International Journal of Celiac Disease

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Authors: Andrew C. Berry, Rahman Nakshabendi, Ozdemir Kanar, Hussein Abidali, Ahmad Nakshabandi, Aaron C. Baltz, James T. Kwiatt

Several studies have described celiac disease patients presenting with esophageal symptoms. We present the case of a 33-year-old Caucasian woman who presented with three months of strictly dysphagia to solids. She reported no weight loss, abdominal pain, or diarrhea and reported no heartburn symptoms. Labs revealed a tissue transglutaminase IgA of >100 units. Biopsies revealed moderate to severe villous blunting and increased intraepithelial lymphocytosis consistent with Marsh 3 celiac disease in the 2nd and 3rd portions of the duodenum. To the best of our knowledge, this case represents the first reported case of dysphagia as initial and sole presentation of celiac disease completely resolved by gluten-free diet.

3

Authors: Pablo Olivera, Juan Lasa

Celiac Disease is a chronic inflammatory disease, caused by an abnormal immune response triggered by intestinal exposure to dietary gluten, the protein fraction of wheat, rye and barley, in genetically susceptible individuals. Among atypical presentations of Celiac Disease, reproductive disorders and adverse pregnancy outcomes have been reported. Infertility is defined as the impossibility of conceiving after 12 months of unprotected intercourse. It can be related to both male and female factors, with the latter subdivided into ovarian, tubal, endometrial or unexplained causes. Celiac Disease has been related to infertility, but the evidence is inconclusive. In this review, we discuss the effect of Celiac Disease in both male and female fertility, as well as the possible mechanisms that may be involved.

3

Authors: Aaron Lerner, Torsten Matthias

Celiac disease, once deemed to be primarily a pediatric disease, is accepted nowadays as a lifelong disease that increasingly affects the elderly. In older patients it is late and underdiagnosed, it is hypo- or asymptomatic and case finding strategy is recommended. Gluten restrictive therapy is problematic but manageable and beneficial, improving symptoms, serology, histology and preventing complications. Increased knowledge and awareness on CD in the third age and a comprehensive, multidisciplinary and holistic approach will improve their outcome.

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Authors: Janaína Luz Narciso-Schiavon, Leonardo L. Schiavon

Celiac disease is known for its classic clinical manifestations such as anemia and diarrhea. Liver involvement in celiac disease has been studied for more than thirty years. We review different etiologies of liver diseases and their possible association with celiac disease and seek to define in which situations serological screening should be performed.

6

Authors: Amaya Oyarzún, Talya Nakash, Jimena Ayala, Yalda Lucero, Magdalena Araya

Background. Celiac disease has a high prevalence globally and to date the only effective treatment is a strict gluten-free diet for life. Diet compliance is difficult due to current unhealthy eating habits and increasing overweight/obesity, especially for school age children. Objectives. To assess availability, cost and nutritional adequacy of gluten-free school snacks. Methods. Five store categories (large, regular-size and wholesale supermarkets, health food stores and corner shops) were assessed in districts representing low, middle and high socioeconomic levels. Three categories of school snacks were surveyed: dairy products (milk boxes, yogurts), cereals (in bulk, cereal bars) and baked goods (various cookies). Portions and prices were standardized and the closest gluten-containing products were matched for comparison. Availability, cost and nutritional quality (total calories, total fat, carbohydrates and sodium) were then evaluated. Results. A total of 1562 products were assessed. Gluten-free products were less available, with significant differences among the socioeconomic levels for cereals and baked goods (P<0.05). Also, they were more expensive than gluten-containing products. Except for cereal calories and sodium in the upper socioeconomic level, less than one third of the products available met FAO/WHO recommendations. Products meeting all 4 characteristics (total calories, total fat, carbohydrates and sodium) analyzed were 7.8%, 7.3% and 7.3% in the upper, middle and low socioeconomic level, respectively. Conclusions. Gluten-free dairy products, cereals and baked snacks available as snacks for school-age celiac children are fewer, with less variety and more expensive than gluten containing counterparts; the majority of them not meeting current nutritional recommendations.

1

Authors: Ana de Andrés Martín

no abstract

2

Authors: Scott W. Radcliffe

no abstract

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Authors: Aaron Lerner, Kai Prager, Torsten Matthias

Transient anti transglutaminase2 and anti endomysial antibody elevation in systemic lupus erythematosus is fundamentally thought-provoking with respect to establishment of autoimmunity and its progression. Celiac disease and systemic lupus erythematosus are both relayed within the mosaic framework of autoimmunity. Transglutaminase2 is a multifunctional enzyme, involved in cell biology and survival and is one of the post translational modifiers of protein, enhancing autoimmunity. TG2 and its specific antibodies are heavily involved in celiac disease. TG2 is essential in clearance of apoptotic cells and experimentally participates in systemic lupus-like induction. However, the role of anti TG2 autoantibodies is far from being unraveled. Despite disappearance of these antibodies on gluten containing diet, in the present case, the boy is at risk of developing celiac disease in the future.

