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Advances in Celiac Disease

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A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 50678

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Prof. Dr. Luis Rodrigo

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Hospital Universitario Central de Asturias (HUCA), Gastroenterology Unit, Oviedo, Spain
Interests: celiac disease; gluten intolerance; Helicobacter pylori; gastrointestinal tumors; liver diseases
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Special Issue Information

Dear Colleagues,

Celiac disease is an autoimmune disorder induced by dietary gluten that affects to genetically predisposed individuals. It has a prevalence of 1–2% in many populations worldwide. New diagnoses have increased substantially in the last decades, due to increased awareness, better diagnostic tools, and probably, by a real increase in its incidence.
The list of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. It is frequently associated along its evolution with a long spectrum of other diseases, mainly autoimmune in nature, that by one side ease its diagnosis and sometimes complicate its clinical evolution.

Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate the diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always is very effective in controlling symptoms or intestinal damage.

We would also like to encourage the submission of original manuscripts, communications, reviews, case reports aimed at providing a comprehensive overview of the recent advances in understanding celiac disease.

Prof. Dr. Luis Rodrigo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Celiac disease
Epidemiology
Autoimmune
Diagnostic methods
Serologic tests
Genetic markers
Immunology
Pathogenesis
Duodenal biopsy findings
Associated conditions
Non-celiac gluten sensitivity
Gluten-free diet
Long-term follow-up
Refractory
Intestinal Lymphoma
Complications

Published Papers (10 papers)

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Editorial

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3 pages, 239 KiB

Open AccessEditorial

Celiac Disease: A Common Unrecognized Health Problem with a Very Delayed Diagnosis

by Luis Rodrigo

Medicina 2020, 56(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56010009 - 26 Dec 2019

Cited by 6 | Viewed by 1994

Abstract

Celiac disease (CD) is a clinical entity of autoimmune nature, related to the presence of a permanent gluten intolerance that affects genetically predisposed individuals, producing a chronic inflammation process that usually occurs in the small bowel [...] Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

Research

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9 pages, 2206 KiB

Open AccessArticle

Translation, Cultural Adaptation, and Evaluation of a Brazilian Portuguese Questionnaire to Estimate the Self-Reported Prevalence of Gluten-Related Disorders and Adherence to Gluten-Free Diet

by Jesús Gilberto Arámburo-Gálvez, Itallo Carvalho Gomes, Tatiane Geralda André, Carlos Eduardo Beltrán-Cárdenas, María Auxiliadora Macêdo-Callou, Élida Mara Braga Rocha, Elaine Aparecida Mye-Takamatu-Watanabe, Vivian Rahmeier-Fietz, Oscar Gerardo Figueroa-Salcido, Feliznando Isidro Cárdenas-Torres, Noé Ontiveros and Francisco Cabrera-Chávez

Medicina 2019, 55(9), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55090593 - 15 Sep 2019

Cited by 9 | Viewed by 2873

Abstract

Background: A Spanish version of a questionnaire intended to estimate, at the population level, the prevalence rates of self-reported gluten-related disorders and adherence to gluten-free diets has been applied in four Latin American countries. However, idiom issues have hampered the questionnaire application in the Brazilian population. Thus, the aim of the present study was to carry out a translation, cultural adaptation, and evaluation of a Brazilian Portuguese questionnaire to estimate the self-reported prevalence of gluten-related disorders and adherence to gluten-free diets in a Brazilian population. Materials and Methods: Two bilingual Portuguese–Spanish health professionals carried out the translation of the original Spanish version of the questionnaire to Brazilian-Portuguese. Matching between the two translations was evaluated using the WCopyFind.4.1.5 software. Words in conflict were conciliated, and the conciliated version of the Brazilian Portuguese instrument was evaluated to determine its clarity, comprehension, and consistency. A pilot study was carried out using an online platform. Results: The two questionnaires translated into Brazilian Portuguese were highly matched (81.8%–84.1%). The questions of the conciliated questionnaire were clear and comprehensible with a high agreement among the evaluators (n = 64) (average Kendall’s W score was 0.875). The participants did not suggest re-wording of questions. The answers to the questions were consistent after two applications of the questionnaire (Cohen’s k = 0.869). The pilot online survey yielded low response rates (9.0%) highlighting the need for face-to-face interviews. Conclusions: The translation and evaluation of a Brazilian Portuguese questionnaire to estimate the self-reported prevalence rates of gluten-related disorders and adherence to gluten-free diets was carried out. The instrument is clear, comprehensible, and generates reproducible results in the target population. Further survey studies involving face-to-face interviews are warranted. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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10 pages, 678 KiB

Open AccessArticle

by Tsvetelina Velikova, Martin Shahid, Ekaterina Ivanova-Todorova, Kossara Drenovska, Kalina Tumangelova-Yuzeir, Iskra Altankova and Snejina Vassileva

Medicina 2019, 55(5), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55050136 - 15 May 2019

