Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation

AIM: To investigate the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults.METHODS: Besides subjects with classical gastrointestinal presentation of celiac disease, the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups. Altogether 405 patients underwent clinical, serological and histological evaluations. After collection of data, the antibody values were further graded as low [endomysial (EmA) 1:5-200, transglutaminase 2 antibodies (TG2-ab) 5.0-30.0 U/L] and high (EmA 1: ≥ 500, TG2-ab ≥ 30.0 U/L), and the serological results were compared with the small intestinal mucosal histology and clinical presentation.RESULTS: In total, 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet.CONCLUSION: Irrespective of the initial serum titers or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.     

Changing presentation of adult celiac disease

The mode of presentation of celiac disease in the United States is not known. We investigated the demographic and clinical features of 227 patients with biopsy-proven celiac disease and determined if there had been changes over time. The patients had been entered into a database; those seen prior to 1990 were retrospectively entered while those seen subsequently were prospectively entered. A symptomatic presentation described the classical presentation of celiac disease with prominent gastrointestinal symptoms: diarrhea and weight loss. Females were younger and had a longer duration of symptoms compared to males. The modes of presentation were symptomatic (62%), anemia or reduced bone density (15%), screening first-degree relatives (13%), and incidental diagnosis at endoscopy (8%). We compared those diagnosed before and after 1993 (when serologic testing was first used), and noted a reduction in those presenting with diarrhea, 73% vs 43% (P = 0.0001) and a reduction in the duration of symptoms, from 9.0 ± 1.1 years to 4.4 ± 0.6 years (P < 0001). In conclusion, the percentage of celiac disease patients presenting with diarrhea has decreased, probably related to the more widespread use of serologic testing for celiac disease.     

Capsule endoscopy in celiac disease

Video capsule endoscopy is an attractive and patient- friendly tool that provides high quality images of the small bowel. Obscure gastrointestinal bleeding is the primary and most evaluated indication to capsule endoscopy; however, indications are expanding and a small number of preliminary reports have been presented concerning the role of video capsule endoscopy in the diagnosis of celiac disease. The purpose of this review is to update the current knowledge and to hypothesize on future perspectives of the use of video capsule endoscopy in patients with celiac disease.     

乳糜泻发生机理与临床研究进展

乳糜泻(CD)是遗传易感者摄入麸质后,由免疫系统介导的以乳糜样腹泻为主的全身性疾病。CD发病与遗传、免疫和环境等因素有关,有地域和种族差异,临床表现复杂多样,并伴有吸收不良引起的贫血、疱疹性皮炎等并发症。随着血清特异性抗体检测、基因分析和小肠活检等方法的研究推广,可进行人群筛选和早期诊治。     

Age-related differences in celiac disease: Specific characteristics of adult presentation

Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients.     

Erythrocytic transglutaminase inhibition hemolysis at presentation of celiac disease

Celiac disease (CD) is a common autoimmune condition.Previously it was considered to be a rare childhood disorder,but is actually considered a relatively common condition,present at any age,which may have multiple complications and manifestations.Hematological disorders of the disease are not uncommon.Among these disorders,the most frequently reported are anemias as a result of iron deficiency,often associated with folate and/or B12 deficiency.Anemias caused by hemolysis are very rarely reported in celiac p...     

Liver complications in celiac disease

Celiac disease (CD) is characterized by sensitivity to gluten, which is found in dietary wheat, barley, and rye. Many extra-intestinal manifestations have been described in association with CD. Liver disease and CD share widespread risk factors. Liver disorders such as autoimmune hepatitis, elevation of liver enzyme levels, primary biliary cirrhosis, nonspecific hepatitis, primary sclerosing cholangitis, and nonalcoholic fatty liver disease have been reported in patients with CD. In this review, we provide information regarding liver disorders that may be found in association with celiac disease and the effect of the treatment of CD on these disorders.     

