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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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2.
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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3.
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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4.
Mechanisms and management of refractory coeliac disease.
van Gils, T, Nijeboer, P, van Wanrooij, RL, Bouma, G, Mulder, CJ
Nature reviews. Gastroenterology & hepatology. 2015;(10):572-9
Abstract
A small subset of patients with coeliac disease become refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. The most common cause of this condition is inadvertent gluten exposure, but concomitant diseases leading to villous atrophy should also be considered and excluded. After exclusion of these conditions, patients are referred to as having refractory coeliac disease, of which two categories are recognized based on the absence (type I) or presence (type II) of a clonal expansion of premalignant intraepithelial lymphocyte population with a high potential for transformation into an overt enteropathy-associated T-cell lymphoma. Type I disease usually has a benign course that can be controlled by mild immunosuppressive treatment, but type II can be more severe with cladribine with or without autologous stem cell transplantation effective as treatment. Patients who fail to respond to cladribine therapy, however, still have a high risk of malignant transformation. Insights into the immunophenotype of these cells and the recognition that type II disease is a low-grade, no-mass lymphoma opens avenues for new treatment strategies, including chemotherapeutic and immunomodulating strategies. This Review will provide an overview of refractory coeliac disease, discussing mechanisms, diagnosis and management.
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5.
Enteropathy-associated T-cell lymphoma: improving treatment strategies.
Nijeboer, P, Malamut, G, Mulder, CJ, Cerf-Bensussan, N, Sibon, D, Bouma, G, Cellier, C, Hermine, O, Visser, O
Digestive diseases (Basel, Switzerland). 2015;(2):231-235
Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a rare and usually rapidly fatal intestinal T-cell non-Hodgkin lymphoma. It arises from intraepithelial lymphocytes and has a high association with coeliac disease. The high mortality of EATL is associated not only with the very aggressive and often chemotherapy-refractory nature of the lymphoma. The poor condition of patients due to prolonged and severe malnutrition compromises the ability to deliver chemotherapy. There are no standardized treatment protocols, and the optimal therapy for EATL remains unclear. The primary step of treatment consists of local debulking, preferably as early as possible after EATL diagnosis. Morbidity and mortality seem to rise with advanced stages of disease due to tumour size progression, worse nutritional status and a higher risk of emergency surgery due to perforation. Standard induction therapy for EATL is anthracycline-based chemotherapy, preferably resumed between 2 and 5 weeks after surgery (depending on clinical condition). Intensification of therapy using high-dose chemotherapy followed by consolidation with BEAM and autologous stem cell transplantation is associated with better outcome. Notably, this treatment strategy has only been applied in patients eligible for this aggressive regimen which might reflect selection bias. Unfortunately, prognosis of EATL remains poor; 5-year survival varies from 8 to 60% depending on the eligibility to receive additional steps of therapy. New treatment strategies are urgently needed for a better prognosis of this lethal complication of coeliac disease. Brentuximab vedotin (anti-CD30) might be promising when added to conventional chemotherapy and is suggested as upfront treatment in EATL.
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6.
Preventing complications in celiac disease: our experience with managing adult celiac disease.
Mulder, CJ, Wierdsma, NJ, Berkenpas, M, Jacobs, MA, Bouma, G
Best practice & research. Clinical gastroenterology. 2015;(3):459-68
Abstract
Celiac disease is, as we know it, rather than being a rare and incurable disease until the 1950's, both quite common in screening studies and readily treatable. Three conditions are triggered by gluten consumption: celiac disease, the skin rash dermatitis herpetiformis and gluten ataxia. We describe our follow up for out clinic management, as evidence based data about such an approach are lacking in current literature. No food, beverages or medications containing any amount of gluten can be taken. Compliance is often difficult especially when patients are asymptomatic. We control a cohort, in daily practice, of over 700 adult patients. The majority of patients manage the diet without any problems. We describe our follow up in general, for serology, laboratory and histology. Forty percent of our newly diagnosed celiac patients do have a BMI over 25 kg/m(2). An appropriate attitude for this problem is lacking. The problem of slowly weaning off Dapsone over 5-10 years in DH is recognized. The bone density is checked in all newly diagnosed celiac patients. We control, if necessary, by telephone and lab controls done in local cities and see our patients only every two years face-to-face for follow up. The main question is if the adherence to a GFD, quality of life and prevention of complications is improved by visiting a dedicated celiac clinic. We hope to standardize this attitude on evidence data in the years to come.
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7.
[Coeliac disease and dentistry].
van Gils, T, de Boer, NK, Bouma, G
Nederlands tijdschrift voor tandheelkunde. 2015;(9):443-8
Abstract
Coeliac disease is a chronic autoimmune enteropathy, which is caused by exposure to dietary gluten in genetically pre-disposed individuals. -Approximately 0.5-1% of the Dutch population has coeliac disease, diag-nosed at both younger and older age. Treatment consists of a strict gluten-free diet. Symptoms can be diverse, including dental and oral manifestations. These dental and oral manifestations are often seen in patients with coeliac disease, although most of them are nonspecific. This is not the case for the symmetric enamel defects described by Aine and colleagues, which are very specific for coeliac disease. Early diagnosing of coeliac disease is important to prevent complications by (vitamin) deficiencies or rare (pre) malignant forms of coeliac disease. There seems to be a role for dentists in early diagnosing of coeliac disease.
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8.
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.
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9.
Gluten-free diet in gluten-related disorders.
Mulder, CJ, van Wanrooij, RL, Bakker, SF, Wierdsma, N, Bouma, G
Digestive diseases (Basel, Switzerland). 2013;(1):57-62
Abstract
A gluten-free diet (GFD) is recommended for all patients with coeliac disease (CD). The spectrum of gluten-related disorders in the early 1980s was simple: CD and dermatitis herpetiformis. In the last few years, wheat allergy, gluten ataxia and noncoeliac gluten sensitivity have become new gluten-related topics. Adherence to GFDs in CD is limited and factors influencing adherence are poorly understood. Noncoeliac gluten sensitivity has stimulated the GFD food industry not only in Australia but all over the world. This article provides an overview of GFD in daily practice.
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10.
[Non-coeliac gluten sensitivity: hype, or new epidemic?].
Nijeboer, P, Mulder, C, Bouma, G
Nederlands tijdschrift voor geneeskunde. 2013;(21):A6168
Abstract
Coeliac disease is an immune-mediated inflammation of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically sensitive individuals. Recently, a novel gluten-related disorder has gained significant interest from the scientific community and mass media. This condition, known as non-coeliac gluten sensitivity, is characterised by gastrointestinal or extra-intestinal symptoms that respond to gluten withdrawal without evidence of underlying coeliac disease. Its symptoms overlap considerably with those of irritable bowel syndrome and the number of individuals embracing a gluten-free diet is rapidly growing. No discriminative markers to support a diagnosis of gluten sensitivity have been identified; the perceived response to a gluten-free diet after exclusion of coeliac disease is currently the best diagnostic and therapeutic marker. Its pathogenesis remains obscure but may be related to non-gliadin molecules in grains that stimulate the innate immune system of the intestine. Here, we summarise the current knowledge on this novel condition.