Cited by 9 | Viewed by 2076

Abstract

Background and objectives: Dermatitis herpetiformis (DH) is a blistering dermatosis, which shares common immunologic features with celiac disease (CD). The aim of the present study was to explore the performance of a panel of CD-related antibodies and IL-17A in Bulgarian patients with DH. Materials and Methods: Serum samples from 26 DH patients at mean age 53 ± 15 years and 20 healthy controls were assessed for anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin antibodies (AAA), and IL-17A by enzyme linked immuno-sorbent assay (ELISA), as well as anti-tTG, anti-gliadin (AGA), and anti-Saccharomyces cerevisiae antibodies (ASCA) using immunoblot. Results: The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and the cytokine IL-17A were at significantly higher levels in patients with DH compared to the average levels in healthy persons which stayed below the cut-off value (p < 0.05). Anti-DGP and anti-tTG antibodies showed the highest diagnostic sensitivity and specificity, as well as acceptable positive and negative predictive value. None of the healthy individuals was found positive for the tested antibodies, as well as for ASCA within the DH group. All tests showed good to excellent correlations (r = 0.5 ÷ 0.9, p < 0.01). Conclusions: Although the diagnosis of DH relies on skin biopsy for histology and DIF, serologic testing of a panel of celiac-related antibodies could be employed with advantages in the diagnosing process of DH patients. Furthermore, DH patients who are positive for the investigated serologic parameters could have routine monitoring for gastrointestinal complications typical for the gluten-sensitive enteropathy. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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Review

Jump to: Editorial, Research

17 pages, 705 KiB

Open AccessReview

The Skin in Celiac Disease Patients: The Other Side of the Coin

by Ludovico Abenavoli, Stefano Dastoli, Luigi Bennardo, Luigi Boccuto, Maria Passante, Martina Silvestri, Ilaria Proietti, Concetta Potenza, Francesco Luzza and Steven Paul Nisticò

Medicina 2019, 55(9), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55090578 - 09 Sep 2019

Cited by 27 | Viewed by 5562

Abstract

Celiac disease (CD) is an autoimmune enteropathy that primarily affects the small intestine and is characterized by atrophy of intestinal villi. The manifestations of the disease improve following a gluten-free diet (GFD). CD is associated with various extra-intestinal diseases. Several skin manifestations are described in CD patients. The present paper reviews all CD-associated skin diseases reported in the literature and tries to analyze the pathogenic mechanisms possibly involved in these associations. Different hypotheses have been proposed to explain the possible mechanisms involved in every association between CD and cutaneous manifestations. An abnormal small intestinal permeability seems to be implicated in various dermatological manifestations. However, most of the associations between CD and cutaneous diseases is based on case reports and case series and a few controlled studies. To better assess the real involvement of the cutaneous district in CD patients, large multicentric controlled clinical trials are required. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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8 pages, 290 KiB

Open AccessReview

Hematologic Manifestations in Celiac Disease—A Practical Review

by Daniel Vasile Balaban, Alina Popp, Florentina Ionita Radu and Mariana Jinga

Medicina 2019, 55(7), 373; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55070373 - 15 Jul 2019

Cited by 28 | Viewed by 3528

Abstract

Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

17 pages, 507 KiB

Open AccessReview

Micronutrients Dietary Supplementation Advices for Celiac Patients on Long-Term Gluten-Free Diet with Good Compliance: A Review

by Mariangela Rondanelli, Milena A. Faliva, Clara Gasparri, Gabriella Peroni, Maurizio Naso, Giulia Picciotto, Antonella Riva, Mara Nichetti, Vittoria Infantino, Tariq A. Alalwan and Simone Perna

Medicina 2019, 55(7), 337; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55070337 - 03 Jul 2019

Cited by 32 | Viewed by 5356

Abstract

Background and objective: Often micronutrient deficiencies cannot be detected when patient is already following a long-term gluten-free diet with good compliance (LTGFDWGC). The aim of this narrative review is to evaluate the most recent literature that considers blood micronutrient deficiencies in LTGFDWGC subjects, in order to prepare dietary supplementation advice (DSA). Materials and methods: A research strategy was planned on PubMed by defining the following keywords: celiac disease, vitamin B12, iron, folic acid, and vitamin D. Results: This review included 73 studies. The few studies on micronutrient circulating levels in long-term gluten-free diet (LTGFD) patients over 2 years with good compliance demonstrated that deficiency was detected in up to: 30% of subjects for vitamin B12 (DSA: 1000 mcg/day until level is normal, then 500 mcg), 40% for iron (325 mg/day), 20% for folic acid (1 mg/day for 3 months, followed by 400–800 mcg/day), 25% for vitamin D (1000 UI/day or more-based serum level or 50,000 UI/week if level is <20 ng/mL), 40% for zinc (25–40 mg/day), 3.6% of children for calcium (1000–1500 mg/day), 20% for magnesium (200–300 mg/day); no data is available in adults for magnesium. Conclusions: If integration with diet is not enough, starting with supplements may be the correct way, after evaluating the initial blood level to determine the right dosage of supplementation. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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19 pages, 1221 KiB