3

Authors: Hugh J. Freeman

A number of studies have explored the role of different serological methods along with endoscopic biopsies for celiac disease population screening as well as case finding in clinical practice. Serological testing with quantitative assays is highly sensitive with a positive predictive value for strongly positive levels of tissue transglutaminase antibodies approaching 80% or more. In a recent comparative study, endoscopic biopsies were reported to have a positive predictive value up to 100% and appear to be especially valuable in selected groups with key symptoms, including diarrhea, weight loss and anemia. Overall, studies have suggested that celiac disease occurs in about 1% of the population in some nations of Europe and the United States. However, in some symptomatic patients referred for endoscopic evaluation, added duodenal biopsy is a critical investigative tool that, in many instances, has been underutilized as a case-finding tool. Some long-term studies have also suggested that detection of celiac disease has increased, possibly due to better awareness and recognition. Others believe that a recent increase in the disease per se may have occurred, possibly related to environmental factors, including newly developed pharmacologic or biologic agents.

4

Authors: Federico Morreale, Nicoletta Pellegrini

no abstract

2

Authors: Imed Ben Ghorbel, Raouf Hajji, Nabil Bel Feki, Thouraya Ben Salem, Mounir Lamloum, Mohammed Habib Houman

Pellagra is an exceptional skin involvement in celiac disease. Ischemic cardiomyopathy is another rare event in celiac disease. Its pathogenesis remains not yet elucidated. We report a case of a 34- year old patient of presenting with pellagra and cardiomyopathy revealing a celiac disease.

3

Authors: Aaron Lerner, Torsten Matthias

The first description of celiac disease associated with dilated cardiomyopathy and pellagra in the same person, brings multiple interesting aspects to discuss. Celiac disease is prevalent in cardiac failure and vice versa, multiple cardiac manifestations exist in celiac disease. Pathophysiologically, autoimmune, nutritional, infectious and thrombophilic pathways can be involved. In some cases the cardiomyopathy respond to gluten free diet. Multiple cutaneous manifestations, including pellagra like rash, were described in CD. Autoimmune mechanisms and much more, (e.g. nutrient deficiencies) might aggravate the skin manifestation. The present editorial highlights the cardiac-cutaneous-intestinal cross talks in celiac disease in order to increase the awareness of the physician community to speed up celiac disease diagnosis in those extraintestinal manifestations.

4

Authors: Juan Sebastian Lasa

Refractory Celiac Disease is a rare condition associated with a substancial mortality rate. Both treatment and follow-up are still matter of debate. The case of a 54 year-old man with refractory celiac disease is presented who required treatment with both budesonide and azathioprine. A concise review of the clinical Management of Refractory Celiac Disease is then performed.

5

Authors: Melisa Jazmín Hidalgo, Roxana Noelia Villafañe, Sonia Cecilia Sgroppo, Eduardo Jorge Marchevsky, Roberto Gerardo Pellerano

Celiac disease is a food intolerance triggered by the ingestion of gluten-containing cereals; the only therapy is a strict gluten-free diet for life. In recent years, gluten-free cereal bars has achieved considerable attention as an interesting alternative food considering its several advantages, such as functional properties, nutritional contents, variety of presentations and flavors. The aim of this study was to determine the contents of three toxic trace elements (arsenic, cadmium and lead) in commercial gluten-free cereal bars marketed in Argentina by ICP-MS and assess the dietary intake of the three toxic elements compared with reference values. The results obtained indicated that the highest total concentration of arsenic is provided by the gluten-free cereal bars with green apple pomace (28.2 μg/kg) and the levels of cadmium were lower than 10 μg/kg or even below MDL in all samples. The lead contents in all bars with honey samples were exceptionally higher than in the other samples (levels greater than 130 μg/kg). The intake of available gluten-free cereal bars are generally safe for consumers, but particular attention should be paid to monitor the content of arsenic and lead gluten-free cereal bars to ensure the quality of the product. Further studies are necessary to achieve an exact risk evaluation, concerning the bioavailability of trace elements in gluten-free food sources.

