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1.
Celiac disease: New therapies on the horizon.
Dieckman, T, Koning, F, Bouma, G
Current opinion in pharmacology. 2022;:102268
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Abstract
Celiac Disease (CeD) is a chronic intestinal disease which occurs in 0.7-1.4% of the global population. Since the discovery of gluten as its disease-inducing antigen, CeD patients are treated with a gluten-free diet which is effective but has limitations for certain groups of patients. Accordingly, over the past few years, there is a growing interest in alternative treatment options. This review summarizes emerging pharmacological approaches, including tolerance induction strategies, tissue transglutaminase inhibition, gluten degradation, and inhibition of interleukin (IL)-15.
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Oral health and salivary function in ulcerative colitis patients.
Goldinova, A, Tan, CX, Bouma, G, Duijvestein, M, Brand, HS, de Boer, NK
United European gastroenterology journal. 2020;(9):1067-1075
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Abstract
BACKGROUND Although ulcerative colitis primarily involves the colon, extra-intestinal manifestations are common and oral and dental complaints are no exception. OBJECTIVE This study aims at evaluating oral and dental health problems and salivary function and composition in ulcerative colitis patients and its correlation with disease activity. METHODS Xerostomia Inventory score, (unstimulated/stimulated) salivary flow rates, salivary amylase and mucin/ Mucin 5B levels, self-reported oral and dental complaints, the oral health related quality of life, Simple Clinical Colitis Activity Index and inflammatory bowel disease-specific health related quality of life were determined. RESULTS The cohort consisted of 51 ulcerative colitis patients. Hyposalivation was experienced by 16% of patients under resting conditions and 24% under chewing-stimulated conditions. Xerostomia was not correlated with salivary flow rates. Disease activity did not influence salivary amylase and Mucin 5B concentrations. The Xerostomia Inventory score was correlated with the Simple Clinical Colitis Activity Index (p = 0.042) and inflammatory bowel disease-specific health related quality of life (p = 0.001). Most reported oral health problems were halitosis (29%) and aphthae (28%). Frequently reported dental problems were cavities (35%) and gum problems (31%). Patients with active disease experienced significantly more oral and dental complaints. The number of oral problems was positively correlated with the Simple Clinical Colitis Activity Index (p = 0.045) and negatively correlated with the inflammatory bowel disease-specific health related quality of life (p = 0.005). CONCLUSION The subjective feeling of a dry mouth (xerostomia) is related to disease activity and disease activity-associated quality of life in ulcerative colitis patients, whereas the objective saliva secretion rate is not. Oral and dental health problems are frequently observed in patients with ulcerative colitis, especially during active disease.
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The Neuropathology of Gluten-Related Neurological Disorders: A Systematic Review.
Rouvroye, MD, Zis, P, Van Dam, AM, Rozemuller, AJM, Bouma, G, Hadjivassiliou, M
Nutrients. 2020;12(3)
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Plain language summary
Coeliac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. A wide range of extraintestinal manifestations has been attributed to CD, changing the classic perception of a disease limited to the intestine, to a multisystem disorder. The aim of this study was to analyse the published neuropathology of confirmed cases of gluten-related neurological dysfunction to aid our understanding of the pathogenesis. CD can therefore manifest with dental problems, consequences of malabsorption, skin and neurological disorders. This study is a systematic review of thirty-two neurological disorder focused studies. Results show that: - the neuropathological findings in gluten-related neurological disorders are widespread and not limited to the cerebellum. - the pathology is immune mediated and not related to vitamin or trace elements deficiencies. - the pathophysiology of neurological damage in the context of gluten sensitivity has an immune mediated basis. - more gluten-related neurological disorders affected men (57%), which was even higher in the ataxia group (76%). - transglutaminase 6 antibodies might be helpful in the diagnostic workup of gluten-related neurological disorders. Authors conclude that the current evidence is suggestive of both humoral and cell-mediated immunological responses. Further research is required to investigate the underlying neuropathological mechanism by characterisation of the inflammatory cell infiltrate and identification of target epitopes.
Abstract
Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated enteropathy is triggered by gluten in genetically predisposed individuals. The underlying pathological mechanism of the neurological dysfunction is not yet clear. The aim of this review is to collate existing neuropathological findings in GRND as a means of aiding the understanding of the pathophysiology. A systematic search of the Pubmed Database yielded 188 articles, of which 32 were included, containing 98 eligible cases with a description of pathological findings in GRND. In gluten ataxia, loss of Purkinje cells, atrophy, gliosis and astrocytosis were apparent, as well as diffuse lymphocytic infiltration and perivascular cuffing with lymphocytes. In patients with large-fiber neuropathy, nerve biopsies revealed axonopathy, loss of myelinated fibers and focal and perivascular infiltration by inflammatory cells. Inflammatory infiltrate was also observed in muscle in myopathy and in cerebrum of patients with encephalopathy and patients with epilepsy. Such changes were not seen in skin biopsies from patients with small fiber neuropathies. The findings from this systematic review suggest an immune mediated pathogenesis for GRND. Future research should focus on the characterization of the inflammatory cell infiltrates and identifying target epitopes.
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Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease).
Sergi, C, Shen, F, Bouma, G
World journal of gastroenterology. 2017;(4):573-589
Abstract
The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy (GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinico-pathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences "across oceans" among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21st century.
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The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update.
Catassi, C, Alaedini, A, Bojarski, C, Bonaz, B, Bouma, G, Carroccio, A, Castillejo, G, De Magistris, L, Dieterich, W, Di Liberto, D, et al
Nutrients. 2017;(11)
Abstract
Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.
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Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.
Catassi, C, Elli, L, Bonaz, B, Bouma, G, Carroccio, A, Castillejo, G, Cellier, C, Cristofori, F, de Magistris, L, Dolinsek, J, et al
Nutrients. 2015;(6):4966-77
Abstract
Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.
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Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.
Catassi, C, Bai, JC, Bonaz, B, Bouma, G, Calabrò, A, Carroccio, A, Castillejo, G, Ciacci, C, Cristofori, F, Dolinsek, J, et al
Nutrients. 2013;(10):3839-53
Abstract
Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a "re-discovered" disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.