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1.
Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders.
Schiepatti, A, Savioli, J, Vernero, M, Borrelli de Andreis, F, Perfetti, L, Meriggi, A, Biagi, F
Nutrients. 2020;(6)
Abstract
The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.
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2.
Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.
Barbaro, MR, Cremon, C, Wrona, D, Fuschi, D, Marasco, G, Stanghellini, V, Barbara, G
Nutrients. 2020;(12)
Abstract
Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
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3.
Celiac disease in children.
Benelli, E, Zin, A, Martelossi, S
Minerva pediatrica. 2019;(1):39-46
Abstract
Celiac disease is a common immune-mediated disease, that may present, after gluten ingestion, with various and heterogeneous symptoms that can vary according to patients' age. The diagnostic screening test is serum anti-tissue transglutaminase IgA level. In doubt cases, antiendomysium IgA and the antideamidated gliadin peptides IgG could be useful to confirm the suspicion, before a biopsy will be perform. Since 2012, guidelines have made it possible to avoid the biopsy in symptomatic pediatric patients with high levels of antitransglutaminase IgA, positivity to antiendomysium IgA, and with HLA DQ2 or DQ8. In all other cases duodenal biopsy is still mandatory to confirm the diagnosis. The therapy of celiac disease is a lifelong gluten free diet. In children prognosis of celiac disease is good, without complications. Here we review and discuss the present literature about celiac disease in childhood.
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4.
Coeliac disease: beyond genetic susceptibility and gluten. A narrative review.
Pes, GM, Bibbò, S, Dore, MP
Annals of medicine. 2019;(1):1-16
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Abstract
Coeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals. However, only a small proportion of subjects harbouring CD-related genetic risk develop the disease. Among the environmental factors that may influence CD risk, pre- and perinatal factors, delivery methods, parental lifestyle, infant feeding practices, seasonality, dietary factors, drug use, childhood infections and variability in gut microbiota are those most widely studied regarding the risk to develop CD. Although for many of these external factors the exact mechanism of action is unknown, most of them are thought to act by disrupting the intestinal barrier, facilitating contact between potential antigens and the immune system effector cells. Management of CD is relatively easy in patients with a definite diagnosis and requires a strict, lifelong, gluten-free diet. Better knowledge of environmental exposures apart from gluten can facilitate understanding of the pathogenesis of the disorder and the wide heterogeneity of its clinical spectrum. The purpose of this review is to discuss current knowledge on environmental CD risk factors, as well as possible interaction between them, on the grounds of the reliable scientific evidence available. Key messages The risk of developing CD is influenced not only by gluten ingestion but also by a number of environmental factors including childhood infections and variability in gut microbiota, pre- and perinatal factors, infant feeding practices, delivery methods, parental lifestyle, seasonality, dietary factors and drug use, acting mainly by disrupting intestinal permeability. Better knowledge of exposure to these factors can facilitate their identification, and subsequent elimination, in the individual patient.
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5.
Celiac Disease: Updates on Pathology and Differential Diagnosis.
Dai, Y, Zhang, Q, Olofson, AM, Jhala, N, Liu, X
Advances in anatomic pathology. 2019;(5):292-312
Abstract
Celiac disease is a gluten-triggered immune-mediated disorder, characterized by inflammation of the enteric mucosa following lymphocytic infiltration and eventually resulting in villous blunting. There have been many developments in refining diagnostic laboratory tests for celiac disease in the last decade. Biopsy-sparing diagnostic guidelines have been proposed and validated in a few recent prospective studies. However, despite these developments, histologic evaluation of duodenal mucosa remains one of the most essential diagnostic tools as it helps in the diagnosis of celiac disease in individuals who do not fulfill the biopsy-sparing diagnostic criteria and in those not responding to a gluten-free diet. Histologic evaluation also allows for the assessment of mucosal recovery after treatment and in the identification of concurrent intestinal diseases. Therefore, pathologists should be familiar with the histologic spectrum of celiac disease and need to be aware of other disorders with similar symptoms and histopathology that may mimic celiac disease. This review aims to provide pathologists with updates on celiac laboratory testing, biopsy-sparing diagnostic criteria, histopathology, complications, and differential diagnoses of celiac disease.
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6.
Gluten Immunogenic Peptides as Standard for the Evaluation of Potential Harmful Prolamin Content in Food and Human Specimen.
Cebolla, Á, Moreno, ML, Coto, L, Sousa, C
Nutrients. 2018;(12)
Abstract
Gluten is a complex mixture of storage proteins in cereals like wheat, barley, and rye. Prolamins are the main components of gluten. Their high content in proline and glutamine makes them water-insoluble and difficult to digest in the gastrointestinal tract. Partial digestion generates peptide sequences which trigger immune responses in celiac and gluten-sensitive patients. Gluten detection in food is challenging because of the diversity, in various food matrices, of protein proportions or modifications and the huge number of immunogenic sequences with differential potential immunoactivity. Attempts to develop standard reference materials have been unsuccessful. Recent studies have reported the detection of a limited number of dominant Gluten Immunogenic Peptides (GIP) that share similarities to epitopes presented in the α-gliadin 33-mer, which showed to be highly proteolytic resistant and is considered to be the most immunodominant peptide within gluten in celiac disease (CD). GIP were detectable and quantifiable in very different kind of difficult to analyze food, revealing the potential immunogenicity by detecting T-cell activity of celiac patients. But GIP were also found in stool and urine of celiac patients on a supposedly gluten-free diet (GFD), showing the capacity to resist and be absorbed and excreted from the body, providing the first simple and objective means to assess adherence to the GFD. Methods to specifically and sensitively detect the most active GIP in food and biological fluids are rational candidates may use similar analytical standard references for determination of the immunopathological risk of gluten exposure in gluten-related diseases.
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7.
Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm.
Losurdo, G, Principi, M, Iannone, A, Amoruso, A, Ierardi, E, Di Leo, A, Barone, M
World journal of gastroenterology. 2018;(14):1521-1530
Abstract
Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.
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8.
Non-celiac gluten sensitivity: All wheat attack is not celiac.
Igbinedion, SO, Ansari, J, Vasikaran, A, Gavins, FN, Jordan, P, Boktor, M, Alexander, JS
World journal of gastroenterology. 2017;(40):7201-7210
Abstract
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.
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9.
Celiac Disease and Gluten Sensitivity.
DeGeorge, KC, Frye, JW, Stein, KM, Rollins, LK, McCarter, DF
Primary care. 2017;(4):693-707
Abstract
Celiac disease is an immune-mediated enteropathy triggered by gluten that affects genetically predisposed individuals, typically causing intestinal symptoms and malabsorption. Diagnosis requires stepwise evaluation with anti-tissue transglutaminase IgA and histologic analysis of the small bowel. Strict adherence to a gluten-free diet is the primary treatment. Patients with symptoms thought to be related to gluten but without evidence of celiac disease are difficult to diagnose and treat. Consider first advising general nutritional improvements. If symptoms persist, involve a trained dietitian for restrictive diets and consider evaluation for small intestinal bacterial overgrowth or other treatments for irritable bowel syndrome.