6

Authors: Aaron Lerner, Torsten Matthias

The surge in incidence of celiac disease (CD) is due more to environmental than to genetic changes. It is paralleled by a food industry that is continuously introducing additives to processed products. Microbial transglutaminase (mTG) is an enzyme that deamidates/transamidates proteins, enabling cross-linkage of molecules and revolutionizing the properties of many food products. It belongs to the family of transaminases and tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Both enzymes de/transamidate gluten, the nutritional environmental factor that induces CD. Although several studies have shown that mTG transamidation of wheat flour/gluten can detoxify gluten peptide in vitro, by inhibiting the response to intestinal gliadin, inducing T cells and reducing INFγ production without influencing their main technological properties, a word of caution is advised. The oral challenge of adult CD patients with mTG transamidated flour was found to be only partially effective, not fulfilling expectations, and there have been multiple recent observations that indicate that mTG transamidated flour/gluten could be dangerous to gluten sensitive populations: mTG cross-linking of gluten may be hazardous in CD since the enzyme can deamidate gluten, thus mimicking endogenous tTG, it can link an extensive repertoire of proteins and other macromolecules with immunogenic potential, mTG treated gluten peptides are immunogenic to celiac patients, inducing specific IgA antibodiesand are recognized by gluten-specific humanT cells. Their effect on CD intestinal permeability has not yet been studied. To better understand the actual processes and events, associated with the suggested mTG therapy, long-term ex vivo and in vitro studies are needed. Until then, it is best to respect the data but suspect the safety of the gluten sensitive populations.

2

Authors: Carlos Castillo-Duran, Johanna Pacheco-Acosta

This editorial highlights the role of micronutrient deficiencies in the clinical presentation of celiac disease. The clinical presentation of celiac disease in children is apparently changing from forms with evident gastrointestinal signs and symptoms to frequent silent clinics. Manifestations of micronutrient deficiencies are frequently found now, especially that of Fe and Zn, but also many other micronutrients, sometimes observed after many years of diagnosis. Celiac disease can be suspected when an unexplained micronutrient deficiency is found and it is recommended to assess micronutrient status periodically during the course of disease.

2

Authors: Sur Genel, Samasca Gabriel, Flonca Emanuela, Rus Anca, Abrudan Carmen, Donca Valer, Deleanu Diana

Celiac disease has many manifestations and the diagnosis is often difficult. We report the case of a child to which extradigestive manifestations of celiac disease masked celiac disease evolution. The association of proven allergic manifestations slowed celiac disease diagnosis.

3

Authors: Kvetoslava Rimarova

Celiac disease is chronic disease with immune disorder which is connected with the allergy reaction on molecule of gluten and prolamine. Celiac disease is expressed in persons with genetic susceptibility. The aim of the study was to follow adherence to gluten-free diet. We designed cross-sectional study where was recruited 125 volunteers, children at age 9 - 15 years old, with diagnosis of celiac diseases confirmed by European Society for Pediatric Gastroenterology Hepatology and Nutrition criteria. The data were collected in 2012-2013. In the selected group of celiac children were 78 girls and 47 boys. Compliance with diet is statistically significantly higher among girls comparing to boys. It means that girls adhered diet better than boys. Also younger group of children have a little bit higher compliance with gluten-free diet comparing to older group, but OR was not statistically significant. Our outputs didn’t confirm fact that duration of disease is important factor which may influence the compliance with gluten-free diet, but more close is a relationship in diet compliance in children with shorter duration of disease.

4

Authors: Nóra Judit Béres, Erna Sziksz, Ádám Vannay, Dolóresz Szabó, Domonkos Pap, Apor Veres-Székely, András Arató, Attila J. Szabó, Gábor Veres

Microbiome is the community of commensal, symbiotic and pathogenic microorganism that share our human body space. Intestinal microbiota has a defensive role in human health, it is implicated in metabolic and nutritional processes and plays an important role in the pathophysiology of several diseases. In recent years special attention has been paid to investigations targeting the changes of intestinal microbiome in various gastrointestinal disorders including inflammatory bowel disease, infectious colitis and celiac disease (CD). The aim of our present review is to summarize the role of the microbiome in CD and the changes of its composition in the intestine of patients suffering from CD.

5

Authors: Wendy Miller, Andrew S Day

In 2012 the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published an updated guideline for the diagnosis of Coeliac disease, allowing symptomatic individuals with appropriate serology and HLA genotype to be diagnosed without a small bowel biopsy. This retrospective study aimed to assess the applicability of this guideline to children in New Zealand. Children less than 16 years of age investigated for coeliac disease with small bowel biopsy in Christchurch Hospital between January 2010 and December 2012 were identified. The results of those with tissue transglutaminase IgA (tTG) levels greater than 50 units (10 times upper limit of normal), positive endomysial antibodies and HLA DQ2/DQ8 were used to calculate sensitivity and specificity. Data from 160 children was available: 70 had biopsy-confirmed Coeliac disease, and 90 had negative biopsies. Limited data precluded application of the guidelines to all patients. Using only tTG data, levels above 50 units provided a sensitivity of 67% and a specificity of 92%. Specificity increased to 97% when limited EMA and HLA DQ2/DQ8 data was added. Despite limited data, applying the ESPGHAN guidelines in the Christchurch paediatric population over this period produced a high specificity (97%). Prospective studies are now required to confirm these findings.