Open AccessEditor’s ChoiceReview

Non-Celiac Gluten Sensitivity: A Review

by Anna Roszkowska, Marta Pawlicka, Anna Mroczek, Kamil Bałabuszek and Barbara Nieradko-Iwanicka

Medicina 2019, 55(6), 222; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55060222 - 28 May 2019

Cited by 59 | Viewed by 15495

Abstract

Background and objectives: Grain food consumption is a trigger of gluten related disorders: celiac disease, non-celiac gluten sensitivity (NCGS) and wheat allergy. They demonstrate with non-specific symptoms: bloating, abdominal discomfort, diarrhea and flatulence. Aim: The aim of the review is to summarize data about pathogenesis, symptoms and criteria of NCGS, which can be helpful for physicians. Materials and Methods: The PubMed and Google Scholar databases were searched in January 2019 with phrases: ’non-celiac gluten sensitivity’, non-celiac gluten sensitivity’, non-celiac wheat gluten sensitivity’, non-celiac wheat gluten sensitivity’, and gluten sensitivity’. More than 1000 results were found. A total of 67 clinical trials published between 1989 and 2019 was scanned. After skimming abstracts, 66 articles were chosen for this review; including 26 clinical trials. Results: In 2015, Salerno Experts’ Criteria of NCGS were published. The Salerno first step is assessing the clinical response to gluten free diet (GFD) and second is measuring the effect of reintroducing gluten after a period of treatment with GFD. Several clinical trials were based on the criteria. Conclusions: Symptoms of NCGS are similar to other gluten-related diseases, irritable bowel syndrome and Crohn’s disease. With Salerno Experts’ Criteria of NCGS, it is possible to diagnose patients properly and give them advice about nutritional treatment. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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11 pages, 982 KiB

Open AccessReview

Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis

by Cristina Capittini, Annalisa De Silvestri, Chiara Rebuffi, Carmine Tinelli and Dimitri Poddighe

Medicina 2019, 55(5), 190; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55050190 - 22 May 2019

Cited by 13 | Viewed by 4548

Abstract

Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case–control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR−, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279–1.642) and 0.187 (CI 0.096–0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302–2.155) and, importantly, the LR− still showed a very good discriminatory power of 0.195 (CI 0.068–0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR− of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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10 pages, 672 KiB

Open AccessReview

Gluten Vehicle and Placebo for Non-Celiac Gluten Sensitivity Assessment

by Oscar Gerardo Figueroa-Salcido, Noé Ontiveros and Francisco Cabrera-Chavez

Medicina 2019, 55(5), 117; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55050117 - 26 Apr 2019

Cited by 8 | Viewed by 3314

Abstract

Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence of celiac disease and wheat allergy. Because of the lack of biomarkers for NCGS diagnosis, the cornerstone for its assessment is a single- or double-blind placebo-controlled (DBPC) gluten challenge. However, there are some non-standardized points in the diagnostic approach proposed by the experts. This complicate comparisons among the results published by different research groups. The gluten vehicle and placebo must be indistinguishable from each other, which entails sensory and technological evaluations of the designed gluten vehicle and placebo products. At the moment, there is no standardized method for the preparation of the gluten vehicle and placebo for carrying out DBPC gluten challenges for NCGS assessment. This review focuses on the challenges that researchers have to face, either for the development of an accepted gluten vehicle and placebo or for identifying NCGS cases on the basis of DBPC gluten challenges. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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8 pages, 605 KiB

Open AccessReview

Pediatric Celiac Disease in Central and East Asia: Current Knowledge and Prevalence

by Dimitri Poddighe, Marzhan Rakhimzhanova, Yelena Marchenko and Carlo Catassi

Medicina 2019, 55(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55010011 - 12 Jan 2019

Cited by 27 | Viewed by 4974

Abstract

The current prevalence of pediatric Celiac Disease (CD) is estimated to be around 1% in the general population, worldwide. However, according to the geographic area, a great variability of CD prevalence has been described. Whereas a number of studies are available from Europe, North and South America, Australia, South-West Asia, and North Africa, the knowledge and awareness of CD in large parts of the remaining world areas is definitively poor. In several countries of Central and East Asia, the consumption of wheat is consistent and/or has significantly increased in recent decades, and CD is supposed to be underdiagnosed in children. In this mini-review, we aimed to summarize the current knowledge about the prevalence of pediatric CD in Central and East Asia, paying attention to the HLA-DQ immunogenetic background as well. Indeed, CD is likely not to be as uncommon as previously or currently thought in countries like Russia, Kazakhstan, and China, in addition to India, where pediatric CD has been clearly showed to be quite prevalent. Therefore, there is an urgent need for population-based studies on the prevalence of CD in those countries, especially in children, in order to increase the awareness of this disease and to improve the diagnostic strategy in these areas. Full article

(This article belongs to the Special Issue Advances in Celiac Disease)

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