The global village of celiac disease

In the last years our knowledge on epidemiology of celiac disease has increased: there is a wide spectrum of its clinical presentation (classical, atypical, silent and latent forms of celiac disease), and of its pathological mucosal intestinal features, which range from early and mild pictures to severe villous atrophy (Marsh stages). In addition, a strong genetic component, associated with the susceptibility to the disease (HLA and non HLA genes), has been found. This knowledge, together with the availability of new high sensitive and specific serological tests (antigliadin, antiendomysium and antitransglutaminase antibodies), has led us to the realization that celiac disease is the most common food intolerance in the world, involving genetically predisposed individuals consuming gluten-containing cereals in their diet. So, today it is well known that celiac disease is a common disorder not only in Europe but also in populations of European ancestry (North and South Americas, Australia), in North Africa, in the Middle East and in South Asia, where until a few years ago it was historically considered extremely rare. Therefore, celiac disease is spread worldwide as in a common "Global Village", and greater levels of awareness and attention on gluten intolerance are needed, both in the Old and in the New World.     

Adult celiac disease in the elderly

There is an increased awareness that celiac disease may occur in the elderly although presentations with either diarrhea, weight loss or both may be less common causing delays in diagnosis for prolonged periods. Higher detection rates also seem evident owing to active case screening, largely through serodiagnostic measures. In some elderly patients who are genetically predisposed, it has been hypothesized that celiac disease might be precipitated late in life by an antigen, possibly from an infectious agent. As a result, peptide mimicry or other poorly-defined mechanisms may precipitate an autoimmune gluten-dependent clinical state. Although diarrhea and weight loss occur, only isolated iron deficiency anemia may be present at the time of initial diagnosis. In addition, the risk of other autoimmune disorders, particularly autoimmune thyroiditis, and bone disease, are increased. Osteopenia may also be associated with an increased risk of fractures. Finally, elderly celiacs have an increased risk of malignant intestinal disease, especially lymphoma.     

The role of ultrasonography in patients with celiac disease

The aim of the present review was to summarize thecurrent evidence on the role of ultrasonography(US)anddoppler-US in the diagnosis of celiac disease.Several ultrasonographic signs have been reported inthe association with celiac disease in studies using real-time US.Firstly,case control studies identified some ofthese US signs and then in a prospective series someof these parameters,due to their high specificity,havebeen shown to be of value in confirming CD diagnosis,whereas others,due to their high sensitivity,have beendemonstrated to be useful in excluding the presence ofthe disease.The pattern of splanchnic circulation in CD haveextensively been investigated by several studies allof which reported similar results and identified a hy-perdynamic mesenteric circulation that reverts to no-rmal values after successful a gluten-free regimen.The last part of this review will deal with the possiblerole of US in identyfing the most severe and commonintestinal complication of CD,i.e.the enteropathy-associated T cell non-Hodgkin lymphoma.     

Role of oats in celiac disease

A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with thiscondition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of glutenfree ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.     

Cutaneous manifestations in celiac disease

Celiac disease(CD)is an autoimmune gluten-dependententeropathy characterized by atrophy of intestinalvilli that improves after gluten-free diet(GFD).CD isoften associated with extra-intestinal manifestations;among them,several skin diseases are described in CDpatients.The present review reports all CD-associatedskin manifestations described in the literature and triesto analyze the possible mechanisms involved in thisassociation.The opportunity to evaluate the possiblepresence of CD in patients affected by skin disorders isdiscussed.     

Refractory celiac disease

Refractory celiac disease (RCD) affects patients who have failed to heal after 6–12 months of a strict gluten-free diet (GFD) and when other causes of symptoms (including malignancy) have been ruled out. It may also occur in patients who previously had responded to a long-term GFD. RCD may be categorized as RCD1 (normal immunophenotype) and RCD2 (aberrant immunophenotype). RCD1 usually responds to a continued GFD, nutritional support, and therapeutic agents such as corticosteroids. In contrast, clinical response in RCD2 is incomplete and prognosis is often poor. RCD (particularly RCD2) is associated with serious complications, such as ulcerative jejunitis and enteropathy-associated T-cell lymphoma (EATL). Strict clinical and laboratory criteria should be used to diagnose RCD and specialized tests for aberrancy and clonality should be interpreted in the context of their sensitivity and specificity. Adequate nutritional support and anti-inflammatory treatment may even allow patients with RCD2 to attain a clinical remission.     