1

Authors: Diana Deleanu, Nicolae Miron, Iulia Lupan, Gabriel Samasca

no abstract

3

Authors: Pavel Kohout

Nutrition plays a key role in patients with celiac disease. Gluten-free diet is main therapeutic option despite of new possibilities keeping the intestinal barrier, modulation of gut microbiome or extraction of gluten from the diet. The prevention of formation the autoimmune reaction against gluten in genetically predisposed patients is the addition of small amount of gluten-rich food during breastfeeding between 4th and 7th months of life. The possible prevention at a later age could include the keeping of gluten-free diet during stress-induced damage of intestinal barrier and/or the influence of gut microbiom using probiotics.Gluten-free diet become to be new phenomenon, new strategy for non-celiac population despite of absency of proven benefits for them. There are defined new clinical entities of gluten intolerance, especially non-celiac gluten sensitivity, but its differentiation from irritable bowel syndrome is very difficult. This issue will require further research.

4

Authors: Erna Sziksz, Apor Veres-Székely, Domonkos Pap, Andrea Fekete, Gábor Veres, Tivadar Tulassay, Attila Szabó, Ádám Vannay

Celiac disease (CD) is the most common autoimmune enteropathy in the western world caused by the intolerance to gluten in genetically predisposed individuals. CD is characterized by a remarkable rearrangement of the mucosal architecture, in which process myofibroblasts play a crucial role. Myofibroblasts (intestinal subepithelial myofibroblasts and interstitial cells of Cajal) are the most represented mesenchymal cell types in the gut mucosa and are involved in a broad range of biological processes including growth, mucosal protection, repair, inflammation and fibrosis. Myofibroblasts actively contribute to the mucosal changes in CD due to their ability to produce an excessive amount of extracellular matrix and basement membrane components (e.g. collagens, fibronectin, and specific enzymes including tissue transglutaminases) and through the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). The enhanced production of ECM components and MMPs and the altered shape and motility of myofibroblasts in the duodenal mucosa of patients with CD suggest that myofibroblasts may play an essential role in the pathogenesis of CD.

5

Authors: Zuzana Mlyneková, Mária Chrenková, Zuzana Formelová

Cereals and legumes rank among the most important group of crop plant production. The aim of this paper was to point out the suitability of cereals and legumes in the diet of people living with an autoimmune disease of the small intestine, the celiac disease. Cereals match the best current ideas of healthy and balanced diet and provide decisive part of the energy intake from food in human nutrition and no small share from the total protein intake. Some cereals contain celiac active polypeptides and in susceptible individuals cause allergic reactions. Celiac active ingredients are found in the prolamin fraction. If the content of prolamine is in an amount of 4-8%, the products can be considered appropriate for the celiac diet. Wheat, barley, rye and oat should be excluded from the diet, if a person has confirmed celiac disease. On a worldwide basis, legumes contribute to about one-third of humankind's direct protein intake. Legumes also accumulate natural products (secondary metabolites) such as isoflavonoids that are considered beneficial to human health through anticancer and other health-promoting activities. The biggest advantage of legumes is that they are gluten-free and are suitable for gluten-free diet.

5

Authors: Aaron Lerner

Celiac disease (CD) is a life-long autoimmune condition affecting the small intestine of genetically susceptible individuals. Gluten is one of the offending inducers of the disease, with structurally related molecules found in barley, rye, and oats, where the offending peptides are called avenins. Avoiding toxic prolamins is the only established therapy but most patients have compliance difficulty on a gluten-free diet. Oats are considered less immunogenic than other cereals, and have high nutritional value, which is very desirable in an often undernourished celiac population; however, the consumption of oats by patients with CD is still controversial and debatable. Most clinical and in vitro studies favor oat consumption, but many of these studies were poorly designed and oat cultivar and purity was not considered. A recent study reported a wide range of susceptibility to avenin peptides in patients with CD. Oat cultivars can be subdivided based on toxicity and immunogenicity into none, partial, or highly immunogenic types. Furthermore, most commercial oat products are likely to be contaminated byprolamins. Those products should be avoided by the celiac population and well labeled for contaminants containing gluten. More basic and clinical research and active national celiac associations efforts are needed to characterize the place of oats in a gluten-free diet and to implement non immunogenic and uncontaminated oat products for the benefit of patients with CD. Great care should be taken when recommending consumption of commercial oat products to patients with CD. The most important messages of the review are: 1. Immunogenic oat cultivars are present in oat products. Patients with CD should be cautioned about using them when on a gluten-free diet. 2. Many oat products are cross contaminated with toxic levels of gluten. 3. Interstudy comparisons are difficult because of variability in design, conditions during testing, and difference in oat cultivars studied. Several studies also had small cohorts or significant patient withdrawals during studies. 4. This review aims to encourage clinical and in vitro studies to investigate the benefits of recommending oats in a gluten-free diet.