysis model with three diagnostic arms was designed using Data Version 3.5: anti-gliadin antibody versus endomysial antibody versus small bowel biopsy. Response to gluten-free diet was considered diagnostic of celiac disease; lack of response prompted a small bowel biopsy to definitively exclude celiac disease. Baseline probabilities were varied using sensitivity analysis. Sensitivity analysis revealed that the endomysial antibody strategy was least costly, provided the prevalence of celiac disease was less than 42%; above this anti-gliadin antibody became the most economical option. In conclusion, initial screening with endomysial antibody is the least costly strategy for diagnosing celiac disease in a low risk population. Antigliadin antibody becomes the cheaper strategy for higher risk populations.     

Celiac disease in South-West of Iran

AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histological features of 52 patients with celiac disease were evaluated. METHODS: In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. RESULTS: Male: female ratio was 1.08. The mean±SD patient age was 21±4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. CONCLUSION: Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.     

Prevalence of Celiac Disease in Turkish Children with Autoimmune Thyroiditis

The close association between celiac disease (CD) and autoimmune disorders is well documented in adult and pediatric patients. The aim of this study is to determine the prevalence of CD in Turkish children with autoimmune thyroiditis (AT). Sera from 101 children with AT (11 boys and 90 girls, from 2 to 18 years of age; mean age 12.28 ± 3.26 years) and 103 healthy children (46 boys and 57 girls, from 3.5 to 17 years of age; mean age 12.18 ± 3.11 years) were screened for CD using the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. IgA anti-tTG was positive in eight children (7.9%) with AT. None of the serum samples of healthy children were positive for IgA anti-tTG antibody. Selective IgA deficiency was not detected in patients or controls. Intestinal biopsy was accepted by seven patients. In five patients (4.9%), subtotal villous atrophy was found. These findings indicate that the prevalence of CD is higher in Turkish children with AT than in healthy controls. Routine screening for CD should be performed in children with AT.     

Correlation of Clinical and Histopathological with Endoscopic Findings of Celiac Disease in the Turkish Population

Endoscopic findings have been described for the diagnosis of celiac disease but the relationship amond the clinical presentation, endoscopic markers, and the degree of histopathological findings is not clear. Thirty patients who were thought to have celiac disease were included in this study. Biopsies taken from the duodenum were examined histopathologically. The relationship among the endoscopic, clinical, and histopathological findings were investigated. Partial villous atrophy was seen in 14 patients (46.6%), and subtotal and total villous atrophy were seen in 6 (20%) patients each. Eighty six percent of patients with a mosaic appearance, 76% of patients with the finding of loss of folds, and 90% of patients with scalloping on endoscopy had either partial villous atrophy, subtotal villous atrophy, or total villous atrophy on biopsy. We conclude that endoscopic findings in celiac disease can reveal valuable information both for diagnosis and for demonstration of the severity of the disease state.     

Increased Risk of Papillary Thyroid Cancer in Celiac Disease

Patients with celiac disease have an increased rate of malignancies that are not limited to lymphomas. Thyroid carcinoma has not previously been associated with celiac disease. However, among a cohort of patients with celiac disease, we identified an increased risk of papillary carcinoma of the thyroid, standard morbidity ratio of 22.52 (95% confidence interval 14.90–34.04; P < .001), compared to United States national surveillance data. These patients were on a gluten-free diet. Only 1 had Hashimoto's thyroiditis, suggesting that mechanisms apart from autoimmune thyroiditis contribute to the increased risk of carcinoma of the thyroid in celiac disease.     

Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study

Background: Seronegative celiac disease (CD) poses a diagnostic challenge.

Aims: Characterize and identify differences between seronegative and seropositive CD.

Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980–2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression.

Results: Of 315?CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p?=?.016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p???.001) and Marsh I lesion (34.6% vs. 3.7%, p???.001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD.

Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.     

Capsule Endoscopy Findings in Celiac Disease

Capsule endoscopy (CE) is a noninvasive imaging method used to evaluate intestinal mucosa. We aimed to examine intestinal mucosal changes in celiac disease (CD) with CE. Eight untreated patients who had anti-endomysial antibody-positive duodenal biopsy results consistent with CD were included in the study. Villous atrophy, scalloping, fissuring, and mosaic pattern (consistent with CD) were detected in seven patients; one patient was excluded for early meal consumption. No patchy involvement was found in the intestine or distal region of the intestine (ileum) in any of the patients. The common feature of all patients was that villous atrophy, scalloping, fissuring, and mosaic patterns detected in the proximal intestine gradually decreased towards the distal intestine. CE provided no diagnostic contribution to CD when compared with duodenal biopsy. It can be used to show villous atrophy in selected cases and to evaluate the extension of intestinal involvement in CD.     

The Prevalence of Celiac Disease in Blood Donors in Iceland

Background Prospective epidemiological studies based on serological methods have shown that celiac disease is more common than previously thought. The aim of this study was to evaluate the prevalence of celiac disease among apparently healthy blood donors in Iceland. Methods Plasma samples were obtained from 813 apparently healthy blood donors at the FSA Hospital Blood Bank in Akureyri, Iceland, between December 2004 and January 2007 and screened for human tissue transglutaminase IgA antibodies. Positive samples were retested and, if the test was again positive, the subject was referred to a gastroenterologist for clinical examination and a duodenoscopy with mucosal biopsies. Results Six subjects tested positive for tissue transglutaminase. The prevalence of biopsy-confirmed celiac disease, according to modified Marsh classification, among apparently healthy blood donors in Iceland was found to be 1:136 (0.74%, 95% confidence interval 1/667–1/75, 0.15–1.33%). Conclusion Prevalence of celiac disease in Iceland is similar to what has been reported in many other countries.     

Celiac Disease Prevalence in Brazilian Dilated Cardiomyopathy Patients

Celiac disease (CD) is a permanent condition of gluten intolerance and a number of autoimmune diseases have been associated with it. In the past few years, a relation between CD and dilated cardiomyopathy (CM) was described in Europe and United States. The aim of this study was to evaluate the prevalence of CD among south Brazilian precardiac transplant patients with advanced CM. A total of 74 patients on a list for heart transplantation were evaluated for the presence CD. The presence of anti-endomisial antibody (IgA-EmA) was determined by indirect immunofluorescence and for the anti-transglutaminase antibody (IgA anti–h-tTG) by ELISA. Serologically positive patients were submitted to upper endoscopy with intestinal biopsy. Two individuals (2.63%) were positive for IgA-EmA and 5 (6.75%) for IgA anti–h-tTG; 1 (1.35%) had both tests positive. Histologic confirmation of CD occurred only in the IgA-EmA positive patients. In conclusion, data from the present study allows recommend the screening for CD in patients with CM using IgA-EmA test as the method of choice.     

Sarcoidosis in Patients with Celiac Disease

Purpose Several case reports and European studies have suggested an association between sarcoidosis and celiac disease; however, they have been inconsistent. We therefore analyzed a large cohort of celiac-disease patients to assess this association. Methods An anonymized database of patients with celiac disease was reviewed to determine the number of patients with sarcoidosis. Age- and gender-adjusted standardized morbidity ratios with corresponding 95% confidence intervals (CI) were calculated by comparing results to US-population-derived prevalence data. Results Ten patients were found to have a comorbid diagnosis of sarcoidosis, representing an age- and gender-adjusted standardized morbidity ratio of 36.8 (95% CI 26.7–50.9). Conclusions In this cohort of patients with celiac disease, there was a significantly increased risk of sarcoidosis when compared with the American white population. This further strengthens prior associations that have been made suggesting a shared mechanism behind the etiologies of celiac disease and sarcoidosis.     

Pulmonary Hemosiderosis in Association with Celiac Disease

A 15-year-old male had a history of increasing dyspnea on exertion, cough, sputum production, fever, weakness, hemoptysis, and diarrhea. Chest radiography demonstrated bilateral alveolar consolidation. Bronchoalveolar lavage fluid analysis revealed extensive hemosiderin-laden alveolar macrophages. On the basis of iron deficiency anemia, diarrhea, raised antigliadin and antiendomysial antibodies, widespread villous atrophy, and crypt hyperplasia on intestinal biopsy, celiac disease was diagnosed. After treatment with a gluten-free diet, all his clinical symptoms and radiographic findings improved within two weeks.     

Mucosal Molecular Pattern of Tissue Transglutaminase and Interferon Gamma in Suspected Seronegative Celiac Disease at Marsh 1 and 0 Stages

Background/Aim:In celiac disease (CD), there is increased mRNA coding for tissue transglutaminase (tTG) and interferon gamma (IFNγ). In seronegative celiac patients, the mucosal immune complexes anti-tTG IgA/tTG are found. We assayed tTG- and IFNγ-mRNA in the mucosa of patients with a clinical suspicion of seronegative CD and correlated the values with intraepithelial CD3 lymphocytes (IELs).Results:Our series was divided into three groups based on IEL count: >25 (14 patients: group A), 15–25 (26 patients: group B), and 0–15 (27 patients: Group C). tTG-mRNA levels were (mean ± SD): CD = 9.8 ± 2.6; group A = 10.04 ± 4.7; group B = 4.99 ± 2.3; group C = 2.26 ± 0.8, controls = 1.04 ± 0.2 (CD = group A > group B > group C = controls). IFNα-mRNA levels were: CD = 13.4 ± 3.6; group A = 7.28 ± 3.6; group B = 4.45 ± 2.9; group C = 2.06 ± 1.21, controls = 1.04 ± 0.4.Conclusions:Our results suggest that tTG- and IFNγmRNA levels are increased in both seropositive and potential seronegative patients with CD, showing a strong correlation with the CD3 IEL count at stage Marsh 1. An increase in both molecules is found even when IELs are in the range 15–25 (Marsh 0), suggesting the possibility of a “gray zone” inhabited by patients which should be closely followed up in gluten-related disorders.     

Response to Hepatitis B Vaccination in Patients with Celiac Disease

Abnormal immune response to gliadin, genetic, and environmental factors play a role in the pathogenesis of celiac disease (CD). Non-responsiveness to hepatitis B virus (HBV) vaccination is related to genetic features. Certain human leukocyte antigen (HLA) genotypes are more prevalent among non-responders to HBV vaccination. There is also a strong relationship between CD and these HLA genotypes. This study investigates the relationship between CD and non-responsiveness to HBV vaccination, with an emphasis on genotypic co-incidence. No statistically significant difference was noted between the ages and gender of CD patients and control subjects. Baseline serum IgA, IgM, and IgG levels of all CD patients were normal. Responsiveness to HBV vaccination was observed in 17 (68%) CD patients and all (100%) control subjects (P = 0.006). In conclusion, CD should also be sought in unresponders to HBV vaccine who are not immunosuppressed.