Screening for celiac disease in Danish adults

Abstract

Objective. The prevalence of celiac disease (CD) as recorded in the Danish National Patient Registry is ～50/100,000 persons. This is much lower than the reported prevalence of CD in other Nordic countries and underdiagnosis is suspected. Our aim was to estimate the prevalence of CD in a population-based study of Danish adults. Methods. A total of 2297 adults aged 24–76 years living in the southwestern part of Copenhagen were screened for CD by immunoglobulin (Ig)A and IgG antibodies to transglutaminases and deamidated gliadin. IgA/IgG-positive participants were invited to a clinical evaluation, including biopsies, by a gastroenterologist. Results. Of the invited 56 participants, 40 underwent a full clinical evaluation and 8 persons were diagnosed with CD; 2 of the 16 persons, who did not complete the clinical evaluation, were considered by experts to have probable CD. None of the above 56 participants had a known history of CD or a recorded diagnosis of CD in National Patient Registry. By combining cases of biopsy-proven CD (n = 8), probable CD (n = 2), and registry-recorded CD (n = 1), the prevalence of CD was estimated to be 479/100,000 (11/2297) persons (95% CI: 197–761). Conclusion. In this general adult population, the prevalence of CD as estimated by screening and clinical evaluation was 10 times higher than the registry-based prevalence of CD. Of 11 participants diagnosed with CD in our screening study, 10 were unaware of the diagnosis prior to the study. Thus, our study suggests that CD is markedly underdiagnosed in Danish adults.     

Pneumococcal vaccination in celiac disease

Introduction: Celiac disease (CD) is an immune-mediated disorder associated with gluten exposure in genetically predisposed subjects.

Areas covered: Infectious disease is one of the causes of morbidity and mortality in CD patients. Invasive streptococcus pneumoniae (pneumococcus) is a particularly dangerous morbid condition in both the general population and celiac patients. Pneumococcal vaccination is the most effective means for its prevention.

Expert opinion: In CD, evaluation of spleen function should be useful to select patients who may benefit from vaccination to reduce the risk of pneumococcal disease. Different strategies could be employed: physicians could search for signs of hyposplenism on peripheral blood smear or abdominal ultrasound. However, the best strategy to identify which patients will benefit from pneumococcal vaccination has not yet been defined.     

Prevalence of celiac disease and celiac autoimmunity in the Toba native Amerindian community of Argentina

BACKGROUND:

Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD.

OBJECTIVE:

To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission.

METHODS:

An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies.

RESULTS:

A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype.

CONCLUSION:

The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.     

Liver involvement in pediatric celiac disease

Celiac disease(CD) is an intestinal inflammatory disease that manifests in genetically susceptible individuals when exposed to dietary gluten. It is a common chronic disorder, with a prevalence of 1% in Europe and North America. Although the disease primarily affects the gut,the clinical spectrum of CD is remarkably varied, andthe disease can affect many extraintestinal organs and systems, including the liver. The hepatic dysfunction presenting in CD ranges from asymptomatic liver enzyme elevations or nonspecific reactive hepatitis(cryptogenic liver disorders), to chronic liver disease.In this article, we review the clinical presentations and possible mechanisms of CD-related liver injury to identify strategies for the diagnosis and treatment of these disorders in childhood.     

Malignancy in adult celiac disease

Prior studies have suggested that the incidence of some neoplastic disorders, particularly malignant lymphoma and small intestinal adenocarcinoma, are increased in celiac disease. Earlier studies from the United Kingdom have also suggested a link between celiac disease and esophageal carcinoma, although this has not been confirmed in North America. The risk oF other gastrointestinal cancers seems to be limited. Gastric cancer does not appear to be detected more frequently, although direct endoscopic visualization of the upper gastrointestinal tract is now very common in patients with celiac disease. Colon cancer also appears to be limited in celiac disease, even in patients first diagnosed with celiac disease late in life. This has led to the hypothesis that untreated celiac disease may be protective, possibly owing to impaired absorption of fat or fat-soluble agents, including hydrocarbons and putative co-carcinogens implicated in the pathogenesis of colon cancer, which may be poorly absorbed and rapidly excreted.     

New aspects in celiac disease

Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA- DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis.